- Email: [email protected]
Analgesic Warfare: Acetaminophen, Really?
PHARMACY COLUMN
Barbara J. Zarowitz
Analgesic Warfare: Acetaminophen, Really? Barbara J. Zarowitz, PharmD, FCCP, BCPS, CGP, FASCP
The first medication recommended in the treatment of mild-to-moderate pain in older persons is almost always acetaminophen.1-3 Acetaminophen is available over the counter (OTC) without a prescription, is inexpensive, and consumers understand how to administer itdor do they? In the United Kingdom, death associated with accidental overdose, suicide, and low-dose chronic ingestion of paracetamol (acetaminophen) resulted in the 1998 policy change in Great Britain to decrease the package size of paracetamol to no greater than 32 tablets in pharmacies and 16 tablets in other retail outlets.4-7 Independent analysis identified that the suicide rates in general declined in the United Kingdom before implementing the decreases in paracetamol package size, leading authors to question what effect, if any, was contributed by the 1998 policy change.7 In the United States, acetaminophen overdose and liver injury continues to be a public health concern.8 In July 2009, the Food and Drug Administration (FDA) announced that it was requiring label changes to OTC acetaminophen products to reduce potential overdose errors.9 Manufacturers were advised to have acetaminophen product labels indicate the following: the ingredient acetaminophen is prominently displayed on the packaging of the product so that consumers can readily identify the active ingredient; acetaminophen is associated with liver injury and that consumers should avoid taking more than the recommended dose of acetaminophen and taking acetaminophen with moderate amounts of alcohol; and consumers should not use acetaminophen with any other drug containing acetaminophen and to ask a doctor or pharmacist if persons are not aware if a drug contains acetaminophen, a warning to ask a doctor before use if persons Geriatric Nursing, Volume 33, Number 1
have liver disease, and a warning to ask a doctor or pharmacist before use if persons are taking the blood-thinning drug warfarin. Subsequently, in July 2011, the FDA released a statement asking manufacturers of prescription products containing acetaminophen (ie, acetaminophen-opioid combination products), to restrict the amount/capsule or tablet to no more than 325 mg of acetaminophen by 2014.10 A boxed warning about potential liver injury was also added to the label. In July 2011, McNeil Consumer Healthcare announced their intent to reduce the recommended maximum daily dose of acetaminophen in Tylenol ES to no more than 3 g or 6 tablets per day.11 The unilateral action for Tylenol ES in 2011 is to be followed by a change in the maximum daily dose of Regular Strength Tylenol, which is anticipated to be 10 tablets or 3250 mg/ day in 2012. The manufacturer indicates that these actions are being taken to reduce the risk of accidental overdose in consumers. Although perhaps well intended to protect consumers, the decision to modify the maximum daily recommended dose in OTC acetaminophen has created confusion in institutionalized settings, such as long-term care where presumably health care personnel are either administering or supervising the administration of acetaminophen products. Surveyors have taken to heart the intent of McNeil Consumer Healthcare to lower the maximum daily dose of Tylenol ES and are looking for changes in practice and documentation that maximum daily dose warnings have been decreased to 3 g per day. It is unclear whether manufacturers of generic acetaminophen products will follow suit but surveyors are generalizing the lowered maximum daily dose to all acetaminophen products. The FDA has subsequently confirmed that the maximum daily dose of acetaminophen is 4 g per day and that 51
McNeil is taking independent action with Tylenol ES and Regular Strength Tylenol.12 Putting regulatory changes aside, there are conflicting data regarding the potential risk of acetaminophen doses exceeding 3 g per day. Acute ingestion over a few days results in a different risk of toxicity than chronic ingestion of lowdose acetaminophen over many weeks to months. Acetaminophen is metabolized by the P450 enzymes through glucuronidation and sulfation.13 A small fraction of acetaminophen is metabolized to N-acetyl-p-benzoquinoneimine (NAPQI), which binds covalently to tissues in zone 3 of the hepatic lobule causing injury. With adequate glutathione stores, the NAPQI is rapidly detoxified and excreted with no resulting damage to the liver. Liver toxicity is evident when hepatic glutathione concentration is less than or equal to 30%. The human supply of glutathione begins to become depleted over the range of 