Speed Dating with Pharmacists: 50 Practical Medication Tips at End of Life Kathryn A. Walker, Pharm.D., BCPS, CPE Asst Professor, University of Maryland Sch of Pharmacy Mary Lynn McPherson, Pharm.D., BCPS, CPE Professor, University of Maryland Sch of Pharmacy 1
Nothing to Disclose
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Learning Objectives • Describe three medication tips related to dosage formulations. • List three medication tips related to medication administration. • List three medication tips related to stopping or starting medications.
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Speed Dating with Drugs DRUGS
• A fast exciting was to meet new people in a relaxed environment
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LOGISTICS
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Medication Tip #1 Medication Storage ď‚Ą
Store all medications in a dry and cool place  Avoid the kitchen and bathroom as heat and
moisture can damage medications
Medication Tip #1 • Controlled substances should be kept in a location only known to the patient or caregiver – Encourage lock boxes if there is concern for diversion from family/friends – However patient should inform a trusted family/friend how to access medications in case they become unable to access on their own
http://www.painfoundation.org/painsafe/healthcare-professionals/pharmacotherapy/opioids/faqs-about-opioids.html
Medication Tip #2 • Disposal of medications – Mix with undesirable substance (e.g. coffee grounds, kitty litter) – Place in a container to prevent leakage (e.g. sealable bag, empty can) – Remove labels or any identifiers from medication containers before throwing them away
Medication Tip #2 Disposal of Controlled Substances • Drug take-back program – DEA sponsoring national program, administered locally
• Flushing – CII’s (e.g., morphine, hydromorphone, – transdermal fentanyl, etc.) 9
Medication Tip #3 Medication Reconciliation • Regimented, documented review to avoid drug errors during transitions in care • Where does hospice stand with this? – Survey of two hospice programs – An average of 8.7 medication discrepancies per patient • 81% omitted medications
– 55 additional drug interactions rated moderate or severe 10
Medication Tip #4 Protocols • Develop protocols to “standardize” care • Validates principles and practices of palliative care • Allows staff to get familiar with drugs/ doses/ indications • Important to include titration and monitoring instructions • They do not stand alone- they require constant education and training • Serve to focus care on what is important
Medication Tip # 5 • Don’t write “D/C all medications”!! • We like to stop maintenance meds in palliative care... but proceed with caution: 1. Could have no effect 2. Could lead to withdrawal events/symptoms • Physical dependence • Physiologic dependence on exogenous drug (steroids)
3. Signs/symptoms of chronic disease may re-appear “D/C all previous medications. If medications is still indicated or requires tapering before D/C, write on separate order sheet.“ 12
Med ADMIN
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Medication Tip #6 All teaspoons are not created equal! • One teaspoon = 5 ml • American and Greek researchers collected 71 teaspoons from 25 homes and found a huge variation in size from 2.5 ml to 7.3 ml
Falagas ME, et al. Int J Clin Pract. 2010; 64: 1185-9.
Medication Tip #7 Oral Opioid Solutions • Bitter! • Best flavors include: – Tutti-fruity – Crème de menthe – Raspberry – Chocolate!
Medication Tip #8 What About Liquid Concentrates? • Data does not support buccal/SL absorption – Morphine – Oxycodone
• Physiochemial properties are not favorable for mucosal absorption • Effect likely related to GI absorption
What About Other Opioids?
Hang H, et al. Clin Pharmacokinet. 2001;41:661-680.
Medication Tip #9 • Methadone is the only long-acting opioid SOLUTION • Usually dosed q12h
Product Information: methadone hydrochloride oral solution, methadone hydrochloride oral solution. Roxane Laboratories Inc, Columbus, OH, 2008
Medication Tip #10 Nystatin Swish and Swallow • Swish for SEVERAL MINUTES – Who remembers the Listerine 30 second TV commercial?
