Published October 14, 2016 Hospital/Health System Medication Therapy Management in Hospitalized Elderly Patients: A Focus on OTC Agents Lynn Chan, PharmDPGY-2 Infectious Disease Pharmacy ResidentAlleghany General HospitalPittsburgh, Pennsylvania Philip J. Gregory, PharmD, MS, FACNAssociate Professor of Pharmacy PracticeDirector, Center for Drug Information and Evidence-Based PracticeCreighton University, Omaha, Nebraska Lee E. Morrow, MD, MSc, FCCPProfessor of Medicine and Pharmacy PracticeDivision of Pulmonary, Critical Care, and Sleep MedicineCreighton University, Omaha, Nebraska Mark A Malesker, PharmD, FCCP, FCCP, FASHP, BCPSProfessor of Pharmacy Practice and MedicineDepartment of Pharmacy PracticeCreighton University, Omaha, Nebraska US Pharm. 2016;41(10):HS16-HS20. ABSTRACT: Despite the widespread use of OTC medications, many patients and healthcare professionals are not fully aware of the potential adverse events associated with these products. OTC agents can be associated with potential adverse effects upon multiple organ systems and numerous laboratory results. Elderly patients are more susceptible to adverse drug events compared to the general population. Many patients and healthcare providers also fail to add OTC drugs to their official medication list. It is critical that pharmacists recognize these concerns and identify appropriate monitoring parameters when completing a comprehensive medication therapy review that includes OTC products with each hospital admission. Many patients, including the elderly, do not seek consultation with their healthcare provider or pharmacist before initiating OTC medications. OTCs are sold in over 750,000 locations in the United States, and the average American household spends approximately $340 per year on OTC products.1 The seemingly endless product selection available, exacerbated by the trend for popular prescription products to become available OTC, has escalated concerns about potential adverse drug reactions (ADRs) in the elderly population, a large consumer group for these products. Like prescription drugs, the potential ADRs associated with OTCs can range from mild to severe and can be manifested by changes in the clinical condition of the patient or laboratory results. Reports have shown that adults >65 years of age represent 13% of the U.S. population but account for 30% of OTC medication use.2 In addition, elderly patients represent 61.5% of emergency room visits associated with ADRs.2 As medication experts and thus essential members of the healthcare team, hospital pharmacists can help reconcile medications for the transition from outpatient to inpatient status. The challenge for the hospital pharmacist is to correctly identify the current medication list and refill history for both prescription and nonprescription drugs. One limiting factor is the lack of accuracy when it comes to the patient’s list of OTC medications, as some patients do not think of OTC products as real drugs. The pharmacist can collect relevant OTC medication and compliance history from multiple sources such as existing patient records, the patient or patient’s family members, and from pharmacies used by the patient. This information is necessary to address any potential medication-related problems and to optimize therapy. An accurate medication list that includes a complete list of OTC products may result in early detection of medication-related problems and allow opportunities to reduce inappropriate use. Medication therapy management (MTM) also includes the evaluation of the patient to detect symptoms or adverse effects that can be caused by current medications and the interpretation, monitoring, and assessments of the patient’s laboratory results.3 As a result, it is essential that pharmacists be familiar with potential complications associated with the use of OTC products. Adverse Effects of OTC Medications OTC products are frequently used for self-limiting conditions such as pain, cough and cold, allergies, sleep disturbances, oral hygiene, skin care, eye care, and gastrointestinal (GI) disorders. It is possible that patients may also be using OTC products for unlabeled uses. A summary of ADRs and laboratory changes from common OTC medications can be found in TABLE 1. Agents With CNS Toxicity Diphenhydramine crosses the blood-brain barrier and can lead to well-recognized