September 2014

The Pharmacist’s News Source

pharmacypracticenews.com

Volume 41 • Number 9 • September 2014

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in this issue UP FRONT

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Readers sound off on medical marijuana.

CLINICAL

8 10

History of herbal medicine comes to the masses via exhibit, app.

Tips for enhancing quality, safety of insulin therapy.

TECHNOLOGY

13

Navigating the barcode-assisted medication preparation market.

OPERATIONS & MGMT

17 22

Taking the sting out of a $3K specialty pharmacy deductible.

Site-of-care cost shifting in crosshairs of CMS.

Filgrastim BLA Approval Nears; Hospitals Ready?

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Post-discharge hospital use cut nearly in half

Pharmacists Spearheading Lower-Cost ‘Medical Homes’

ith the recent announcement that the FDA has accepted its first biologics license application (BLA) for a biosimilar version of filgrastim, many stakeholders are wondering how the drug will affect formulary decision-making and other drug-stocking protocols.

But according to Robert Adamson, PharmD, the vice president of clinical pharmacy services at Barnabas Health, in West Orange, N.J., the model for handling biosimilars in the United States has already been created in many hospitals. Indeed, most facilities will probably handle the drugs the same way they manage many other products, including immune globulin.

“When a physician writes an order for IVIG [IV immune globulin] in the hospital, the pharmacy selects whatever one they have on their formulary,” Dr. Adamson said.

“IVIG comes from various donors around the country and is made

new community-based, pharmacist-centered initiative could be a lower cost alternative to patient-centered medical homes (PCMHs). The model, named the Primary Care Resource Center (PCRC), uses small teams composed of one pharmacist, three nurse care managers and an administrative person to provide the type of care coordination and medication management that is delivered by larger PCMHs.

see FILGRASTIM BLA, page 7

see MEDICAL HOME, page 20

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The Primary Care Resource Center (PCRC) provides care coordination and medication management.

Here, Thanh Lam, PharmD, reviews inhaler technique with a patient in the Butler Hospital PCRC.

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WEB EXCLUSIVES

pharmacypracticenews.com W Ernie Anderson Jr., MS, RPh, on knowing oneself as a powerful tool for effective pharmacy leadership.

Web Portal Helps Cancer Patients Control Symptoms

W A BMJ investigation linking dabigatran to a spike in major bleeds has sparked debate about whether recipients should have plasma drug concentrations monitored.

ith the aid of a Web-based assessment tool, patients undergoing chemotherapy can rein in the severity of their symptoms and stress, according to a study by investigators at Harvard Medical School and the University of Washington.

“If we can give [patients] support in the comfort of their own homes— or on their cell phones—without requiring a trip to the clinic, we can

W In wake of Robin Williams’ suicide, tips for counseling patients on the interplay between antidepressants and Parkinson’s disease.

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see PATIENT PORTAL, page 15

Are Hospitals Still Striking Out On Key Med Safety Standards?

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ospitals appear to be in a two-year slump when it comes to complying with potentially lifesaving medication safety standards. And much like baseball managers who often take the fall for their players’ failure to perform at peak levels, pharmacy directors are at risk for termination if they can’t get their staffers to toe the line when it comes to following safe medication practices.

That was the message espoused during a recent Institute for Safe Medication Practices (ISMP) webinar, where the lagging statistics on medication safety were front and center.

New Product FDA approves Plegridy for relapsing multiple sclerosis.

See page 19

Indeed, as many as 35% of hospitals surveyed by the Joint Commission in 2013 did not comply with medication-related standards in 2013, according to data provided by webinar presenters. The rates of noncompliance remained nearly unchanged between 2012 and 2013, and the most frequent issues were related to drug storage, ordering, pharmacist order reviews, improper labeling and medication reconciliations (Table, page 18).

The findings prompted Darryl Rich, PharmD, MBA, a medication safety specialist

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see JOINT COMMISSION, page 18

NOW available! iPad App

Is IV Ibuprofen the Missing Piece to Your Surgical Pain Management Puzzle?

BRIEF SUMMARY OF PRESCRIBING INFORMATION CALDOLOR ® (ibuprofen) Injection WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS Cardiovascular Risk • Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk [see Warnings and Precautions (5.1)].

• Caldolor is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4.3) and Warnings and Precautions (5.1)].

Gastrointestinal Risk • NSAIDs increase the risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events [see Warnings and Precautions (5.2)].

1 INDICATIONS AND USAGE: 1.1 Analgesia (Pain): Caldolor is indicated in adults for the management of mild to moderate pain and the management of moderate to severe pain as an adjunct to opioid analgesics.

1.2 Antipyretic (Fever): Caldolor is indicated for the reduction of fever in adults.

4 CONTRAINDICATIONS 4.1 HYPERSENSITIVITY: Caldolor is contraindicated in patients with known hypersensitivity (e.g., anaphylactoid reactions and serious skin reactions) to ibuprofen [see Warnings and Precautions (5.7, 5.8)].

4.2 ASTHMA AND ALLERGIC REACTIONS: Caldolor is contraindicated in patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal anaphylactic-like reactions to NSAIDs have been reported in such patients [see Warnings and Precautions (5.7, 5.12)].

4.3 CORONARY ARTERY BYPASS GRAFT (CABG): Caldolor is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery [see Warnings and Precautions (5.1)].

5 WARNINGS AND PRECAUTIONS: 5.1 Cardiovascular Thrombotic Events: Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur. Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke [see Contraindications (4.3)].

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious gastrointestinal (GI) events [see Warnings and Precautions (5.2)]. 5.2 Gastrointestinal Effects: Risk of Ulceration, Bleeding, and Perforation: NSAIDs, including ibuprofen, can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately

1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue ysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the and symptoms of serious skin manifestations, and to discontinue Caldolor at the first appearance of skin rash course of therapy. However, even short-term therapy is not without risk. Prescribe NSAIDs, including Caldolor, or any other sign of hypersensitivity. 5.9 Pregnancy: Starting at 30 weeks gestation, Caldolor, and other NSAIDs, with extreme caution in those with a prior history of ulcer disease or GI bleeding. Patients with a prior history should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may occur [see of peptic ulcer disease and/or GI bleeding who use NSAIDs have a greater than 10-fold increased risk for devel- Use in Specific Populations (8.1)]. 5.10 Masking Inflammation and Fever: The pharmacological activity of oping a GI bleed compared to treated patients with neither of these risk factors. Other factors that increase the ibuprofen in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting risk of GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoag- complications of presumed noninfectious, painful conditions. 5.11 Hematological Effects: Caldolor must be ulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most diluted prior to use. Infusion of the drug product without dilution can cause hemolysis [see Dosage and reports of spontaneous fatal GI events are in elderly or debilitated patients, and therefore special care should be Administration (2.3)]. Anemia may occur in patients receiving NSAIDs, including ibuprofen. This may be due to taken in treating this population. To minimize the potential risk for an adverse GI event in patients treated with fluid retention, occult or gross GI blood loss, or an incompletely described effect on erythropoiesis. In patients an NSAID, use the lowest effective dose for the shortest possible duration. Patients and physicians should remain on long-term treatment with NSAIDs, including ibuprofen, check hemoglobin or hematocrit if they exhibit any alert for signs and symptoms of GI ulcerations and bleeding during NSAID therapy and promptly initiate addi- signs or symptoms of anemia or blood loss. NSAIDs inhibit platelet aggregation and have been shown to protional evaluation and treatment if a serious GI event is suspected. This should include discontinuation of the long bleeding time in some patients. Unlike aspirin, their effects on platelet function are less severe quantitatively, NSAID until a serious GI adverse event is ruled out. For high-risk patients, alternate therapies that do not involve of shorter duration, and reversible. Carefully monitor patients who may be adversely affected by alterations in NSAIDs should be considered. 5.3 Hepatic Effects: Borderline elevations of one or more liver tests may occur platelet function, such as those with coagulation disorders or patients receiving anticoagulants. 5.12 Pre-existing in up to 15% of patients taking NSAIDs, including ibuprofen. These laboratory abnormalities may progress, may Asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirinremain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approxi- sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross-reactivity mately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clin- between aspirin and NSAIDs has been reported in such aspirin-sensitive patients, including bronchospasm, ical trials with NSAIDs. In addition, rare cases of severe hepatic reactions have been reported, including jaundice, Caldolor is contraindicated in patients with this form of aspirin sensitivity and should be used with caution in all fulminant hepatitis, liver necrosis and hepatic failure, some with fatal outcomes. A patient with symptoms and/or patients with pre-existing asthma. 5.13 Ophthalmological Effects: Blurred or diminished vision, scotomata, and signs suggesting liver dysfunction, or with abnormal liver test values, should be evaluated for evidence of the changes in color vision have been reported with oral ibuprofen. Discontinue ibuprofen if a patient develops such development of a more severe hepatic reaction while on therapy with ibuprofen. If clinical signs and symptoms con- complaints, and refer the patient for an ophthalmologic examination that includes central visual fields and color sistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), ibuprofen vision testing. 5.14 Aseptic Meningitis: Aseptic meningitis with fever and coma has been observed in patients should be discontinued. 5.4 Hypertension: NSAIDs, including ibuprofen, can lead to onset of new hyper- on oral ibuprofen therapy. Although it is probably more likely to occur in patients with systemic lupus erythetension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of matosus and related connective tissue diseases, it has been reported in patients who do not have underlying CV events. Use NSAIDs, including ibuprofen, with caution in patients with hypertension. Monitor blood pressure chronic disease. If signs or symptoms of meningitis develop in a patient on ibuprofen, give consideration to closely during the initiation of NSAID treatment and throughout the course of therapy. Patients taking ACE whether or not the signs or symptoms are related to ibuprofen therapy. 5.15 Monitoring: Because serious GI tract inhibitors, thiazides, or loop diuretics may have impaired response to these therapies when taking NSAIDs. ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms 5.5 Congestive Heart Failure and Edema: Fluid retention and edema have been observed in some patients tak- of GI bleeding. Patients on long-term treatment with NSAIDs should have CBC and chemistry profiles checked ing NSAIDs. Use Caldolor with caution in patients with fluid retention or heart failure. 5.6 Renal Effects: Use cau- periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestation when initiating treatment with Caldolor in patients with considerable dehydration. Long-term administration tions occur (e.g., eosinophilia, rash), or abnormal liver tests persist or worsen, discontinue Caldolor. of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in 6 ADVERSE REACTIONS: The following serious adverse reactions are discussed elsewhere in the labeling: patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these • Cardiovascular thrombotic events [see Boxed Warning and Warnings and Precautions (5.1)] patients, administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and, sec- • Gastrointestinal effects [see Boxed Warning and Warnings and Precautions (5.2)] ondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this • Hepatic effects [see Warnings and Precautions (5.3)] reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics or ACE • Hypertension [see Warnings and Precautions (5.4)] inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment • Congestive heart failure and edema [see Warnings and Precautions (5.5)] state. No information is available from controlled clinical studies regarding the use of Caldolor in patients with • Renal effects [see Warnings and Precautions (5.6)] advanced renal disease. If Caldolor therapy must be initiated in patients with advanced renal disease, closely mon- • Anaphylactoid reactions [see Warnings and Precautions (5.7)] itor the patient’s renal function. 5.7 Anaphylactoid Reactions: As with other NSAIDs, anaphylactoid reactions • Serious skin reactions [see Warnings and Precautions (5.8)] may occur in patients without known prior exposure to ibuprofen. Caldolor is contraindicated in patients with The most common adverse reactions reported in clinical studies are nausea, flatulence, vomiting, and headache. the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or The most common reason for discontinuation due to adverse events in controlled trials of Caldolor is pruritus (<1%). without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs 6.1 Clinical Studies Experience: Because clinical trials are conducted under widely varying conditions, adverse [see Contraindications (4.2)]. 5.8 Serious Skin Reactions: NSAIDs, including ibuprofen, can cause serious skin reaction rates observed in the clinical trials of a drug cannot be compared directly to rates in the clinical trials of adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrol- another drug and may not reflect the rates observed in practice. During clinical development, 560 patients were

• Caldolor reduces surgical pain1,2,3 • Caldolor can be used prior to surgery1 • Caldolor reduces narcotic consumption1 • Caldolor offers an Anti-Inflammatory action3

> Caldolor offers New Price Assurance Program For more information, please contact Caldolor@CumberlandPharma.com

Caldolor is indicated in adults for the management of:3 • Mild to moderate pain • Moderate to severe pain as an adjunct to opioid analgesics • Reduction of fever • Caldolor must be diluted prior to use. Infusion of the drug product without dilution can cause hemolysis.3 • The most common adverse reactions are nausea, flatulence, vomiting, headache, hemorrhage, and dizziness (>5%).3 1. Singla N, Rock A, Pavliv L. Pain Med. 2010; 11: 1284-93.

2. Data on file, Cumberland Pharmaceuticals Inc. Nashville, TN. 3. Prescribing Information for Caldolor, 2014. Cumberland Pharmaceuticals Inc. Nashville, TN.

See full Prescribing Information including Boxed Warning at www.Caldolor.com exposed to Caldolor, 438 in pain and 122 with fever. In the pain studies, Caldolor was started intra-operatively and administered at a dose of 400 mg or 800 mg every six hours for up to three days. In the fever studies, Caldolor was administered at doses of 100 mg, 200 mg, or 400 mg every four or six hours for up to 3 days. The most frequent type of adverse reaction occurring with oral ibuprofen is gastrointestinal. Pain Studies: The incidence rates of adverse reactions listed in the following table were derived from multi-center, controlled clinical studies in post-operative patients comparing Caldolor to placebo in patients also receiving morphine as needed for post-operative pain.

Table 1: Post-operative Patients with Adverse Reactions Observed in ≥ 3% of Patients in any Caldolor Treatment Group in Pain Studies* Caldolor 400 mg 800 mg Placebo Event (N=134) (N=304) (N=287) Any Reaction 118 (88%) 260 (86%) 258 (90%) Nausea 77 (57%) 161 (53%) 179 (62%) Vomiting 30 (22%) 46 (15%) 50 (17%) Flatulence 10 (7%) 49 (16%) 44 (15%) Headache 12 (9%) 35 (12%) 31 (11%) Hemorrhage 13 (10%) 13 (4%) 16 (6%) Dizziness 8 (6%) 13 (4%) 5 (2%) Edema peripheral 1 (<1%) 9 (3%) 4 (1%) Urinary retention 7 (5%) 10 (3%) 10 (3%) Anemia 5 (4%) 7 (2%) 6 (2%) Decreased hemoglobin 4 (3%) 6 (2%) 3 (1%) Dyspepsia 6 (4%) 4 (1%) 2 (<1%) 4 (3%) 4 (1%) 4 (1%) Wound hemorrhage Abdominal discomfort 4 (3%) 2 (<1%) 0 Cough 4 (3%) 2 (<1%) 1 (<1%) Hypokalemia 5 (4%) 3 (<1%) 8 (3%) * All patients received concomitant morphine during these studies.

Fever Studies: Fever studies were conducted in febrile hospitalized patients with malaria and febrile hospitalized patients with varying causes of fever. In hospitalized febrile patients with malaria, the adverse reactions observed in at least two Caldolor-treated patients included abdominal pain and nasal congestion. In hospitalized febrile patients (all causes), adverse reactions observed in more than two patients in any given treatment group are presented in the table below.

Table 2: Patients with Adverse Reactions Observed in ≥ 3% of Patients in any Caldolor Treatment Group in All-Cause Fever Study Caldolor 100 mg 200 mg 400 mg Placebo Event N=30 N=30 N=31 N=28 Any Reaction 27 (87%) 25 (83%) 23 (74%) 25 (89%) Anemia 5 (17%) 6 (20%) 11 (36%) 4 (14%) Eosinophilia 7 (23%) 7 (23%) 8 (26%) 7 (25%) Hypokalemia 4 (13%) 4 (13%) 6 (19%) 5 (18%) Hypoproteinemia 3 (10%) 0 4 (13%) 2 (7%) Neutropenia 2 (7%) 2 (7%) 4 (13%) 2 (7%) Blood urea increased 0 0 3 (10%) 0 Hypernatremia 2 (7%) 0 3 (10%) 0 Hypertension 0 0 3 (10%) 0 Hypoalbuminemi 3 (10%) 1 (3%) 3 (10%) 1 (4%) Hypotension 0 2 (7%) 3 (10%) 1 (4%) Diarrhea 3 (10%) 3 (10%) 2 (7%) 2 (7%) Pneumonia bacterial 3 (10%) 1 (3%) 2 (7%) 0 Blood LDH increased 3 (10%) 2 (7%) 1 (3%) 1 (4%) Thrombocythemia 3 (10%) 2 (7%) 1 (3%) 0 Bacteremia 4 (13%) 0 0 0 7 DRUG INTERACTIONS: 7.1 Aspirin: When ibuprofen is administered with aspirin, ibuprofen’s protein binding is reduced, although the clearance of free ibuprofen is not altered. The clinical significance of this interaction is not known; however, as with other NSAIDs, concomitant administration of Caldolor and aspirin is not generally recommended because of the potential for increased adverse effects. 7.2 Anticoagulants: The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that the users of both drugs together have a higher risk of serious GI bleeding than users of either drug alone [see Warnings and Precautions (5.2)]. 7.3 ACE Inhibitors: NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors. 7.4 Diuretics: Clinical studies and postmarketing observations have shown that ibuprofen can reduce the natriuretic effects of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, observe patients closely for signs of renal failure, as well as to assure diuretic efficacy [see Warnings and Precautions (5.6)]. 7.5 Lithium: NSAIDs have produced elevations of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance of lithium decreased by 20%. This effect has been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, observe patients carefully for signs of lithium toxicity. 7.6 Methotrexate: NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This indicates that NSAIDs may enhance the toxicity of methotrexate. Use caution when NSAIDs are administered concomitantly with methotrexate. 7.7 H-2 Antagonists: In studies of human volunteers, co-administration of cimetidine or ranitidine with ibuprofen had no substantive effect on ibuprofen serum concentrations.

8 USE IN SPECIFIC POPULATIONS: 8.1 Pregnancy: Teratogenic effects - Pregnancy Category C prior to 30 weeks gestation; Category D starting at 30 weeks gestation. Starting at 30 weeks gestation, Caldolor, and other NSAIDs, should be avoided by pregnant women as premature closure of the ductus arteriosus in the fetus may

occur. Caldolor can cause fetal harm when administered to a pregnant woman starting at 30 weeks gestation.

There are no adequate, well-controlled studies in pregnant women. Prior to 30 weeks gestation, Caldolor should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Reproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. 8.2 Labor and Delivery: The effects of Caldolor on labor and delivery in pregnant women are unknown. In rat studies, maternal exposure to NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, increased the incidence of dystocia and delayed parturition, and decreased pup survival. 8.3 Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Caldolor, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use: Safety and effectiveness of Caldolor for management of pain and reduction of fever has not been established in pediatric patients below the age of 17 years. 8.5 Geriatric Use: Clinical studies of Caldolor did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients are at increased risk for serious GI adverse events.

10 OVERDOSAGE: The following signs and symptoms have occurred in individuals following an overdose of oral ibuprofen: abdominal pain, nausea, vomiting, drowsiness, and dizziness. There are no specific measures to treat acute overdosage with Caldolor. There is no known antidote to ibuprofen. In case of an overdosage, discontinue Caldolor therapy and consider contacting a regional poison control center at 1-800-222-1222.

Manufactured for: Cumberland Pharmaceuticals Inc., Nashville, TN 37203 US Patent Number 6,727,286

PAD1470714

©2014 Cumberland Pharmaceuticals Inc. All rights reserved.

4 Up Front

Pharmacy Practice News • September 2014

Letters Four Reasons for Forgoing The Marijuana Business Re: ‘If Pot Is a Drug, Why Aren’t More Pharmacists Involved?’ (June 2014, page 1)

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here are many reasons pharmacists may not want to be involved with medical marijuana. Here are mine: 1) It has already become a huge business, mainly for recreational use. I am not against the use of the drug, but I have yet to see any peer-reviewed studies supporting its medicinal qualities. 2) It is a drug, but so is alcohol and nicotine, and we don’t dispense those substances; most pharmacies sell them as a front-end product. 3) How would the supply chain work? Would we have to grow our own pot plants? Would we also offer food products infused with marijuana? 4) Banks are reluctant to get involved, so that’s why the “dispensaries” accept cash only, making them a target for robbery, resulting in the necessity for a high level of security. I don’t want to deal with all of that (no pun intended). However, now speaking not as a pharmacist but as a citizen, I think it is ridiculous to have our jails filled with nonviolent users.

