Acetaminophen Contraindications and Precautions
- acetaminophen hypersensitivity
- alcoholism
- anemia
- asthma
- bone marrow suppression
- breast-feeding
- children
- G6PD deficiency
- hepatic disease
- hepatitis
- immunosuppression
- infection
- neutropenia
- phenylketonuria
- pregnancy
- renal disease
- salicylate hypersensitivity
- tobacco smoking
Acetaminophen Contraindications and Precautions
Acetaminophen is contraindicated in patients with a known acetaminophen hypersensitivity. Acetaminophen hypersensitivity reactions are rare, but severe sensitivity reactions are possible.
Patients with alcoholic hepatic disease, viral hepatitis or alcoholism are at risk for acetaminophen-induced hepatotoxicity since glucuronide conjugation of the drug may be decreased. Depletion of hepatic glutathione reserves limits the ability of the liver to conjugate acetaminophen which predisposes the patient to further hepatic injury. Although it is always prudent to use the smallest dose of acetaminophen for the shortest duration necessary, short courses (< 5 days) of normal adult doses have been administered safely to patients with stable chronic liver disease. Acetaminophen should not be used for self-medication in patients who consume 3 or more alcoholic beverages per day. Acetaminophen-induced hepatotoxicity should be suspected in alcoholic patients with aminotransferase levels > 1000 U/L and acetaminophen blood levels should be checked in these patients.
Chronic acetaminophen administration should be avoided in patients with underlying renal disease; however it is the analgesic of choice for episodic pain in these patients. Case control studies have found an increased risk of developing papillary necrosis, chronic renal failure or end-stage renal disease with chronic acetaminophen use. There are many confounding factors in these studies which limit the ability to determine the actual role of chronic acetaminophen use as a single risk factor for renal disease. In a case-controlled study of patients with early renal failure, the regular use of acetaminophen (without aspirin ) was associated with a risk of chronic renal failure that was 2.5-times as high as that for non-acetaminophen users. The risk increased with an increasing cumulative acetaminophen lifetime dose. The average dose used during periods of regular acetaminophen use also correlated with risk as those who took > 500 g per year (>=1.4 g/day) during periods of regular use had an odds ratio for chronic renal failure of 5.3; duration of therapy was unrelated to risk. In this study, it appears that pre-existing renal disease or systemic disease is a required precursor to the development of analgesic-induced renal failure; patients without preexisting renal disease who used analgesics had only a small risk of developing end-stage renal disease.
Patients with G6PD deficiency who overdose with acetaminophen may be at increased risk for drug-induced hemolysis. During acetaminophen overdose, cyanosis may not be apparent in patients with pre-existing anemia, in spite of dangerously high blood concentrations of methemoglobin.
Acetaminophen should be used cautiously in patients with salicylate hypersensitivity. A patient with salicylate hypersensitivity may also be hypersensitive to acetaminophen. Of 163 patients with a history of urticaria induced by aspirin, but without a history of chronic urticaria, 11% had cross-reactivity to acetaminophen. Also, of 50 patients with aspirin-sensitive asthma, 17 had a naso-ocular or bronchospastic reaction after ingestion of either 1000 mg or 1500 mg of acetaminophen. The magnitude of FEV1 decline after a mean aspirin dose of 47 mg was similar to the decline seen after a mean acetaminophen dose of 1227 mg. The lower the aspirin provocative dose, the more likely patients were to cross-react to acetaminophen. For example, 5 of 6 patients with aspirin-induced bronchospasm after a dose of 30 mg or less had cross-reactivity to acetaminophen whereas no patients had cross-reactivity when the provocative aspirin dose was at least 150 mg. The acetaminophen challenges were performed before any aspirin challenges and all patients had a FEV1 of at least 70% of predicted or best previously recorded value, an absolute value greater than 1.5 liters, and a fall of less than 15% in FEV1 from morning baseline during placebo challenges. The mechanism(s) of hypersensitivity cross-reactivity have not been clearly elucidated. Some cases of cross-reactivity appear to be caused by prostaglandin inhibition, and some cases appear to be caused by an IgE-mediated mechanism. Although unproven, the metabolic breakdown of the parent molecule of some NSAIDs and acetaminophen could yield structurally similar chemical moieties, which could result in IgE production. Patients with a history of aspirin-induced anaphylaxis may be more likely to cross-react to acetaminophen.