• What to do about those dentures? – Get 6 oz. of nystatin solution – Fill denture cup (3 oz), soak for 24 hours – Dump, refill, repeat 19
Medication Tip #11
Fluconazole – Oropharyngeal Candidiasis • Single dose fluconazole (Diflucan) in HIV pts – 150 mg fluconazole x 1 dose vs. 100 mg itraconazole once daily for a week – 75% of fluconazole patients cured on day 8 – 24% of itraconazole patients cured on day 8
• 220 HIV-infected patients – 750 mg oral fluconazole x 1 vs. 150 mg oral fluconazole daily for two weeks – Equivalent outcomes J Int Med Res 1998;26(3):159-170; Clin Infect Dis 2008;47(10):1270-1276
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Medication Tip #12
Question of the Day: Can you take any old tablet or capsule (intended for oral administration) and insert it rectally?? Seriously? 21
Biopharmaceutics Classification System (BCS) • For an orally-administered drug to be absorbed, it must be solubilized and then permeate into the body • BCS is a regulatory tool used by FDA to assess risk of bioinequivalence and risk of poor oral drug absorption • BCS is also used in oral drug product development by companies, since it is easier to develop drug that is well absorbed than poorly absorbed • Four BCS classes – – – –
Class 1: High solubility – High permeability (34% of drugs) Class 2: Low solubility – High permeability (34% of drugs) Class 3: High solubility – Low permeability (25% of drugs) Class 4: Low solubility – Low permeability (7% of drugs)
Toshihide T, et al. Molecular Pharmaceutics. 2006;3(6):631-643.
Small Intestinal Drug Absorption versus Large Intestinal Drug Absorption • Small intestine designed to absorbed what we swallow • Large intestine design to absorb/recover water, and not much else • Many marketed drugs not viable for extended-release, since not well enough absorbed from large intestine • Need high intestinal permeability to be absorbed from large intestine or rectum, which many drugs do not have • Need to be solubilized before can be absorbed from rectum, which many drugs probably do not sufficiently do
Rectal Opioids New Oxycontin Formulation??
Rectal Administration of MS Contin • MS Contin is not approved for rectal administration, but it has been studied. • Comparable extent of absorption following rectal or oral administration – Reduced maximal plasma morphine concentration and delayed time to peak plasma level.
• Switch patients to the same dose of rectal morphine. (e.g., MS 30 mg po q12h = MS 30 mg pr q12h)
Medication #13 MDIs: Patient Use • 86 regular MDI users – 31% adequate (only 6 % “faultless”) – 27% actuated at END of inhalation – 41% “adequate” after instruction
• Patients revert to poor technique without reinforcement J Clin Pharm Therap 1988;13:139-43
Meter Dose Inhalers 1. Position inhaler (use spacer!) 2. At end of breath out, just as inhalation starts, press inhaler ONCE to release medicine 3. Continue inhaling slowly (over 3-5 sec) until lungs are full 4. Hold breath 10 seconds 5. Exhale normally 6. Wait > 1 minute before next puff 7. Rinse/gargle and spit after steroids
“New” MDI Inhalers • Drug Delivery Characteristics – Smaller particle size – Improved lung deposition • Use – Shaking – Cleaning – Priming
Resolving MDI Problems • • • •
Use a spacer! Identify specific problem(s) with technique Correct specific problem, retrain and observe If necessary: • • • •
Add a spacer and retrain Change to a breath actuated inhaler and retrain Switch to a dry powder inhaler and retrain Change to a nebulizer and retrain
Medication Tip #14 Advair & Flovent & Serevent Diskus • Open: grasp dark part and insert thumb into grip on light part, push away until clicks open. • Hold horizontally to load dose: press lever away until it clicks. • Exhale fully (mouth away from mouthpiece). • Inhale with lips tightly around mouthpiece forcefully and fully to lung capacity. • Hold breath 10 seconds. • Close the Diskus. • Rinse, gargle and expectorate.