Pot Is No Drug

Regulation, Not Criminalization

Re: ‘If Pot Is a Drug, Why Aren’t More Pharmacists Involved?’ (June 2014, page 1)

Re: ‘NIDA Study Cites Dangers of Marijuana Use in Teens’ (July 2014, page 14)

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ore pharmacists aren’t involved because we can see that the “medical” category is just a temporary phase on the pathway to recreational status (like alcohol). And that is where it should be. Marijuana is no more a medication than alcohol. I don’t object to marijuana, but I do object that it is referred to as “medical” or “medicinal.” If it was medicine, it would be tested, vetted and the FDA would regulate it.

—jeffr … via Web comment, 6/13/2014

A Sherlock Moment Re: ‘NIDA Study Cites Dangers of Marijuana Use in Teens’ (July 2014, page 14)

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ow … marijuana is dangerous. You mean lighting something on fire and sucking in the smoke is unhealthy? Shocking.

—atjco … via Web comment, 6/15/2014

Talk Is Cheap— Actions Matter Re: ‘ASHP Highlights Need for Strong Ambulatory Pharmacy Biz Models: Part 3 of a 4-Part Series’ (July 2014, page 1)

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nce again, ASHP [American Society of Health-System Pharmacists] promotes pharmacist advancement with no clear path for documentation or selfevaluation of our value and impact. The statement that “once pharmacists have … gathered outcomes and cost data via IT systems …” demonstrates the dream world in which our thought leaders live.

Until there are clear-cut metrics and information systems that can actually extract

have more of a question than a comment: In light of this evidence, wouldn’t we be acting more responsibly by regulating cannabis rather than allowing the current situation to continue? As it is now, children often obtain cannabis from black-market dealers who don’t care about their age and who also often have harder drugs available, as well. They don’t call them pushers for nothing and this exposure certainly exacerbates our drug problem.

If we put marijuana sales into the hands of responsible retailers who are licensed to sell the substance and who are at risk for losing that license by selling to underaged children, wouldn’t we be making this situation better?

—rchar … via Web comment, 7/24/2014

such data to assess just what benefit pharmacists provide to patient care, we will be swimming upstream. Unless health care IT systems magically align themselves to permit effective analysis of the effects of pharmacist intervention—and the bean counters agree on the actual value of said interventions—we will be endlessly documenting what we do and letting someone else figure out what it is ultimately worth to patient care (i.e., reimbursement value). Many informed experts propose that the health care system will implode long before any of these things happen. In the meantime, doing the right thing and adding value to care

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is what we should alll be doing. Let’s get to it and recognize that talk is cheap and actions matter.

—tmccl … via Web comment, 7/17/2014

MD Rx Model Operating in Reverse Re: ‘Gap in Herpes, VTE Prevention Seen in Myeloma’ (June 2014)

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hese findings are not in the least bit surprising. When clinical pharmacists alert oncologists (many locum tenens, perhaps that’s why) to the need for herpes and VTE prophylaxis in these patients, and we make the appropriate recommendation for intervention, but

—tedwr … via Web comment, 7/18/2014

then are rejected or put off, clinicians often justify that resistance by explaining that they assess the patient’s risk on a “case-bycase basis.” Sad to say, their treatment model is operating in reverse; the case-by-case evaluation should instead be used in finding the unusual patient who is nott appropriate for prophylaxis. Choose your oncologist wisely, because obviously the risk and morbidity associated with treatment omission is concerning.

—tmccl … via Web comment, 6/24/2014

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Volume 41 • Number 9 • September 2014 • pharmacypracticenews.com

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Product Name

Fast-Acting

Long-Lasting

Betamethasone Sodium Phosphate & Betamethasone Acetate* Injectable Suspension, USP

Kenalog g速 (Triamcinolone Acetonide) Injectable Suspension, USP 速 Depo-Medrol p

(Methylprednisolone Acetate Injectable Suspension, USP)

Recommended Doses for Intra-articular Injection Size of Joint

Location

Dose (mL)

Very Large Large Medium Small (metacarpophalangeal, interphalangeal, sternoclavicular)

Hip Knee, Ankle, Shoulder Elbow, Wrist Hand, Chest

1.0 - 2.0 1.0 0.5 - 1.0 0.25 - 0.5

A portion of the administered dose of Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension is absorbed systemically following intra-articular injection. In patients being trated concomitantly with oral or parenteral corticosteroids, especially those receiving large doses, the systemic absorption of the drug should be considered in determining intra-articular dosage. For additional dosing information please refer to package insert on our website at www.DualAgentBeta.com

Kenalog速 is a registered trademark of Bristol-Myers Squibb. Depo-Medrol速 is a registered trademark of Pfizer Inc.

*Betamethasone 6 mg/mL as 3 mg/mL Betamethasone Sodium Phosphate and 3 mg/mL Betamethasone Acetate The intra-articular or soft tissue administration of Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, synovitis of osteoarthritis.

Important Safety Information: Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use.

As with any potent corticosteroid, adverse events have been associated with Betamethasone Sodium Phosphate and Betamethasone Acetate, Injectable Suspension, USP including fluid and electrolyte disturbances, as well as adverse reactions involving the following systems: allergic reactions, cardiovascular, dermatologic, endocrine, gastrointestinal, metabolic, musculoskeletal, neurological/psychiatric, and ophthalmic. Corticosteroids may also affect immune response. Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy.

Betamethasone Sodium Phosphate and Betamethasone Acetate, Injectable Suspension, USP should not be administered intravenously or used in systemic fungal infections. Vaccination administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision, to advise any medical attendants that they are taking corticosteroids and to seek medical advice at once should they develop fever or other signs of infections. Persons who are on corticosteroids should be warned to avoid exposure to chicken pox or measles and to seek medical advice without delay if exposed.

Please see next page for Brief Summary of Full Prescribing Information BB034 Rev. 7/2014

One Luitpold Drive - PO Box 9001 - Shirley, NY 11967 | 800-645-1706

www.DualAgentBeta.com

Betamethasone Sodium Phosphate and Betamethasone Acetate

Injectable Suspension, USP

6 mg per mL

Rx only DESCRIPTION Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension, USP is a sterile aqueous suspension containing betamethasone 3 mg per milliliter as betamethasone sodium phosphate, and betamethasone acetate 3 mg per milliliter. Inactive ingredients per mL: dibasic sodium phosphate 7.1 mg; monobasic sodium phosphate 3.4 mg; edetate disodium 0.1 mg; and benzalkonium chloride 0.2 mg as a preservative. The pH is adjusted to between 6.8 and 7.2.

INDICATIONS AND USAGE When oral therapy is not feasible, the intramuscular use of Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension is indicated as follows: Allergic States Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, perennial or seasonal allergic rhinitis, serum sickness, transfusion reactions.

Dermatologic Diseases Bullous dermatitis herpetiformis, exfoliative erythroderma, mycosis fungoides, pemphigus, severe erythema multiforme (Stevens-Johnson syndrome).

Endocrine Disorders Congenital adrenal hyperplasia, hypercalcemia associated with cancer, nonsuppurative thyroiditis.

Hydrocortisone or cortisone is the drug of choice in primary or secondary adrenocortical insufficiency. Synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance.

Gastrointestinal Diseases To tide the patient over a critical period of the disease in regional enteritis and ulcerative colitis.

Hematologic Disorders Acquired (autoimmune) hemolytic anemia, Diamond-Blackfan anemia, pure red cell aplasia, selected cases of secondary thrombocytopenia.

Miscellaneous Trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used with appropriate antituberculous chemotherapy.

Neoplastic Diseases For palliative management of leukemias and lymphomas.

Nervous System Acute exacerbations of multiple sclerosis; cerebral edema associated with primary or metastatic brain tumor or craniotomy.

Ophthalmic Diseases Sympathetic ophthalmia, temporal arteritis, uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids.

Renal Diseases To induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome or that due to lupus erythematosus.

Respiratory Diseases Berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, idiopathic eosinophilic pneumonias, symptomatic sarcoidosis.

Rheumatic Disorders As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis; acute rheumatic carditis; ankylosing spondylitis; psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy). For the treatment of dermatomyositis, polymyositis, and systemic lupus erythematosus.

The intra-articular or soft tissue administration of Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, synovitis of osteoarthritis.

The intralesional administration of Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension is indicated for alopecia areata; discoid lupus erythematosus; keloids; localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus (neurodermatitis), and psoriatic plaques; necrobiosis lipoidica diabeticorum.

Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension, may also be useful in cystic tumors of an aponeurosis or tendon (ganglia).

CONTRAINDICATIONS Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension is contraindicated in patients who are hypersensitive to any components of this product. Intramuscular corticosteroid preparations are contraindicated for idiopathic thrombocytopenic purpura.

WARNINGS Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension should not be administered intravenously.

Serious Neurologic Adverse Reactions with Epidural Administration Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use.

General Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroid therapy.

In patients on corticosteroid therapy subjected to any unusual stress, hydrocortisone or cortisone is the drug of choice as a supplement during and after the event.

Cardio-renal Average and large doses of corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium.

Literature reports suggest an apparent association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with corticosteroids should be used with great caution in these patients.

Endocrine Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment.

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.

Infections General Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan, or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents. These infections may be mild to severe. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of current infection.

Fungal Infections Corticosteroids may exacerbate systemic fungal infections and therefore should not be used in the presence of such infections unless they are needed to control drug reactions. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see PRECAUTIONS, Drug Interactions, Amphotericin B Injection and Potassium-Depleting Agents section).

Special Pathogens Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, and Toxoplasma. It is recommended that latent amebiasis or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea.

Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Corticosteroids should not be used in cerebral malaria.

Tuberculosis The use of corticosteroids in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen.

If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

Vaccination Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered. However, the response to such vaccines cannot be predicted Viral Infections Chickenpox and measles can have a more serious or even fatal course in pediatric and adult patients on corticosteroids. In pediatric and adult patients who have not had these diseases, particular care should be taken to avoid exposure. If exposed to chickenpox, prophylaxis with varicella zosterr immune globulin (VZIG) may be indicated.

If exposed to measles, prophylaxis with immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chicken pox develops, treatment with antiviral agents should be considered.

Neurologic Reports of severe medical events have been associated with the intrathecal route of administration (see ADVERSE REACTIONS, Gastrointestinal and Neurologic/ Psychiatric sections).

High doses of corticosteroids, including Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension, should not be used for the treatment of traumatic brain injury.

Ophthalmic Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex.

PRECAUTIONS General This product, like many other steroid formulations, is sensitive to heat. Therefore, it should not be autoclaved when it is desirable to sterilize the exterior of the vial.

The lowest possible dose of corticosteroid should be used to control the condition under treatment. When reduction in dosage is possible, the reduction should be gradual.

Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.

Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

Cardio-renal As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with congestive heart failure, hypertension, or renal insufficiency.

Endocrine Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy. Therefore, in any situation of stress occurring during that period, naturally occurring glucocorticoids (hydrocortisone cortisone), which also have salt-retaining properties, rather than betamethasone, are the appropriate choices as replacement therapy in adrenocorticoal deficiency states.

Gastrointestinal Steroids should be used with caution in active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis, since they may increase the risk of a perforation.

Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent.

There is an enhanced effect of corticosteroids in patients with cirrhosis.

Intra-Articular and Soft Tissue Administration Intra-articular injected corticosteroids may be systematically absorbed.

Appropriate examination of any joint fluid present is necessary to exclude a septic process.

A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.

Injection of a steroid into an infected site is to be avoided. Local injection of a steroid into a previously injected joint is not usually recommended.

Corticosteroid injection into unstable joints is generally not recommended.

Intra-articular injection may result in damage to joint tissues (see ADVERSE REACTIONS, Musculoskeletal section).

Musculoskeletal Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (ie, decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (ie, postmenopausal women) before initiating corticosteroid therapy.

Neuro-psychiatric Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect (see DOSAGE AND ADMINISTRATION). An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (eg, myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (eg, pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

Ophthalmic Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.

Information for Patients Patients should be warned not to discontinue the use of corticosteroids abruptly or without medical supervision, to advise any medical attendants that they are taking corticosteroids and to seek medical advice at once should they develop fever or other signs of infection.

Persons who are on corticosteroids should be warned to avoid exposure to chicken pox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.

Drug Interactions Aminoglutethimide Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression.

Amphotericin B Injection and Potassium-Depleting Agents When corticosteroids are administered concomitantly with potassium-depleting agents (ie, amphotericin-B, diuretics), patients should be observed closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.

Antibiotics Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance.

Anticholinesterases Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

Anticoagulants, Oral Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

Antidiabetics Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.

Antitubercular Drugs Serum concentrations of isoniazid may be decreased.

Cholestyramine Cholestyramine may increase the clearance of corticosteroids.

Cyclosporine Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.

Digitalis Glycosides Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.

Estrogens, Including Oral Contraceptives Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect.

Hepatic Enzyme Inducers (eg, barbiturates, phenytoin, carbamazepine, rifampin) Drugs which induce hepatic microsomal drug-metabolizing enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased.

Ketoconazole Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased riskk of corticosteroid side effects.

Nonsteroidal Anti-inflammatory Agents (NSAIDS) Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

Skin Tests Corticosteroids may suppress reactions to skin tests.

Vaccines Patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines.

Route administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS, Infections, Vaccination section).

Carcinogenesis, Mutagenesis, Impairment of Fertility No adequate studies have been conducted in animals to determine whether corticosteroids have a potential for carcinogenesis or mutagenesis.

Steroids may increase or decrease motility and number of spermatozoa in some patients.

Pregnancy Teratogenic Effects Pregnancy Category C Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well-controlled studies in pregnant women. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Nursing Mothers Systematically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when corticosteroids are administered to a nursing woman.

Pediatric Use The efficacy and safety of corticosteroids in the pediatric population are based on the well-established course of effect of corticosteroids, which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (>2 years of age), and aggressive lymphomas and leukemias (>1 month of age). Other indications for pediatric use of corticosteroids, eg, severe asthma and wheezing, are based on adequate and wellcontrolled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations.

The adverse effects of corticosteroids in pediatric patients are similar to those in adults (see ADVERSE REACTIONS). Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, thromboembolism, peptic ulcers, cataracts, and osteoporosis. Pediatric patients who are treated with corticosteroids by any route, including systematically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of HPA axis suppression (ie, cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The linear growth of pediatric patients treated with corticosteroids should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of treatment alternatives. In order to minimize the potential growth effects of corticosteroids, pediatric patients should be titrated to the lowest effective dose.

Geriatric Use No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and young patients, but greater sensitivity of some older individuals cannot be ruled out.

ADVERSE REACTIONS (listed alphabetically, under each subsection) Allergic Reactions Anaphylactoid reaction, anaphylaxis, angioedema.

Cardiovascular Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction (see WARNINGS), pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.

Dermatologic Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.

Endocrine Decreased carbohydrate and glucose tolerance, development of cushingoid state, glucosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.

Fluid and Electrolyte Disturbances Congestive heart failure in susceptible patients, fluid retention, hypokalemic alkalosis, potassium loss, sodium retention.

Gastrointestinal Abdominal distention, bowel/bladder dysfunction (after intrathecal administration), elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis.

Metabolic Negative nitrogen balance due to protein catabolism.

Musculoskeletal Aseptic necrosis of femoral and humeral heads, calcinosis (following intra-articular or intralesional use), Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, postinjection flare (following intra-articular use), steroid myopathy, tendon rupture, vertebral compression fractures.

Neurologic/Psychiatric Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychic disorders, vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration (see WARNINGS, Neurologic section).

Ophthalmic Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, rare instances of blindness associated with periocular injections.

Other Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.

OVERDOSAGE Treatment of acute overdose is by supportive and symptomatic therapy. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage of the corticosteroid may be reduced only temporarily, or alternate day treatment may be introduced.

DOSAGE AND ADMINISTRATION Benzyl alcohol as a preservative has been associated with a fatal “Gasping Syndrome” in premature infants and infants of low birth weight. Solutions used for further dilution of this product should be preservative-free when used in the neonate, especially the premature infant. The initial dosage of parenterally administered Betamethasone Sodium Phosphate and Betamethasone Acetate Injectable Suspension may vary from 0.25 to 9.0 mg per day depending on the specific disease entity being treated. However, in certain overwhelming, acute, life-threatening situations, administrations in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages.

It Should Be Emphasized That Dosage Requirements Are Variable and Must Be Individualized on the Basis of the Disease Under Treatment and the Response of the Patient.

After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.

SEE FULL PRESCRIBING INFORMATION FOR FULL DOSAGE AND ADMINISTRATION DIRECTIONS. BS1019 Revised July 2014

Clinical 7

Pharmacy Practice News • September 2014

Drug Development

FILGRASTIM BLA continued from page 1

with various levels of reagents. They are similar, but not the same.”

Dr. Adamson sees the same model working for biosimilar products once they receive approval in the United States. This is likely to be sooner rather than later, given the FDA’s acceptance of the filgrastim BLA—and the fact that the “review clock” for the drug is approximately 10 months, according to the Biosimilar User Fee Agreements.

Filgrastim is a human granulocyte colony-stimulating factor (G-CSF) that reduces the risk for infection in cancer patients who are at risk for severe neutropenia with fever. In the United States, Amgen creates and distributes filgrastim under the name Neupogen.

Outside the U.S., Sandoz’s biosimilar filgrastim is called Zarzio.

“We have been using the IVIG experience as sort of a precedent and guideline as to how we would handle the biosimilars coming to the marketplace in the future,” Dr. Adamson said.

Biosimilars are highly similar versions of branded biologic products (reference products). Many people will think of them as “generic” versions, but the FDA’s Leah Christl, PhD, said the term is incorrect. “Unlike generic drugs, whose structure can usually be completely defined and entirely reproduced, biologic products are typically more complex,” said Dr. Christl, the associate director for therapeutic biologics at the FDA Office of New Drugs. “Biosimilar and interchangeable biological products are unlikely to be shown to be structurally identical to a previously licensed biologic product.”

Generic drugs are small-molecule, chemical compounds. If the generic manufacturer follows the formula, it will result in an exact copy of the original.

Biologics, in contrast, are large-molecule, complex products that are manufactured in living organisms. Biosimilars should have similar efficacy and the same action in the body as the reference product, but they would not be structurally identical because they are manufactured in a different cell line.

“This manufacturing process results in differences among batches, also called ‘batch-to-batch variability,’” said Carlos Sattler, MD, the vice president of U.S. Clinical Development and Medical Affairs at Sandoz. That variability is normal for all biosimilars, he explained.

Biologics and recombinant products are expensive, Dr. Adamson said, so the pricing structure will be an important consideration for biosimilars, but buyers are unlikely to see huge discounts on the products. The complexity of producing them would keep the cost of these drugs higher than the traditional generic formulations, he noted.

Dr. Sattler agreed that the discounts won’t match those of traditional generics. “By introducing competition in the United States, costs will be brought down, creating overall savings,” he said.

“In general, we expect discounts on biosimilars to be in the range of 10% to 30% below the reference biologic. However, this will depend on therapeutic area, market, channel, number of competitors and reimbursement situation.”

That might not seem like a very large discount, when some generics are discounted more than 50%, but Dr. Adamson said that one has to remember the high cost of the reference products.

“Typically, biologics tend to have premium pricing; they cost thousands per dose. If someone says, ‘we can give you the same thing for 30% less—30% of a lot of money is a lot of money,” he said.

Producta

Global Salesb

U.S. Patent Expiration Date

Adalimumab (Humira)

9.1

2016

Etanercept (Enbrel)

7.7

2028 (extended)

Infliximab (Remicade)

7.5

2018

Insulin glargine (Lantus)

7.1

2014

Rituximab (Rituxan)

6.2

2016

Bevacizumab (Avastin)

5.6

2017

Insulin aspart (NovoLog)

5.4

2015

Interferon β-1a (Avonex, Rebif)

5.4

Expired

Trastuzumab (Herceptin)

5.1

2019

Glatiramer acetate (Copaxone)

4.7

2014

Pegfilgrastim (Neulasta)

4.3

2014

Ranibizumab (Lucentis)

4.2

2016

a

U.S. brand names

b

As of June 2013, $ billions

by the

numbers

Biologics Market Share of Sales, % 9.1

7.5 13.2

48.6 21.6

No Deep Discounts

Table. Patent Expirations for Top Biologics

Rigorous Approval Pathway The pathway to U.S. approval of biosimilars will be stringent and will require highly sophisticated and sensitive analytical data to compare the biosimilar product with the reference version. (For more on the biosimilar pathway and its development, go to

(http://bit.ly/1z0QFH0). IMS estimated that the global market for biologics was close to $170 billion in 2012 and was expected to be $250 billion by 2020. Biosimilars and non-original biologics will represent 4% to 10% of that market, and 49% of all biologic sales are in the United States (Figure), according to IMS. Several of these blockbuster biologic drugs will lose their market protection within the next decade, according to IMS (Table).

www.pharmacypracticenews.com.)

