Tadalafil Ketoconazole

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... 

Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20-mg single-dose exposure (AUC) by 312%. Other CYP inhibitors—Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Ketoconazole and itraconazole markedly raise the levels of sildenafil, tadalafil and vardenafil. 

In an open label, randomised study in 12 healthy subjects, ketoconazole 200 mg daily increased the AUC of a single 10-mg dose of tadalafil by twofold, and ketoconazole 400 mg daily increased the AUC fourfold. The manufacturers predict that itraconazole will interact similarly. This prediction has been borne out by a case report of a 56-year-old man who was taking itraconazole 400 mg daily for 7 days each month. Within a few hours of his first 10-mg dose of tadalafil he developed priapism, which lasted for more than 4 hours. The same reaction occurred when he took tadalafil during the following month. He had seemingly previously taken sildenafil with itraconazole without adverse effect. ... 

Sildenafil, tadalafil and vardenafil are all metabolised by the cytochrome P450 isoenzyme CYP3A4. Ketoconazole and itraconazole are potent inhibitors of CYP3A4, and therefore inhibit sildenafil, tadalafil and vardenafil metabolism, which leads to an increase in their levels. 

For tadalafil, the UK manufacturer advises caution and the US manufacturer advises that the dose of tadalafil should not exceed 10 mg in a 72-hour period for patients taking potent CYP3A4 inhibitors such as ketoconazole. However, note that this dose has caused priapism in one patient taking itraconazole. 

Although the manufacturer of vardenafii does not mention CYP3A4 inducers, like tadalafil and sildenafil, vardenafii is principally metabolised by CYP3A4, and its levels are markedly raised by CYP3A4 inhibitors such as ketoconazole , (p. 1270). It is therefore very likely that vardenafii levels will be reduced by rifampicin and similar drugs, and concurrent use should be monitored. 

Ketoconazole , (p.l270), doubles tadalafil levels. The manufacturers therefore predict that other CYP3A4 inhibitors such as erythromycin will interact similarly. 

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