Medication Tip #15 • IV Ketamine can be given orally for refractory pain – Indication: neuropathic pain, hyperalgesia, ischemic pain – Bitter taste (can be flavored) – Ketamine 50 mg/5mL • Initial: 5-10mg PO TID-QID • Titrate as needed 0.5-1mg/kg Q8H
– Side effects: tachycardia, hypertension, vision problems – If patient experiences dysphoria/hallucinations reduce dose – Caution use in hypertension, cardiac failure, previous CVA 1. http://www.palliativecareguidelines.scot.nhs.uk/documents/Ketamine%20PIL.doc.pdf 2. http://www.palliativecareguidelines.scot.nhs.uk/documents/Ketaminefinal.pdf 3. http://www.stelizabethhospice.org.uk/documents/document_library/Guidelines_for_the_use_of_ketamine.pdf 4. Blonk M, Koder B, Van den Bempt P, Huygen F. Use of Oral Ketamine in Chronic Pain Management: A Reivew. Eur J Pain. 2009.
Medication Tip #16 Ketamine for Localized Pain • Ketamine (a dissociative anesthetic agent) has been shown to be effective in treating localized pain – Wound care, intractable mucositis
• May be given parenterally, orally, or compounded into a topical product • May be given as an oral rinse
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Medication Tip #17 • Morphine sulfate can be formulated into a topical formulation for wound pain (ulcers) – 10 mg of IV morphine sulfate + 8 grams of intrasite gel (compound pharmacy) – Apply to wound 1-3 times daily – Limited systemic absorption – Side effects: site irritation (e.g. itching, burning, redness) 1. Krajnik M, Zylicz Z, Finlay I et al. Potential uses of topical opioids in palliative care – report of 6 cases. Pain. 1999; 80:121-125 2. Porzio G, Marchetti P. Topical morphine in the treatment of painful ulcers. J Pain Symptom Manage. 2005; 30:304-305 3. Twillman RK, Long TD, Cathers TA. Treatment of painful skin ulcers with topical opioids. J Pain Symptom Manage. 1999; 17:288-292 4. Zeppetella G, Paul J, Ribeiro MDC. Analgesic efficacy of morphine applied topically to painful ulcers. J Pain Symptom Manage. 2003; 25:555-558 5. Zeppetella G, Ribeiro MDC. Morphine in Intrasite gel applied topically to painful ulcers. J Pain Symptom Manage. 2005; 29:118-119 6. Jacobsen, J. #185 Topical Opioids for Pain. EPERC. 2007. http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_185.htm
Pain Grab-Bag!
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Medication Tip 18 Make those dosage increases count! • Increase the total daily dose of opioid by 2550% for mild to moderate pain • Increase the total daily dose of opioid by 50100% for moderate to severe pain • DON’T increase by a pre-conceived milligram amount!
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Medication Tip #19 Quantifying PRN Opioid use • Determining the total daily dose of opioids – “How many tablets do you take a day at home?” – Vs – “How many tablets per day do you need to stay comfortable?”
• This conveys that you believe the patient, and realize they need the opioid to achieve comfort 35
Medication Tip #20 Equianalgesic Opioid Dosing Drug Morphine Buprenorphine Codeine Fentanyl Hydrocodone Hydromorphone Meperidine Oxycodone Oxymorphone Tramadol
Equianalgesic Doses (mg) Parenteral Oral 10 0.3 100 0.1 NA 1.5 100 10* 1 100*
30 0.4 (sl) 200 NA 30 7.5 300 20 10 120
McPherson ML. Demystifying Opioid Conversion Calculations: A Guide For Effective Dosing. Amer Soc of Health-Systems Pharm, Bethesda, MD, 2010. Copyright ASHP, 2010. Used with permission. NOTE: Learner is STRONGLY encouraged to access original work to review all caveats and explanations pertaining to this chart. *Not available in the US
Medication Tip #21 Converting to Transdermal Fentanyl • Use caution relying on the manufacturer’s guidelines for converting to TDF – Intentionally conservative – CANNOT use in reverse
• Total daily dose of oral morphine ~ transdermal fentanyl patch strength in mcg/ml – Oral morphine TDD 100 mg ~ TDF 50 mcg/hour
• Consider body habitus 37
Medication Tip #22 Speaking of body habitus… • One study confirms that thin, cachectic cancer patients don’t receive the anticipated benefit from TDF as expected • When converting OFF TDF, use the last dose where patient responded
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Medication Tip #23 • WHERE is the transdermal fentanyl patch? • I know it’s here somewhere!