0.5-3 g of acetaminophen.14 Necrosis occurs when the production of NAPQI exceeds glutathione hepatic tissue binding. Factors that decrease glutathione in the liver are alcohol, malnutrition, and P450 enzyme inducers such as rifampin, phenytoin, isoniazid, and phenobarbital.13 The Rocky Mountain Poison and Drug Center prepared comments for the FDA docket on the effects of acetaminophen acute ingestion on hepatic injury.15 In its review of clinical trials and case series in which subjects ingested between 3 and 6 g per day of acetaminophen for between 3 and 14 days, only transient increases in alanine aminotransferase (ALT), which reversed during continued therapy, were observed. Several of the studies reviewed included subjects with a variety of underlying illnesses such as alcoholic liver disease or hepatitis C. Although exposure was limited by the short duration of ingestion in these observations, the authors concluded that 4 g per day of acetaminophen is safe even in populations with risk factors for liver toxicity and that when ALT increases occur, they are unlikely to progress to clinically significant liver injury.15 The subjects’ ages were not delineated in this report. There are reports of patients, with and without risk factors, developing hepatotoxicity after taking acetaminophen doses of 2.6-6.5 g per day over a period of time ranging from unknown to many years.16 Davies’s Textbook of Adverse Drug Reactions recommends administration of no more than 2 g per day of acetaminophen in patients that consume more than 60 g of ethanol/day 52
(approximately four 12-oz beer cans, 16 oz of wine, or 6 oz of 80-proof whiskey).17 The first American Geriatric Society guidelines on management of persistent pain in older persons recommended decreasing the maximum daily dose of acetaminophen by 50-75% in patients with hepatic impairment or alcohol abuse, although this caution was deleted in the subsequent update.2,3 In addition to dose-related concerns of hepatotoxicity, acetaminophen in doses of greater than 2.6 g per day is associated with significantly more adverse gastrointestinal events including dyspepsia, gastric ulcers, and gastrointestinal distress requiring hospitalization.18 In this retrospective cohort study, elderly patients prescribed acetaminophen doses greater than 2.6 g per day experienced gastrointestinal adverse effects not different than those prescribed nonsteroidal anti-inflammatory drugs in doses of 3.25 g per day. Acetaminophen toxicity can also take the form of renal failure in patients with mild liver impairment.19 In a case series, patients presented with decreased urine output that required management of fluid and electrolytes, with or without dialysis, over the course of approximately 1 week after which time the renal function slowly returned to normal. Authors noted that there was no mortality due to the acetaminophenassociated renal failure in the absence of severe hepatic impairment. A decline in renal function on average of 30 mL/min/1.73 m2 or 30% under baseline has been associated with lifetime use (11 years) of acetaminophen greater than 3000 g compared with women who consumed less than 100 g (odds ratio 2.04; 95% confidence interval 1.28e3.24).20 In summary, there remains conflicting information regarding the safety of acetaminophen in higher doses: Glutathione, which is responsible for detoxification of the metabolite NAPQI, begins to deplete with acetaminophen doses of 0.5 to 3 g per day. The Rocky Mountain Poison Center concluded that in doses up to 4 g per day, acetaminophen is safe for short-term use (3e14 days) in a variety of populations. With chronic ingestion of acetaminophen, hepatotoxicity has been observed at total daily doses of between 2.6 and 6.5 g per day. At acetaminophen doses of greater than 2.6 g per day, gastrointestinal adverse effects are Geriatric Nursing, Volume 33, Number 1
similar to those reported with high-dose NSAIDs. Acetaminophen toxicity can present as renal failure with or without concomitant hepatic toxicity. Lifetime use of acetaminophen greater than 3000 g has twice the risk of causing a 30% decline in renal function than lifetime use of less than 100 g. It would seem that as safe as acetaminophen is purported to be, initiation of the lowest possible dose that will offset pain is a prudent approach. Titration to the minimally effective dose, ideally less than 2.6 g per day, is recommended. Although there is no guarantee that at doses less than 2.6 g per day older persons will not experience adverse gastrointestinal effects, renal decline, or hepatic injury, to the extent that these potential adverse consequences are doserelated, total daily acetaminophen doses of less than 2.6 g per day are likely to be safe.