The purpose of these stringent requirements is to assure that newly approved biosimilars will perform as well as the reference product. Whether that will convince U.S. physicians is hard to say, according to Dr. Adamson.

“What will happen is we will make a substitution and some of our clinicians will ask: ‘Can we study this to make sure we get the same level of response that we got with the branded product?’ We will also have other physicians who will say: ‘It has been available in Europe for years; let’s just move forward.’ I think physicians will become more comfortable once two or three biosimilars are approved.

For now, we talk about IVIG, insulin and human growth hormone to remind them that they have been doing this all along.”

The future for biosimilars in the United States can also be glimpsed by looking at overseas experience with the compounds. Zarzio, for example, has been available in several markets outside this country since 2009. “Under the brand name Zarzio, the Sandoz biosimilar filgrastim has been marketed in more than 40 countries outside the U.S., generating nearly 6 million patient-exposure days of experience,” Dr. Sattler said. “It is now the No. 1 prescribed daily G-CSF.” In Europe, Zarzio has more than 30% market share and is the first biosimilar to surpass its reference product (Neupogen) and the market leader (Chugai’s Granocyte), according to Dr. Sattler.

Dr. Adamson said that kind of track record would help a biosimilar’s acceptance in the United States.

A white paper by IMS Health called biologics the “darlings of the pharmaceutical industry, with sales growing at twice the rate of the market as a whole”

Source: IMS Midas, June 2013, IMS Patent focus; copaxone may see a conventional generic copy, not a biosimilar.

Share of Growth, % 8.1 14.7 49.8

13.3 14.1

Japan Emerging markets Rest of the world European Union United States

IMS Health predicts the global biologics market will reach $250 billion by 2020. Above is the breakdown of sales and growth.

Source: IMS Health, MIDAS, MAT Dec. 2012

Pricing is very important in a hospital where margins are razor thin, he noted, but they are not the only consideration; supply is equally important.

“People are enamored by the idea that biosimilars will be lower in price, but we also have to look for guarantees of supply,” Dr. Adamson said.

That makes him cautious, he added, because to accept the discount price, one may have to forgo an established relationship. “You move away from the branded product because this new one is cheaper and then it is not available. Now, you have to go back to the branded product and end up paying full price. So, now this is costing you money, rather than saving you money.”

The cost of the branded product may come down to remain competitive, Dr. Adamson pointed out. There has been some historical precedent for this, particularly in the oncology market. “Many years ago, when they lost their patent, some companies told us if we kept using them, they would match the generic price,” he said. “For us, that was great.”

—Marie Rosenthal None of the sources reported any relevant financial conflicts of interest.

8 Clinical

Pharmacy Practice News • September 2014

History of Pharmacy

From Ancient Rome to iTunes App The eternal lure of medicinal plants

P

research collection, the LuEsharmacognosy—the study ther T. Mertz Library. For examof medicinal herbs—dates back to the earliest days of ple, the Garden’s recently pubrecorded history. But at the lished book, “The Renaissance New York Botanical Garden, Herbal,” features rare illustrainterest in the science and beautions and historic material that ty behind these healing plants dates back to 350 b.c. It is filled is hotter than ever. Garden with richly illustrated texts that officials recently announced show how ancient and medieval that its exhibit, “Wild Mediknowledge about the medicinal cine: Healing Plants Around plants was recorded and passed the World,” which drew nearon to future generations. ly 250,000 visitors in 2013, is Ancient Roots coming back in 2015, giving the public a new opportunity “The Renaissance Herbal” is not the only historical referto view the Garden’s collection of more than 500 plants and ence of its kind. Several seminal texts—many included in the their influence on human history, culture and health.

Garden’s reference collection— have helped kick-start the sciFor those who can’t go to the Garden to see the exhibit, which ence behind medicinal herbs. runs from Jan. 24 to Feb. 22, the One of the oldest, “Inquiry Into Garden can come to them via Plants,” has several chapters an interactive three-dimensional on medicinal plants. Its Greek iPhone app that just won a gold author, Theophrastus (c. 371medal for best mobile technol287 b.c.), often called “the father ogy from the American Alliance of botany,” studied the plants Cinchona, an early precursor to quinine, along with rosy periwinkle (top and bottom left), ephedra and of Museums (sidebar). from Egypt and India that Alex“Some 30,000 plants world- willow (top and bottom right), are part of the “Wild Medicine: Healing Plants Around the World” exhibit ander the Great sent back. coming back to the New York Botanical Garden in Winter 2015. wide have been identified as havPefanis Discords, a Roman Source: All photos courtesy of New York Botanical Garden. army surgeon under Nero, ing medicinal properties,” said ethnobotanist Michael J. Balick, described nearly 600 medicia similar-looking plant. “For centuries, the exhibit, appears numerous times vice president for Botanical Scinal plants used by physicians. ence at the Garden, who curated the any plant you could call a mandrake had in a 4,000-year-old Sumerian tablet “De Material Medical” was considered a exhibit. “An estimated 4.5 billion people the aura of magic!” More recently, that describing already known medical pre- precursor to all modern pharmacopoeias. use plants in some way for health care. association was reinforced by frequent scriptions. Making a tincture of willow “His book was used for 1,500 years,” Ms. Today, about one-fourth of prescription mentions of mandrake in the Harry Pot- bark in ethanol was a common mode of D’Avanza said. Around the same time, medicines are made from plant ingre- ter books, she noted. administration. For thousands of years, Pliny the Elder wrote an encyclopedia dients or have plant chemicals as their Present-day health care consumers willow bark has been used to treat of natural history. Five of 37 volumes in base. This exhibition included histori- are likely more familiar with the medici- aches, pains, fevers and any flu-like “Naturalism Historian” discuss plants. cally important medicinal plants, and nal properties of quinine, another fea- symptom. Its long tradition was well In the second century, Galen, a Roman some that have led to lifesaving treat- tured plant in the Wild Medicine Exhib- founded: In 1928, scientists discov- physician, was the first to classify plants it. “The first account of quinine was ered that willow bark contains salicin, into groups and provide formulas for ments in recent years.” when Jesuit missionaries wrote it down, which is closely related to aspirin. creating remedies. His descriptions and Healing Plants—Then and Now in the 17th century,” noted Ina VandeRosy periwinkle, a beautiful garden classifications formed the basis of plant Plants chosen for the exhibit often broek, ethnomedical research specialist plant, has been part of traditional Indi- medicine. “The works of plant medihave both a lengthy history and cur- at the Garden’s Institute of Economic an and Chinese medicine for thou- cine that were produced in the Renaisrent relevance. Mandrake, frequently Botany. Seeing Peruvians trying to ward sands of years. It’s taken as a drink to sance frequently cited their sources, and mentioned in early medical botany, off shivers from working in Spanish treat diabetes, toothache, indigestion Galen is a source that we see again and including an Egyptian papyrus from mines by chewing cinchona tree bark and constipation. More recently, the again. The authors of these works were 1536, “seemed magical because of its (in which quinine is an active chemi- plant, known as Cathanthus roseus to re-examining foundational writings of hallucinogenic properties and similarity cal), the Jesuits began using the bark to the taxonomically inclined, became the the past, and noting any errors they recsource of vincristine and vinblastine. ognized,” Ms. D’Avanza said. to the human body. People thought it counter malarial shivers. looked like two legs, the way the taproot Quinine became a traditional treat- Despite the toxicity of these drugs, After Al-Dinar (828-896), the foundbifurcated,” noted exhibitions coordina- ment for all kinds of fevers—and led many people in the Caribbean casually er of Arabic botany, described medicitor Mia D’Avanza. By the Middle Ages, to a popular cocktail. By 1825, British drink rosy periwinkle infusions, appar- nal properties of several hundred local “mandrake was trendy, expensive and sailors in tropical areas were mixing ently with no ill effects. That’s because species, Persian physician Avicenna in high demand. Especially in Britain, it their quinine tonics with gin, water, the chemotherapy drugs’ concentration (980-1037) wrote “Canon of Mediwas fashionable as a magical charm and sugar and lime to lessen the bitter in each rosy periwinkle is minimal—it cine.” It laid the foundation for modfor its use as a narcotic, hallucinogen, taste. In the 21st century, Venezuelans has the lowest percentage of an alka- ern pharmacology. use cinchona bark to help fight cancer; loid per dry weight of any known plant. violent purgative and aphrodisiac.”

However, the Mediterranean plant Brazilians take it to decrease fatigue or Indeed, it takes 15 tons of leaves to Apothecaries Also Recognized simply didn’t grow well in the North, increase appetite. (Cinchona is in the make 1 oz of vincristine or vinblastine.

The plants don’t always get top billing Ms. D’Avanza suspects, and a black Garden’s permanent display.)

Many details on these and other herbal in these historical texts. The LuEsther market arose. Scammers began selling The ancient symbol for willow, plants in the Wild Medicine Exhibit came T. Mertz Library at the Botanical Garfake ‘mandrake charms,’ using Brionia, another medicinal herb featured in from the Botanical Garden’s extensive den owns a 1592 book by apothecary

Clinical 9

Pharmacy Practice News • September 2014

History of Pharmacy Fabio Colonna, a member of a prestigious scientific academy in Italy. For his epilepsy, he sought a cure in Discords’ ancient work, and tried valerian as a possible cure for his seizures. Convinced that better plant descriptions would be helpful, he wrote “Phytobasanos,” based on actual plant specimens.

John Parkinson, founder of the Society of Apothecaries in England, furthered this scholarly tradition when he wrote “Theatrum Botanicum” in 1640. Its 1,688 pages describe 3,800 plants—a breadth of research that underscored this successful London apothecary’s devotion to discovering and documenting new healing plants he could introduce to England.

Web Exclusive The dangers of “Whorehouse Tea” and other cautionary tales about ancient remedies that can cause modern problems when mixed with 21st-century medications.

native Medicine (NCCAM), part of the National Institutes of Health, has been compiling the scientific evidence for a number of complementary alternative medicines (CAM), including herbal remedies.

Why We Need To Know

Where’s the Evidence?

Ethnobotany is based largely on oral tradition, Ms. Vandebroek stressed. “This is ancient knowledge, yet it’s still dynamic, growing and changing. The contemporary communities we work with still use mostly oral tradition. Ethnobotanists write it down—often for the first time—so it doesn’t get lost.”

On international research trips, Ms. Vandebroek learned firsthand how some plant-based remedies originate.

In 2001, she recalled, a young Bolivian healer hurt his foot while climbing in the Andes. “Walking up the mountain became difficult. He had to stop when the pain was too strong. Since he was near a shrub, Eriolarynx fasciculata, in the nightshade family, he decided to experiment with its leaves. After applying them to his wound, he was able to continue up the mountain. Now, he uses leaves of that plant for other people’s pain.”

Ms. Vandebroek works with the Dominican community in New York City, where Ruellia tuberosa (native to the West Indies, India and the Caribbean) is used to treat infertility, vaginal infections, labor pains, kidney problems and gonorrhea. “People feel confident in it, but it’s understudied in the literature,” she acknowledged.

However, the body of scientific evidence about medicinal plants continually grows. Researchers in a Brazilian clinical trial involving 475 patients reported that medicinal plants or related natural products had “significant effects on improving symptoms of fibromyalgia” (Evid Based Complement Alternat Med d 2013 Jun 4. [Epub ahead of print]). At Shahed University in Tehran, a study involving 120 students concluded: “Treatment of primary dys-

“Theatrum Botanicum,” by John Parkinson, a London apothecary (left), described 3,800 medicinal plants.

Pliny the Elder wrote “Naturalis Historia” (right).

menorrhea with ginger for five days had a statistically significant effect on reducing the intensity and duration of pain” ((BMC Complement Altern Med d 2012 Jul 10. [Epub ahead of print]).

Federal health agencies are also

delving into the evidence behind healing plants. Such efforts are due in part to the dearth of scientific evidence about herbal remedies. The National Center for Complementary and Alter-

A Wild (Medicine) App For Pharmacognosy

T

he New York Botanical Garden’s “Wild Medicine” exhibit, coming back for a second run this January, will display more than 500 medicinal plants. But for those who can’t make the trip out to the Bronx, a free awardwinning iTunes app makes it possible to virtually visit and interact with the plants on display.

“Wild Medicine is designed as a repository of information about some important healing plants,” said Chris Sojka, the creative director at Madwell, the Brooklynbased creative marketing agency that created the app.

“It allows you to jump to any plant in the permanent Wild Medicine collection, and learn its active part and how it heals. s You’ll find great images, many key facts and an audio clip explaining how each plant was collected.” More content is being developed.

Mr. Madwell spent four months completing the app, after eight months of research. Although the core features of Wild Medicine can be used anywhere, an interactive 3D component can only be activated at the Garden with newly installed, high-tech signs for 15 important medicinal plants. “By simply holding up the application to the sign, users will activate hidden information and animations that unfurl in front of their eyes,” Mr. Sojka explained.

Although interactive technology like this, known as augmented reality, has existed for a few years, it has rarely been used to tell an educational story. “This is augmented reality at the next level,” he said. “We’re using models that a pharmaceutical company might use to show how a drug works in the body. For example, we display a human skin patch with an irritation, and then apply aloe to demonstrate the healing process. Wild Medicine deepens the actual [exhibit] experience to be much more interactive. We’re very excited about it.”

Medicinal plants on permanent display are kava, saw palmetto, coconut palm, cacao, jaborandi, curare, lotus, cinchona, tropical blueberries, ephedra, aloe, citrus, tea, olive and eucalyptus.

Download the free app at http://bit.ly/1vz50hi.

—C.M.

“As humans, we have inherited the accumulated wisdom and practices of beneficial plants—whether used for food, fiber, fragrance, ceremonial and/or medicinal values. The more information we have about their former uses, the more we gain insights into the cultures of those times,” said Mark Blumenthal, the executive director of the American Botanical Council (ABC) in Austin, Texas. “We [could] use such information as guides to determine potential medicinal uses for many plants, including possible sources for new drug development.”

ABC, an independent nonprofit research and education organization, reports on historical, traditional and folkloric medicinal information, as well as modern scientific information, particularly from human clinical trials. ABC was one of the first groups to produce English-language versions of the German Commission E monographs, a seminal review of the safety and efficacy data on more than 300 medicinal herbs. Such research “continually supports and validates [medicinal plants’] historical uses,” said Mr. Blumenthal, a former adjunct associate professor of medicinal chemistry at University of Texas College of Pharmacy.

Should we all be better students of this discipline? “Absolutely,” Mr. Blumenthal said. “The development of medicinal plants is a necessary, integral part of the fascinating history of medicine, pharmacy and human cultural evolution.”

—Carol Milano None of the sources reported any relevant financial conflicts of interest.

10 Clinical

Pharmacy Practice News • September 2014

Practice Pearl

Enhancing Quality and Safety of Insulin Therapy A multidisciplinary approach to create and validate continuous infusion insulin protocols Komal A. Pandya, PharmD, BCPS Pharmacy Specialist, Emergency Medicine & Adult Critical Care

Table 1. Multidisciplinary Task Forces: Members and Roles

Patricia Parker, PharmD, BCPS

Member Type

Contributions

Assistant Chief and Clinical Coordinator, Inpatient Pharmacy Services Director, Pharmacy Practice Residency Program

Pharmacists

Identification of medication safety problem; development of evidence-based CIIT protocols; educational outreach on new protocols; conduction of postimplementation validation research

Rachelle Firestone, PharmD, BCPS

Physicians

Development of evidence-based CIIT protocols

Nurses

Review of protocols to ensure safe administration by end users

Health care executives

Leadership support; setting of expectation that medication safety is of top value

Information technology analysts

Development of CIIT order sets and infusion rate calculator

Pharmacy Specialist, Adult Critical Care

Jeremiah Duby, PharmD, BCPS Senior Pharmacist, Adult Critical Care Director, PGY2 Critical Care Residency Program University of California, Davis Medical Center Sacramento, California

H

yperglycemia is associated with increased mortality in the ICU, worse outcomes after critical illness, and myocardial infarction in the cardiac surgery population.1 Continuous infusion insulin therapy (CIIT) commonly is used to manage hyperglycemia in the acute care setting. Although earlier data supported CIIT with blood glucose target of 80 to 110 mg/dL (tight glycemic control [TGC]),2 in the wake of the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Surviving Using Glucose Algorithm Regulation) trial demonstrating that patients treated with TGC had an increased number of severe hypoglycemic episodes and a higher 90-day mortality,3 the American Diabetes Association and the American Association of Clinical Endocrinologists presented updated guidelines recommending a liberal target range of 140 to 180 mg/dL for most patients in the acute care setting.4 These guidelines also emphasize a gradual correction of hyperglycemia to prevent cerebral edema, which was further supported by recent findings that glycemic variability is associated with increased mortality.5,6 The new guidelines for the management of hyperglycemia as well as diabetic ketoacidosis and hyperglycemic hyperosmolar state (DKA/HHS) highlight the appropriate blood glucose targets for patients and emphasize minimizing glycemic variability, but they do not offer any validated protocols for achieving these goals.

To address this void, multidisciplinary task forces led by pharmacists at the University of California, Davis Medical Center (UCDMC) systematically evaluated the following UCDMC CIIT protocols: ICU hyperglycemia management, ward hyperglycemia management, and DKA/HHS (Table 1). Each of the 3 pro-

CIIT, continuous infusion insulin therapy

tocols was evaluated in a pre-post protocol implementation study designed to assess the safety and efficacy of the existing protocols and newly implemented protocols. The end points included rates of hypoglycemia (blood glucose <70 mg/dL) and severe hypoglycemia (blood glucose <40 mg/dL), ICU length of stay (LOS), hospital LOS, duration of mechanical ventilation, glycemic variability, and protocol adherence.

During the baseline assessment phase, the task forces analyzed the existing protocols. Specifically, they evaluated use of the ICU hyperglycemia management protocol in 454 ICU patients being managed with CIIT, and found that 53% experienced hypoglycemia, with an average of 3 hypoglycemic episodes per patient. Looking at use of the ward hyperglycemia protocol in 42 ward patients who received CIIT, they found that 35% experienced hypoglycemia. The baseline evaluation of the use of the DKA/HHS protocol in 100 patients receiving CIIT for DKA/HHS uncovered that 34% of that group experienced hypoglycemia, with an average of 1.7 episodes per patient. Glycemic

variability was measured using the common variability parameter of glucose standard deviation. Patients experienced variability in blood glucose averaging 148.7 mg/dL while receiving CIIT. Based on these results, it was clear that the current methods of glycemic management at UCDMC were not safe or efficacious.

In response to the baseline results, the multidisciplinary task forces were charged to develop, test, implement, and validate new CIIT protocols, considering potential barriers to implementation (Table 2). The shared goals for these task forces were defined in advance of planning and implementation and included supporting nursedriven bedside management of hyperglycemia; incorporating wide safety thresholds and risk-mitigating strategies; employing evidence-based targets for glycemic control; employing parallel design features of each new protocol emphasizing usability; and consolidating protocols to provide effective hyperglycemia management across the continuum of care, from the emergency department to the ICU to the wards. The development of new

Table 2. Solutions for Identified Barriers To Implementation Barriers

Solutions

Organizational silos

Inclusion of key stakeholders in early phases of project development to encourage collaboration and change patterns of interaction

Ambitious undertaking with a broad scope

Proof-of-concept approach for successful implementation

Challenges to hospital staff execution of protocol

Use of robust order set, extensive educational outreach, easy-to-use online infusion rate calculator, smart-pump technology, and medication administration barcoding

protocols involved comprehensively changing the management of hyperglycemia, empowering and equipping the bedside nurse, simplifying calculations for infusion-rate titration to individual dose–response, and creating safety thresholds and mechanisms. With these goals in mind, the task forces developed 2 hospital-wide protocols, one for the management of hyperglycemia and one for the management of DKA/HHS, thus eliminating the need for separate protocols dependent on patient acuity or location.