side effects such as sedation, delirium, dementia, and anticholinergic effects (e.g., dry mouth, urinary retention, next-day hangover effect, blurred vision). In one study, there was a 70% increased risk of cognitive decline observed in elderly patients who were given diphenhydramine.4,5 Gray et al analyzed the cumulative anticholinergic exposure over 10 years in patients >65 years of age and concluded that there is an increased risk for dementia in patients with accruing use of anticholinergic medications.6 A recent German study concluded that the avoidance of a proton pump inhibitor (PPI) may prevent the development of dementia.7 Omeprazole, lansoprazole, and esomeprazole are the PPIs available OTC. The histamine2 receptor antagonist (H2RA) famotidine is known to cause neuropsychiatric disturbances in elderly patients. Multiple case reports of famotidine-induced mental changes in elderly patients demonstrate symptom resolution upon withdrawal of the medication.8 This is likely a class effect, and the same concern exists for mental status changes with other OTC H2RAs (cimetidine, ranitidine, nizatidine). Healthcare professionals should routinely evaluate the renal function of patients receiving H2RAs, recommend dosage adjustments, and follow product labeling to minimize the CNS effects of these agents. Phenylephrine is a direct alpha-adrenergic agonist commonly found in combination with acetaminophen and other ingredients in OTC cold products. Common side effects of oral phenylephrine include dizziness, insomnia, nervousness, and anxiety. A recent report revealed that an acetaminophen dose of 1,000 mg when combined with phenylephrine 10 mg resulted in quadrupling the plasma concentrations of phenylephrine, thus increasing the potential risk of ADRs.9 Magnesium-containing products (antacids, laxatives, mineral supplements, magnesium oxide) resulting in hypermagnesemia have the potential to precipitate myasthenia gravis. Elderly patients with renal insufficiency should generally avoid magnesium-containing antacids or laxatives.10 A published case report indicated that transdermal nicotine can also worsen symptoms of myasthenia gravis.11 Agents With Pulmonary Toxicity Elderly patients often use low-dose salicylates such as aspirin (ASA) at 81 mg/day for prevention of heart attacks or strokes. Error in medication administration or cognitive dysfunction can result in chronic salicylate toxicity. Respiratory alkalosis due to direct stimulation of the respiratory center has been reported following the use of high-dose salicylates in cases of overdose.12 One concern for use of PPIs and H2RAs is the risk of pneumonia as a result of increased gastric pH.13 In three meta-analyses, short-term PPI use increased the rate of pneumonia by 27%.14 The possible mechanism behind PPI-associated pneumonia may be multifactorial but is thought to stem from compromising the stomach’s “acid mantle” against gastric colonization of acid-labile pathogenic bacteria, which then may be aspirated. A secondary theory is that PPIs may reduce the acidity of the upper digestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus, and lungs.15 Elderly and debilitated patients are at greatest risk for aspiration of mineral oil and the development of lipoid pneumonia. Lipoid pneumonia is actually a chronic pneumonitis as compared to aspiration pneumonia, which is caused by aspirated anaerobes. There have also been over 20 case reports of lipoid pneumonia linked to mineral oil use in elderly patients.16 Increased respiration (hyperventilation) is a potential consequence of caffeine and iron. Caffeine can increase heart rate and subsequently respiratory rate. Drugs that act centrally to decrease respirations (hypoventilation) include diphenhydramine, cimetidine, and nicotine. Magnesium and vitamin A derivates can contribute to hypoventilation secondary to muscle weakness.17 Anticholinergics increase the risk of community-acquired pneumonia (CAP) in older patients due to possible sedation and altered mental status, which contribute to aspiration events and poor pulmonary hygiene. Results from a recent population-based, case-controlled study showed an association between acute and chronic use of anticholinergics (ranitidine, diphenhydramine, meclizine, fexofenadine, and cetirizine) and greater risk of CAP when compared to nonusers.18 Agents With