Rifabutin Zidovudine

Already, the virion-associated reverse transcriptase has been highlighted as a target. The RT gene has been cloned, and the gene product can be produced in large quantities. Several molecules of very diverse molecular structure, such as zidovudine, suramin, and rifabutin, have been shown to cause inhibition of the... 

Drugs that may affect fluconazole include cimetidine, hydrochlorothiazide, and rifampin. Drugs that may be affected by fluconazole include alfentanil, benzodiazepines, buspirone, carbamazepine, cisapride, oral contraceptives, corticosteroids, cyclosporine, haloperidol, HMG-CoA reductase inhibitors, losartan, nisoldipine, phenytoin, protease inhibitors, rifabutin, sirolimus, sulfonylureas, tacrolimus, theophylline, tolterodine, tricyclic antidepressants, vinca alkaloids, warfarin, zidovudine, and zolpidem. 

Drugs that may affect nelfinavir include anticonvulsants, azithromycin, azole antifungals, efavirenz, delavirdine, HMG-CoA reductase inhibitors, indinavir, interleukins, nevirapine, rifabutin, rifampin, ritonavir, saquinavir, St. John s wort. Drugs that may be affected by nelfinavir include amiodarone, antiarrhythmics (amiodarone, quinidine), azithromycin, benzodiazepines, efavirenz, ergot alkaloids, delavirdine, didanosine, fentanyl, indinavir, lamivudine methadone, nonsedating antihistamines, oral contraceptives, phenytoin, pimozide, quinidine, rifabutin, saquinavir, sildenafil, sirolimus, tacrolimus, zidovudine. 

Drugs that might be affected by amprenavir include antiarrhythmics, anticonvulsants, azole antifungals, benzodiazepines, calcium channel blockers, cisapride, clarithromycin, cyclosporine, ergot alkaloids, fentanyl, HMG-CoA reductase inhibitors, indinavir, methadone, nelfinavir, oral contraceptives, pimozide, rifabutin, ritonavir, saquinavir, sildenafil, tacrolimus, trazodone, tricyclic antidepressants, warfarin, and zidovudine. 

Fluconazole, probenecid and atovaquone increase the risk of myelotoxicity by zidovudine. This may be attributed to an increased plasma concentration of zidovudine in the presence of these drugs, perhaps through their inhibitory effects on glucuronose transferase. Rifabutin and rifampin decrease plasma concentrations, and clarithromycin decreases the absorption of zidovudine. Zidovudine and stavu-dine should not be used in combination because they compete for intracellular phosphorylation. 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

Clinically important, potentially hazardous interactions with abacavir, atorvastatin, bepridil, bupropion, carbamazepine, clarithromycin, cyclosporine, dexamethasone, digoxin, felodipine, fluticasone propionate, fosamprenavir, itraconazole, ketoconazole, lovastatin, methadone, midazolam, nicardipine, nifedipine, phenobarbital, phenytoin, rifabutin, simvastatin, sirolimus, St John s wort, systemic lidocaine, tacrolimus, tenofovir, trazodone, vinblastine, vincristine, voriconazole, warfarin, zidovudine... 

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. 

Ritonavir exhibits additive to synergistic effects against HIV when used in combination with reverse-transcriptase inhibitors such as zidovudine or zalcitabine. Ritonavir pro-dnces a large increase in the plasma concentration of amio-darone, astemizole, bepridil, bupropion, cisapride, clozapine, encainide, flecainide, meperidine, peroxicam, propafenone, propoxyphene, quinidine, rifabutin, and terfenadine. 

Items 6-7 A patient with AIDS has a CD4 count of 45/ xL. He is being maintained on a three-drug regimen of indinavir, zalcitabine, and zidovudine. For prophylaxis against opportunistic infections, he is also receiving cidofovir, fluconazole, rifabutin, and trimethoprim-sulfamethoxazole. 

Items 92-93. A 30-year-old hospitalized AIDS patient has a CD4 cell count of 50/ tL. He is being treated with a highly active antiretroviral therapy (HAART) regimen consisting of zidovudine (ZDV), lamivudine (3TC), and indinavir. Other drugs being administered to this patient include acyclovir, clarithromycin, foscamet, rifabutin, and trimethoprim-sulfamethoxazole. 

Didanosine, stavudine and zalcitabine are not expected to interact with rifabutin, but rifabutin may modestly increase the clearance of zidovudine. An isolated case describes undetectable rifabutin levels in a patient taking antiretrovirals including buffered didanosine. 

The pharmacokinetics of rifabutin are not affected by the concurrent use of zidovudine in AIDS patients, " and rifabutin does not affect the pharmacokinetics of zidovudine in HIV-positive patients, although one review found a trend towards increased zidovudine clearance. No increase in adverse effects appears to occur when rifabutin is given with zidovudine."... 

In a retrospective study of healthy subjects and HIV-positive individuals, the clearance of zidovudine was increased by 132% by rifampicin and by 50% by rifabutin, suggesting that the enzyme-inducing effects of rifabutin are less than those of rifampicin, so less significant interactions would be expected. ... 

Narang PK, Nightingale S, Lewis RC, Colbom D, W) e B, Li R Concomitant zidovudine (ZDV) dosing does not affect rifabutin (RIF) disposition in AIDS patients. 9 International Conference AIDS 4 STD World Congress, Berlin, June 6-11,1993. Abstiact PO-B31-... 

LiRC,Nightii ale S, Lewis RC, Colburn DC, NarangPK. Lack of effect of concanitant zidovudine on rifabutin kinetics in patients with AIDS-related ccmplex. Antmncrob Agents... 

Narang PK, Sale M. Population based assessment of rifabutin (R) effect on zidovudine (ZDV) disposition in AIDS patients. Clin Pharmacol Ther 99 S) 53,219. 

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