15 minute read
USP Chapters still a must-read for 2021
95% USP Adherence at Ascencion a Team Effort
Complying with compounding guidance is an onerous task for any institution, but rolling out a standardized compounding compliance program across 146 health systems and achieving 95% adherence is Herculean— and a feat that Ascension can claim to have achieved.
According to Shewan Aziz, RPh, PhD, the vice president of pharmacy at Ascension Texas, in Austin, the key to his facility’s success has been implementing standardized system-level guidance while also meeting the needs of individual hospitals.
“In addition to working on a national level to develop best-practice compounding guidance, we work with each hospital to provide them with the resources and tools they need to assess their own compounding preparation management risk and to create action plans, implement best practices and track their in-house compliance,” Aziz explained at the ASHP 2020 Midyear Clinical Meeting and Exposition.
The path to near-perfect USP compliance at Ascension started in 2012, when the organization created a compounding subcommittee. The committee, which consisted of compounding experts from individual Ascension hospitals, scoured existing compounding guidance documents, literature and best practices issued not only by USP but by the National Institute for Occupational Safety and Health, the Occupational Safety and Health Administration, and state boards of pharmacy, Aziz said. Using these sources, the task force developed two Ascension-specific guidelines: one for nonhazardous compounds and one for hazardous compounds, he explained.
According to Aziz, the guidelines outline a variety of best practices for everything from IV room contamination management to use of compounding robotics, IV workflow systems and standardized closed system drug-transfer devices for chemotherapy.
The subcommittee also created documents that include compliance tips and “pearls,” he added, and they developed standardized policies and procedures that individual hospitals could implement, as well as training and competency assessment modules they could use for their staff.
When it came to procuring funds for capital projects, the national team also provided this to each hospital, helping them design and build USP-compliant IV rooms.
To further enhance the safety of compounded drug management, the national compounding subcommittee even created auxiliary warning labels with handling instructions for all IV hazardous drug preparations, and they built in hazardous drug alerts for automated dispensing cabinets and electronic medication administration systems, Aziz said.
Finally, the team developed key performance indicators and compounding metrics to help individual hospitals ensure they are complying with the national-level guidance, he said.
“In 2012, before we undertook this standardization initiative, we had 55% compliance with USP <797>, and that’s gone up to 95% today,” said Aziz, noting that the outlying 5% of hospitals are expected to be compliant with the Ascension compounding guidance by August 2021.
With regard to USP <800> compliance and any additional changes that might be contained in the revised USP <795> and <797> chapters once they are finalized and made official, “given all the work and effort that has gone on at our hospitals to adhere to our own compounding guidances, we will be ready to meet all compounding standards when the USP appeals are resolved,” Aziz said.
“I think our experience shows that if you want to implement best practices and improve care, you can do it,” he said.
Still Some Confusion
Ascension’s success doesn’t mean there isn’t work to be done regarding USP compounding compliance. With the appeals process for USP General Chapters <795> and <797> now over and the chapters remanded, and with <800> currently informational, healthsystem pharmacies may be confused about which protocols and procedures they should be implementing.
“None of us know what the future will hold” with regard to changes to these chapters, Robert Campbell, PharmD, the director of clinical standards interpretation for hospital and ambulatory programs at the Joint Commission, in Oakbrook Terrace, Ill., said
The Joint Commission’s Top Reasons for USP Noncompliance
The reasons for noncompliance with USP compounding standards vary and change from year to year, ranging from inadequate competency assessments to incomplete environmental testing. But “one thing we continue to see that hasn’t changed since day one is that those responsible for compounding are not taking the time to fully review their testing certification reports,” said Robert Campbell, PharmD, the director of clinical standards interpretation for hospital and ambulatory programs at the Joint Commission, in Oakbrook Terrace, Ill.
“Too often, facilities getting the testing done do not hand the results to leadership, or pharmacy leadership takes a look at the front page of a report and does not look at the nuts and bolts of the report’s findings,” Campbell said at the ASHP 2020 Midyear Clinical Meeting and Exposition.
Apart from a lack of attention to reports, Campbell pointed to several other top reasons for noncompliance, including: • for personnel: a lack of competency assessments completed, a lack of didactic testing scoring and incomplete initial competency assessments; • for products: drug shortages leading to changes in compounding products that are not accompanied by necessary changes to environment and beyonduse dating, and a lack of proper labeling; and • for environmental standards: incomplete testing and certification reports and improper resolution of these report results.
Going back to the basics of USP compliance—the need to review reports in detail—“any issues identified by a certifier need to be examined,” Campbell said. at the ASHP Midyear meeting.
For the time being, Brian Serumaga, PhD, RPh, a scientific liaison at USP, in Rockville, Md., said his organization “has continued to emphasize through stakeholder engagement and webpage updates that due to the remand of the 2019 revisions of <795> and<797>, the currently official versions of <795> and <797> are those last revised in 2014 and 2008, respectively.”
