Ketoconazole Darunavir

Darunavir (TMC114) Prezista 300 mg tablet Dexamethasone, erythromycins, voriconazole, itrraconazole, ketoconazole, aspirin, fluconazole, NSAIDS, diclofenac topical... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

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... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, clindamycin, darunavir, dasatinib, dihydroergotamine, eplerenone, ergot derivatives, fentanyl, garlic, ixabepilone, ketoconazole, lapatinib, methysergide, midazolam, phenytoin, pimozide, rifampin, ritonavir, sildenafil, solifenacin, St John s wort, temsirolimus, tolvaptan... 

Clinically important, potentially hazardous interactions with atazanavir, clarithromycin, darunavir, delavirdine, efavirenz, erythromycin, fosamprenavir, indinavir, itraconazole, ketoconazole, rifampin, ritonavir, telithromycin, tipranavir... 

Pharmacokinetic changes have been seen with the concurrent use of ketoconazole and darunavir/ritonavir the darunavir AUC was raised by 42% and the ketoconazole AUC was increased about threefold. ... 

The data on the effect of protease inhibitors on ketoconazole are more limited. Amprenavir caused a modest increase in ketoconazole levels, and the UK manufacturer of amprenavir suggests that no ketoeonazole dose adjustment is necessary with amprenavir alone, although the US manufacturer recommends increased monitoring for adverse effeets and states that a dose reduction may be needed in patients receiving ketoconazole in doses of more than 400 mg daily. However, a marked effect was seen for ritonavir alone and for ritonavir combined with darunavir, fosamprenavir, lopinavir, saquinavir and theoretically tipranavir. This may increase the adverse effects of ketoconazole. Most protease inhibitor manufacturers say that doses greater than 200 mg a day of ketoconazole are not recommended. Similarly, the UK manufacturers of ketoconazole and ritonavir say that a dose reduction of ketoconazole should be considered when it is given with ritonavir. ... 

Darunavir The interaction of ketoconazole with darunavir alone and in combination with low-dose ritonavir has been investigated in HIV-negative volunteers, who took ketoconazole 200 mg bd, darunavir 400 mg bd, darunavir 400 mg bd plus ketoconazole 200 mg bd, darunavir + ritonavir 400/ 100 mg bd, or darunavir + ritonavir 400/ 100 mg bd plus ketoconazole 200 mg bd all the treatments were taken with food for 6 days [3P]. Ketoconazole increased the AUCo uh Cmax tmd C in of darunavir by 155% (80, 261), 78% (28, 147), and 179% (58, 393) respectively. Darunavir AUCo uh... 

Cmcm Cmin increased by 42% (23, 65), 21% (4, 40), and 73% (39, 114) respectively during darunavir + ritonavir and keto-conazole co-administration. Ketoconazole pharmacokinetics were unchanged by coadministration of darunavir alone. Ketoconazole AUCq—,22h> max, and Cnun increased by 212% (165, 268), 111% (81,144), and 868% (544,1355) respectively during co-administration of darunavir + ritonavir. The increase in darunavir exposure by ketoconazole was lower than that observed previously with ritonavir. A maximum ketoconazole dose of 200 mg/day is recommended if it is used concomitantly with darunavir + ritonavir, and no dose adjustments of darunavir + ritonavir is required. 

Sekar VJ, Lefebvre E, De Pauw M, Vangeneugden T, Hoetelmans RM. Pharmacokinetics of darunavir/ritonavir and ketoconazole following co-administration in HIV-healthy volunteers. Br J Clin Pharmacol 2008 66 215-21. 

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