Tadalafil Ritonavir

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 medications - For patients taking concomitant potent inhibitors of CYP3A4 (eg, ketoconazole, ritonavir), the maximum recommended dose of tadalafil is 10 mg, not to exceed once every 72 hours. 

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. 

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 tadalafil, the US manufacturer advises that the dose should not exceed 10 mg every 72 hours in patients taking ritonavir, whereas the UK manufacturer advises caution on concurrent use. It is probably prudent to apply this advice to patients taking any protease inhibitor. 

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