http://journal.nzma.org.nz/journal/121-1276/3124/
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Medication Tip #24 • Heat increases absorption of medication from transdermal patches, including fentanyl and buprenorphine – Avoid applying heating pads or direct heat to patch – Caution in patients who are continuously feverish (increased body temperature can increase absorption of medication)
Medication Tip # 25 Opioid allergy? • True allergies are rare • Intolerable side effects commonly reported – May even mimic immune reactions: mild itching, urticarial, bronchospasm, hypotension
• Anaphylaxis is a systemic IgE mediated reaction – Include nasal congestion, flushing, pruritus, angioedema – Can develop nausea, diarrhea, urinary urgency, bronchospasm, hypotension, and death Opioid Class
Examples
Phenanthrenes
morphine, codeine, hydrocodone, oxycodone, oxymorphone,hydromorphone, levoraphanol
Phenylpiperadines
fentanyl, meperidine, sufentanil, remifentayl
Diphenylheptanes
methadone
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Medication Tip #26 Pain Management in OAT Patients • OAT patients are those on chronic buprenorphine or methadone, recovering from heroin abuse • Buprenorphine patient options: – Change buprenorphine dosing to every 4 hours – Give a different opioid for pain control and continue buprenorphine – DC buprenorphine and begin alternate opioid, titrating to therapeutic response 42
Medication Tip #26 Pain Management in OAT Patients • OAT patients are those on chronic buprenorphine or methadone, recovering from heroin abuse • Methadone patient options: – Divide the once a day methadone dose into two or three doses per day and titrate to therapeutic resposne
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Medication Tip # 27 Opioid Continuous Infusions • Opioid continuous infusions are not recommended post-operatively in opioidnaïve patients – Lack of proven benefit; increased risk toxicity
• Palliative care patients frequently require a continuous infusion of opioid – Do not titrate the continuous infusion more often than every 10-12 hours 44
Medication Tip #28 • PCA Dosing – Continuous only appropriate if opioid tolerant – Bolus dose generally equal to ½ continuous hourly dose (i.e., 1 mg/hr morphine infusion should have 0.5 mg bolus with lockout 8 minutes) – Don’t titrate using lockout – Can increase bolus dose every hour if needed – May administer clinician boluses to “catch up” – Hour-limit is often omitted due to multiple dose increases usually required to titrate 45
Medication Tip # 29 • Write clear orders for use in scenarios where acute/severe symptoms are expected (e.g., ventilator withdrawal) – Opioids used first for SOB – Benzodiazepines used second for agitation related to SOB – Don’t repeat ineffective doses- titrate! • Include titration parameters • Titrate BOLUS first, then continuous 46
Medication Tip #30 Naloxone in Opioid-Tolerant Patients • Is it opioid intoxication or impending death? – Mottling, urine output – Pupils, respiratory rate
• Use small doses of naloxone if indicated (don’t totally reverse the opioid – patient will go into screaming withdrawal) – Dilute one amp (0.4 mg) in 10 ml normal saline – Give 1 ml (0.04 mg) every minute until patient responds. – No response after two amps – it’s not the opioid! 47
STOPPING/ STARTING MEDS
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Medication Tip #31 Cold Turkey vs. Taper – Stopping Meds • Most medications can be stopped abruptly • CNS and cardiovascular medications should generally be tapered – Beta-blockers (don’t “hold” some days) – Clonidine – Antidepressants, anxiolytics – Opioids
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Medication Tip #32 Corticosteroids – Why Stop? • Don’t stop abruptly: Corticosteroids • Suppression of HPA axis occurs after 3 weeks, or earlier if high dose (≥40 mg prednisone= 6 mg dex) • Slow taper to allow HPA axis recovery (weeks-months)
– Reduce at 2.5-5 mg q1-3 days until at 5-10mg/day, then slow taper to 1 mg per week – If likely disease will relapse: reduce more slowly (i.e., 2.5-5 mg q1-2 weeks) – Long term use: reduce even more slowly (i.e., 1 mg q3-4 weeks)
• May need to increase dose during periods of stress (i.e., infection) or sg.sx of withdrawal – anorexia, hypotension, nausea, weakness, fever, myalgia, arthralgia, weight loss
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Medication Tip #33 • Toprol XL may be cut in half – Tablet is scored – DO NOT CRUSH
• If you want to stop a beta-blocker, think twice!