Although the appeals focused on the framework for establishing beyond-usedates (BUDs) for sterile and nonsterile compounded preparations, and for extending BUDs beyond the defaults in the chapters, “the Compounding Expert Committee may consider additional changes,” Serumaga said.
“In March 2020, the USP appeals panel made a decision remanding the chapters to the compounding expert committee, with a recommendation that the committee carry out further stakeholder engagement on the issues touched on in the appeals,” added Serumaga, who spoke at the ASHP meeting.
In regard to USP <800>, Serumaga said USP considers it informational only, but the organization “encourages” early adoption of the chapter, and “regulatory bodies and oversight organizations may make their own determinations regarding the applicability and enforceability of <800> for entities within their jurisdiction.”
Indeed, for early USP <800> adopters, Campbell said the Joint Commission surveyors will be surveying according to criteria from that chapter, and <800> guidelines will supersede the 2008 version of <797> when the two chapters conflict, Campbell said.
“For example, the 2008 version of USP <797> states that you cannot compound hazardous drugs in a segregated compounding area, whereas <800> allows for compounding these preparations in a contained segregated compounding area,” Campbell noted. “If you want to adopt <800>, you need to meet all the requirements for a contained area.”
Campbell emphasized that early adopters of USP <800> who are in the midst of construction projects, and therefore can’t be tested for full compliance, should ensure they are protecting staff and patients during the transition. The Joint Commission’s surveyors will be verifying that hazardous drug vapors are not escaping and personal protective equipment is being worn by compounding staff, he said.
—David Wild
Simplist® DILAUDID® INJECTION (hydromorphone hydrochloride) for intravenous, intramuscular, or subcutaneous use, CII
BRIEF SUMMARY OF PRESCRIBING INFORMATION
This brief summary does not include all the information needed to use DILAUDID INJECTION safely and effectively. Please see full prescribing information, including BOXED WARNING, for DILAUDID INJECTION atwww.fresenius-kabi.com/us.
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISK FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse DILAUDID INJECTION exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing DILAUDID INJECTION and monitor all patients regularly for the development of these behaviors and conditions
Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of DILAUDID INJECTION. Monitor for respiratory depression, especially during initiation of DILAUDID INJECTION or following a dose increase.
Neonatal Opioid Withdrawal Syndrome Prolonged use of DILAUDID INJECTION during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. • Reserve concomitant prescribing of DILAUDID and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. • Limit dosages and durations to the minimum required. • Follow patients for signs and symptoms of respiratory depression and sedation.
INDICATIONS AND USAGE
DILAUDID INJECTION is an opioid agonist indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate.
Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve DILAUDID INJECTION for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: • Have not been tolerated, or are not expected to be tolerated • Have not provided adequate analgesia, or are not expected to provide adequate analgesia
CONTRAINDICATIONS
DILAUDID INJECTION is contraindicated in patients with: • Significant respiratory depression. • Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. • Known or suspected gastrointestinal obstruction, including paralytic ileus. • Known hypersensitivity to hydromorphone, hydromorphone salts, sulfitecontaining medications, or any other components of the product.
WARNINGS AND PRECAUTIONS (also see BOXED WARNING)
• Life-Threatening Respiratory Depression in Patients with Chronic
Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients:
Monitor closely at initiation, dose titration. See Contraindications for use in patients with bronchial asthma. • Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper. • Adrenal Insufficiency: If diagnosed, wean the patient off of the opioid and treat with physiologic replacement doses of corticosteroids. • Severe Hypotension: Monitor during dosage initiation and titration.
Avoid use in patients with circulatory shock. • Risks of Use in Patients with Increased Intracranial Pressure, Brain
Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression. Avoid use of DILAUDID INJECTION in patients with impaired consciousness or coma. • Risks of Use in Patients with Gastrointestinal Conditions: The hydromorphone in DILAUDID INJECTION may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase.
Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. • Increased Risk of Seizures in Patients with Seizure Disorders: Monitor patients with a history of seizure disorders for worsened seizure control. • Withdrawal: When discontinuing DILAUDID INJECTION in a physicallydependent patient, gradually taper the dosage. Do not abruptly discontinue therapy in physically-dependent patients. • Risks of Driving and Operating Machinery: DILAUDID INJECTION may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of DILAUDID INJECTION and know how they will react to the medication. • Sulfites: DILAUDID INJECTION contains sodium metabisulfite. See
Contraindications.
• Increased Risk of Hypotension and Respiratory Depression with Rapid
Intravenous Administration: should be given very slowly.
ADVERSE REACTIONS (see Boxed Warning and Warnings and Precautions)
Serious adverse reactions: Addiction, abuse, and misuse, lifethreatening respiratory depression, neonatal opioid withdrawal syndrome, interactions with benzodiazepines and other CNS depressants, adrenal insufficiency, severe hypotension, gastrointestinal adverse reactions, seizures, withdrawal, respiratory depression and apnea, circulatory depression, respiratory arrest, shock, and cardiac arrest.
