Azoles Astemizole

Azole anti fungal s Arrhythmias with astemizole... 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

The azole antifungals raise the levels of astemizole and terfena-dine, which can result in life-threatening arrhythmias. Arrhythmias have been reported for astemizole with ketoconazole, and terfenadine with itraconazole, ketoconazole, and even topical ox-iconazole. Consequently all azoles are contraindicated with astemizole and terfenadine. 

The interactions of astemizole with ketoconazole, and terfenadine with itraconazole or ketoconazole are established and clinically important, although much of the evidence for them is indirect. Astemizole would also be expected to interact similarly with itraconazole. The risk of an interaction with terfenadine or astemizole and other azole antifungals seems smaller. 

The incidence of an interaction is probably low, but because of the potential severity and unpredictability of this interaction, the concurrent use of astemizole and terfenadine is contraindicated with all azole antifungals... 

Protease inhibitors are inhibitors of the cytochrome P450 isoenzyme CYP3A4, by which astemizole is metabolised. On the basis of the interaction of astemizole with other CYP3A4 inhibitors, such as the azoles , (p.584), the concurrent use of astemizole with any protease inhibitor is contraindicated. This seems a sensible precaution. 

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