Indinavir Vardenafil

Sildenafil doses should be decreased when any potent cytochrome P450 3A4 inhibitor is used (e g., cimetidine, erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir, and saquinavir). Vardenafil doses vary accordingto which agent is used (2.5 mg q 72 h for ritonavir, 2.5 mg q 24 h for indinavir, ketoconazole 400 mg daily, and itraconazole 400 mg daily and 5 mg q 24 h for ketoconazole 200 mg daily, itraconazole200 mg daily, and erythromycin). Tadalafil doses are reduced only when it is used with the most potent cytochrome P450 3A4 inhibitors (e g., ketoconazole or ritonavir). 

Concomitant mecf/caf/ons - The dosage of vardenafil may require adjustment in patients receiving certain CYP3A4 inhibitors. For ritonavir, do not exceed a single dose of 2.5 mg vardenafil in a 72-hour period. For indinavir, ketoconazole 400 mg/day, and itraconazole 400 mg/day, do not exceed a single dose of 2.5 mg vardenafil in a 24-hour period. For ketoconazole 200 mg/day, itraconazole 200 mg/day, and erythromycin, do not exceed a single dose of 5 mg vardenafil in a 24-hour period. 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Indinavir, saquinavir and ritonavir can cause marked rises in serum sildenafil levels. A fatal heart attack occurred in a man taking ritonavir and saquinavir when he also took sildenafil Similar marked interactions occur between vardenafil and indinavir or ritonavir, and are predicted to occur between vardenafil and the other protease inhibitors. Ritonavir caused less marked increases in tadalafil levels. 

When a single 10-mg dose of vardenafil was given with indinavir 800 mg three times daily, the AUC of vardenafil was inereased 16-fold, and the maximum plasma level was inereased sevenfold. Moreover, ritonavir 600 mg twice daily produced a 49-fold increase in the AUC of vardenafil, and prolonged the half-life to 26 hours. ... 

Protease inhibitors inhibit the aetivity of the cytochrome P450 isoenzyme CYP3A4, the enzyme that metabolises silden l, tadalafil and vardenafil. This results in an increase in their serum levels. Ritonavir is the most potent CYP3A4 inhibitor, followed by indinavir, nelfinavir, amprenavir, and then saquinavir, see Antivirals , (p.772)). 

For vardenafil, due to the very large rises in levels, the UK manufaeturer contraindicates its use with protease inhibitors that are potent CYP3A4 inhibitors (they name ritonavir and indinavir). In contrast, the US preserib-ing information recommends dose restrictions as follows the dose of vardenafil should not exceed 2.5 mg in 24 hours when used with atazana-vir, indinavir, or saquinavir, and should not exeeed 2.5 mg in 72 hours when used with ritonavir. ... 

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