The 3 previous CIIT protocols required manual, mathematical calculation for each dose titration by the bedside nurse. Identifying technology infrastructure as a resource that could minimize the labor requirements and error rates associated with manual calculations, the task forces developed and extensively tested an online infusion rate calculator for each new CIIT protocol. After validation, the calculator was embedded within the electronic health record (EHR) order set for CIIT. Additional medication safety measures included use of smart-pump technology with a standardized drug library and infusion alerts; barcode medication administration (BCMA) that confirms the right patient and medication;

•

see INSULIN THERAPY, page 12

12 Technology

Pharmacy Practice News • September 2014

Adherence

Medication Adherence Apps Coming of Age A

pproximately 30% herence. “Although most to 50% of U.S. adults people don’t want to cardo not adhere to their ry around their pill callong-term medications, endars or boxes, there’s resulting in an estimated not too many people out there anymore who don’t $100 billion in avoidable have their smartphone costs every year (JAMA ( 2013;309:2105-2106). handy,” Dr. Dayer said.

With 129.4 million smart“People are busy with their lives and work, and phone owners in the United States, according especially if they’re takto a recent report by coming multiple prescripScore, many experts now tions and doses at differview the technology as an ent times, these apps can affordable and accessible be extremely helpful. Not medium to reduce medi- AdhereTech medicine bottles only do they [medication automatically measure if adherence apps] serve as cation nonadherence.

But choosing an adher- patients are adherent, and all reminders, but they can ence app among the data are wirelessly transmit- also assist with the eduted and analyzed in real time. hundreds that are now Source: AdhereTech. cation of patients.” available for download To develop the list, can be a daunting challenge. That’s why the UAMS team searched the available a team of researchers from the Univer- medication adherence–themed apps, sity of Arkansas for Medical Sciences provider websites and app sources for (UAMS), College of Pharmacy, in Little Apple iTunes, Android Marketplace and Rock, identified and ranked 160 medica- BlackBerry App World during August tion adherence applications to provide and September 2012. Specific features an overview of the technology and to were graded using a 3-point rating sysdiscuss its potential role in decreasing tem, and the 10 highest-rated apps were medication nonadherence ((J Am Pharm evaluated and tested by patients. Some of the higher-ranked features were Assoc 2013;53:172-181).

Lindsey Dayer, PharmD, BCACP, an online data entry, complex medication assistant professor of pharmacy prac- instructions and the ability to track tice at UAMS College of Pharmacy, and missed and taken doses. a clinical pharmacist in an ambulatory Here are details on the top five apps care clinic, said the research effort is an with the highest number of desirable important one, because well-designed features: technology has the potential to make a 1. MyMedSchedule features a free significant dent in medication nonad- online companion website ((www.

mymedschedule.com) m that allows pro- one is not limited to prescription medividers to input patients’ prescribed regi- cations: vitamins, herbal supplements, mens and then push them directly to the birth control pills and other over-thepatients’ devices. This feature removes counter products can be included in the the data-entry burden from the patient app, which costs $9.99 per year. and reduces the possibility of patient3. MedSimple features a medication generated medication regimen mistakes, database that enables patients or proaccording to the app developers. The viders to save time and improve accuwebsite offers regimen-building options racy when entering regimens. It also that can be useful for patients in specialty allows for the ability to track taken areas that often carry a and missed doses and high medication burden. export those data to 2. MyMeds also comes health professionals with a supplementary for review. This feature website that enables can provide informapatients to enter their tion to help health care regimens online rather providers assess medithan doing so only on cation adherence. The their device. This feature app is available in a free offers the convenience version, as well as an of patient privacy–comenhanced version that costs $9.99 per year, pliant cloud data storage that can be retrieved and according to the develmodified from any Interoper’s website (http:// net-accessible computer bit.ly/1oKalc7). and pushed back to the 4. Meds Agenda patients’ mobile devicallows for complex medication instructions es. Individual profiles can be made for up to 10 to be entered, as well family members, accordas iCloud data storage for backup. It can genering to the product’s webThe MyMeds app features a site (http://about.myate reminders without patient privacy–compliant Internet connectivity, meds.com). m Customized cloud data storage comporeminders can be set for nent that can be retrieved and which could be useful each profile, including modified from any Internetif the patient’s phone via text, email and mobile accessible computer and loses service. alarm. Similar to some of pushed back to the patients’ 5. RxmindMe Prethe other apps singled out mobile devices. scription is a free app Source: MyMeds, Inc. see MED APPS, page 14 by the researchers, this

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CLINICAL

Practice Pearl

INSULIN THERAPY continued from page 10

a robust order set that facilitates implementation of the protocol; easy-to-find hyperlinks to guidelines and reference materials embedded within the medication administration record in the EHR; and multiple educational approaches to assure compliance with the new CIIT protocols. After identifying potential barriers to initiative implementation, the task force also developed an electronic learning module and assigned it to all inpatient nurses and pharmacists and conducted educational in-services hospital-wide with nurses on all adult units. They developed case-based scenarios that required use of the infusion rate calculator and adjustment of the infusion based on the administration instructions in the EHR order sets. Each nurse also completed a written test to demonstrate his or her understanding

of the protocol and calculator. Additionally, information technology (IT) analysts developed a daily report of patients receiving CIIT that clinical pharmacists used to assess the safety of the protocol as well as end-user compliance in real time. If the clinical pharmacists identified a titration deviation, they conducted face-to-face, just-in-time training and coaching, focusing on the appropriate use of the protocol. Each educational activity was designed, tested, and implemented under the leadership of pharmacy, with collaboration from nursing, IT, physicians, and administrators.

After implementation of the 2 new protocols, the task forces conducted protocol validation studies to confirm the safety and efficacy of the new protocols. Compared with the previously used protocol, the new protocol dramatically reduced the rates of hypoglycemia and severe hypoglycemia in the ICU: 11% versus 53% ((P<0.0001) and

0% versus 9% ((P=0.0004), respectively.

This group also experienced a statistically significant reduction in ICU LOS, hospital LOS, and duration of mechanical ventilation. The new protocol also dramatically reduced rates of hypoglycemia in ward patients compared with the previous protocol: 14% versus 35% ((P<0.0001). In the validation phase for the DKA/HHS protocol, there was a significant reduction in the risk for hypoglycemia (35% vs 0.99%) and severe hypoglycemia (4% vs 0%) with the new protocol compared with the previous protocol ((P<0.005). They also found a decrease in blood glucose variability, from 148.7 mg/dL with the old protocol to 106.3 mg/dL with the new one.

In conclusion, a pharmacist-led multidisciplinary effort was successful in designing and implementing an innovative process for systematically optimizing the safety and efficacy of CIIT.

References 1. Mesotten D, Van den Berghe G. Clinical benefits of tight glycemic control: focus on the intensive care unit. Best Pract Res Clin Anaesthesiol. 2009;23(4):421-429.

2. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345(19):1359-1367.

3. NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283-1297.

4. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15(4):1-17.

5. Badawi O, Waite MD, Fuhrman SA, Zuckerman IH. Association between intensive care unit-acquired dysglycemia and in-hospital mortality. Crit Care Med. 2012;40(12):3180-3188.

6. Jacobi J, Bircher N, Krinsley J, et al. Guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. Crit Care Med. 2012;40(12):3251-3276.

Technology 13

Pharmacy Practice News • September 2014

Automation

Navigating the BCMP Medication Preparation Market Informatics Consultant Fresno, California

orders make their way to BCMP systems via direct HealthLevel 7 interfaces or print streams.

Mark Neuenschwander

Compounding Tools

Jerry Fahrni, PharmD

Cofounder The unSUMMIT for Healthcare Barcoding President, The Neuenschwander Co. Bellevue, Washington

A

lthough barcode medication administration (BCMA) has already made its way into most hospitals nationwide ((Am J Health Syst Pharm 2013;70[9]:787803), only a few hundred have incorporated barcode-assisted medication preparation (BCMP) into their medication-use processes. We anticipate, however, that this disparity will diminish before the end of the decade.

We recently researched BCMP technologies and conducted site visits for six months to create a report on these systems and variations. Our research showed that most technologies reside in hospital pharmacy cleanrooms to assist in preparing compounded sterile products (CSPs), but at least one is being used outside the cleanroom to prepare nonsterile, oral liquid products as well.

For inclusion in our report, systems had to include computerized workflow processes, which require barcode-scanning of CSP containers and ingredients to verify that they match orders, and produce barcode-labeled CSPs for scanning at the point of care. A dozen systems, on or soon to hit the market, meet these criteria. Here are some of our findings and observations.

Categories Semiautomated manual systems: People handle the products during the compounding process and barcode readers verify the accuracy of the selected products. The vast majority of BCMP implementations are semiautomated and are used to prepare virtually all of a hospital’s CSPs. Highly automated robotic systems: Robotic arms perform most of the compounding activities, and internal readers verify product selection with barcode scans, confirm drug amounts with scales and capture images of critical steps for documentation purposes. Robotic systems fill limited formularies of sterile products (six to 12 at sites we visited), and in some cases, process hazardous drugs exclusively. Although they are capable of producing patient-specific doses, most robots are used to produce batches of their hospital’s highest moving CSPs, akin to small-scale manufacturing.

Pharmacy information system interfaces: All products are interfaced to hospital pharmacy information systems. Drug

BCMP systems vary with the information and tools provided, and in most instances, hospital formularies must be cross-referenced to National Drug Code numbers. Some vendors use third-party databases to manage these files, whereas others rely on hospitals to build and maintain their own.

Most vendors offer customizable drug-recipe catalogues. Recipes may include formulas, ingredients, diluents, containers and final solutions, as well as beyond-use dating and special instructions for preparation and handling.

Recipes assist in standardizing preparation processes, improving safety and efficiency and equipping pharmacies to meet state pharmacy board documentation requirements. A few BCMP systems provide dose-and-volume calculation utilities, as well as reference tools for permitted diluents, known stabilities and drug-storage conditions.

Remote Access Most BCMP systems are Web-based, allowing users full or partial system access from anywhere via desktop computers, laptops, tablets and some smartphones. Direct computer interfaces, as well as Internet access, enable pharmacists to retrospectively verify CSP orders by viewing production images without having to enter cleanrooms. We expect the remaining systems to migrate to Web access in the near future.

Workflow Workflow software, the core of BCMP systems, guides users from one step to the next during the compounding process. Most versions include forcing functions, which prevent users from proceeding until particular steps are completed (barcode scans have verified products and/or scales have verified weights).

Robot algorithms include internal forcing functions, which do not allow CSP production to continue should scanning and/or weighing fail to confirm the right containers, drugs and volumes. During the checking process, pharmacists compare orders with multiple production images to verify accuracy—what we think of as an enforcing function.

Labels All BCMP systems produce barcoded labels for application to final IV products, which may be used for tracking CSPs en route to points of care and for scanning at the points of administration. Most systems only use one barcoded label, which

is applied to containers at the beginning of the process, scanned during various preparation steps and finally at the point of care. One semiautomated system uses two barcode labels: one during the preparation process, and another after orders have been satisfactorily completed and approved by a pharmacist. This serves as a forcing function to prevent incomplete or inaccurate CSPs from being administered to patients.

Code Readers All BCMP systems use imagers for reading multidimensional, as well as linear barcodes on containers, syringes, diluents and drugs.

Some semiautomated systems provide gravimetrics for determining the accuracy of doses drawn into syringes, removed from vials and injected into infusion containers. Source: jerryfahrni.com

Images Most BCMP systems use cameras for capturing images of compounding activity. Semiautomated systems capture images at various user-determined stages in the preparation process. Pharmacists can check completed orders remotely instead of gowning up and entering cleanrooms. Likewise, robotic systems capture images of critical steps during the compounding processes, which are archived for future reference.

Although pharmacists, by law, must inspect CSPs, they do not routinely have access to robot-captured images when verifying compounding accuracy and must trust that the robots have fulfilled their tasks correctly.

Measuring Methods BCMP systems offer several methods for verifying the amount of drugs drawn and injected into infusion containers, such as image-assisted volumetric analysis and scale-assisted gravimetric analysis. Some systems offer both options.

Traditional pullback: Traditional volumetrics is commonly used when making CSPs. Preparers draw drugs into syringes and visually confirm amounts against markings on syringe barrels before injecting the contents into IV containers. They then “pull back” the syringe plungers to the previous volume marking, only using their memory, before placing the empty syringes with the drug vials for pharmacists to check.

We support the Institute for Safe Medication Practices warning, “While the ‘syringe pullback’ checking process is standard in many hospitals, it is less than ideal because the check is made post-preparation and is based on the preparer’s memory of how much product was added to the bag.”

Image-assisted volumetric analysis: Most BCMP systems add image assistance to the volumetric analysis process.

During compounding, images of all drug containers used are captured, as well as

Remote telepharmacy technology enables pharmacists to retrospectively verify CSP orders by viewing production images without having to enter cleanrooms. Source: ScriptPro.com

images of corresponding drawn syringes before their contents are injected into IV containers. During the checking process, pharmacists visually verify images of drawn syringes taken before they are emptied into containers. Although preparers may still draw wrong amounts and proceed on, image-assisted checking serves as an enforcing function, mitigating opportunities for technician errors being missed.

This is a safer practice than the traditional pullback method. Nevertheless, it should be noted that even with image-assisted volumetric analysis, both compounding technicians and checking pharmacists are capable of visually misreading volumes ordered and/or actual volumes in syringes.

Scale-assisted gravimetric analysis: Gravimetric analysis is the process of determining drug amounts using scales and a drug’s specific gravities. Some semiautomated systems provide gravimetrics for determining the accuracy of doses drawn into syringes, removed from vials and injected into infusion containers. Weighing each before and after adding or removing substances reveals exactly how much of each ingredient was added or removed with accuracy equal to or surpassing the International Organization for Standardization syringe tolerance of plus or minus 5%.

•

see NAVIGATING, page 14

14 Technology

Pharmacy Practice News • September 2014

Adherence

FDA Eyes Adherence Apps

MED APPS continued from page 12

now offered by Walgreens that allows users to enter drug regimens, set up reminders, and can be used to track taken and missed doses. According to the Walgreens website (http://bit.ly/1oNtP4r), r the app can be customized with nine different types of reminders based on the dosage frequency. Prescription history can be exported and emailed and can be password protected. But the Walgreens site has the following disclosure statement: “Warning: RxmindMe is for entertainment purposes only. You should not rely on this app alone to remember to take medications.”

Apps Not a Cure-All Kevin Clauson, PharmD, an associate professor of pharmacy practice at Lipscomb University College of Pharmacy in Nashville, Tenn., echoed the Walgreens warning against relying too heavily on one app to ensure drug compliance. He suggested that bridge technology is a more promising strategy, especially in older adults.

Bridge technology starts with something familiar, like a physical pillbox with compartments that list the days of the week, and then translates that to a digital solution, he said. For example, the Pillboxie app has an interface that looks like a physical pillbox that can show patients the names and images of their medication, in addition to providing them with reminders (www.pillboxie.tumblr.com).

AdhereTech (www.adheretech.com ( m) uses the same premise for prescription medication vials, which are able to connect to a cloud service wirelessly and collect usage data. It uses a common pill bottle, but incorporates a mechanism where the bottle actually alerts the patient when it’s time to take medication.

The notification can be integrated into an

NAVIGATING continued from page 13

Weighing products adds time to the process and decreases throughput.

However, it serves as a forcing function that prevents compounders from proceeding should they draw too much or too little of a product before it goes to a pharmacist for review. Because robotics replaces human eyes and hands, gravimetrics is the only way these machines can ensure that proper volumes of drugs have been drawn before being injected into containers and safeguard against the injection of wrong product amounts.

Throughput Semiautomated system throughput varies greatly depending on hospital policies, procedures and product con-

T

o address the influx of medical device mobile apps, the FDA released a document in 2013 to inform manufacturers and distributors how it intends to apply its regulatory power to ensure the safety of these patient-focused technologies (http://1.usa.gov/1baa4bO).

Although some mobile apps meet the definition of a medical device, the agency will not enforce any regulatory requirements because most don’t pose a major health risk to the public. The agency will, however, monitor medical device mobile apps whose functionality could pose a safety risk to patients if it were to malfunction.

The FDA wants to encourage innovative technologies and solutions that would enhance patient engagement and help patients comply better with medication adherence, according to Bakul Patel, MS, MBA, a senior policy advisor of the FDA’s Center for Devices and Radiological Health.

“Understanding and balancing the benefits to the risks of these technologies, we think that an approach that does not enforce the regulatory requirements on tools that enhance medication adherence is beneficial in promoting public health,” Mr. Patel told Pharmacy Practice News.

The document listed apps that are intended for health care providers to use as educational tools for medical training, such as medical flash cards, as an example that it will not regulate. Conversely, the agency will exercise its regulatory oversight over some apps, including those that measure and display the electrical signal produced by the heart.

—P.B.

‘Probably the strongest evidence [supporting adherence apps] is for texting because it has been examined with promising results across the board.’

—Kevin Clauson, PharmD app, or comes in the form of a blinking light, text message or phone call.

“This type of device has a lot of potential to improve medication adherence as it attacks the problem in multiple ways,” Dr. Clauson said. “Also, because it comes in the form of a familiar pill bottle that patients already use, it does not force them to integrate a new device into their lives. Since sensors could actually measure how many pills are in the bottle as well as stream the data to the patient, pharmacist or physician, it also offers

a potentially useful data stream to help with tailoring therapy and interventions.”

Although smartphone apps may boost the efficiency and reduce the costs of conventional medication adherence interventions, their effectiveness currently is untested. Data demonstrate, however, that text messaging improves adherence and behavior in the short term ((J Am Med Inform Assoc 2012;19:696-704).

“Probably the strongest evidence is for texting because it has been examined with promising results across the board,”

figurations. Some pharmacies that have experienced increases in hood time have also experienced decreases in overall production times by avoiding preparation of discontinued doses and automating documentation.

Throughput for robots varies based on the number of ingredients per product and availability of labor resources to attend to a robot’s needs and pace.

Inventory must be manually loaded and completed orders must be manually removed before robots can proceed.

Robots have faster throughput when compounding batches than when filling patient-specific orders on demand.

However, semiautomated systems produce significantly higher doses per hour than robots.

Existing pharmacy space may limit which products or devices will work

in a given facility. Semiautomated systems may easily operate within spaces currently allotted for CSP preparation; however, robotic devices with larger footprints may require additional floor space for installation, operation and maintenance. Increasing load-bearing support may be requisite for installation. All systems require network access and some require additional utilities, such as upgrading electrical outlets and plumbing for water-cooling systems.

Potential Benefits Hospitals using BCMP technologies say they have realized a return on their investments; Baxter reports that more than 5% of products prepared with its product identify and intercept errors in the compounding process. These systems are also protecting patients and

Dr. Clauson said, citing a study in the American Journal of Health-System Pharmacyy (2013;70:1348-1352). “It’s incredibly accessible; it’s incredibly cheap; and it doesn’t come with any side effects. As technology advances, we’ll see a continued trend with wearable devices, further integration of smartphone apps and further integration in health systems.”

One feature that could facilitate this trend and prove very beneficial, especially for health care providers, is a level of connectivity to the electronic health record, Dr. Dayer said. It would enable providers to better evaluate how and when patients take their medications, and possibly lead to better treatment outcomes, she continued.

“We’ve spent a lot of time examining many different types of apps, and strongly believe they can really improve medication nonadherence,” she said.

“Nevertheless, there needs to be testing in the clinical setting because it’s the one area that really hasn’t been explored. With so much time and money being wasted, and with a restricted level of patient success, providers and researchers should delve into this area and work toward a proven solution.”

—Paul Bufano None of the sources reported any relevant financial conflicts of interest.

Web Exclusive For hospitals that offer specialty pharmacy services, there are a host of apps from SP providers and other entities designed to boost medication adherence. For an overview, scan the adjacent 2D barcode.

caregivers from CSP compounding and dispensing errors. Of increasing importance is the documentation assistance these systems provide for hospitals in meeting regulatory compliance.

It is time for hospitals to apply the same barcode safety technologies to the medication preparation process as so many already have to the medication administration process. Given the high risks associated with IV medications, it could be argued that if a hospital had neither, the best place to start might be with BCMP. Dr. Fahrni will be presenting on this subject at The unSUMMIT in New Orleans.

