OBJECT DRUGS

• Fosphenytoin (Cerebyx)
• Phenytoin (Dilantin, etc.)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Amiodarone (Cordarone, etc.)
• Androgens
• Capecitabine (Xeloda)
• Chloramphenicol
• Cimetidine (Tagamet, etc.)
• Co-trimoxazole (Bactrim)
• Danazol (Danocrine)
• Delavirdine (Rescriptor)
• Disulfiram (Antabuse)
• Efavirenz (Sustiva)
• Fluconazole (Diflucan)
• Fluorouracil (5-FU)
• Fluoxetine (Prozac, etc.)
• Fluvoxamine (Luvox, etc.)
• Imatinib (Gleevec)
• Isoniazid (INH)
• Leflunomide (Arava)
• Metronidazole (Flagyl, etc.)
• Sulfinpyrazone (Anturane)
• Tamoxifen (Nolvadex)
• Ticlopidine (Ticlid)
• Voriconazole (Vfend)

Comment:

Inhibitors of CYP2C9 (and to a lesser extent CYP2C19) may increase phenytoin levels; phenytoin toxicity may occur. Depending on the baseline phenytoin serum concentration, it may take as long as several weeks for phenytoin toxicity to occur after starting an inhibitor.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Azole Antifungals: Ketoconazole (Nizoral), posaconazole (Noxafil), and itraconazole (Sporanox) appear to be less likely to affect phenytoin.
• Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) have minimal effects on drug metabolism.
• Fluvastatin: Statins other than fluvastatin do not appear to inhibit CYP2C9.
• SSRIs: The use of SSRIs that do not inhibit CYP2C9 [eg, paroxetine (Paxil) or venlafaxine (Effexor) ] should be considered.
• Monitor: Monitor for altered phenytoin effect if an inhibitor is initiated, discontinued, or changed in dosage. Evidence of phenytoin toxicity includes nystagmus, ataxia, diplopia, drowsiness, and lethargy; severe cases may result in asterixis and coma.