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
Enzyme Inhibitors:
- Amiodarone (Cordarone, etc.)
- Amprenavir (Agenerase)
- Aprepitant (Emend)
- Atazanavir (Reyataz)
- Boceprevir (Victrelis)
- Ceritinib (Zykadia)
- Cobicistat (Stribild)
- Conivaptan (Vaprisol)
- Cyclosporine (Neoral, etc.)
- Darunavir (Prezista)
- Delavirdine (Rescriptor)
- Diltiazem (Cardizem, etc.)
- Dronedarone (Multaq)
- Grapefruit
- Imatinib (Gleevec)
- Indinavir (Crixivan)
- Lapatinib (Tykerb)
- Lomitapide (Juxtapid)
- Mifepristone (Korlym)
- Nelfinavir (Viracept)
- Ritonavir (Norvir)
- Saquinavir (Invirase)
- Telaprevir (Incivek)
- Verapamil (Isoptin, etc.)
Comment:
Inhibition of CYP3A4 may result in substantial increases in the plasma concentrations of these corticosteroids, even when the corticosteroids are given nasally or by inhalation. This can lead to Cushing's syndrome and adrenal suppression. For example, ritonavir was found to dramatically increase plasma fluticasone concentrations, accompanied by marked suppression of endogenous cortisol production. Although inhaled budesonide or fluticasone are not intended to act systemically, numerous cases have appeared of Cushing's syndrome and adrenal insufficiency due to concurrent use of a potent CYP3A4 inhibitor.
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.
- Calcium channel blockers: Calcium channel blockers other than diltiazem and verapamil are unlikely to inhibit CYP3A4.
- Grapefruit Orange juice does not appear to inhibit CYP3A4.
- Monitor: If CYP3A4 inhibitors are used with these corticosteroids, monitor for evidence of corticosteroid toxicity such as hypertension, edema, diabetes, poor wound healing, mood swings, muscle weakness, myopathy, ocular toxicity, and Cushing's syndrome (moon face, central obesity, bruising, hirsutism, acne).