OBJECT DRUGS

• Acetaminophen (Tylenol, etc.)

PRECIPITANT DRUGS

Enzyme Inducers:

• 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. 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 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.