Rifabutin Azithromycin

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. 

A triple therapy regimen with combinations of clarithromycin or azithromycin plus ethambutol plus rifabutin is the current standard of care. However rifabutin may be omitted in HIV-infected patients on protease inhibitors because of significant interactions (Table 19). 

M avium complex Pulmonary disease in patients with chronic lung disease disseminated infection in AIDS Amikacin, azithromycin, clarithromycin, ciprofloxacin, ethambutol, rifabutin... 

Mycobacterium avium complex HIV-infected patients with CD4 count < 75/14. Azithromycin, clarithromycin, or rifabutin Excellent... 

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. 

The effects of combining azithromycin and rifabutin have been studied in 50 subjects with or without HIV infection, of whom 19 took azithromycin 1200 mg/day and rifabutin 600 mg/day, and 31 took azithromycin 600 mg/day and rifabutin 300 mg/day (28). Neutropenia was the most common adverse event, in 33 of 50 subjects. Low-grade nausea, diarrhea, fatigue, and headache were also common, and most subjects had more than one type of event. There was no significant pharmacokinetic interaction between the two drugs. 

An interaction involving azithromycin with rifabutin, and less commonly rifampicin, was observed in patients with MAC infections (51). 

Hafner R, Bethel J, Standiford HC, Follansbee S, Cohn DL, Polk RE, Mole L, Raasch R, Kumar P, Mushatt D, Drusano G DATRI (X)1B Study Group. Tolerance and pharmacokinetic interactions of rifabutin and azithromycin. Antimicrob Agents Chemother 2001 45(5) 1572-7. 

Of 26 patients who received rifabutin 600 mg/day in combination with ethambutol, streptomycin, and either clarithromycin (500 mg bd n — 15) or azithromycin (600 mg/day n — 11), there were rifabutin-related... 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Unfortunately, MAC is resistant to the standard drugs used for tuberculosis, such as isoniazid and pyrazinamide. Multiple agents such as rifampin, rifabutin (ansamycin), clofazimine, imipenem, amikacin, ethambutol, ciprofloxacin, clarithromycin, and azithromycin have varying degrees of in vitro anti-MAC activity. Controversy formerly existed as to whether treatment for MAC is beneficial, but data indicate that an aggressive therapeutic approach decreases symptoms... 

MAC prophylaxis is now strongly recommended for all HIV-infected adults and adolescents with CD4 counts of fewer than 50 cells/mcL. The first-line choices are either azithromycin (1200 mg once weekly) or clarithromycin (500 mg twice daily) rifabutin is an alternative. Persons considered for prophylaxis should be evaluated to be sure that they do not have active disease owing to MAC or M. tuberculosis. 

Havlir D, Dube M, Sattler F, et al. Prophylaxis against disseminated Mycobacterium avium complex with weekly azithromycin, daily rifabutin, or both. N Engl J Med 1996 335 392-398. 

Clarithromycin or azithromycin is recommended as first-line therapy for prophylaxis and treatment of disseminated infection caused by M. avium-intracellulare in AIDS patients and for treatment of pulmonary disease in non-HIV-infected patients. Azithromycin (1.2 g once weekly) or clarithromycin (500 mg twice daily) is recommended for primary prevention for AIDS patients with fewer than 50 CD cells per mm. Single-agent therapy should not be used for treatment of active disease or for secondary prevention in AIDS patients. Clarithromycin (500 mg twice daily) plus ethambutol (15 mg/kg once daily) with or without rifabutin is an effective combination regimen. Azithromycin (500 mg once daily) may be used instead of clarithromycin, but clarithromycin appears to be slightly more efficacious. Clarithromycin also has been used with minocychne for the treatment of Mycobacterium leprae in lepromatous leprosy. 

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. 

Clarithromycin has been shown to be an effective prophylactic agent against MAC infection in patients with advanced HIV infection. In a prospective, doubleblind, placebo-controlled trial, clarithromycin prevented 69% of the expected cases of MAC disease [64]. Other studies have demonstrated that clarithromycin alone or in combination with rifabutin prevents MAC infections in AIDS patients and prolongs survival [65, 66]. However, a large prospective study failed to show that the combination of clarithromycin plus rifabutin combination was more effective than clarithromycin alone [67]. Drug-resistant MAC has been reported in 29-58% of patients who developed disseminated infection while taking prophylaxis with clarithromycin [64, 67]. Resistance to clarithromycin and other macrolides is a serious potential problem due to cross-resistance with azithromycin that narrows the therapeutic options available for MAC disease [68]. 

M. avium complex Clarithromycin or azithromycin -1- ethambutol with or without rifabutin Rifabutin rifampin ethionamide cycloserine moxifloxacin or gatifloxacin... 

Clarithromycin (500 mg twice daily) or azithromycin (500 mg daily) is used in combination with ethambutol, with or without rifabutin, for treatment of MAC infection. Treatment should be lifelong in HIV-infected individuals. Azithromycin has minimal effect on drugs metabolized by CYP3A4. 

M avium complex (MAC) is a cause of disseminated infections in AIDS patients. Currently, clarithromycin or azithromycin is recommended for prophylaxis in patients with CD4 counts less than 50/ xL. Treatment of MAC infections requires a combination of drugs, one favored regimen consisting of azithromycin or clarithromycin with ethambutol and rifabutin, a congener of rifampin. 

Drugs for M avium complex A combination of azithromycin or clarithromycin with ethambutol, with or without rifabutin, is favored. 

MAC is much less susceptible than M tuberculosis to conventional antimycobacterial drugs. Both isoniazid and pyrazinamide have minimal activity against MAC. Currently, the optimum regimen consists of clarithromycin for azithromycin) with ethambutol and rifabutin. The answer is (D). 

Rifabutin and azithromycin seem not to affect the serum levels of each other, but a very high incidence of neutropenia was seen in one study of the combination. Both rifabutin and rifampicin markedly reduce the serum levels of clarithromycin. Clarithromycin increases the serum levels of rifabutin and the combination is associated with an increased risk of uveitis and neutropenia. Rifampicin (rifampin) greatly reduces telithromycin levels and concurrent use is not recommended. 

Uveitis did not develop in 8 patients taking rifabutin and azithromycin 500 mg daily, although cases of uveitis have been reported in patients taking rifabutin, fluconazole, and azithromycin 1.2 g weekly but they have been attributed to an interaction between rifabutin and fluconazole. See Azoles -i- Rifabutin , p.219. 

Information regarding neutropenia with maerolides and rifamycins is very limited but what is known suggests that white cell counts should be monitored closely if rifabutin is given with azithromycin or clarithromycin. Rifabutin is known to cause polyarthritis on rare occasions, but in conjunction with clarithromycin it appears to happen at much lower doses. Careful monitoring is necessary. 

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