Cardiac Toxicity The chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen and ibuprofen in older adults has been linked with hypertension and exacerbation of heart failure. The use of ibuprofen with ASA 81 mg has the potential to interfere with antiplatelet activity of aspirin, thus increasing the risk of cardiovascular events in the elderly population.19,20 NSAIDs should ideally not be used for prolonged periods of time in older patients. In July 2015, the FDA issued a safety communication regarding NSAIDs and the increased risk of heart attack or stroke.21 Hypertension can also be precipitated in certain patients with uncontrolled or unrecognized hypertension following the ingestion of sympathomimetic vasoconstrictors, including pseudoephedrine and phenylephrine.22 Famotidine has the potential to cause QT prolongation.23 Caution should be advised when prescription drugs that can cause a prolonged QT are concurrently used with famotidine. Individually or in combination, caffeine and pseudoephedrine can cause tachycardia.24 Agents With Hematologic Toxicity H2RAs and PPIs have well-established data for causing hematologic disorders such as agranulocytosis, hemolytic anemia, and thrombocytopenia.25,26 Elderly patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency should be careful since hemolytic anemia has been reported in patients who have overdosed on ASA. NSAIDs are also capable of causing immune hemolytic anemia through immune complex mechanisms.27 Large doses of acetaminophen can increase the international normalized ratio (INR) in patients taking warfarin. Multivitamin supplements with minerals may contain vitamin K, which may antagonize the effect of warfarin. Agents With GI Effects and Hepatotoxicity Studies have linked PPIs to Clostridium difficile infections due to the ability of microbes to survive when the gastric pH is increased. The risk of C difficile infections was 1.4 to 2.5 times higher in patients who were exposed to PPI therapy.13 NSAIDs, H2RAs, and laxatives can cause drug-induced diarrhea via several mechanisms. Examples of laxatives include stimulants (bisacodyl, magnesium citrate, senna), osmotics (sorbitol, polyethylene glycol), and stool softeners (docusate sodium, docusate calcium). Magnesium products (magnesium gluconate, magnesium oxide, magnesium citrate) may cause diarrhea if taken in large doses.28 Constipation can be problematic for elderly patients who take medications that contain aluminum (antacid combinations), calcium (calcium carbonate, calcium citrate) and iron supplements (ferrous sulfate, ferrous fumarate, multi-vitamins).29-31 Ingestion of calcium-, magnesium-, and aluminum-based antacids can result in metabolic alkalosis and acidosis, as well as milk-alkali syndrome.32 ASA and NSAIDs are known to cause several common ADRs such as gastric ulceration, dyspepsia, and bleeding. The risk for GI bleeding with the use of NSAIDs and salicylates increases for patients aged >65 years and has been correlated to a rise in hospitalization and mortality.33,34 Hepatocellular injury has been reported with acetaminophen, NSAIDs, and omeprazole.35,36 PPIs, when taken chronically, can decrease cyanocobalamin (vitamin B12) stores, which can be especially significant in nutritionally deficient elderly patients.37 Agents With Renal Toxicity and Altered Electrolyte Homeostasis NSAIDs, via vasoconstriction of the afferent arterioles of the kidneys, can cause fluid retention and worsen blood pressure control.38 OTC products such as antacids, laxatives (sorbitol), NSAIDs, and PPIs may lead to electrolyte imbalance.39 PPIs, acetaminophen, and nicotine replacement therapies (transdermal patch, gum, lozenges) are known to cause hyponatremia through inappropriate antidiuretic hormone secretion, while NSAIDs cause inhibition of prostaglandins and potentiate vasopressin effect on the renal tubules. Hypocalcemia is commonly caused by ASA through decreases in parathyroid hormone secretion, and the use of phosphate-containing products will chelate with calcium, leading to a decrease in calcium concentrations. Hypercalcemia occurs secondary to both vitamin D and vitamin A, which cause an increase in bone resorption and calcium absorption in the body. Hypophosphatemia is seen with antacids (aluminum or magnesium products), insulin, acetaminophen overdose, and ASA overdose. Hyperphosphatemia