Protease inhibitors 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-... 

PROTEASE INHIBITORS ANTIHISTAMINES-ASTEMIZOLE, CHLORPHENAMINE, TERFENADINE Possibly t adverse effects with amprenavir, atazanavir, indinavir, ritonavir (with or without lopinavir), saquinavir and tipranavir Inhibition of CYP3A4-mediated metabolism of astemizole the risk is greatest in patients who are slow CYP2D6 metabolizers because chlorphenamine and terfenadine are also metabolized by this route Avoid co-administration... 

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... 

Nelflnavir markedly increases terfenadine levels, which is expected to increase the risk of QT prolongation and torsade de pointes arrhythmias. Other protease inhibitors are predicted to interact similarly with both terfenadine and astemizole, and concurrent use Is contraindicated. Ritonavir modestly increases cetirizine levels, and in vitro data suggests that saquinavir will have a similar effect, but this Is not considered to be clinically relevant. Based on in vitro data, ritonavir is predicted to markedly raise fexofenadine levels, but this may not be of any clinical relevance. 

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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