For more information on the event, go to www.unsummit.com. Dr Fahrni and Mr. Neuenschwander disclosed receiving consulting fees from numerous vendors in the barcoding market.

Technology 15

Pharmacy Practice News • September 2014

Telemedicine

PATIENT PORTAL continued from page 1

actually reduce symptom distress,” said investigator Donna Berry, PhD, RN, an associate professor in the Department of Medicine at Harvard Medical School, in Boston.

In a randomized clinical trial, the ESRA-C (Electronic Self-Report Assessment—Cancer) II, Dr. Berry and her colleagues enrolled 752 patients with more than 15 types of cancer. Dr. Berry said they tried to cast a wide net so that they would be able “to generalize this to all patients with cancer going through therapy.”

Participants in the intervention group (n=374) were free to use the ESRA-C software to evaluate their symptoms at home or in a clinical setting, as well as during each of three or four clinician assessments, over a period of up to eight weeks. The control group (n=378) did not have access to the program, but received three or four assessments.

who scored, on average, 1.93 points lower on the SDS-15 compared with the

control group (95% confidence interval, –3.16 to –0.70; P=0.002). No signifi-

cant change was detected as a result of the intervention among participants younger than age 50 ((P=0.40). Dr. Berry postulated that younger patients, in general, are more familiar with accessing information from the Internet.

“That’s a big assumption,” she said, but patients older than age 50 might “need the structure that this program was able to give them.”

The ESRA-C program was designed to help patients determine the appropriate course of action given certain

•

see PATIENT PORTAL, page 16

When MH strikes,

Keep cool in the crisis with administration in

LESS THAN 1 MINUTE

‘It’s not that we were able to simply lower the [symptoms] ... of the intervention group and the control group stayed the same. The control group got worse.’

—Donna Berry, PhD, RN In a comparison between the two groups, the investigators calculated that access to the ESRA-C program was associated with an average Symptom Distress Scale (SDS-15) score that was 1.21 points lower in the intervention group than the control arm (P ( =0.02).

“It’s not that we were able to simply lower the [symptom distress of the] intervention group and the control group stayed the same,” Dr. Berry said.

“The control group got worse,” with an average change of 1.27 points, indicating increased distress from baseline.

A change in the SDS-15 score by one or two points, Dr. Berry said, is equal to the difference between giving a major symptom (such as fatigue or pain intensity) a mild rating compared with a moderate or severe rating.

This study is an “excellent example of testing a large sample in the community,” to show how patients can benefit from a symptom reporting system, said Xin Shelley Wang, MD, MPH, a professor in the Department of Symptom Research at the University of Texas MD Anderson Cancer Center, in Houston.

The program was most effective for participants aged 50 years or older,

ADVANCING THE STANDARD IN MALIGNANT HYPERTHERMIA (MH) TREATMENT. RYANODEX® (dantrolene sodium) for injectable suspension is changing how MH is treated.

• Less time for reconstitution and administration – Less than 1 minute for a loading dose (2.5 mg/kg) of dantrolene sodium in an MH crisis1,2 • Less risk of complications with less fluid – Over 99% less sterile water for injection than other dantrolene sodium IV treatments3-5 • Less effort to stay cool in an MH crisis – 1 vial provides a loading dose for patients up to 100 kg and can be administered by 1 healthcare professional (eg, an anesthesia provider)1,3 To request that RYANODEX® be stocked in your institution or obtain ordering information, visit RYANODEX.com/ppn or call 855.318.2170.

References: 1. Data on file. Eagle Pharmaceuticals, Inc. 2. Managing an MH crisis. Malignant Hyperthermia Association of the United States website. http://www.mhaus.org/healthcareprofessionals/managing-a-crisis.

Accessed June 18, 2014. 3. RYANODEX [package insert]. Woodcliff Lake, NJ: Eagle Pharmaceuticals, Inc.; 2014. 4. Dantrium Intravenous [package insert]. Rochester, MI: JHP Pharmaceuticals, LLC; 2008. 5. Revonto [package insert]. Louisville, KY: US WorldMeds, LLC; 2011.

Please see Brief Summary of Prescribing Information on the following page. © 2014 Eagle Pharmaceuticals, Inc. All rights reserved.

50 Tice Blvd, Suite 315 Woodcliff Lake, NJ 07677 (201) 326-5300 RYN14-0027-01 8/2014

INDICATION RYANODEX® (dantrolene sodium) for injectable suspension is indicated for the treatment of malignant hyperthermia in conjunction with appropriate supportive measures, and for the prevention of malignant hyperthermia in patients at high risk.

IMPORTANT SAFETY INFORMATION RYANODEX® is not a substitute for appropriate supportive measures in the treatment of malignant hyperthermia (MH), including: • Discontinuing triggering • Instituting cooling when necessary anesthetic agents • Administering diuretics to prevent late kidney injury due to • Increasing oxygen myoglobinuria (the amount • Managing the of mannitol in RYANODEX® is metabolic acidosis insufficient to maintain diuresis)

16 Technology

Pharmacy Practice News • September 2014

Telemedicine

PATIENT PORTAL continued from page 15

symptoms. “Patients are often at home when they’re having problems,” Dr. Berry said, and they may not know if their symptoms are serious enough to merit a call to their doctors. “More often than not, they don’t call.”

When the program detects that a patient has reported high levels of pain or another severe symptom, it prompts the patient to contact his or her physician. If, on the other hand, a patient’s

RYANODEX® (dantrolene sodium) for injectable suspension, for intravenous use.

Brief Summary of Prescribing Information. See Package Insert For Full Prescribing Information INDICATIONS AND USAGE RYANODEX® is indicated for the: • Treatment of malignant hyperthermia in conjunction with appropriate supportive measures (see Dosage and Administration) • Prevention of malignant hyperthermia in patients at high risk.

DOSAGE AND ADMINISTRATION (Selected Information) In addition to RYANODEX treatment, institute the following supportive measures: • Discontinue use of malignant hyperthermia (MH)-triggering anesthetic agents (i.e., volatile anesthetic gases and succinylcholine).

• Manage the metabolic acidosis • Institute cooling when necessary • Administer diuretics to prevent late kidney injury due to myoglobinuria (the amount of mannitol in RYANODEX is insufficient to maintain diuresis) Administer RYANODEX by intravenous push at a minimum dose of 1 mg/kg. If the physiologic and metabolic abnormalities of MH continue, administer additional intravenous boluses up to the maximum cumulative dosage of 10 mg/kg.

If the physiologic and metabolic abnormalities reappear, repeat RYANODEX dosing by intravenous push starting with 1 mg/kg.

Dosage for Prevention of Malignant Hyperthermia The recommended prophylactic dose of RYANODEX is 2.5 mg/kg administered intravenously over a period of at least 1 minute, starting approximately 75 minutes prior to surgery.

Avoid agents that trigger MH. If surgery is prolonged, administer additional individualized RYANODEX doses during anesthesia and surgery.

Dosage for Pediatric Patients The recommended weight-based dose of RYANODEX for pediatric patients in the treatment and prevention of MH is the same as for adults for these indications (see Dosage and Administration).

Reconstitution and Administration Instructions The supplied lyophilized powder must be reconstituted prior to administration: Reconstitute each vial of RYANODEX lyophilized powder by adding 5 mL of sterile water for injection (without a bacteriostatic agent).

Do not reconstitute with any other solution (e.g., 5% dextrose injection, 0.9% sodium chloride injection).

Shake the vial to ensure an orange-colored uniform suspension. Visually inspect the vial for particulate matter and discoloration prior to administration.

Must use the contents of the vial within 6 hours after reconstitution. Store reconstituted suspensions at controlled room temperature (68°F to 77°F or 20°C to 25°C).

(For complete Dosage and Administration Section, see full Prescribing Information)

RYANODEX has been associated with dysphasia. Assess patients for difficulty swallowing and choking.

Somnolence and Dizziness Somnolence and dizziness can occur following administration of RYANODEX and may persist up to 48-hours post-dose. Patients should not be permitted to ambulate without assistance until they have normal strength and balance. Patients must not operate an automobile or engage in other hazardous activities for 48-hours post-dose.

The concomitant use of sedative agents with RYANODEX may increase the risk of somnolence and dizziness.

Potential for Tissue Necrosis with Extravasation Care must be taken to prevent extravasation of RYANODEX into the surrounding tissues due to the high pH of the reconstituted RYANODEX suspension and potential for tissue necrosis.

ADVERSE REACTIONS Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a study designed to evaluate the safety and tolerability of RYANODEX, healthy volunteers were randomly assigned to receive treatment with RYANODEX or an active comparator at doses ranging from 1 mg/kg to 2.5 mg/kg.

• The RYANODEX dose was infused over the course of 1 minute for each of the doses evaluated.

• The active comparator was an injectable formulation of dantrolene sodium that differed from RYANODEX in that it contained dantrolene sodium and mannitol at concentrations of 0.33 mg/mL and 50 mg/mL, respectively, when reconstituted according to the product’s prescribing information. The active comparator was infused at a rate that administered 20 mg of dantrolene per minute for each of the doses evaluated.

Table 1 displays the most common adverse events in this study. These data are not an adequate basis for comparison of the types or frequencies of adverse event types between RYANODEX and the dantrolene sodium comparator.

Adverse events increased in frequency with increasing doses in the trial, but did not differ in frequency between the two treatment groups.

RYANODEX-treated subjects were more likely to report immediate adverse events of flushing, dystonia, and dysphagia than those receiving the active comparator.

In all dose groups, hand grip strength declined after dosing. In general, the decline in hand grip strength was more pronounced and occurred more rapidly in the RYANODEX-treated subjects in the 1.0, 1.75, 2.0 and 2.25 mg/kg treatment groups.

In the 2.5 mg/kg treatment group, the decline in hand grip strength both in amount and duration was similar between the two treatment groups.

Table 1: Adverse Events in Healthy Volunteers Number(%) of subjects RYANODEX [N=30]

DANTROLENE SODIUM COMPARATOR [N=31]

Flushing

8 (27)

1 (3)

Somnolence

5 (17)

4 (13)

Dysphonia

4 (13)

1 (3)

Dysphagia

3 (10)

4 (13)

Nausea

3 (10)

3 (10)

Feeling abnormal

3 (10)

3 (10)

CONTRAINDICATIONS None.

WARNINGS AND PRECAUTIONS Muscle Weakness RYANODEX is associated with skeletal muscle weakness. The administration of RYANODEX in human volunteers has been associated with loss of grip strength and weakness in the legs.

Patients should not be permitted to ambulate without assistance until they have normal strength and balance.

RYANODEX has been associated with dyspnea, respiratory muscle weakness, and decreased inspiratory capacity. Monitor patients for the adequacy of ventilation.

symptoms are not as severe, the program provides self-care information. It will suggest that a patient drink plenty of water, for example, if he or she reports having mild diarrhea.

This system could also “provide good information to post-therapy patients,” Dr. Wang said, such as patients receiving concurrent chemoradiation therapy who may not have scheduled follow-up visits in the peak of symptom burden. Patients finished with chemotherapy may still experience persistent symptoms, but a symp-

Headache

1 (3)

4 (13)

Vomiting

1 (3)

2 (6)

Vision blurred

1 (3)

1 (3)

Pain in extremity

1 (3)

1 (3)

Muscular Weakness/ Asthenia

1 (3)

1 (3)

Atrioventricular block

1 (3)

0

Tachycardia

1 (3)

0

Infusion site pain

1 (3)

0

Dizziness

1 (3)

0

tom-monitoring program could help with the transition.

Cancer associations and foundations may offer online systems that track symptoms, but some of these symptom trackers may require up to grade 12 reading skills, Dr. Berry said. The ESRA-C was designed with a sixthgrade reading level in mind. “We’ve gone to great lengths to make it usable by people who’ve never touched a computer.” To make the program more accessible, Dr. Berry envisions that future plans could include installing

Postmarketing Experience The following adverse reactions have been identified during postapproval use of another formulation of dantrolene sodium for injection.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Pulmonaryy Edema There have been reports of pulmonary edema developing during the treatment of malignant hyperthermia crises with another dantrolene sodium dosage form. The contributory effect of the diluent volume and mannitol in these cases is not known.

Thrombophlebitis p and Tissue Necrosis There have been reports of thrombophlebitis following administration of intravenous dantrolene.

Tissue necrosis secondary to extravasation has been reported (see Warnings and Precautions).

Hypersensitivity/Anaphylactic yp y p y Reactions There have been reports of urticaria and erythema possibly associated with the administration of dantrolene sodium for injection. Anaphylaxis has been reported.

Injection j Site Reactions Injection site reactions including pain, erythema, and swelling, commonly due to extravasation, have been reported.

DRUG INTERACTIONS Calcium Channel Blockers Cardiovascular collapse in association with marked hyperkalemia has been reported in patients receiving dantrolene in combination with calcium channel blockers. The concomitant use of RYANODEX and calcium channel blockers is not recommended during the treatment of malignant hyperthermia.

Muscle Relaxants The concomitant administration of RYANODEX with muscle relaxants may potentiate the neuromuscular block.

Antipsychotics and Antianxiety Agents The concomitant administration of RYANODEX with antipsychotic and antianxiety agents may potentiate their effects on the central nervous system (see Warnings and Precautions).

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy g y Category g yC Adequate and well controlled studies have not been conducted with RYANODEX in pregnant women. However, animal reproduction studies have been conducted with dantrolene sodium. In these studies, dantrolene sodium administered to rats and rabbits produced embryolethality (rabbits) and decreased pup survival (rats) at doses seven times the human oral dose. RYANODEX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery In one uncontrolled study, 100 mg per day of prophylactic oral dantrolene sodium was administered to term pregnant patients awaiting labor and delivery. Dantrolene readily crossed the placenta, with maternal and fetal whole blood levels approximately equal at delivery; neonatal levels then fell approximately 50% per day for 2 days before declining sharply. No neonatal respiratory and neuromuscular side effects were observed in this study.

Nursing Mothers Dantrolene is present in human milk. In one case report, low dantrolene concentrations (less than 2 micrograms per milliliter) were measured in the breast milk of a lactating woman during repeat intravenous dantrolene administration over 3 days. Because of the potential for serious adverse reactions of respiratory depression and muscle weakness in nursing infants from dantrolene, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use The safety and efficacy of RYANODEX in the treatment and prevention of malignant hyperthermia in pediatric patients is based on clinical experience with other intravenous dantrolene sodium products, which suggests adult weight-based doses are appropriate for pediatric patients.

Geriatric Use Clinical studies of RYANODEX did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

OVERDOSAGE Overdosage Symptoms Overdosage symptoms include, but are not limited to, muscular weakness and alterations in the state of consciousness (e.g., lethargy, coma), vomiting, diarrhea, and crystalluria.

Management of Overdosage Employ general supportive measures for acute overdosage of RYANODEX. PATIENT COUNSELING INFORMATION Inform patients, their families, or their caregivers of the following: Muscle Weakness Muscle weakness (i.e. decrease in grip strength and weakness of leg muscles, especially walking down stairs) is likely to occur with the use of RYANODEX. Patients should be provided assistance with standing and walking until their strength has returned to normal (see Warnings and Precautions).

Difficultyy Swallowingg Caution is indicated at meals on the day of administration because difficulty swallowing and choking have occurred with the use of dantrolene sodium products in general; dysphagia has been reported with the use of RYANODEX (see Warnings and Precautions).

Dizziness and Somnolence The use of RYANODEX has been associated with dizziness and somnolence. (see Warnings and Precautions).

Drivingg or Operating p g Machineryy Symptoms such as “lightheadedness” may occur.

Since some of these symptoms may persist for up to 48 hours, patients must not operate an automobile or engage in other hazardous activity during this time (see Warnings and Precautions).

Revised: 7/2014 Marketed by: Eagle Pharmaceuticals, Inc. Woodcliff Lake, NJ 07677

© 2014 Eagle Pharmaceuticals, Inc. All rights reserved.

50 Tice Blvd, Suite 315 Woodcliff Lake, NJ 07677 (201) 326-5300 8/2014

iPads in waiting rooms.

“A few years ago, there would have been a bigger barrier” to patient adoption, Dr. Wang said. “But now, even if you don’t have a computer, you can use an iPhone or smartphone, or an iPad,” she added, predicting that technology such as this will have a “bigger and bigger impact every day in oncology care.”

—Ben Guarino Drs. Berry and Wang reported no relevant financial conflicts of interest.

Parents: Web Portals To Child’s Health Records Are Useful

A

lmost 70% of parents who used a Web portal to access their child’s electronic medical record (EMR) thought that the portal improved their ability to understand and manage their child’s condition, and 62% thought that it improved communication with health care providers, according to a recent study from Cincinnati Children’s Hospital Medical Center (CCHMC) in Ohio.

Terri L. Byczkowski, PhD, and her colleagues at CCHMC wanted to know if parents of children with chronic conditions (cystic fibrosis, diabetes and juvenile idiopathic arthritis) would use a portal that provided access to laboratory results and other medical information, and enabled them to email health care providers and upload documents, such as school forms, among other functions.

In all, 530 parents had access to the portal and 215 were identified as portal users; 315 were deemed portal nonusers because they accessed the portal fewer than three times ((Health Informatics J 2014;20:151-162). Of the portal users, 126 (59%) participated in a telephone survey.

Most users said the portal was useful, accurate and timely. Additionally, more than half of the parents noted that they never had any difficulty using the portal.

Many of the parents said the portal’s email function was particularly helpful, with more than one-third saying they used the tool for contacting health care providers. Of the parents who used the email function, 81% said it was very useful; 74% said they always received the desired information; and 71% said responses came in a timely fashion.

Some parents suggested that the site could be improved by offering additional explanations of test results and medical terminology.

Based on the results, the authors concluded that “Web-based patient portals have the potential to be a useful tool for parents of children with chronic disease.”

—Marie Rosenthal

Operations & Management 17

Pharmacy Practice News • September 2014

Finances For hospitals offering specialty pharmacy services:

Tips for Taking the Sting out of a $3K Deductible W

hen a hospital or health system makes the decision to add inhouse specialty pharmacy capabilities— either in a limited employees-only form, or more broadly for the general patient population—one key service to provide is patient financial assistance.

The National Center for Health Statistics recently reported that, as of early 2013, more than 30% of group health care plan participants were enrolled in a high-deductible plan, up from 17.1% in 2008. The end result for patients who require high-cost specialty medications is that they may get dinged as much as $6,350 for an individual, or more than $12,000 for a family at the beginning of each year before insurance begins to pay for their therapy.

Financial assistance programs are at the heart of the specialty pharmacy mission, according to Kyle Skiermont, PharmD, the director of specialty/infusion operations at Fairview Pharmacy Services, Minneapolis, one of the nation’s leading health system–based specialty pharmacies. “A key element specialty pharmacy offers is to work with patients to find alternate sources of funding for their medications,” Dr. Skiermont said.

That’s true for any specialty pharmacy, but particularly for those that are based in hospitals and health systems.

“The health-system mission is providing access to care for our patients,” he pointed out. “It’s not just a prescription that came in your door: You as the health system have been caring for that patient since his or her diagnosis and sometimes before. You’ve done all the work to diagnose them and educate them about their condition and its treatment. But if there’s a financial barrier when it comes time to put that treatment in their hands, all of that work is for naught.”

When a patient comes to Fairview with a prescription for dimethyl fumarate (Tecfidera, Biogen Idec), Humira (adalimumab, AbbVie) or any other specialty drug, and they are covered by a high-deductible insurance plan that front-loads a lot of the expense for that medication from the patient’s pockets, that patient’s financial worries also become the problem of Aubree Dorr.

Ms. Dorr, Fairview’s specialty pharmacy liaison, supervises its staff of patient financial advocates (PFAs)—the specialists whose job it is to know all of the options for coping with the two-ton weight of deductibles and coinsurance, and to walk patients through that often confounding maze. Fairview currently has around nine full-time employees who

A Question of Cost— And Also Adherence

T

he burdens caused by high deductibles on specialty drugs are not limited to finances: The steep price tags also can have a profound effect on drug adherence. In one study, high-deductible health plans were found to reduce adherence to prescription medication regimens in four of five conditions evaluated: hypertension, dyslipidemia, diabetes and depression ((Am J Managed Care 2013;19:e400-e407).

‘It’s almost a full-time job just keeping up with the [patient assistance] grants.’

—Aubree Dorr do nothing but this, all day, every day.

“We are generally the first ones to find out that there’s this really high copay because of the proactive processes we’ve employed here,” Ms. Dorr said.