can be due to excess phosphate administration with phosphate-containing laxatives and enemas (e.g., Fleet). Hypermagnesemia is caused by enemas, laxatives, and antacids, which contain magnesium as a component (magnesium citrate, milk of magnesia).39 PPIs deplete magnesium stores if taken for a long duration.40,41 Low magnesium stores can also lead to hypokalemia and hypocalcemia. Recent data from over 10,000 patients have linked PPI use with the risk of chronic kidney disease.42 The urine can appear bright yellow or orange as a result of vitamin B2 (riboflavin) excretion in the urine. PPIs and NSAIDs can lead to drug-induced acute interstitial nephritis.43 Agents With Miscellaneous Toxicity OTC products can cause a false-positive drug screen. Ranitidine use results in false-positive amphetamine and methamphetamine; diphenhydramine, in false-positive methadone; dextromethorphan, in false-positive phencyclidine (PCP); and ibuprofen, in false-positive cannabinoid and barbiturate results.44 OTC hypersensitivity reactions range from mild rash to severe anaphylaxis. NSAIDs cause angioedema as a result of the release of local mediators such as histamine and/or bradykinin. Topical benzocaine found in gels, liquids, creams, lotions, and aerosol sprays can lead to the development of methemoglobinemia.45 Elevated temperatures have been reported with ASA, cimetidine, and folic acid.46 Lactic acidosis can be precipitated from salicylates or iron therapy.47 The adulterated use of pseudoephedrine can cause methamphetamine toxicity.48,49 Hypoglycemia induced by insulin has been reported to cause seizures.50 Bismuth subsalicylate (Pepto-Bismol) can cause discoloration of the tongue and grayish-black stools.51 Role of the Pharmacist Many consumers and even some healthcare providers consider OTC agents to be completely safe and do not consider these products to be “real medications.” From the patient perspective, medication monitoring of OTC products primarily focuses on the efficacy related to relief of symptoms rather than potential adverse effects or laboratory changes. Unfortunately, comprehensive MTM is often limited when it comes to OTC products due to an incomplete medication list. The challenge for the healthcare professional is to identify the true medication list for each patient and to ensure that each patient’s medications (prescription and OTC) are appropriate, the safest possible alternative, the most effective for each condition, void of duplication, and used correctly. Medication reconciliation can be a challenging and time-consuming task. Pharmacy technicians, pharmacy students, and nursing staff can all work with pharmacists in verifying an up-to-date, accurate medication list. Pharmacists in the hospital setting should be individually assessing each new admission and provide recommendations for medication discontinuation or adjustment based upon patient presentation. Pharmacists can collaborate with providers to optimize medication therapy goals for each patient. Elderly patients are more susceptible to ADRs compared to the general population.52 The physiological changes with aging also can affect the pharmacokinetic properties of both prescription and OTC products.53 Elderly patients may also be taking five or more medications (polypharmacy) for chronic illnesses, increasing the likelihood of drug interactions.54 OTC products with significant drug-drug interaction potential include acetaminophen, ASA, NSAIDs, cimetidine, and omeprazole.55 Finally, older adults with decreases in visual acuity and hearing, along with memory impairment, can forget to take their medications correctly. It is reasonable for the pharmacist to counsel patients on medications upon discharge. This discussion should include the appropriate use of prescription and OTC medications, what medications to avoid, and the potential for side effects. In addition, the importance of follow-up with a single community pharmacy provider and regular mediation review with providers and their pharmacists should be stressed in order to keep the medication profile updated. Finally, it is important to remind patients to seek counsel from their caregivers before starting and continuing OTC medications for long-term use. Conclusion OTC medications are frequently used in the elderly for acute and chronic conditions. OTC products can be associated with potential adverse effects upon various organ systems and laboratory results. Thus, it is critical that the hospital pharmacist not overlook OTC agents during medication reconciliation and be familiar with potential complications and safety concerns associated with these products. REFERENCES 1. Consumer Healthcare Products Association. Statistics on OTC use. www.chpa.org/marketstats.aspx. Accessed August 11, 2015.2. Albert SM, Bix L, Bridgeman MM, et al. Promoting safe and effective use of OTC medications: CHPA-GSA National Summit. Gerontologist. 