OBJECT DRUGS

• Tizanidine (Zanaflex)

PRECIPITANT DRUGS

Enzyme Inhibitors:

• Atazanavir (Reyataz)
• Cimetidine (Tagamet, etc.)
• Ciprofloxacin (Cipro, etc.)
• Enoxacin (Penetrex)
• Ethinyl Estradiol
• Fluvoxamine (Luvox, etc.)
• Mexiletine (Mexitil)
• Tacrine (Cognex)
• Zileuton (Zyflo, etc.)

Comment:

Potent CYP1A2 inhibitors such as fluvoxamine and ciprofloxacin can produce dramatic increases in tizanidine plasma concentrations; tizanidine toxicity is likely. Other CYP1A2 inhibitors would generally have less effect on tizanidine, but it would be prudent to avoid the combinations when possible.

Management Class 2: Use Only if Benefit Felt to Outweigh Risk [Ciprofloxacin, Enoxacin, Fluvoxamine]

• Use Alternative: Given the magnitude of the increase in tizanidine plasma concentrations, it would be prudent to avoid these combinations.
• Fluvoxamine: Sertraline (Zoloft), fluoxetine (Prozac), venlafaxine (Effexor), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro) are not known to inhibit CYP1A2.
• Fluoroquinolones: Gemifloxacin (Factive), levofloxacin (Levaquin), lomefloxacin (Maxaquin), moxifloxacin (Avelox), norfloxacin (Noroxin), and ofloxacin (Floxin) appear to have little effect on CYP1A2.
• Monitor: If the combination is used, monitor for evidence of tizanidine toxicity such as hypotension and excessive CNS depression.

Management Class 3: Assess Risk and Take Action if Necessary [Atazanavir, Cimetidine, Ethinyl Estradiol, Mexiletine, Tacrine, Zileuton]

• Consider Alternative: If available, use a drug that is not an inhibitor of CYP1A2.
• Cimetidine: Famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac) have no known effects on CYP1A2 activity.
• Monitor: If the combination is used, monitor for evidence of tizanidine toxicity such as hypotension and excessive CNS depression.