“We run a test claim to find out exactly what the insurance is going to charge to patient responsibility, and then we start our research process.”

PFAs may be called by a different name depending on where they are, but at any good-sized specialty pharmacy, there will probably be at least a few of these savvy experts on the ins and outs of manufacturer’s coupons, Medicare Part D extensions and foundation grants. Fairview assigns its PFAs to one or two particular specialty disease states, so that they can develop deep knowledge of each drug and therapy and their support programs.

The PFAs usually follow a three-step process to find financial support for patients who can’t manage their crushing pharmacy costs.

Step 1: Manufacturer’s coupons or copay/coinsurance assistance cards.

“These can be the quickest and easiest go-to solutions,” Ms. Dorr said. The coupons and cards have no income criteria, and are essentially open access to anyone prescribed the applicable medication.

“There are a lot of instances I’ve seen where a copay card will cover all but $5 to $50 of the patient’s responsibility,” she added. These cards can generally be renewed annually, although Ms. Dorr said she has seen some cards lasting

through a total dollar amount of coverage. The cards generally look like any other insurance card, and the pharmacy will put it through the billing system as a secondary claim. “If, for example, $400 comes back, we then bill it to the copay card, and they will pay all except $5 or $10 or whatever the amount is.”

To qualify for a manufacturer’s free drug program, patients must meet certain income thresholds. These vary, but generally range from 250% of the federal poverty level at the very low end, to somewhere closer to 400% of the federal poverty level at the high end. If a patient qualifies, he or she will have a profile and a case manager in place at the manufacturer’s assistance hub— typically, a website that offers a variety of patient assistance tools—and the hub coordinates with the manufacturer about the source of the medication. “At that point, it takes us out of the loop,” Ms. Dorr said. “The drug comes from another pharmacy or the manufacturer directly.” But the specialty pharmacy PFA is invaluable in getting the patient through the application process for the free drug program in the first place.

Step 2: Foundations and Grants. If manufacturer programs don’t meet a patient’s needs, the next sources the PFAs tap are foundations such as the Patient Access Network (PAN) Foundation, the HealthWell Foundation and CancerCare (solely for oncology patients). “Their grants open and close on an annual, quarterly or monthly basis,” Ms. Dorr said. “Every founda-

tion and grant for every diagnosis is different. It’s almost a full-time job just keeping up with the grants. As soon as they open up, they could be absorbed in a day, or it could take all month—it just depends on the need in the nation.”

When a grant is set to be replenished with funds, PFAs “line up”—virtually, or by phone—much like avid ticket buyers for a show. “You’ll know that, at the stroke of 8 a.m. EST on July 1, there will be another $1 million in this fund,” Ms. Dorr said. “For some funds, like PAN, you can apply online; for others, you have to call. Some require that the patient call as well; we do setup on the front end and open the case, and then the patient calls to give their information.”

Step 3: Specialty Pharmacy Assistance. When the first two sources of financial aid are exhausted or unavailable, some specialty pharmacies—particularly those affiliated with larger health systems—may have their own payment plans, grants or other systems for helping patients afford their medications. Fairview has its Fairview Foundation, which basically allows access to a lump sum of money for pharmacy patients whose copays have become burdensome. The pharmacy also has insurance gap assistance, with a similar application process and financial guidelines to those for manufacturer coupons and cards, which can offer a one-time write-off of 25% or more of copay costs annually.

“We’re going to do all that we can to make sure patients, especially those in critical situations, get the medications they need,” Ms. Dorr said. “We bend over backward and, knock on wood, most of the time we are able to come up with what the patient needs.”

Room for Variation Of course, not all health systems need to take the same approach. Dr. Skiermont noted, for example, that the PFA function doesn’t necessarily need to be placed within specialty pharmacy. “We’ve chosen to concentrate it there, but it might be elsewhere in the system, such as a nurse or a social worker or a financial counselor within specialty clinics for certain conditions,” he said. “But no matter where it’s located, you have to have the person power and the expertise to provide this financial support. It’s not something that just happens. However you set it up, this expertise is key to having a successful specialty pharmacy.”

—Gina Shaw The sources reported no relevant financial conflicts of interest.

18 Operations & Management

Pharmacy Practice News • September 2014

Medication Safety

JOINT COMMISSION continued from page 1

at the ISMP in Horsham, Pa., to urge pharmacy directors to work with other departments to avoid potential consequences of noncompliance. “In my experience, hospitals that are accredited by the Joint Commission and receive a report showing noncompliance with a lot of medication management standards typically hold the pharmacy director responsible, even when the issues involve other departments,” said Dr. Rich, who moderated the ISMP webinar. “Unfortunately, I have known of pharmacy directors who were fired because of a poor report.”

Pat Adamski, RN, MS, MBA, the director of projects in the Division of Healthcare Improvement at the Joint Commission, and who shared these findings on compliance during the ISMP webinar, said that a common struggle emerged during field reviews.

“Many of the issues we observed were related to poor communication between pharmacists, nurses and physicians,” she said. “Organizations can have defined policies and protocols in place, but if they’re not doing a good job of communicating these [steps] to everyone, they’ll get into trouble.”

Storage Wars Gaps in communication may have been partly responsible for rates of noncompliance with the Joint Commission’s medication storage standard (Medication Management [MM] standard 03.01.01), Ms. Adamski said. She reported that Joint Commission surveyors found medication carts left unattended in unlocked rooms, and discovered instances of unauthorized personnel and former employees having access to locked medication areas and automated dispensing devices.

“If staff are using bio-identification for automated dispensers, they need to be reminded to log out when they’re done,” Ms. Adamski said. “That’s a gap in communications that can be easily fixed.”

Other issues of noncompliance with the medication storage standard included storage of drugs that were not clearly labeled as to their contents, expiration dates and applicable warnings. “We primarily saw this with sterile, injectable multidose vials, which need to be relabeled with a revised date after the multidose vial is accessed the first time,” she explained.

These instances of noncompliance also may be partly a function of some confusion regarding the definition of a “revised date,” Ms. Adamski said. For those seeking clarity on the matter, she pointed to the Joint Commission’s FAQ section on the topic (http://bit.ly/XBnGhr), which states that “multidose vials are to be discarded 28 days after first use unless the manufacturer specifies otherwise.”

Standard Number

Description

2012a

2013b

MM.03.01.01

Medication storage

35%

35%

dard specifies. Following this dictum limits the number of times an agent is manipulated and handled before administration, and therefore reduces the likelihood of contamination or dosing errors, Ms. Adamski explained.

MM.04.01.01

Medication orders

26%

22%

Ordering Issues

MM.05.01.01

Pharmacist review

15%

16%

NPSG.03.04.01

Labeling in procedures

14%

13%

NPSG.03.06.01

Medication reconciliation

6%

6%

MM.01.01.03

High alert medications

5%

5%

MM.05.01.09

Medication labeling

5%

5%

MM.05.01.07

Medication preparation

5%

5%

Nearly one-fourth of surveyed hospitals failed to comply with the medication ordering standard (MM.04.01.01), according to Ms. Adamski. The most frequent type of noncompliance with this standard was improper implementation of medication order policies. “It’s always a challenge to have people follow written policies, especially when they’re in a time crunch,” she observed.

Time crunches may have led some staff to place orders without complete instructions as to the route of administration, frequency of use and titration measures, as Joint Commission surveyors found was sometimes the case.

Ms. Adamski reiterated the importance of clear communication, urging pharmacy nursing and medical directors “to work with front-line staff to understand why they’re not following policies.”

Other instances of noncompliance with this standard that surveyors found included standing orders without the required approvals, orders that were not patient-specific and orders that were not based on the most up-to-date evidence, Ms. Adamski said.

Table. Noncompliance With Top Medication Standards Scores in 2013

a

1,483 full surveys in 2012

b

1,413 full surveys in 2013

Another storage issue that Joint Commission surveyors found, and that potentially could compromise the safety and efficacy of drugs, is storage at temperatures outside the range specified by manufacturers. “Although we’ve been seeing greater diligence in recording and monitoring temperatures, the problem we’re finding now is that there is sometimes no evidence that steps were taken in light of documented temperature fluctuations,” Ms. Adamski said.

Pharmacists can help mitigate the risk for administering compromised medications by developing and communicating clear protocols that outline what personnel need to do and who they need to notify if they notice tem-

perature fluctuations, she suggested.

Within the medication storage standard, Ms. Adamski said Joint Commission surveyors found expired drugs were sometimes in storage areas.

“One step that can reduce the likelihood of stocking expired medications is to ask staff to inspect the medication areas in units or departments they don’t work in, to see it with fresh eyes,” she said. “You get so used to your own area that you can miss things.”

Outside of the pharmacy storage area, Joint Commission surveyors found drugs that had not been delivered to patient care areas in the most readyto-administer form, as one of the elements of the medication storage stan-

Exceptions for Pharmacist Medication Order Review

M

M.05.01.01 EP [Element of Performance] 1 specifies that before dispensing or removing medications from floor stock or from an automated dispensing machine, a pharmacist needs to review all medication orders unless: • A Licensed Independent Practitioner (LIP) controls the ordering, preparation and administration of the medication, including remaining at the patient’s bedside during administration. In an emergency department, an LIP is not required to remain at the bedside when the medication is administered. However, an LIP must be available to provide immediate intervention should a patient experience an adverse drug event.

• A delay would harm the patient in an urgent situation. Organizations are expected to determine what qualifies as urgent.

• In radiology areas, a pharmacist does not need to review contrast agent orders but the hospital is expected to define, through protocol or policy, the role of the LIP in the direct supervision of a patient during and after intravenous contrast media is administered.

—D.W.

Pharmacist Review Can Be Tricky In 16% of surveyed hospitals, Joint Commission surveyors found medication orders that had not been appropriately reviewed by a pharmacist.

Ms. Adamski said there are exceptions that allow orders to be filled without pharmacist review (MM.05.01.01; see sidebar), but hospitals need to clearly define and document what those exceptions are, based on the requirements detailed in the elements of performance (EPs).

“We don’t want to delay care, but we need hospitals to develop clear policies and guidelines regarding which scenarios do not require pharmacist order reviews,” she explained.

Improper Labeling Joint Commission surveyors also found improperly labeled agents in procedural areas in 10% of surveyed hospitals (National Patient Safety Goal 03.04.01). Appropriate labeling in these settings is particularly crucial if agents are not being “immediately administered,” Ms. Adamski said. “The definition of ‘immediately administered’ is that an authorized staff member prepares or obtains the medication, takes it directly to the patient, and administers it to the patient without a break in the process.”

Operations & Management 19

Pharmacy Practice News • September 2014

Medication Safety Medication Reconciliation Six percent of hospitals failed to fully comply with the Commission’s medication reconciliation standard (NPSG 03.06.01), although some of these were related to the absence of written policies and procedures, Ms. Adamski said.

She noted that individual hospitals may decide on the type of information to collect during medication reconciliations, and that this can even vary across departments and scenarios, but surveyors require clear documentation of these policies and evidence that staff is implementing them.

Notably, surveyors found instances in which staff had obtained medication information from patients but failed to complete the most crucial element of the reconciliation process.

“In some cases, they were not comparing the information they received from medication histories to the inhospital orders,” she noted. “Collecting the information isn’t good enough—you need to make sure you’re doing something with it by identifying and resolving any discrepancies.”

Ms. Adamski concluded by singling out

‘If you do nothing else, please get your organization to talk about what process you have in place to perform medication management systems evaluations [MM 08.01.01].’

—Pat Adamski, RN, MS, MBA a standard with relatively low rates of noncompliance but potentially profound implications if not properly followed.

“If you do nothing else, please get your organization to talk about what process

you have in place to perform medication management systems evaluations [MM 08.01.01],” she urged.

The standard calls for organizations to collect data on the performance of

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their medication management systems, to identify points that carry safety risks and to address weaknesses using best practices and published evidence.

“Rip apart your processes and evaluate or assess everything,” Ms. Adamski said. “If you do a good job of evaluating your medication management system, the rest of the standards will fall into place.”

—David Wild Ms. Adamski and Dr. Rich reported no relevant financial conflicts of interest.

20 Operations & Management

Pharmacy Practice News • September 2014

Ambulatory Care 50

30-day hospital utilization, %

MEDICAL HOME continued from page 1

The PCRC model addresses an important need among community hospitals and clinicians outside large health systems or academic settings, according to Hae Mi Choe, PharmD, the director of Innovative Ambulatory Pharmacy Practices at the University of Michigan Health System and a clinical associate professor in the College of Pharmacy at the University of Michigan in Ann Arbor.

“This group really deserves kudos for providing a creative solution to what I’ve found is a significant challenge for community primary care physicians [PCPs], who sometimes cannot afford to hire all PCMH team members for their small, independent practices,” said Dr. Choe, who is not involved in the project.

Keith Kanel, MD, the chief medical officer at the Pittsburgh Regional Health Initiative (PRHI), the nonprofit organization that developed the PCRC model, said there are seven PCRCs in the greater Pittsburgh area. The PCRCs aim to avoid “preventable readmissions,” in patients with chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF) or acute myocardial infarction (AMI).

“We queried the Pennsylvania Health Care Cost Containment Council database and found these three conditions were the top three drivers of readmissions in the state,” Dr. Kanel explained.

His group’s early research also identified some of the causes of preventable readmissions. “For example, many patients aren’t having their medications explained to them well or they have access issues, which leads to improper use of drugs,” Dr. Kanel explained.

“Pharmacists are the ideal providers to resolve many of these issues.”

Close Relationships Crucial Joyce Yager, RPh, a PCRC pharmacist at Sharon Regional Health System in Sharon, Pa., explained that the care process begins in the hospital, where the PCRCs are located. “Our care starts once we’re alerted through the hospital’s electronic health records system that a patient has been admitted due to one of the three conditions [COPD, CHF or AMI] we’re focusing on,” Ms. Yager said.

She and a nurse care manager introduce themselves to the patient at the bedside, explain the program and then begin the enrollment process. Ms. Yager said enrollment in the PCRC has been very high, partly because the service is free, and because many patients are eager to empower themselves and engage in their own care.

Together, the PCRC team and the patient review the patient’s medication

42%

48%

40

less likely to utilize hospital acute-care servicesb

30 22% 20

CMS Funds Program Expansion 10

0

Patients not reached

Patients reached

Figure. Pharmacist post-discharge phone follow-up: reduction in hospital utilization over 6 months.a a

Includes emergency department visits, observation stays or hospital admission, May-October 2012, Monongahela Valley Hospital. b

by phone by the pharmacist after discharge were 48% less likely to use acute hospital services 30 days after discharge than those who could not be reached by phone (Figure).

“The scale of this reduction was striking,” Dr. Kanel said.

Statistically significant.

‘Many patients aren’t having their medications explained to them well or they have access issues, which leads to improper use of drugs.’

—Keith Kanel, MD list and identify any new drugs that have been prescribed or initiated during the inpatient stay, Ms. Yager noted.

“Patients in these three groups can be given so many new medications in hospital,” she said. “We want to make sure the plan of care is carried out.”

At discharge, Ms. Yager and her colleagues confirm the patient has in hand any new written prescriptions. They ensure that patients understand what the new drugs are used for, how to take them and what types of adverse events to expect, which could prevent some patients from discontinuing medications on their own. Additionally, they address any access issues that might prevent patients from acquiring their newly prescribed medications.

‘Patients … can be given so many new medications in hospital.

We want to make sure the plan of care is carried out.’

—Joyce Yager, RPh “For example, if a COPD patient has been prescribed an inhaler and has cost barriers, we can arrange to get samples from the hospital pulmonologist,” said Ms. Yager, noting that within three days of discharge her team sends the PCP or specialist a summary of their encounter with the patient.

Also during the discharge visit, the PCRC team ensures patients have scheduled a follow-up appointment with their PCP, helping them obtain an appointment if necessary.

The close relationship continues after discharge, Ms. Yager said.

Patients receive a phone call within 72 hours after leaving the hospital and have an opportunity to ask questions about their medications. The PCRC staff repeat the medication review process, this time asking the patient or family members to list any other medications the patient takes, including herbal medicines and supplements.

This step improves drug safety and reduces the risk for drug duplication, Ms. Yager said.

Patients are offered a home visit or a follow-up appointment at the clinic, during which Ms. Yager’s team reinforces the care plan, addresses any medication adherence issues and identifies any dose adjustments the team believes need to be made. Although they cannot conduct clinical interventions on their own, the team works with the patient’s PCP or specialist to adjust dosages or to add or discontinue medications.

“The iterative process of medication review in an unhurried environment is both effective and appreciated by the patient,” Dr. Kanel said.

Proof of efficacy was demonstrated by findings from a pilot study of almost 200 patients who participated in the first PCRC program. Patients who had an in-hospital interaction with the PCRC staff and were also contacted

The pilot study findings compelled the Centers for Medicare & Medicaid Services (CMS) to award PRHI $10.4 million so that it could replicate the model at six additional sites in the Pittsburgh area.

The governmental interest and support is encouraging, but other hospitals and PCPs interested in developing and implementing their own PCRC would likely need investment from other stakeholders, said Toni Fera, BS, PharmD, an independent pharmacy consultant located in Pittsburgh who helped create the PCRC model.

Dr. Fera said she and the PRHI team have not yet generated the financial numbers needed to make a business case to persuade stakeholders to invest.

However, there is interest in the model, Dr. Fera said.

“From the perspective of primary care physicians, PCRC staff can provide a depth of counseling that [primary care physicians] can’t give,” she explained, adding more than 3,100 patients were enrolled at the seven PCRC sites by the end of May. Additionally, payors improve their bottom line by reducing use of acute hospital care, Dr. Fera added.

The only ambivalence regarding the model has come from hospitals, she noted. “When we proposed the program to the first hospital we worked with, they were reluctant to do it because they feared losing revenue because of reduced readmission rates,” Dr. Fera said. But there is a counterargument to such concerns. “Although incentives have been slow to align, the business case for pharmacist-provided ambulatory care services is strengthening as there are penalties now for readmissions, and reimbursement for most plans now includes payment for quality performance.”

Dr. Kanel said he expects that to change as health systems and hospitals face reimbursement penalties imposed by the CMS for high rates of 30-day readmissions in various patient groups, including those targeted by the PCRCs. “As that happens, the goals of the PCRCs in reducing readmissions will align with hospital goals,” he said.

“They will increasingly see the value of PCRCs.” —David Wild None of the participants reported any relevant financial conflicts of interest.

Operations & Management 21

Pharmacy Practice News â&#x20AC;˘ September 2014

Finances Part 2 of a four-part series

The Power of Pharmacy To Improve Hospital Bottom Lines

P

harmacyâ&#x20AC;&#x2122;s stature within hospitals and health systems is on a steady upswing, according to new data from KitCheck, which surveyed pharmacy directors at more than 600 hospitals (http://bit.ly/1sVFijF).

The survey found that nearly 75% of pharmacy directors feel they have been â&#x20AC;&#x153;very successfulâ&#x20AC;? or â&#x20AC;&#x153;successfulâ&#x20AC;? in getting senior leadership to understand the value that clinical pharmacy brings to the hospital. Only 5.66% categorized their efforts as â&#x20AC;&#x153;not successful.â&#x20AC;?

Whether you are in that successful 75% and want to remain there, or are in the lower 25% and want to scramble up the ladder, Cardinal Healthâ&#x20AC;&#x2122;s Mary Baxter, MBA, RPh, said that pharmacists who want to position themselves as strategic assets to their hospital or health systemâ&#x20AC;&#x201D; rather than simply managers of another cost centerâ&#x20AC;&#x201D;must focus on what Cardinal Health calls the â&#x20AC;&#x153;Four Fâ&#x20AC;? Framework: â&#x20AC;˘ Find meaningful growth â&#x20AC;˘ Fix inefficiencies â&#x20AC;˘ Fulfill the quality care mission â&#x20AC;˘ Follow the patient In this second in a series of articles on strategic positioning for hospital pharmacy, we focus on that second F: fixing inefficiencies. â&#x20AC;&#x153;Health care is a team sport, with multiple caregivers helping the patient,â&#x20AC;? said Ms. Baxter, the vice president and national practice leader of Cardinal Healthâ&#x20AC;&#x2122;s Innovative Delivery Solutions business. â&#x20AC;&#x153;If there are inefficiencies throughout the system with regard to medication use, the pharmacy needs to work very diligently to make those go away, so that weâ&#x20AC;&#x2122;re not taking the nurseâ&#x20AC;&#x2122;s, or the physicianâ&#x20AC;&#x2122;s, or our own time away from patient care.â&#x20AC;?