Most common adverse reactions: Lightheadedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus. Less frequently observed adverse reactions: tachycardia, bradycardia, palpitations, blurred vision, diplopia, miosis, visual impairment, constipation, ileus, diarrhea, abdominal pain, weakness, feeling abnormal, chills, injection site uticaria, fatigue, injection site reactions, peripheral edema, biliary colic, anaphylactic reactions, hypersensitivity reactions, increase in hepatic enzymes, decreased appetite, muscle rigidity, headache, tremor, paraesthesia, nystagmus, increased intracranial pressure, syncope, taste alteration, involuntary muscle contractions, presyncope, convulsion, drowsiness, dyskinesia, hyperalgesia, lethargy, myoclonus, somnolence, agitation, mood altered, nervousness, anxiety, depression, hallucination, disorientation, insomnia, abnormal dreams, urinary retention, urinary hesitation, antidiuretic effects, erectile dysfunction, bronchospasm, laryngospasm, dyspnea, oropharyngeal swelling, injection site pain, urticaria, rash, hyperhidrosis, flushing, hypotension, hypertension, serotonin syndrome, and androgen deficiency.
To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA at 1-800-551-7176 option 5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
USE IN SPECIFIC POPULATIONS
• Pregnancy: May cause fetal harm (see BOXED WARNING for neonatal opioid withdrawal syndrome). • Labor or Delivery: Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.
Naloxone must be available for reversal. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. • Lactation: Low levels of opioid analgesics have been detected in human milk. Monitor infants for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of hydromorphone is stopped, or when breast-feeding is stopped. • Females and Males of Reproductive Potential: Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible. • Pediatric Use: The safety and effectiveness of DILAUDID INJECTION in pediatric patients has not been established. • Geriatric Use: Patients 65 years of age or older may have increased sensitivity to hydromorphone. Start at the low end of the dosing range, titrate the dosage slowly and monitor for signs of CNS and respiratory depression. • Hepatic and Renal Impairment: Start patients on one-fourth to onehalf the usual starting dose depending on the degree of impairment and closely monitor during dose titration.
DRUG INTERACTIONS
Clinically significant drug interactions with DILAUDID INJECTION: benzodiazepines and other CNS depressants, serotonergic and anticholinergic drugs, monoamine oxidase inhibitors (MAOIs), mixed agonist/antagonist and partial agonist opioid analgesics, muscle relaxants, diuretics.
OVERDOSAGE
Acute overdose with DILAUDID INJECTION can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis, rather than miosis, may be seen with hypoxia in overdose situations. In case of overdose, reestablish patent and protected airway, institute assisted or controlled ventilation, manage circulatory shock, pulmonary edema, cardiac arrest or arrhythmias, as indicated. Administer opioid antagonists only for clinically significant respiratory or circulatory depression. Carefully monitor the patient until spontaneous respiration is reestablished. Administration of opioid antagonist in aphysically dependent patient should be initiated with care and by titration with smaller than usual doses of the antagonist.
For full Prescribing Information please go to www.simplist-us.com
The lowest Dilaudid® dose available on the market
exclusively from Fresenius Kabi
NDC 76045-121-11
Dilaudid® 0.2 mg per 1 mL presentation available in a ready-to-administer prefilled syringe helps reduce waste and eliminates steps in medication preparation.
INDICATIONS AND USAGE
DILAUDID INJECTION is indicated for the management of pain severe enough to require an opioid analgesic and for which alternate treatments are inadequate. Limitations of Use: Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve DILAUDID INJECTION for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: have not been tolerated, are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia
IMPORTANT SAFETY INFORMATION
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning. • DILAUDID INJECTION exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and monitor regularly for these behaviors and conditions. • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. • Prolonged use of DILAUDID INJECTION during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.
DILAUDID INJECTION is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment, known or suspected gastrointestinal obstruction, including paralytic ileus, known hypersensitivity to hydromorphone, hydromorphone salts, sulfite-containing medications, or any other components of the product. Life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients: Monitor closely, particularly during initiation and titration. Adrenal insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. Severe hypotension: Monitor during dosage initiation and titration. Avoid use in patients with circulatory shock. Risks of use in patients with increased intracranial pressure, brain tumors, head injury, or impaired consciousness: Monitor for sedation and respiratory depression. Avoid use patients with impaired consciousness or coma. DILAUDID INJECTION contains sodium metabisulfite. There is a risk of anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people. Additional serious adverse reactions: Apnea, circulatory depression, respiratory arrest, shock, cardiac arrest, seizures, withdrawal, anaphylaxis. Most common adverse reactions: Lightheadedness, dizziness, sedation, nausea, vomiting, sweating, flushing, dysphoria, euphoria, dry mouth, and pruritus.
To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176, option 5, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Overdosage: Acute overdose can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, miosis (or mydriasis when hypoxia is present), and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death.