2014;54(6):909-918.3. American Pharmacists Association, National Association of Chain Drug Stores Foundation. Medication therapy management in community pharmacy practice: core elements of an MTM service (version 2.0). J Am Pharm Assoc. 2008;48(3):341-353.4. Catic AG. Identification and management of in-hospital drug-induced delirium in older patients. Drugs Aging. 2011;9:737-748.5. Agostini JV, Leo-Summers LS, Inouye SK. Cognitive and other adverse effects of diphenhydramine use in hospitalized older patients. Arch Intern Med. 2001;161(17):2091-2097.6. Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401-407.7. Gomm W, von Holt K, Thome F, et al. Association of proton pump inhibitors with risk of dementia. A pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73(4):410-416.8. Catalano G, Catalano MC, Alberts VA. Famotidine-associated delirium. A series of six cases. Psychosomatics. 1996;37(4):349-355.9. Atkinson HC, Stanescu I. Increased phenylephrine plasma levels with administration of acetaminophen. N Engl J Med. 2014;370:1171-1172.10. Musso CG. Magnesium metabolism in health and disease. Int Urol Nephrol. 2009;41:357-362.11. Wittbrodt ET. Drugs and myasthenia gravis. Arch Intern Med. 1997;157:399-408.12. Merdith TJ, Vale AJ. Non-narcotic analgesics. Problems of overdosage. Drugs. 1986;32(suppl 4):177-205.13. Wilhelm SM, Rjater RG, Kale-Pradhan PB. Perils and pitfalls of long-term effects of proton pump inhibitors. Expert Rev Clin Pharmacol. 2013;6(4):443-451.14. Durand C, Willett KC, Desilets AR. Proton pump inhibitors use in hospitalized patients: is overutilization becoming a problem? Clin Med Insights Gastroenterol. 2012;5:65-76.15. Fohl AL, Regal RE. Proton pump inhibitor-associated pneumonia: not a breath of fresh air after all? World J Gastrointest Pharmacol Ther. 2011;2(3):17-26.16. Weinstein M. First do no harm: the dangers of mineral oil. Paediatr Child Health. 2001;6(3):129-131.17. Herlihy A, Corbett SM, Sessler CN. Drug-induced acute respiratory failure. In: Papadopoulos J, Cooper B, Kane-Gill S, et al, eds. Drug-Induced Complications in the Critically Ill Patients: A Guide for Recognition and Treatment. Mount Prospect, IL: Society of Critical Care Medicine; 2012:87-103.18. Paul KJ, Walker RL, Dublin S. Anticholinergic medications and risk of community-acquired pneumonia in elderly adults: a population-based case-control study. J Am Geriatr Soc. 2015;63(3):476-485.19. Howard PA, Delafontaine P. Nonsteroidal anti-inflammatory drugs and cardiovascular risk. J Am Coll Cardiol. 2004;43:519-525.20. Phillips AC, Polisson RP, Simon LS. NSAIDs and the elderly. Toxicity and economic implications. Drugs Aging. 1997;10(2):119-130.21. Non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs): Drug safety communication—FDA strengthens warning of increased chance of heart attack or stroke. July 9, 2015. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm454141.htm. Accessed August 11, 2016.22. Eccles R. Substitution of phenylephrine for pseudo-ephedrine as a nasal decongestant. An illogical way to control methamphetamine abuse. Br J Clin Pharmacol. 2007;63(1):10-14.23. Woosley RL. The University of Arizona Center for Education and Research on Therapeutics—QT drug lists. https://crediblemeds.org/. Accessed August 31, 2016.24. Zeynettin K, Abdullah T. Adverse cardiac effects of decongestant agents. Eur J Gen Med. 2013;10(suppl 1):32-35.25. Anderson F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by non-chemotherapy drugs. Ann Intern Med. 2007;146:657-665.26. Priziola JL, Smythe MA, Dager WE. Drug-induced thrombocytopenia in critically ill patients. Crit Care Med. 2010;38(6 suppl):S145-S154.27. Sanford-Driscoll M, Knodel LC. Induction of hemolytic anemia by nonsteroidal anti-inflammatory drugs. Drug Intell Clin Pharm. 