Purchasing and Inventory In many hospitals, Ms. Baxter pointed out, there are several key areas of efficiency crying out for pharmacyâ&#x20AC;&#x2122;s intervention. â&#x20AC;&#x153;First of all, there is availability,â&#x20AC;? she noted. â&#x20AC;&#x153;You need to ensure good purchasing and inventory processes to have the drug there when the patient needs it.

Anticipate what you need, and make sure you have appropriate processes in place like continual evaluation of minimum and maximum levels of products to trigger ordering inventory at the right time.â&#x20AC;?

This is a very dynamic processâ&#x20AC;&#x201D;you canâ&#x20AC;&#x2122;t just buy a drug and let it sit on the shelf until it is used. â&#x20AC;&#x153;You need a constant analysis of what you have coming in and going out and when you need to increase or decrease levels, so that instead of having dollars tied up on a shelf, they can be used for more strategic projects,â&#x20AC;? Ms. Baxter said. â&#x20AC;&#x153;Automation allows this to become metric-drivenâ&#x20AC;&#x201D;you canâ&#x20AC;&#x2122;t go

around and look at every shelf every day.

But a well-trained pharmacist can look at the data ... to determine how drugs are being used, see trends and determine how you need to move forward to optimize purchasing and inventory.â&#x20AC;?

The pharmacy at the Riverside Regional Medical Center at Riverside Health System, the largest of the Newport News,

Va.-based health systemâ&#x20AC;&#x2122;s five acute care and two specialty hospitals, moved into a new building in February 2013 and added its carousel inventory management system that spring. â&#x20AC;&#x153;It has really helped us manage inventory so that we can slice and dice the data any way we need it,â&#x20AC;? said Mike Doucette, the senior vice president/ administrator for the hospital. â&#x20AC;&#x153;If we

have a pharmacy expense spiking, we can identify it by physician, by floor, by area.

Almost every month, he added, â&#x20AC;&#x153;youâ&#x20AC;&#x2122;ll see a spike somewhere in our pharmacy expense. Our pharmacy manager can drill down, for example, and say, â&#x20AC;&#x2DC;This month, 50% of the inpatient expense increase was due to volume, but the other

â&#x20AC;˘

see BOTTOM LINES, page 22

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22 Operations & Management

Pharmacy Practice News • September 2014

Reimbursement Matters New proposed OPPS rule reveals a hot button for CMS:

Site-of-Care Cost Shifting in the Spotlight F

ederal health officials have released the proposed 2015 rule for the Hospital Outpatient Prospective Payment System (OPPS), along with those for ambulatory surgery centers, and judging by some of the new content, it’s clear that certain payment practices will be under increased scrutiny if the draft sees the light of day.

Centers for Medicare & Medicaid Services (CMS) released the proposal on July 3, and posted it July 14 in the Federal Register (http://1.usa.gov/1pAHbjk).

But as in previous years, much of the addenda providing important details on the new payment policies are not included in the rule itself; they must be accessed separately from the CMS website (http://go.cms.gov/O89Ga7; http:// go.cms.gov/1pNO1U2).

The next several columns will cover segments of the 2015 OPPS Payment Rules and delve into sections of particular interest to pharmacy. In this month’s discussion, I focus on CMS’ new request to collect data on clinical services furnished in what the agency terms offcampus provider-based departments.

What precipitated this request? In a nutshell, the ever-increasing trend of hospitals purchasing specialty physician practices and then raising the prices for the care provided—to the extent that federal regulators opted not to turn a blind eye to the tactics. Bloomberg Businessweek published a fascinating piece succinctly delineating this in July (http:// buswk.co/Y0XGfD).

D The article critically

examined the steady increase in prices after practice acquisition in multiple areas, including oncology services where drug pricing is exposed, as well as other specialty areas that also involve immunotherapy and cardiology services.

The article detailed how watchdogs, including the Medicare Payment Advisory Commission (MedPAC), which advises Congress, sounded the alarm. In May, Mark Miller, the executive director of MedPAC, testified before Congress that Medicare should ensure that payment rates are constricted so as “to limit the incentive to shift cases to higher-cost settings.” That led CMS to establish the rule requiring the recording of the volume of outpatient care that is occurring in hospital-owned settings. The justification is that CMS is seeking a better understanding of how this trend affects payments under the physician fee schedule (PFS) and OPPS. CMS also has serious concerns about the financial hardships posed by high deductibles, copays and other beneficiary cost-sharing obligations that result from these business practices. In many cases, it is the patients themselves who have raised concerns over these practices.

CMS collects vast volumes of claims data, and analysis of this big data pool has shown a divide between the total payment amount for outpatient services made by Medicare (generally higher) and the total payment amount made by Medicare when a physician provided those same services in a freestanding clinic or in a physician’s office (gener-

ally lower). As just discussed, MedPAC has questioned the appropriateness of increased Medicare payment and beneficiary cost sharing when physician offices become, in effect, hospital outpatient departments, and has recommended that Medicare pay selected hospital outpatient services at PFS rates.

CMS intends to develop a better understanding of expenses that are typically incurred by the hospital versus those that accrue from services provided by physicians and other providers in non-hospital practice sites. To advance that effort, the agency has proposed the creation of a Healthcare Common Procedure Coding System (HCPCS) modifier that will be reported beginning Jan. 1, 2015. The modifier will include every code for physician and outpatient hospital services furnished in an off-campus providerbased model. The codes will be included on both the CMS-1500 claim form for physicians’ services and the UB-04 form for hospital outpatient services. CMS is very specific in its definitions: According to the agency, an off-campus facility is provider-based if it meets the requirements of 42 C.F.R. § 413.65, and “campus” is defined in 42 C.F.R. 413.65(a)(2).

These proposed rules are open for public comment until Sept. 2, and any changes or other proposed mechanisms will be published with the final rule before the end of 2014.

Action Steps: Foster a discussion with your finance and revenue cycle teams about the need for transparent, realistic

BOTTOM LINES

do traditional order entry, or use video verification of how IV fluids are prepared to ensure safety,” Ms. Baxter said.

“That frees up the pharmacist to be on the floor to do more specific clinical initiatives with patients.”

With such a strategy, “you still keep patients absolutely safe, and instead of pharmacists running into and out of a cleanroom, you can have the tech in the room and the pharmacist observing.”

Remote pharmacy services also are beneficial in rural areas, where many hospitals find it difficult to secure pharmacists to work after-hours shifts. Cardinal Health has a remote service that it staffs for clients, but other systems have other models—for example, one large hospital in a system might provide this for its affiliated smaller hospitals.

chael, PharmD, the VISN 21 pharmacy executive for the VA Sierra Pacific Network. “Hospital pharmacies have gotten good at doing this with antibiotics due to antimicrobial stewardship campaigns—we’re decreasing resistance and improving outcomes, but we’re also saving money,” Dr. Carmichael said. “But in other areas, we’re not as prudent about medication stops. If we apply what we’ve learned from antimicrobial stewardship across chronic care areas, to patients who are on drugs for a long time, over the years, we can achieve even more significant savings.”

With improper drug administration being a significant issue across the country, hospital pharmacies can find value in even the most expensive therapies with strategies that help to ensure “right drug, right patient, right time.”

Dr. Carmichael and her team created a drug safety dashboard, using 19 key metrics found within the electronic health record, which identifies and displays

continued from page 21

50% were in these five drug areas, related to these physicians, these patients, these problems. And here’s what we can do about it.’ It’s not a difficult data search, either. We can get to it very easily.”

Pharmacists also can use data to identify inappropriate diagnosis-related group (DRG) coding. “For example, let’s say a patient has been coded in a simple pneumonia DRG, when they’re actually in for complications related to some other lung disease, like cystic fibrosis,” Ms. Baxter said. “Pharmacists can tell by the drugs being used that the patient has been coded incorrectly and the hospital is being paid less as a result.”

Automation and remote pharmacy services are other areas that offer rich opportunities for pharmacy to improve efficiency and benefit the entire health system. “For example, you can automate and use remote pharmacy models to

Know When To Stop Drugs Another key area of inefficiency that pharmacy can address is when to stop drugs, according to Jannet M. Carmi-

“Reimbursement Matters” is a tool for maintaining your health system’s fiscal health.

Please email the author at bkirschen@aol.com with suggestions on reimbursement issues that you would like to see covered.

Bonnie Kirschenbaum, MS, FASHP

and defensible pricing of at least the pharmacy and drug administration components of the Charge Description Master.

Additionally, if your facility participates in the 340B federal drug discount program, make sure all of its requirements are being met and there is a clear understanding of the eligible patient definition that is supported by your information technology infrastructure.

Good luck!

■

Web Exclusive: CMS Coding Updates CMS has released several important coding updates that go live Oct. 1 and that your reimbursement department will need to heed in order to avoid billing errors. To access the updates, scan the adjacent 2D barcode.

potential drug–drug, or drug–disease adverse events. Pharmacist-run teams can then identify individual patients for population management. During its first three years in use, the dashboard significantly decreased mortality rates and hospital and emergency department admissions.

For example, the dashboard flags heart failure patients who are receiving eplerenone or spironolactone, but whose records either fail to show a recent potassium or serum creatinine level, or whose blood work shows high potassium or serum creatinine levels. Using dashboard alerts to keep a closer eye on these patients allowed the hospital to reduce hospitalizations due to hyperkalemia, and drop the mortality rate for these patients from 9.3% to 7.5%—an improvement in outcomes as well as quality and efficiency.

—Gina Shaw None of the sources reported any relevant financial conflicts of interest.

Read Pharmacy Practice News Anywhere, Anytime!

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REPORT Clinical and Cost Considerations For Managing Postsurgical Pain: Elastomeric Pumps and Continuous Catheters, or a Single-Dose Non-Opioid Local Analgesic Faculty Susan E. Downey, MD, FACS

John Pilcher, MD, FACS, FASMBS

Clinical Associate Professor of Surgery (Plastic) Department of Surgery University of Southern California Keck School of Medicine Los Angeles, California

Medical Director, Bariatric Surgery TexSan Heart Hospital San Antonio, Texas

Jacob Hutchins, MD

Andrew Rogalski, PharmD, BCPS

Director, Regional and Acute Pain Program Department of Anesthesiology University of Minnesota Medical Center

Clinical Pharmacy Specialist Program Director, Pharmacy Practice (PGY1) Residency University Medical Center of Princeton at Plainsboro Plainsboro, New Jersey

Minneapolis, Minnesota

P

ostsurgical pain is a common phenomenon and can have a significant effect on patient outcomes and health care costs. For example, in 2003, Apfelbaum and colleagues1 conducted a survey of 250 adults who recently had undergone surgical procedures, and reported that 80% of patients experienced acute pain after surgery; 86% reported moderate, severe, or extreme pain.

Furthermore, 23% of patients who received pain

medications experienced adverse effects (AEs). More recently, Gan and colleagues2 conducted a survey of a random sample of 300 adults who had undergone surgery within the previous 5 years. Approximately 86% experienced pain after surgery and of these, 75% had moderate or extreme pain during the immediate postsurgical period (Figure 1).1,2 After being discharged from the hospital, 74% reported a continuation of these pain levels.

Supported by

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as respiratory depression, also were noted.8 In 2012, the Joint Commission issued a Sentinel Event Alert regarding the use of opioids in the inpatient setting. This alert described several populations that were at particularly high risk for experiencing AEs in response to opioids, including the elderly, patients with morbid obesity, and those with sleep apnea.9-11 One strategy to obviate the effect of opioid-related AEs is to employ a multimodal analgesic approach.12 Multimodal analgesia, the use of different classes of analgesics that act on different pathways and receptors, has gained increased acceptance and use over the past decade as a potential strategy for managing postsurgical pain while simultaneously reducing the incidence of AEs related to any single analgesic agent.13-15 Several studies have reported that a multimodal approach that reduces opioid use may result in improved outcomes, increased patient satisfaction, and lower cost of care.6,14,16 These benefits have led both the American Society of Anesthesiologists and the Joint Commission to endorse the use of multimodal analgesia in postsurgical patients.4,9

Undermanaged postsurgical pain has broad implications for clinical care.3-5 Indeed, various studies have demonstrated that undermanaged pain after surgery is associated with longer hospital lengths of stay, a higher rate of complications (including cardiovascular, pulmonary, renal, and psychological sequelae), increased risk for developing chronic pain syndromes, and decreased patient satisfaction.3,5 Because health care utilization organizations are tracking pain-related end points as measures of quality of care in surgical patients (eg, within the Hospital Consumer Assessment of Healthcare Providers and Systems survey), these suboptimal outcomes may have a direct effect on hospital reimbursements.6 Opioids are the current mainstay of postsurgical pain management but have idiosyncratic or dose-limiting side effects that can be serious.7,8 The study by Gan and colleagues showed that 88% of postsurgical patients received analgesic medication after surgery and that opioids were the most commonly administered.2 However, 80% of those patients reported AEs. Although the most common AEs were not severe (eg, drowsiness and constipation), serious AEs, such

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Apfelbaum et al.

86 82

Patients, %

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60 45

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40 25

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Slight

Moderate

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Figure 1. Percentage of patients reporting various postsurgical pain levels in 2 different studies.

Based on references 1 and 2.

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Elastomeric Pumps and Continuous Catheters er strategy that uses local anesthetics or other agents in an effort to augment pain control while simultaneously avoiding the AEs associated with opioids.17-19 However, the duration of action of traditional local anesthetics, such as bupivacaine HCl, does not match the time course of postsurgical pain.1,20 In order to offer longer-lasting pain relief compared with that offered by traditional local anesthetics infiltrated into tissue that may or may not be associated with a nerve block, elastomeric pumps and catheters for continuous infusions of local anesthetics were introduced in the 1990s and are increasingly used in the inpatient postsurgical setting.21-23 The utility of these strategies is promoted by the fact that these analgesic routes can be continued even when the patient is discharged from the hospital. Continuation of these advanced analgesic strategies after hospital discharge more closely mirrors the prolonged time course of postsurgical pain.

However, the use of an indwelling catheter for continuous delivery of local anesthetics has several defined disadvantages (Table). 21,24-32 Indwelling catheter use carries a risk for catheter-related complications, such as dislodgment, migration, infection, or bleeding. 24-26 Additionally, continuous delivery using a pump and catheter incurs financial costs associated with the equipment and the resources needed to safely manage these systems both inside and outside the hospital setting.27

Concerns Raised by the FDA and ISMP Both the Institute for Safe Medication Practices (ISMP) and the FDA have raised concerns about the safety of elastomeric pumps in clinical practice.28,29 In May 2009, the ISMP published a report noting an association between the ON-Q速 system and cartilage destruction, especially in cases in which local anesthetic is infused into a joint rather than the surrounding tissue.28 Similarly, the FDA recommended that elastomeric infusion devices not be used for continuous intra-articular infusion in patients after orthopedic surgery due to the risk for chondrolysis.29

Table. Drawbacks, Limitations, and Safety Issues Associated With Use of Elastomeric Pumps and Indwelling Catheters for Postoperative Analgesia Elastomeric pumps Variable infusion rates and concentrations Administration of additional medications instead of analgesic alone Extended use and refilling may result in infection Premature emptying of the bulb Not suitable for outpatient use for individuals with suboptimal health literacy or who live alone Costs associated with the equipment and the resources needed to safely manage these systems

Indwelling catheters Catheter dislodgment Catheter migration Infection and/or bleeding Potential for cartilage destruction, especially in cases in which local anesthetic is infused into a joint rather than the surrounding tissue Based on references 21 and 24-32.

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90

Easypump ((n=300) Infusor LV5 (n=130)

Expected Flow Rate, %

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-30

-60

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200 300 Number of Elastomeric Pumps p

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Figure 2. Elastomeric pumps are associated with a significant incidence of out-of-target flow rates.

The gray area represents the theoretical normal range (±15%) of the set flow rate (5 mL/h).

Based on Remerand F, et al. Elastomeric pump reliability in postoperative regional anesthesia: a survey of 430 consecutive devices.

Anesth Analg. 2008;107(6):2079-2084. Reprinted with permission.

In July 2009, the ISMP followed up with a report calling for safer practices with the use of ON-Q elastomeric pumps.28 In this report, the ISMP noted several other issues regarding the use of these pumps, including variable infusion rates and concentrations, administration of medication including the vasoconstrictor epinephrine instead of analgesic alone, and extended use and refilling that may result in infection.28 The ISMP warned that elastomeric pump devices are filled outside of the pharmacy, typically in the operating room (OR), which raises concerns regarding accurate filling, labeling, and documentation of the administered medication.28

Clinical Experience In a review of experience at a major regional level 1 trauma center, Birrer and colleagues experienced firsthand many of the issues outlined in the ISMP alert.21 The investigators reported that the hospital’s pharmacy and therapeutics committee did not review the use of the ON-Q system because the pumps used a medication already on the formulary

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(bupivacaine). Therefore, there was a lack of training or education in use of the device, leading to a lack of involvement from the pharmacy team and increased human error by the OR staff. As a result, there were several serious incidents.

In one incident, a physician inserted 2 pumps with 4 lumens into a patient with traumatic brain injury and rib fractures. In another incident, the pump’s infusion rate was unpredictable, leading to the clearing of the pump’s bulb in 36 hours, despite the fact that it was expected to last 72 hours.21 In a small pilot study evaluating the use of the Homepump Eclipse for the management of acute and chronic pain, 30 investigators reported several safety incidents when using the pumps, including premature emptying of the bulb and variations in drug delivery times. They also highlighted the importance of patient selection when choosing an elastomeric pump, noting that patients with suboptimal health literacy or those who live alone are not good candidates for this strategy. 30 Capdevila and colleagues studied the use of continuous

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peripheral nerve block to manage pain in 1,416 patients after orthopedic surgery. 24 They reported that this strategy was associated with a significant risk for AEs, most of which were related to the catheter and its associated devices (eg, kinked catheter, inadvertent withdrawal of the catheter, and undesired stoppage of the pump). Bacterial colonization of the catheters also was a common occurrence.24 Grant and colleagues also reviewed their experience with 32 elastomeric pumps.31 After excluding data from 1 pump due to a leak, the investigators reported a pattern of over infusion in 7 of the pumps in the first hour after refilling. Furthermore, they reported that pump infusion flow-rate accuracy was variable over time.31 In a study of 430 pumps, Remerand and colleagues found a variety of issues with both the pumps and the catheters (Figure 2).33 For example, 20.5% of pumps did not deflate correctly, and 2 catheters were obstructed. Spontaneous deflation occurred in 40 cases at 6 to 43 hours after connection. These dysfunctions were associated with a decrease in analgesic efficacy during the first postsurgical night, leading to many catheters being removed by the anesthesiologist after 11 to 72 hours.33

EXPAREL—A Long-Acting Single-Dose Formulation of Bupivacaine The bupivacaine in EXPAREL® (bupivacaine liposome injectable suspension) is encapsulated within multivesicular liposomes (DepoFoam® ) that slowly break down and release the agent over a longer period of time than with a conventional bupivacaine formulation, thereby producing longer-lasting analgesia without the need for a continuous catheter.34,35 Due to the DepoFoam carrier matrix, there is only minimal uptake of bupivacaine into the lymphatics and systemic circulation after injection, reducing systemic exposure and toxicity.34 In several studies, administration of EXPAREL led to prolonged concentrations of bupivacaine through 72 hours with plasma levels detectable up to 96 hours, which more closely matches the time course of postsurgical pain.20,36 EXPAREL has demonstrated safety and efficacy in 2 pivotal Phase III trials of patients undergoing bunionectomy or hemorrhoidectomy.37,38 In both cases, EXPAREL was delivered via wound infiltration at the conclusion of the surgical procedure.