References 1. American Medical Directors Association Clinical Practice Guideline. Pain management in the long-term care setting. American Medication Directors Association. 2003. Available at http://amda.networkats.com/ members_online/members/viewitem.asp? item5CPG11R&catalog=CPGS&pn51&af5AMDA. Cited December 15, 2011. 2. American Geriatric Society Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002;50:S205-24. 3. American Geriatric Society Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. 2009. Available at www.american geriatrics.org/files/documents/2009_Guideline.pdf. Cited November 14, 2011. 4. Bridger S, Henderson K, Glucksman E, et al. Deaths from low-dose paracetamol poisoning. BMJ 1998;316:1724-5. 5. Emergency treatment of poisoning. In: British National Formulary, No 35. London: British Medical Association, Royal Pharmaceutical Society of Great Britain; 1998. p. 20-1. 6. Management of acute paracetamol poisoning. Guidelines agreed by the UK National Poisons Information Service. Supplied to accident and emergency centres in the United Kingdom by the Paracetamol Information Centre in collaboration with the British Association for Accident and Emergency Medicine. 1995. 7. Bateman DN. Limiting paracetamol pack size: has it worked in the UK? Clin Toxicol 2009;47:536-41. 8. Anonymous. Acetaminophen overdose and liver injurydbackground and options for reducing injury. Food and Drug Administration. Available at www.fda. gov/ohrms/dockets/ac/09/briefing/2009-4429b1-01FDA.pdf. Cited November 14, 2011.
Geriatric Nursing, Volume 33, Number 1
9. Food and Drug Administration. Questions and answers on final rule for labeling changes to over-the-counter pain relievers. April 29, 2009. Available at www.fda.gov/Drugs/ NewsEvents/ucm144068.htm. Cited November 14, 2011. 10. Food and Drug Administration. Questions and answers about oral prescription acetaminophen products to be limited to 325 mg per dosage unit. Updated August 1, 2011. Available at www.fda.gov/Drugs/DrugSafety/ InformationbyDrugClass/ucm239871.htm. Cited November 14, 2011. 11. Johnson and Johnson. McNeil Consumer Healthcare announces plans for new dosing instructions for Tylenol products. July 28, 2011. Available at www.jnj.com/ connect/news/all/mcneil-consumer-healthcare-announ ces-plans-for-new-dosing-instructions-for-tylenol-pro ducts. Cited November 14, 2011. 12. Personal Communication. Fitzpatrick C. Project Manager, Safe use initiative, Food and Drug Administration/Center for Drug Evaluation and Research/ Office of the Director/Safe Use Section. August 3, 2011. 13. Lane JE, Belson MG, Brown K, et al. Chronic acetaminophen toxicity: a case report and review of the literature. J Emerg Med 2002;23:253-6. 14. Slattery JT, Wilson JM, Kalhorn TF, et al. Dose dependent pharmacokinetics of acetaminophen: evidence of glutathione depletion in humans. Clin Pharmacol Ther 1987;41:413-8. 15. Dart RC, Heard KJ, Green JL, et al. Comments on liver injury related to the use of acetaminophen. Comments on Docket FDA-2009-N-0138, Rocky Mountain Poison and Drug Center, June 8, 2009. Available at www.fda.gov/ downloads/advisorycommittees/committeesmeeting materials/drugs/drugsafetyandriskmanagementa dvisorycommittee/ucm168775.pdf. Cited November 14, 2011. 16. Bolesta S, Haber SL. Hepatotoxicity associated with chronic acetaminophen administration in patients without risk factors. Ann Pharmacother 2002;36:331-3. 17. Davis M. Hepatic disorders. In: Davies DM, Ferner RE, DeGlanville H, editors. Davies’s textbook of adverse drug reactions. 5th ed. New York: Chapman and Hall Medical; 1998. p. 275-338. 18. Rahme E, Petitt D, LeLorier J. Determinants and sequelae associated with utilization of acetaminophen versus traditional non-steroidal anti-inflammatory drugs in an elderly population. Arthritis Rheum 2002;46:3046-54. 19. Maze GL, Lee M. Acute renal failure associated in an alcoholic patient taking therapeutic doses of acetaminophen. J Am Board Fam Pract 1988;11:410-3. 20. Curham GC, Knight EL, Rosner B. Lifetime nonnarcotic use and decline in renal function in women. Arch Intern Med 2004;164:1519-24. BARBARA J. ZAROWITZ, PharmD, FCCP, BCPS, CGP, FASCP, is Chief Clinical Officer and Vice President of Professional Services at Omnicare, Inc., and Adjunct Professor of Pharmacy Practice at the College of Pharmacy and Allied Health Sciences, Wayne State University, Detroit, MI. 0197-4572/$ - see front matter Ó 2012 Mosby, Inc. All rights reserved. doi:10.1016/j.gerinurse.2011.11.004
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Barbara J. Zarowitz
Analgesic Warfare: Acetaminophen, Really? Barbara J. Zarowitz, PharmD, FCCP, BCPS, CGP, FASCP
