Rifabutin with nelfinavir

The most common adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea often responds to antidiarrheal medications but can be dose-limiting. Nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur (Tables 49-3 and 49-4). An increased dosage of nelfinavir is recommended when co-administered with rifabutin (with a decreased dose of rifabutin), whereas a decrease in saquinavir dose is suggested with concurrent nelfinavir. Co-administration with efavirenz should be avoided due to decreased indinavir levels. Nelfinavir has a favorable safety and pharmacokinetic profile for pregnant women compared with that of other Pis (Table 49-5) there is no evidence of human teratogenicity. 

Rifabutin bioavailability is increased by amprenavir, atazanavir, fosamprenavir/ritonavir, indinavir, lopinavir/ritonavir, nelfinavir, tipranavir/ritonavir, and especially ritonavir, with an increased risk of toxicity. Rifabutin modestiy decreases the bioavailability of indinavir, neifinavir, and particuiarly saquinavir (with an increased risk of therapeutic faiiure), but has no effect on amprenavir, atazanavir, and ritonavir-boosted fosamprenavir. The combination of rifabutin with protease inhibitors may be used, but dosage adjustments of rifabutin or both drugs are often necessary. 

Rifampin Daily for 4 months For persons who are contacts of patients with isoniazid-resistant rifampin susceptible TB. In HIV-infected patients, protease inhibitors or NNRTIs generally should not be administered concurrently with rifampin rifabutin can be used as an alternative for patients treated with indinavir, nelfinavir, amprenivir, ritonavir, orefavirenz, and possibly with nevirapine or soft-gel saquinavir5 B (II) B (III)... 

Drugs that may interact with rifabutin include the following Anticoagulants, azole antifungal agents, benzodiazepines, beta blockers, buspirone, corticosteroids, cyclosporine, delavirdine, doxycycline, hydantoins, indinavir, rifamycins, losartan, macrolide antibiotics, methadone, morphine, nelfinavir, quinine, quinidine, theophylline, aminophylline, tricyclic antidepressants, and zolpidem. 

RIFABUTIN PROTEASE INHIBITORS t efficacy and t adverse effects of rifabutin Inhibition of CYP3A4-mediated metabolism. Nelfinavir also competitively inhibits 2C19 1 rifabutin dose by at least 50% when given with amprenavir, indinavir or nelfinavir, and by 75% with atazanavir, ritonavir (with or without lopinavir) or tipranavir... 

The use of rifampicin with the protease inhibitors indinavir, nelfinavir, and amprenavir is contraindicated. However, these agents can be used with rifabutin after appropriate dosage reduction. Failure to reduce the dosage of rifabutin can result in toxic manifestations, such arthralgia and uveitis. 

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, ritonavir, saquinavir, St John s wort, troleandomycin, voriconazole, warfarin... 

Clinically important, potentially hazardous interactions with aminophylline, anticonvulsants, aprepitant, bedomethasone, bosentan, budesonide, cigarette smoking, danazol, efavirenz, exenatide, flucloxacillin, flunisolide, fluticasone, hydrocortisone, insulin detemir, lamotrigine, licorice, lymecycline, methylprednisolone, modafinil, nelfinavir, prednisolone, prednisone, rifabutin, rifampin, ritonavir, saw palmetto, selegiline, St John s wort, triamcinolone, troleandomycin, tuberculostatics, ursodeoxycholic acid, zolmitriptan... 

Rifabutin is effective for the prevention of MAC infection in HIV-infected individuals. At a dose of 3(X) mg per day, rifabutin decreased the frequency of MAC bacteremia (2%). However, azithromycin or clarithromycin are more effective and less likely to interact with highly active antiretroviral therapy (HAART) drugs. Rifabutin also is commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients, as it has a less profound CYP-dependent interaction with indinavir and nelfinavir. Rifabutin also is used in combination with clarithromycin and ethambutol for the therapy of MAC disease. 

Although a less potent inducer of CYPs than rifampin, rifabutin does induce hepatic microsomal enzymes, with its administration decreasing the half-life of a number of different compounds, including zidovudine, prednisone, digi-toxin, quinidine, ketoconazole, propranolol, phenytoin, sulfonylureas, and warfarin. It has less effect than does rifampin on serum levels of indinavir and nelfinavir. 

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