OBJECT DRUGS

Corticosteroids:

• Budesonide (Entocort, etc.)
• Cortisone (Cortone)
• Dexamethasone (Decadron, etc.)
• Fluticasone (Flovent, etc.)
• Methylprednisolone (Medrol, etc.)
• Mometasone (Asmanex, etc.)
• Prednisolone (Prelone, etc.)
• Prednisone (Orasone, etc.)
• Triamcinolone (Aristocort, etc.)

PRECIPITANT DRUGS

Antimicrobials:

• Ciprofloxacin (Cipro, etc.)
• Clarithromycin (Biaxin, etc.)
• Erythromycin (E-Mycin, etc.)
• Fluconazole (Diflucan)
• Itraconazole (Sporanox, etc.)
• Ketoconazole (Nizoral, etc.)
• Posaconazole (Noxafil)
• Telithromycin (Ketek)
• Troleandomycin (TAO)
• Voriconazole (Vfend)

Comment:

Inhibition of CYP3A4 by these antimicrobials may result in substantial increases in the plasma concentrations of these corticosteroids. This can lead to Cushing's syndrome and adrenal suppression. Although inhaled budesonide or fluticasone are not intended to act systemically, numerous cases have been reported of Cushing's syndrome and adrenal insufficiency due to concurrent use of potent CYP3A4 inhibitors such as itraconazole and ritonavir.

Class 3: Assess Risk & Take Action if Necessary

• Consider Alternative:
• Corticosteroids: Clinical evidence suggests that prednisone and prednisolone are less affected by CYP3A4 inhibitors, but one should still be alert for evidence of corticosteroid toxicity. Theoretically, beclomethasone is unlikely to be affected by CYP3A4 inhibitors.
• Azole Antifungals: Itraconazole and ketoconazole are potent inhibitors of CYP3A4; fluconazole appears weaker, but in larger doses it also inhibits CYP3A4. Terbinafine (Lamisil) does not appear to affect CYP3A4, and would not be expected to interact with corticosteroids.
• Macrolide Antibiotics: Unlike erythromycin, clarithromycin and troleandomycin, azithromycin (Zithromax) and dirithromycin* do not appear to inhibit CYP3A4. (*not available in US)
• Telithromycin: The use of azithromycin (Zithromax) or a quinolone antibiotic other than ciprofloxacin should be considered.
• Monitor: If CYP3A4 inhibitors are used with dexamethasone or methylprednisolone, monitor for evidence of corticosteroid toxicity such as hypertension, edema, diabetes, poor wound healing, mood swings, muscle weakness, ocular toxicity, and Cushing's syndrome (moon face, central obesity, bruising, hirsutism, acne).