The first medication recommended in the treatment of mild-to-moderate pain in older persons is almost always acetaminophen.1-3 Acetaminophen is available over the counter (OTC) without a prescription, is inexpensive, and consumers understand how to administer itdor do they? In the United Kingdom, death associated with accidental overdose, suicide, and low-dose chronic ingestion of paracetamol (acetaminophen) resulted in the 1998 policy change in Great Britain to decrease the package size of paracetamol to no greater than 32 tablets in pharmacies and 16 tablets in other retail outlets.4-7 Independent analysis identified that the suicide rates in general declined in the United Kingdom before implementing the decreases in paracetamol package size, leading authors to question what effect, if any, was contributed by the 1998 policy change.7 In the United States, acetaminophen overdose and liver injury continues to be a public health concern.8 In July 2009, the Food and Drug Administration (FDA) announced that it was requiring label changes to OTC acetaminophen products to reduce potential overdose errors.9 Manufacturers were advised to have acetaminophen product labels indicate the following: the ingredient acetaminophen is prominently displayed on the packaging of the product so that consumers can readily identify the active ingredient; acetaminophen is associated with liver injury and that consumers should avoid taking more than the recommended dose of acetaminophen and taking acetaminophen with moderate amounts of alcohol; and consumers should not use acetaminophen with any other drug containing acetaminophen and to ask a doctor or pharmacist if persons are not aware if a drug contains acetaminophen, a warning to ask a doctor before use if persons Geriatric Nursing, Volume 33, Number 1
have liver disease, and a warning to ask a doctor or pharmacist before use if persons are taking the blood-thinning drug warfarin. Subsequently, in July 2011, the FDA released a statement asking manufacturers of prescription products containing acetaminophen (ie, acetaminophen-opioid combination products), to restrict the amount/capsule or tablet to no more than 325 mg of acetaminophen by 2014.10 A boxed warning about potential liver injury was also added to the label. In July 2011, McNeil Consumer Healthcare announced their intent to reduce the recommended maximum daily dose of acetaminophen in Tylenol ES to no more than 3 g or 6 tablets per day.11 The unilateral action for Tylenol ES in 2011 is to be followed by a change in the maximum daily dose of Regular Strength Tylenol, which is anticipated to be 10 tablets or 3250 mg/ day in 2012. The manufacturer indicates that these actions are being taken to reduce the risk of accidental overdose in consumers. Although perhaps well intended to protect consumers, the decision to modify the maximum daily recommended dose in OTC acetaminophen has created confusion in institutionalized settings, such as long-term care where presumably health care personnel are either administering or supervising the administration of acetaminophen products. Surveyors have taken to heart the intent of McNeil Consumer Healthcare to lower the maximum daily dose of Tylenol ES and are looking for changes in practice and documentation that maximum daily dose warnings have been decreased to 3 g per day. It is unclear whether manufacturers of generic acetaminophen products will follow suit but surveyors are generalizing the lowered maximum daily dose to all acetaminophen products. The FDA has subsequently confirmed that the maximum daily dose of acetaminophen is 4 g per day and that 51
McNeil is taking independent action with Tylenol ES and Regular Strength Tylenol.12 Putting regulatory changes aside, there are conflicting data regarding the potential risk of acetaminophen doses exceeding 3 g per day. Acute ingestion over a few days results in a different risk of toxicity than chronic ingestion of lowdose acetaminophen over many weeks to months. Acetaminophen is metabolized by the P450 enzymes through glucuronidation and sulfation.13 A small fraction of acetaminophen is metabolized to N-acetyl-p-benzoquinoneimine (NAPQI), which binds covalently to tissues in zone 3 of the hepatic lobule causing injury. With adequate glutathione stores, the NAPQI is rapidly detoxified and excreted with no resulting damage to the liver. Liver toxicity is evident when hepatic glutathione concentration is less than or equal to 30%. The human supply of glutathione begins to become depleted over the range of 0.5-3 g of acetaminophen.14 Necrosis occurs when the production of NAPQI exceeds glutathione