51 Product Information: TOPROL-XL(TM) extended release oral tablet, metoprolol succinate extended release oral tablet. AstraZeneca LP, Wilmington, DE, 2010
Medication Tip #34 Having “Those” Drug Conversations • “Frankly Mrs. Smith, your husband can stop the Zocor now. He probably only has a couple of weeks left so it really doesn’t matter.” • Seriously? Did someone miss the empathy lecture? • BENEFITS and BURDENS of drug therapy is the discussion point!
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Medication Tip # 35 • Benefit lasts after discontinuing – Bisphosphonates • Beneficial effects seen within one year • LONG half life due to skeletal storage – If used for 5 years, ongoing reduction in risk of fracture for next 5 years)
– Amiodarone (long half life= average 58 days)
Black DM, et al. JAMA 2006;296:2927–38.
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Medication Tip #36 Diabetes Goal-Setting at EOL • A1c? – You CAN get to heaven with an A1c > 7!
• BG – 140-300 mg/dl • Sliding scale insulin? • Long-acting insulin? – Lantus? Levemir?
• Erratic meal intake? – Rapid-acting insulin secretogogues 54
Medication Tip #37 • Benzodiazepine Equivalents Medication
Equiv. Doses
Active Metabolites
Onset
Duration
Diazepam (Valium)
5 mg
+++
Rapid
Long
Lorazepam (Ativan)
1 mg
-
Intermediate
Intermediate
Oxazepam (Serax)
15 mg
-
Intermediate
Intermediate
Temazepam (Restoril)
10 mg
-
Intermediate
Intermediate
Alprazolam (Xanax)
0.5
+
Intermediate
Short
Clonazepam
0.25
-
Rapid
Long
25 mg
+++
Intermediate
Long
Chlordiazepoxide (Librium)
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OTHER SYMPTOMS
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Medication Tip #38 Drying Up Secretions • Tertiary amines – Scopolamine, atropine, hyoscyamine – Cross BBB and cause sedation, delirium
• Quaternary amines – Glycopyrrolate – does not cross BBB
• Consider onset of action – Scopolamine 12 hours
• Ease of administration – atropine ophthalmic 57
Medication Tip #39 Managing Seizures • How to prevent or manage seizures at EOL when patients are NPO, without using an IV? • Oral lorazepam concentrated solution • To prevent seizures: – 0.5-1 mg in the buccal cavity every 6 hours
• To treat seizure activity: – 1 mg in buccal cavity every 5 minutes, up to 4 doses, or until seizure activity starts 58
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Medication Tip #40 Frozen Vaseline Balls • Roll/squeeze vaseline into “pea-sized” balls. • Roll in confectioners sugar (for taste). • Freeze balls. • Have patient swallow 23 balls; will lubricate bowel and ease defecation. http://www.hospicepharmacia.com (Medication Use Guidelines – constipation)
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Medication Tip # 41 Lactulose for Hepatic Encephalopathy? • What is the correct dose? • Until the patient produces 2 or 3 “pudding soft” stools per day. • Sorry Mr. Cosby!
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Oil in water? Water in oil?
