OBJECT DRUGS

Codeine Derivatives:

• Codeine
• Dihydrocodeine (Synalgos-DC)
• Hydrocodone (Vicodin, Lortab)
• Oxycodone (Percodan, Percocet, etc.)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Abiraterone (Zytiga)
• Amiodarone (Cordarone, etc.)
• Cimetidine (Tagamet, etc.)
• Cinacalcet (Sensipar)
• Clobazam (Onfi)
• Diphenhydramine (Benadryl, etc.)
• Haloperidol (Haldol)
• Mirabegron (Myrbetriq)
• Propafenone (Rythmol, etc.)
• Propoxyphene*
• Quinidine (Quinidex)
• Ritonavir (Norvir)
• Terbinafine (Lamisil, etc.)
• Thioridazine (Mellaril)

* Propoxyphene (Darvon) was withdrawn from the US market.

Comment:

Inhibitors of CYP2D6 prevent the conversion of codeine to its active metabolite, morphine; inhibition of analgesic effect may result. Preliminary evidence suggests that the analgesic effect of hydrocodone, oxycodone, and dihydrocodeine is also reduced in the absence of CYP2D6 activity. The analgesic effect of tramadol (Ultram) appears to be only partially dependent on CYP2D6, and thus it may have some analgesic activity in the presence of CYP2D6 inhibitors. Note that because terbinafine has an extraordinarily long terminal half-life, the inhibitory effect of terbinafine on CYP2D6 may last for many weeks after terbinafine is discontinued.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Analgesic: Consider using an analgesic that does not require conversion to an active metabolite, e.g., morphine, methadone (Dolophine), fentanyl (Duragesic), hydromorphone (Dilaudid), butorphanol (Stadol), or oxymorphone (Numorphan).
• Cimetidine: Other H₂-receptor antagonists such as famotidine (Pepcid), nizatidine (Axid), or ranitidine (Zantac) may be substituted for cimetidine.
• Monitor: Monitor for loss of analgesic efficacy.