Results showed that patient satisfaction and pain scores were significantly better for EXPAREL than for placebo at the primary end point (72 hours for hemorrhoidectomy, 24 hours for bunionectomy), and the opioid requirements were reduced when compared with placebo.37,38 In another study, pooled safety data were generated from an analysis of 10 randomized, double-blind studies including 823 patients who received EXPAREL at the surgical site.39 The most common AEs in the EXPAREL arms were nausea, constipation, and vomiting.39 Serious AEs were reported in 2.7% of patients receiving EXPAREL, and in 5.4% and 1.1% of patients who received bupivacaine HCl and placebo, respectively. Additionally, 6.4% of patients experienced a cardiac

AE consisting of either tachycardia or bradycardia; however, the cardiac events were mild or moderate in severity, and none required therapeutic intervention.39 Studies of EXPAREL suggest that it does not adversely affect wound healing. For example, in a review of all 10 Phase II and III studies of the efficacy and tolerability of EXPAREL when administered into the surgical site, investigators found that EXPAREL did not adversely affect wound or bone healing for up to 2 years in some patients. There were also no reported instances of chondrolysis, although the number needed to detect this is quite large.40 Additionally, the investigators reported that infections occurred in 5% of patients administered bupivacaine HCL, 3% of patients administered EXPAREL, and 2% of patients administered placebo.40 These are all critical factors to consider when choosing the optimal postsurgical analgesic regimen.

Based on these and other studies, the FDA approved the use of EXPAREL in October 2011 for single-dose infiltration into the surgical site to produce postsurgical analgesia.41 EXPAREL is supplied in a ready-to-use aqueous suspension.42 The volume can be expanded with up to 280 mL preservative-free normal sterile saline as necessary to accommodate administration into a larger surgical site, allowing for a single maximum dose containing 20 mL of EXPAREL without the need for a catheter or pump.43

A Review of the Recent Literature Several studies in 2013 and 2014 reported more recent experience with EXPAREL since its approval for clinical use.

For example, Hollander and colleagues compared the efficacy of EXPAREL (diluted with 40 mL normal saline and injected subfascially before closure of the fascia) versus subfascial continuous local anesthesia (SFCLA; subfascial tunneled catheters and a ropivacaine pump) and patient-controlled analgesia (PCA; morphine) in 195 patients undergoing laparoendoscopic single-site donor nephrectomy.32 Patients managed with PCA required more supplemental narcotics than those on EXPAREL (63.3 vs 29.4 mg; P<0.01) or SFCLA (vs 32.9 mg; P<0.01), but narcotic use was similar between patients treated with EXPAREL and those receiving SFCLA. Pain control (as demonstrated by maximal pain score according to the visual analog scale [VAS]) was comparable between patients receiving EXPAREL and SFCLA (6.3 vs 6.2). Operating time was longer for SFCLA compared with EXPAREL (219.8 vs 199.3 minutes; P<0.01) and PCA (vs 202 minutes; P<0.01). Based on these data, the investigators concluded that EXPAREL was as effective as SFCLA for perioperative analgesia and also was associated with decreased costs and operative time, likely due to its comparative ease of administration.32 Emerson and colleagues compared continuous femoral nerve block (FNB) to wound infiltration with EXPAREL as part of a multimodal pain program in 72 patients undergoing total knee replacement.44 On average, patients receiving EXPAREL required significantly lower amounts of opioid medication during their inpatient stay than those treated with an FNB (hydrocodone equivalent doses: 82.2 vs 176.6 mg; P<0.001), and

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requested fewer narcotic doses (7.5 vs 14.3; Figure 3).44 There was a trend (P=0.09) toward lower inpatient VAS pain scores with EXPAREL compared with FNB (1.8 vs 2.3; P=0.09). In the EXPAREL group, investigators found no incidence of quadriceps weakness, a common drawback to administering traditional local anesthetics via continuous FNB. The investigators concluded that wound infiltration with EXPAREL yielded equivalent postsurgical analgesia compared with a continuous FNB and with significantly less narcotic medication. As a result, they suggested that use of EXPAREL would replace the traditional opioid-reliant model of postsurgical analgesia.44 In another study, Richard and colleagues compared EXPAREL to the ON-Q system in controlling pain at the extraction and stapler insertion sites in patients undergoing

laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB).45 Patients in the EXPAREL group used significantly less narcotics (hydrocodone/acetaminophen) in the immediate postsurgical period than patients in the ON-Q group (<10 vs 30 mg; P= 0.001).45 Additionally, in a single-institution, single-surgeon, retrospective study of 108 patients undergoing robotic-assisted laparoscopic urologic surgeries, Walker and colleagues compared the efficacy of 0.5% ropivacaine delivered via an ON-Q pump (through 2 catheters placed under the fascia at the wound sites at the end of the surgery) versus wound infiltration with EXPAREL (injected subcutaneously into the incision sites and circumferentially along the trocars above and below the fascia down to the peritoneum).46 The investigators

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Figure 3. Patients receiving EXPAREL required significantly lower amounts of opioid medication during their inpatient stay than those treated with an FNB (hydrocodone equivalent doses: 82.2 vs 176.6 mg; P<0.001).

FNB, femoral nerve block Based on reference 44.

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Figure 4. Comparison of the efficacy of wound infiltration with EXPAREL versus 0.5% ropivacaine delivered via the ON-Q system following robotic-assisted laparoscopic urologic surgery.

Based on reference 46.

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reported that the mean morphine equivalent dose was less in the EXPAREL group than in the ON-Q group (23.8 vs 65.9; P<0.0001). Furthermore, the mean time to first opioid use was delayed in favor of EXPAREL (186.0 vs 63.9 minutes; P=0.0043; Figure 4).46 Of particular note, 5 patients in the EXPAREL group and 1 in the ON-Q group did not require any supplemental opioids. Based on these data, the investigators concluded that the use of EXPAREL was an effective strategy for postsurgical analgesia in patients undergoing minimally invasive surgery and was associated with a significant reduction in narcotic use.46

Conclusion Postsurgical pain is common and is associated with worse patient outcomes and higher health care costs. Although the use of local anesthetics as part of a multimodal analgesic approach can reduce opioid use and its associated AEs, the use of elastomeric pumps and continuous catheters needed to

match the protracted time course of postsurgical pain is associated with a variety of potential complications for the patient and can be generally inconvenient and costly to clinicians and institutions. Furthermore, some patients may not be sufficiently health care literate to manage these devices on their own after being discharged, and the devices may require valuable time in the office to be removed if the patient prefers not to do so.

The duration of action of EXPAREL more closely matches the time course of postsurgical pain through a single administration. Multiple trials, both clinical and â&#x20AC;&#x153;real world,â&#x20AC;? have demonstrated that wound infiltration with EXPAREL is effective at reducing pain for up to 72 hours after surgery while simultaneously reducing opioid requirements. Furthermore, EXPAREL administered via wound infiltration obviates the need for elastomeric pumps and continuous catheters and their associated complications and limitations. As a result, EXPAREL is well suited for use as a part of the multimodal analgesic approach across a wide range of patients and procedures.

Case Study 1 A 66-year-old woman presented for open total abdominal hysterectomy, bilateral salpingooophorectomy, periaortic lymphadectomy, and omentectomy for ovarian cancer.

Jacob Hutchins, MD

T

he patient had a history of an abnormal right ovary with elevated CA-125. She had no other past medical history and this was her first surgery. She declined to have an indwelling catheter to manage postsurgical pain because neither she nor her husband felt comfortable removing it at home. The decision was made to provide postsurgical analgesia with bilateral classic transversus abdominal plane (TAP) infiltration with EXPAREL. Before surgery, in the preoperative block area, the patient received bilateral ultrasound-guided TAP infiltration.

She received 30 mL total volume per side (10 mL EXPAREL and 20 mL normal saline). She was then taken to the OR where she was induced with 100 mg propofol, 100 mcg fentanyl, 100 mg lidocaine, and 50 mg rocuronium. She received a total of 400 mcg of fentanyl intraoperatively and 1 mg hydromorphone for a procedure that lasted 264 minutes. Final pathology showed stage IIc adenocarcinoma of the right fallopian tube.

The patientâ&#x20AC;&#x2122;s postoperative pain was well controlled, with her maximal pain score in the postanesthesia care unit (PACU) at 3 out of 10 on the NRS. While in the PACU, she received 50 mcg fentanyl and 1 mg hydromorphone IV. During her first 24 hours postoperatively, her maximal pain score was 3 out of 10 and she received 0.1 mg IV hydromorphone, 5 mg oxycodone, 30 mg IV ketorolac, and 325 mg oral acetaminophen.

During the first postoperative 24 to 48 hours, her maximal pain score was 4 out of 10 and she used only 15 mg ketorolac IV and 1,200 mg ibuprofen. She denied nausea or vomiting during the entire postoperative period. She was discharged home with oral opioids and enoxaparin injections 40.15 hours after surgery. When contacted on postoperative day (POD) 2, she reported continued good pain control without the need for additional opioids and was satisfied with the method of pain management.

Commentary Continuous TAP instillation with a pump and catheter provides incisional pain coverage and can be continued once discharged, but may be contraindicated or not desired in certain patients. By using TAP infiltration with EXPAREL instead of a continuous catheter and pump, a similar duration of analgesia can be provided and all postoperative anticoagulation needs can be met. Additionally, those with limited mental ability or assistance can still receive up to 72 hours of incisional pain relief. This technique also eliminates the potential for accidental catheter removal. With the change to EXPAREL, we have been able to provide postoperative incisional pain control to a more diverse population of total abdominal hysterectomy patients.

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Case Study 2 A 44-year-old man undergoing a skin graft following multiple surgeries.

Susan E. Downey, MD, FACS

T

he patient was previously healthy and had developed chest pain. His medical history was notable for hypertension but he was not on medication. Stress test confirmed an ascending aortic aneurysm. He underwent elective ascending aortic replacement with a femoral artery cut down and repair. Later that same day he began to complain of severe calf pain and was found to have a compartment syndrome in his left calf.

He was taken back emergently to the OR and underwent fasciotomies of the calf. A week later, he developed shortness of breath and was found to have a pericardial effusion. This required another return to the OR and subxiphoid drainage.

Two weeks later, a plastic surgery consultation was obtained for a skin graft for the fasciotomy wounds on his calf.

The nursing staff and the rest of his medical team were concerned about his postoperative pain management because he had been on narcotics in the ICU for several weeks. Due to his many complications and surgical procedures in such a short period of time, the patient was having pain control issues. The Palliative Care Department had been consulted and was following him with the diagnosis of â&#x20AC;&#x153;intractable pain.â&#x20AC;? He was maintained on a hydromorphone PCA 0.9 mg per hour continuous drip with 0.3 mg every 10 minutes as needed and a 3-mg per hour lockout.

The patient was taken to the OR and a split-thickness skin graft was harvested from his upper thigh using a dermatome.

The dermatome was set at 18/100,000 of an inch. EXPAREL 20 mL with 40 mL saline (total volume 60 mL) was injected into the donor site. The donor site was dressed with xeroform and a bulky dressing. The skin graft was secured to the recipient site with staples and Adaptic gauze. No local anesthetic was injected into the recipient site.

Immediately after the skin graft procedure, the PCA was stopped and the patient was switched to hydromorphone IV push 0.5 mg every 3 hours as needed for pain. Oxycodone/ acetaminophen was administered for breakthrough pain. He was discharged home 2 days after the skin graft procedure on oral oxycodone/acetaminophen alone.

Commentary When harvesting skin grafts, the donor site can be as painful as a second-degree burn. It can take days or even weeks for the pain to subside, and an injection of marcaine or lidocaine only lasts a few hours. A pain pump cannot be used because the harvesting of the skin graft does not leave a cavity for a catheter. The patient was informed that EXPAREL would be used in the donor site before surgery to minimize his postoperative pain. After surgery, the patient was found to be resting comfortably and reported no pain in the donor site.

Case Studies 3 and 4 53- and 46-year-old women undergoing Roux-en-Y gastric bypass.

John Pilcher, MD, FACS, FASMBS

The 53-Year-Old Woman: Using an ON-Q Pump and Catheter

T

he patient suffered from many years of weight gain despite regular diet and exercise. Her medical problems included hypertension, hyperlipidemia, asthma, chronic low back pain, and knee pain. She had previously undergone laparoscopic cholecystectomy and total abdominal hysterectomy. She also had a history of atrial fibrillation and spontaneous deep vein thrombosis 4 years before her initial encounter with the bariatric surgical team. She took ibuprofen regularly for moderate knee and back pain, but was not taking any narcotic pain medication before surgery. Her height was 163 cm and her weight was 113 kg, with a body mass index (BMI) of 43 kg/m2. Medications before surgery included lisinopril,

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metoprolol, spironolactone, atorvastatin, and cetirizine.

The bariatric surgical team recommended RYGB to treat the patientâ&#x20AC;&#x2122;s progressive metabolic obesity disease. The surgery was performed laparoscopically, without any unusual events.

The gastrojejunal anastomosis was accomplished using a size 25 circular stapler, which was introduced into the abdomen by removing the left flank trocar and dilating the site to accommodate the device. At the end of the procedure, the fascia and muscle at the site that had been dilated were closed using a single vicryl suture. The other trocars (all nonbladed) were simply removed and no fascial closure was deemed necessary. No drains were deemed necessary.

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Bupivacaine 0.5% plus epinephrine was infiltrated preemptively at each trocar site after the abdomen was prepped and draped, and an additional 20 mL was infiltrated at the end of the procedure into the left flank fascia where the suture closure was accomplished. An ON-Q catheter was threaded into the preperitoneal plane on the left flank, lateral to the site of the suture closure. The 48-hour elastomeric ON-Q pump was charged with a 120-mL volume of bupivacaine 0.25%, which infused gradually through the catheter during the 2-day hospital stay.

The patient received the standard postoperative pain and nausea regimen, which included 2 mg PCA morphine in 10-minute intervals with 30/4-hour lockout; 15 to 30 mL of hydrocodone/acetaminophen elixir (7.5/500 mg per 15 mL) orally every 4 hours as needed for pain; 4 doses of 30 mg IV ketorolac every 8 hours beginning at 4 hours postsurgery; 4 doses of 4 mg IV ondansetron every 6 hours (standing), then 8 mg IV every 6 hours as needed for nausea; and 10 mg of IV metoclopramide every 6 hours as needed for nausea, if ondansetron was not effective.

The postoperative stay was unremarkable, and the patient was discharged home on POD 2. During her hospital stay she received 26 mg morphine via PCA, 120 mL hydrocodone/acetaminophen elixir; ketorolac as scheduled; ondansetron as scheduled followed by 2 additional doses of ondansetron as needed; 20 mg of metoclopramide (2 doses as needed as backup for ondansetron); and bupivacaine via ON-Q catheter, with catheter removal just before discharge.

At time of discharge, the patient received a standard prescription for additional hydrocodone/acetaminophen elixir. At her first follow-up visit, the patient reported that she took the as-needed prescription “very regularly” for the first few days at home, obtained the permitted refill (each fill = 1 pint), then used “about one-fourth” of the second pint. Approximately 1 week post-discharge the patient experienced very severe constipation, requiring 2 enemas and self-disimpaction.

In long-term follow-up, the patient had experienced substantial weight loss and health improvement. There was no longterm pain, nausea, or constipation sequelae.

The 46-Year-Old Woman: Using EXPAREL

T

he patient presented to the bariatric clinic for consideration of bariatric surgical intervention. Her height was 170 cm and her weight was 129 kg, with a BMI of 45 kg/m2. Her medical history included gastroesophageal reflux disease, hypertension, obstructive sleep apnea, and depression. She also had longstanding chronic back and knee pain, for which she took approximately 15 mg hydrocodone per day as-needed.

Other medications included lisinopril, duloxetine, and zolpidem.

She had previously undergone right total knee replacement, and lumbar laminectomy.

RYGB was selected in this case as well. The operation was accomplished laparoscopically according to routine. In the same manner as the previous case, the gastrojejunal anastomosis was accomplished using a size 25 circular stapler with dilation of the skin and muscle at the left flank trocar site. The fascia at this location was closed using a single vicryl suture, and suture closure of the other trocar sites was deemed unnecessary. No drain was deemed necessary.

A 20 mL dose of EXPAREL was combined with 100 mL sterile normal saline. Approximately 60 mL was infiltrated preemptively at the skin level and the fascia level at each trocar placement site at the beginning of the case. When the procedure was complete, 30 mL was infiltrated into the left flank fascia at the site of suture closure, and 30 mL was

infiltrated into the left TAP lateral to this fascial site.

Following surgery, this patient received an updated postoperative pain and nausea regimen, which included 2 to 4 mg morphine every 2 hours as needed for pain (not PCA); 15 to 30 mL of hydrocodone/acetaminophen elixir (7.5/500 mg per 15 mL) orally every 4 hours as needed for pain; 4 doses 30 mg of IV ketorolac every 8 hours beginning at 4 hours postoperatively; 4 doses of 4 mg IV ondansetron every 6 hours (standing) followed by 8 mg IV every 6 hours as needed for nausea; and 10 mg of IV metoclopramide every 6 hours for nausea, if ondansetron was not effective.

The postoperative stay was unremarkable, and the patient was discharged home on POD 1. During her hospital stay she received 8 mg morphine; 75 mL hydrocodone/acetaminophen elixir; ketorolac as scheduled; ondansetron as scheduled, no as-needed doses required; and metoclopramide was available but not required.

At time of discharge, the patient received a standard prescription for additional hydrocodone/acetaminophen elixir. At her first follow-up visit she reported that she took the as-needed medication only twice, and was pleasantly surprised at how little pain she experienced. In long-term follow-up, the patient had experienced substantial weight loss and health improvement. There was no long-term pain, nausea, or constipation sequelae.

Commentary Although these are 2 different patients, they underwent similar procedures. However, when EXPAREL was

administered, less narcotics were used, resulting in fewer postsurgical side effects.

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A Pharmacist’s Clinical Perspective Andrew Rogalski, PharmD, BCPS ur institution began using EXPAREL in 2012, and it is now used in general, orthopedic, and gynecologic procedures by multiple practitioners. We have seen a number of advantages throughout the institution since making it a part of our multimodal pain control strategy.

In discussions with providers, caregivers, and patients there has been a nearly universal description of reduction in requirements for rescue narcotics in the postoperative period, with consistent results into POD 3. Our nurses have even reported narcotic-free PACU discharges for several same-day procedures.

Operationally, we had been using considerable numbers of elastomeric infusers and CADD infusers for regional anesthesia and nerve blocks. Many of our surgeons have abandoned these modalities and adopted EXPAREL for its superior simplicity with excellent results.

When accounting for costs, we found that the acquisition costs for the infusion devices and standard anesthetics were

O

initially slightly less than EXPAREL, but when the cost of the catheters, tubing, and preparation time were tabulated, the costs were essentially equivalent. For example, preparation of infusers required a minimum of 12 hours of pharmacy technician resources each week, which have now virtually been eliminated.

We have elected to provide EXPAREL at room temperature in a centrally located automated dispensing cabinet (Pyxis) within the OR core. Because of frequency of use, we have encountered no issues with the limited beyond-use dating when removed from refrigeration. Speculative concerns for look-alike issues with propofol have not been observed in our practice; however, as a precaution, our circulating nurses retrieve the EXPAREL and our anesthesiologists have no role in its administration. Our organization has seen many successes with the adoption of EXPAREL as part of our multimodal approach to pain management. When drug, device, and operational costs are considered in totality, we have found it to be at least cost-neutral to other regional anesthetic modalities.

Important Safety Information EXPAREL is contraindicated in obstetrical paracervical block anesthesia. EXPAREL has not been studied for use in patients younger than 18 years of age.

Non–bupivacaine-based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL. Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of EXPAREL as with other local anesthetic products.

Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations.

In clinical trials, the most common adverse reactions (incidence ≥10%) following EXPAREL administration were nausea, constipation, and vomiting.

Please see full Prescribing Information for EXPAREL.

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Disclosures: Dr. Downey reported that she has acted as a consultant for Allergan, Inc. and Ethicon, Inc. Dr. Hutchins reported that he has received research grants, honoraria, and has served as a consultant for Pacira Pharmaceuticals, Inc. He also reported that he has served on the speakers’ bureaus for I-Flow, LLC and Pacira Pharmaceuticals, Inc. Dr. Pilcher reported that he has served as a consultant for Ethicon, Inc., Intuitive Surgical, Inc., and Pacira Pharmaceuticals, Inc. Dr. Rogalski reported that he has received honoraria from the American Society of Health-Systems Pharmacists and Pacira Pharmaceuticals, Inc. Disclaimer: This monograph is designed to be a summary of information. While it is detailed, it is not an exhaustive clinical review. McMahon Publishing, Pacira Pharmaceuticals, Inc., and the authors neither affirm nor deny the accuracy of the information contained herein. No liability will be assumed for the use of this monograph, and the absence of typographical errors is not guaranteed. Readers are strongly urged to consult any relevant primary literature.

Copyright © 2014, McMahon Publishing, 545 West 45th Street, New York, NY 10036. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form.

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