hepatic tissue binding. Factors that decrease glutathione in the liver are alcohol, malnutrition, and P450 enzyme inducers such as rifampin, phenytoin, isoniazid, and phenobarbital.13 The Rocky Mountain Poison and Drug Center prepared comments for the FDA docket on the effects of acetaminophen acute ingestion on hepatic injury.15 In its review of clinical trials and case series in which subjects ingested between 3 and 6 g per day of acetaminophen for between 3 and 14 days, only transient increases in alanine aminotransferase (ALT), which reversed during continued therapy, were observed. Several of the studies reviewed included subjects with a variety of underlying illnesses such as alcoholic liver disease or hepatitis C. Although exposure was limited by the short duration of ingestion in these observations, the authors concluded that 4 g per day of acetaminophen is safe even in populations with risk factors for liver toxicity and that when ALT increases occur, they are unlikely to progress to clinically significant liver injury.15 The subjects’ ages were not delineated in this report. There are reports of patients, with and without risk factors, developing hepatotoxicity after taking acetaminophen doses of 2.6-6.5 g per day over a period of time ranging from unknown to many years.16 Davies’s Textbook of Adverse Drug Reactions recommends administration of no more than 2 g per day of acetaminophen in patients that consume more than 60 g of ethanol/day 52
(approximately four 12-oz beer cans, 16 oz of wine, or 6 oz of 80-proof whiskey).17 The first American Geriatric Society guidelines on management of persistent pain in older persons recommended decreasing the maximum daily dose of acetaminophen by 50-75% in patients with hepatic impairment or alcohol abuse, although this caution was deleted in the subsequent update.2,3 In addition to dose-related concerns of hepatotoxicity, acetaminophen in doses of greater than 2.6 g per day is associated with significantly more adverse gastrointestinal events including dyspepsia, gastric ulcers, and gastrointestinal distress requiring hospitalization.18 In this retrospective cohort study, elderly patients prescribed acetaminophen doses greater than 2.6 g per day experienced gastrointestinal adverse effects not different than those prescribed nonsteroidal anti-inflammatory drugs in doses of 3.25 g per day. Acetaminophen toxicity can also take the form of renal failure in patients with mild liver impairment.19 In a case series, patients presented with decreased urine output that required management of fluid and electrolytes, with or without dialysis, over the course of approximately 1 week after which time the renal function slowly returned to normal. Authors noted that there was no mortality due to the acetaminophenassociated renal failure in the absence of severe hepatic impairment. A decline in renal function on average of 30 mL/min/1.73 m2 or 30% under baseline has been associated with lifetime use (11 years) of acetaminophen greater than 3000 g compared with women who consumed less than 100 g (odds ratio 2.04; 95% confidence interval 1.28e3.24).20 In summary, there remains conflicting information regarding the safety of acetaminophen in higher doses: Glutathione, which is responsible for detoxification of the metabolite NAPQI, begins to deplete with acetaminophen doses of 0.5 to 3 g per day. The Rocky Mountain Poison Center concluded that in doses up to 4 g per day, acetaminophen is safe for short-term use (3e14 days) in a variety of populations. With chronic ingestion of acetaminophen, hepatotoxicity has been observed at total daily doses of between 2.6 and 6.5 g per day. At acetaminophen doses of greater than 2.6 g per day, gastrointestinal adverse effects are Geriatric Nursing, Volume 33, Number 1
similar to those reported with high-dose NSAIDs. Acetaminophen toxicity can present as renal failure with or without concomitant hepatic toxicity. Lifetime use of acetaminophen greater than 3000 g has twice the risk of causing a 30% decline in renal function than lifetime use of less than 100 g. It would seem that as safe as acetaminophen is purported to be, initiation of the lowest possible dose that will offset pain is a prudent approach. Titration to the minimally effective dose, ideally less than 2.6 g per day, is recommended. Although there is no guarantee that at doses less than 2.6 g per day older persons will not experience adverse gastrointestinal effects, renal decline, or hepatic injury, to the extent that these potential adverse consequences are doserelated, total daily acetaminophen doses of less than 2.6 g per day are likely to be safe.
