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 (eg, hypotension, CHS depression). Other CYP1A2 inhibitors would generally have less effect on tizanidine, but it would be prudent to avoid the combinations when possible. For example, oral contraceptives are normally considered only moderate inhibitors of CYP1A2, but a product containing ethinyl estradiol and gestodene produced large increases in tizanidine plasma concentrations.

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.