OBJECT DRUGS

• Acetaminophen (Tylenol, etc.)

PRECIPITANT DRUGS

Enzyme Inducers:

• Alcohol (Chronic, excessive)
• Barbiturates
• Carbamazepine (Tegretol, etc.)
• Efavirenz (Sustiva)
• Isoniazid (INH)
• Nevirapine (Viramune, etc.)
• Oxcarbazepine (Trileptal, etc.)
• Phenytoin (Dilantin, etc.)
• Primidone (Mysoline)
• Rifabutin (Mycobutin)
• Rifampin (Rifadin, etc.)
• Rifapentine (Priftin)
• St. John's Wort

Comment:

Enzyme inducers have been reported to increase the formation of a toxic acetaminophen metabolite, thus increasing the risk of hepatotoxicity in patients taking overdoses of acetaminophen (or large and/or prolonged therapeutic doses). The analgesic effect of acetaminophen may also be reduced by enzyme inducers due to enhanced acetaminophen metabolism. There is debate about whether chronic excessive alcohol use increases the risk of acetaminophen toxicity, but caution is advised pending more data. Isoniazid has a biphasic effect, first reducing and then increasing the formation of toxic acetaminophen metabolites.

Management Class 3: Assess Risk & Take Action if Necessary

• Circumvent/Minimize: Patients on enzyme inducers (or who regularly have 3 or more daily drinks of alcohol) should avoid prolonged use of large therapeutic doses of acetaminophen. A safe amount of acetaminophen for such patients is not established, but it would be prudent to limit intake of acetaminophen to 2 g/day or less.
• Consider Alternative: Since acetaminophen analgesia may be reduced, doses considered safe may be ineffective. Thus, it may be necessary to use alternative analgesics. Note, however, that salicylates and NSAIDs may produce additive toxicity with excessive alcohol intake.