1986;20(12):925-934.28. Chassany O, Michaux A, Bergmann JF. Drug-induced diarrhea. Drug Saf. 2000;22:53-72.29. Talley NJ, Jones M, Nuyts G, et al. Risk factors for chronic constipation based on a general practice sample. Am J Gastroenterol. 2003;98(5):1107-1111.30. National Digestive Diseases Information Clearing-house. Constipation. http://digestive.niddk.nih.gov/ddiseases/pubs/constipation/. Accessed August 25, 2016.31. Rimon E, Kagansky N, Kagansky M, et al. Are we giving too much iron? Low-dose iron therapy is effective in octogenarians. Am J Med. 2005;118:1142-1147.32. Watson SC, Dellinger BB, Jennings K, et al. Antacids, altered mental status and milk-alkali syndrome. Case Rep Emerg Med. 2012;2012:942452.33. Scheiman JM. Unmet needs in non-steroidal anti-inflammatory drug-induced upper gastrointestinal diseases. Drugs. 2006;66(suppl 1):15-21.34. Thomas J, Straus WL, Bloom BS. Over-the-counter nonsteroidal anti-inflammatory drugs and risk of gastrointestinal symptoms. Am J Gastroenterol. 2002;97:2215-2219.35. Navarro VJ, Senior JR. Drug-related hepatotoxicity. N Engl J Med. 2006;354:731-739.36. Lat I, Foster DR, Erstad B. Drug-induced acute liver failure and gastrointestinal complications. Crit Care Med. 2010;38(6 suppl):S175-S187.37. Rozgony NR, Fang C, Kuczmarski MF, Bob H. Vitamin B(12) deficiency is linked with long-term use of proton pump inhibitors in institutionalized older adults: could a cyanocobalamin nasal spray be beneficial? J Nutr Elder. 2010;29(1):87-99.38. Furey SA, Vargas R, McMahon FG. Renovascular effects of nonprescription ibuprofen in elderly hypertensive patients with mild renal impairment. Pharmacotherapy. 1993;13:143-148.39. Buckley MS, LeBlanc JM, Cawley MJ. Electrolyte disturbances associated with commonly prescribed medications in the intensive care unit. Crit Care Med. 2010;38(6 suppl):S253-S264.40. Broeren MA, Geerdink EA, Vader HL, et al. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med. 2009;151(10):755-756.41. Hoorn EJ, Van der Hoek J, de Man RA, et al. A case series of proton pump inhibitor-induced hypomagnesemia. Am J Kidney Dis. 2010;56(1):112-116.42. Lazarus B, Chen Y, Wilson FP, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246.43. Kannji S, Chant C. Allergic and hypersensitivity reactions in the intensive care unit. Crit Care Med. 2010;38(6 suppl):S162-S168.44. Brahm NC, Yeager LL, Fox MD, et al. Commonly prescribed medications and potential false-positive urine drug screens. Am J Health Syst Pharm. 2010;67(16):1344-1350.45. Benzocaine topical products: sprays, gels and liquids—risk of methemoglobinemia. FDA MedWatch. April 7, 2011. www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm250264.htm. Accessed August 25, 2016.46. Herling A, Corbett SM, Sessler CN. Drug-induced hyperthermia. In: Papadopoulos J, Cooper B, Kane-Gill S, et al, eds. Drug-Induced Complications in the Critically Ill Patients: A Guide for Recognition and Treatment. Mount Prospect, IL: Society of Critical Care Medicine; 2012:87-105.47. Buckley MS, Cawley MJ. Electrolyte and acid-base disorders in the ICU. In: Papadopoulos J, Cooper B, Kane-Gill S, et al, eds. Drug-Induced Complications in the Critically Ill Patients: A Guide for Recognition and Treatment. Mount Prospect, IL: Society of Critical Care Medicine; 2012:145-170.48. Pray WS. Pseudoephedrine: stricter controls in the future? US Pharm. 2010;35(1):17-19.49. Brzeczko AW, Leech R, Stark JG. The advent of a new pseudoephedrine product to combat methamphet-amine abuse. Am J Drug Alcohol Abuse. 2013;39(5):284-290.50. Lapenta L, Di Bonaventura C, Fattouch J, et al. Focal epileptic seizure induced by transient hypoglycemia in insulin-treated diabetes. Epileptic Disord. 2010;(1):84-87.51. Pepto-Bismol Original Liquid. Procter & Gamble. www.pepto-bismol.com/en-us/products/liquid/original-liquid. Accessed August 25, 2016.52. Routledge PA, O’Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol. 2003;57(2):121-126.53. Thomas JA, Burns RA. Important drug-nutrient interactions in the elderly. Drugs Aging. 1998;3:199-209.54. Wallace J, Paauw DS. Appropriate prescribing and important drug interactions in older adults. Med Clin N Am. 2015;99:295-310.55. Hersh EV, Pinto A, Moore PA. Adverse drug interactions involving common prescription and over-the-counter analgesic agents. Clin Ther. 2007;29(suppl):2477-2497. To comment on this article, contact rdavidson@uspharmacist.com.