OBJECT DRUGS

• Theophylline

PRECIPITANT DRUGS

Antimicrobials:

• Ciprofloxacin (Cipro, etc.)
• Clarithromycin (Biaxin, etc.)
• Enoxacin (Penetrex)
• Erythromycin (E-Mycin, etc.)
• Troleandomycin (TAO)

Comment:

Theophylline is metabolized by CYP1A2 and to a lesser extent CYP3A4. Inhibitors of these isozymes can increase theophylline serum concentrations; some patients may develop theophylline toxicity. Ciprofloxacin and especially enoxacin are strong inhibitors of CYP1A2, and can produce serious theophylline toxicity. Clarithromycin, erythromycin, and troleandomycin usually do not increase theophylline concentrations as much, but toxicity can still occur.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• Macrolides: Unlike erythromycin, clarithromycin and troleandomycin, azithromycin (Zithromax) and dirithromycin* do not inhibit CYP450 isozymes. (*not available in US)
• Quinolones: Levofloxacin (Levaquin), lomefloxacin (Maxaquin), ofloxacin (Floxin), and moxifloxacin (Avelox) appear to have little effect on CYP1A2 or CYP3A4.
• Monitor: Monitor for altered theophylline response if a CYP1A2 inhibitor is initiated, discontinue, or the dose is changed. Evidence of theophylline toxicity includes nausea, vomiting, diarrhea, restlessness, irritability, and insomnia. Higher serum concentrations can result in cardiac arrhythmias or seizures.