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Medication Tip #42 • Water in oil lubricant is preferred for dry or sensitive skin – W/O agents have more oil to sooth dry skin and minimize water loss from the skin
• Patients PREFER oil in water products however • The outer phase is what you “feel” – W/O is oily – O/W is soluble and not oily 1. http://www.makingcosmetics.com/articles/27-how-to-make-water-in-oil-emulsions.pdf 2. http://www.healthinaging.org/public_education/pef/dry_skin.php
Medication Tip #43
James Hallenbeck, Palliative Care Perspective s
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Comparing Antiemetic Receptor Binding
The LOWER the number, the tighter the binder, the greater the receptor blockade. James Hallenbeck, Palliative Care Perspectives
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Medication Tip #44 Haloperidol Rocks My World! • Haloperidol is a friend to palliative care patients – Available as a tablet, oral concentrate, IV
• Useful for preventing and treating nausea • Useful for preventing and treating delirium
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Medication Tip #45 Partial Bowel Obstruction • Consider dexamethasone and haloperidol, especially for a partial bowel obstruction • If obstruction becomes complete, consider octreotide
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Medication Tip # 46 • Tricyclic antidepressants are not all created equal – Secondary amines best (i.e., nortriptyline, desipramine) • NOT amitriptyline (tertiary amine)
– Effect on neuropathic pain is independent from antidepressant properties Sedation
Antichol Effects
Hypotensi Cardiac on Effects
Seizures
Weight Gain
Tertiary Amines
+++
+++
+++
+++
++
++
Secondary Amines
0/+
+
+
++
+
+
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Medication Tip # 46 Buprenorphine and Pain • Partial agonist but tightly binds to mu receptor – Can block effects of other opioids for 24-60 hours – Analgesia duration much shorter (6-8 hours) and ceiling dose= 32 mg SL/day OPTION 1 Buprenorphine + high dose opioid
OPTION 2 Replace buprenorphine with full agonist (e.g., methadone)
OPTION 3 Buprenorphine used for mild-moderate pain
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Medication Tip #47 Phenytoin (Dilantin) Serum Levels • Therapeutic level is 10-20 mcg/ml • With normal albumin, only 10% is UNBOUND – Free fraction therapeutic level is 1-2 mcg/ml
• What about the patient with hypoalbuminemia? – If 20% of drug is unbound? – Therapeutic level would be a total of 5-10 mcg/ml – Because 20% would be 1-2 mcg/ml
• Order a TOTAL and UNBOUND/Free phenytoin level! 70
Medication Tip #48 DO NO HARM • Which medications to avoid in people at risk of delirium: a systemic review (Clegg and Young) – Reviewed 18,878 studies – Odds ratio: • • • • • •
Benzodiazepines (3.0) Opioids (2.5) Dihydropyridines (2.4) Antihistamines (1.8) Neuroleptics (0.9) Digoxin (0.5)
Conclusion: For people at risk of delirium, avoid new prescriptions of benzodiazepines or consider reducing or stopping when possible. Use opioids with caution (but recognize that untreated pain can trigger delirium). Caution with dihydropyridines and H1 blockers.
Clegg A, Young JB. Age and Ageing 2011;40:23-29.
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Medication Tip #49 Antipsychotic Agents in Dementia • Black box warning on antipsychotic agents regarding the increased risk of death when used in patients with dementia • Antipsychotic agents increase relative risk of death by 1.6-1.7 compared to placebo • Number needed to harm is 10-15 fold higher than number needed to treat • Use good clinical judgment 72
Medication Tip # 50 Antidepressant Use in Dementia Patients
• The Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) – 326 elderly patients (mean age 79 years) – January 2007 – December 2009 – All participants had comorbid depression for > 4 weeks and a score of > 8 on the Cornell scale for depression in dementia Banergee S et al. The Lancet 2011;378(9789):403-411.
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Antidepressant Use in Dementia Patients • Study groups included (1:1:1): – Sertraline (target dose 150 mg/day) – Mirtazapine (45 mg) – Placebo (control group)
• Primary outcome was reduction in depression at 13 weeks • Decreases in depression scores at 13 weeks did not different between 111 controls and 107 participants allocated to either drug, or between drugs. Banergee S et al. The Lancet 2011;378(9789):403-411.
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Antidepressant Use in Dementia Patients • Adverse reactions occurred in: – 26% placebo group – 43% sertraline group – 41% mirtazapine group
• Conclusion: – Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in AD should be reconsidered. Banergee S et al. The Lancet 2011;378(9789):403-411.
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The Best Tip of All! And Palliative Care!
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