Symptoms of acute infection (e.g., fever, pain) can be masked during treatment with acetaminophen in patients with bone marrow suppression, especially neutropenia, or immunosuppression.
Certain acetaminophen products containing aspartame (Nutrasweet®) should be avoided in patients who have phenylketonuria or who must restrict intake of phenylalanine. Patients should not self-medicate with acetaminophen for the treatment of pain > 5 days in children or > 10 days in adults. Fever should not be treated longer than 3 days in children or adults without consulting a physician or other health care professional. Factors that can lead to inadvertent overdoses in children include substituting adult acetaminophen formulations for pediatric formulations for convenience, misreading or interpreting instructions or administering more acetaminophen due to persistent fever. Repeated overdoses of acetaminophen in children in combination with decreased nutrition may lead to changes in the metabolism of acetaminophen leading to hepatotoxicity. This combination leads to decreases in sulfation, glucuronidation and glutathione production.
Acetaminophen should be used during pregnancy only if the benefits to the mother outweigh the potential risks to the fetus or infant. Acetaminophen crosses the placenta and is classified as a FDA pregnancy category B drug. No overall increase in fetal mortality, determined by pregnancy outcomes of mothers that overdosed on various amounts of acetaminophen, was apparent amongst 300 women. Treatment with acetylcysteine or methionine did not appear to affect fetal or neonatal toxicity. Of 235 infants exposed to an overdose of only acetaminophen, 168 were normal, 8 had malformations, 16 were spontaneously aborted, and 43 were electively terminated. None of the infants with malformations were exposed during the first trimester, but all of the spontaneous abortions were subsequent to first trimester exposure.
Acetaminophen should be used during breast-feeding only if the benefits to the mother outweigh the potential risks to the infant. Acetaminophen also crosses into breast milk, with a concentration ranging from 0.1 - 1.85% of the maternal dose. According to the American Academy of Pediatrics (AAP), acetaminophen has not been associated with any observable changes in nursing infants of mothers that took acetaminophen while breast-feeding. The AAP regards acetaminophen as a maternal medicine that is usually compatible with breast feeding.
Tobacco smoking induces the cytochrome P450 isoenzyme CYP1A2 and may potentially increase the risk for acetaminophen-induced hepatotoxicity during overdose via enhanced generation of acetaminophen’s hepatotoxic metabolite, NAPQI. In one study, current tobacco smoking was found to be very frequent in patients admitted with acetaminophen poisoning. Tobacco smoking appears to be an independent risk factor of severe hepatotoxicity, acute liver failure and death following acetaminophen overdose.
[ Last revised: 12/14/2006 1:53:00 PM ]
References
. Benson GD. Acetaminophen in chronic liver disease. Clin Pharmacol Ther 1983;33:95 - 101.
. Settipane RA et al. Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects. J Allergy Clin Immunol 1995;96:480 - 5.
. Heubi JE, Barbacci MB, Zimmerman HJ. Therapeutic misadventures with acetaminophen: hepatotoxicity after multiple doses in children. J Pediatr 1998:132:22 - 7.
. Fored CM, Ejerblad E, Lindblad P, et al. Acetaminophen, aspirin, and chronic renal failure. N Engl J Med 2001;345:1801 - 8.
. American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776 - 89.
. McElhatton PR, Sullivan FM, Volans GN. Paracetamol overdose in pregnancy. Analysis of the outcomes of 300 cases referred to the teratology information service. Reproductive Toxicol 1997;11:85 - 94.
. Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2007 Edition. Freeland, WA: H&H Publications; 2007:159 - 175.
. Schmidt LE, Dalhoff K. The impact of current tobacco use on the outcome of paracetamol poisoning. Aliment Pharmacol Ther 2003;18:979 - 85.
. Asero R. Risk factors for acetaminophen and nimesulide intolerance in patients with NSAID-induced skin disorders. Ann Allergy Asthma Immunol 1999;82(6):554 - 8.
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