References 1. American Medical Directors Association Clinical Practice Guideline. Pain management in the long-term care setting. American Medication Directors Association. 2003. Available at http://amda.networkats.com/ members_online/members/viewitem.asp? item5CPG11R&catalog=CPGS&pn51&af5AMDA. Cited December 15, 2011. 2. American Geriatric Society Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002;50:S205-24. 3. American Geriatric Society Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. 2009. Available at www.american geriatrics.org/files/documents/2009_Guideline.pdf. Cited November 14, 2011. 4. Bridger S, Henderson K, Glucksman E, et al. Deaths from low-dose paracetamol poisoning. BMJ 1998;316:1724-5. 5. Emergency treatment of poisoning. In: British National Formulary, No 35. London: British Medical Association, Royal Pharmaceutical Society of Great Britain; 1998. p. 20-1. 6. Management of acute paracetamol poisoning. Guidelines agreed by the UK National Poisons Information Service. Supplied to accident and emergency centres in the United Kingdom by the Paracetamol Information Centre in collaboration with the British Association for Accident and Emergency Medicine. 1995. 7. Bateman DN. Limiting paracetamol pack size: has it worked in the UK? Clin Toxicol 2009;47:536-41. 8. Anonymous. Acetaminophen overdose and liver injurydbackground and options for reducing injury. Food and Drug Administration. Available at www.fda. gov/ohrms/dockets/ac/09/briefing/2009-4429b1-01FDA.pdf. Cited November 14, 2011.
Geriatric Nursing, Volume 33, Number 1
9. Food and Drug Administration. Questions and answers on final rule for labeling changes to over-the-counter pain relievers. April 29, 2009. Available at www.fda.gov/Drugs/ NewsEvents/ucm144068.htm. Cited November 14, 2011. 10. Food and Drug Administration. Questions and answers about oral prescription acetaminophen products to be limited to 325 mg per dosage unit. Updated August 1, 2011. Available at www.fda.gov/Drugs/DrugSafety/ InformationbyDrugClass/ucm239871.htm. Cited November 14, 2011. 11. Johnson and Johnson. McNeil Consumer Healthcare announces plans for new dosing instructions for Tylenol products. July 28, 2011. Available at www.jnj.com/ connect/news/all/mcneil-consumer-healthcare-announ ces-plans-for-new-dosing-instructions-for-tylenol-pro ducts. Cited November 14, 2011. 12. Personal Communication. Fitzpatrick C. Project Manager, Safe use initiative, Food and Drug Administration/Center for Drug Evaluation and Research/ Office of the Director/Safe Use Section. August 3, 2011. 13. Lane JE, Belson MG, Brown K, et al. Chronic acetaminophen toxicity: a case report and review of the literature. J Emerg Med 2002;23:253-6. 14. Slattery JT, Wilson JM, Kalhorn TF, et al. Dose dependent pharmacokinetics of acetaminophen: evidence of glutathione depletion in humans. Clin Pharmacol Ther 1987;41:413-8. 15. Dart RC, Heard KJ, Green JL, et al. Comments on liver injury related to the use of acetaminophen. Comments on Docket FDA-2009-N-0138, Rocky Mountain Poison and Drug Center, June 8, 2009. Available at www.fda.gov/ downloads/advisorycommittees/committeesmeeting materials/drugs/drugsafetyandriskmanagementa dvisorycommittee/ucm168775.pdf. Cited November 14, 2011. 16. Bolesta S, Haber SL. Hepatotoxicity associated with chronic acetaminophen administration in patients without risk factors. Ann Pharmacother 2002;36:331-3. 17. Davis M. Hepatic disorders. In: Davies DM, Ferner RE, DeGlanville H, editors. Davies’s textbook of adverse drug reactions. 5th ed. New York: Chapman and Hall Medical; 1998. p. 275-338. 18. Rahme E, Petitt D, LeLorier J. Determinants and sequelae associated with utilization of acetaminophen versus traditional non-steroidal anti-inflammatory drugs in an elderly population. Arthritis Rheum 2002;46:3046-54. 19. Maze GL, Lee M. Acute renal failure associated in an alcoholic patient taking therapeutic doses of acetaminophen. J Am Board Fam Pract 1988;11:410-3. 20. Curham GC, Knight EL, Rosner B. Lifetime nonnarcotic use and decline in renal function in women. Arch Intern Med 2004;164:1519-24. BARBARA J. ZAROWITZ, PharmD, FCCP, BCPS, CGP, FASCP, is Chief Clinical Officer and Vice President of Professional Services at Omnicare, Inc., and Adjunct Professor of Pharmacy Practice at the College of Pharmacy and Allied Health Sciences, Wayne State University, Detroit, MI. 0197-4572/$ - see front matter Ó 2012 Mosby, Inc. All rights reserved. doi:10.1016/j.gerinurse.2011.11.004
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