Rifabutin (Mycobutin) is an antibiotic drug used for the treatment and prevention of Mycobacterium avium intracellulare (MAI) and tuberculosis. It is manufactured by Pfizer.
Rifabutin is an approved drug in the United States for the prevention of MAI in HIV-positive people with CD4 cell counts below 50 cells/mm3. Clinical trials have shown that it reduces the number of MAI organisms detectable in the blood, delay the onset of symptoms and prolong survival.1 2
Rifabutin may also be used as part of combination to prevent the reactivation of latent tuberculosis in HIV-positive people. Those with CD4 cell counts below 100 cells/mm3 who are taking rifabutin as part of the continuation phase of tuberculosis treatment should dose rifabutin daily or three times a week to reduce the risk of drug resistance.
Rifabutin may also be an effective preventive treatment for cryptosporidiosis in patients with CD4 cell counts below 100 cells/mm3.3
Rifabutin prophylaxis is not standard practice in the United Kingdom. Some centres routinely encourage people with CD4 cell counts below 50 copies/mm3 to take it, while others are less enthusiastic because the evidence about its efficacy is inconclusive and because they have concerns that drug-resistant strains of MAI or tuberculosis might develop.
Rifabutin may also be used in combination as part of treatment regimens for MAI and tuberculosis. As a treatment for tuberculosis, rifabutin is an alternative to rifampicin (Rifadin / Rimactane), which has substantial drug interactions with anti-HIV drugs. It is also being used in the treatment of multi-drug resistant tuberculosis.
Side-effects of rifabutin can include rash, fever, nausea, low white blood cell and platelet counts and liver inflammation. There have also been reports of eye problems among people receiving rifabutin, which usually resolve if the rifabutin dose is reduced and inflammation is reduced using steroids.4 5 6 People taking rifabutin should contact a doctor or an ophthalmologist if they notice any change in vision, blurring or discomfort in bright light, floating spots in the line of sight or redness or pain in the eye.
Taking antiretroviral therapy and rifabutin is safe, but involves a number of drug interactions since rifabutin is broken down by the CYP3A4 enzyme.7 The following dose adjustments are necessary:
- Atazanavir (Reyataz): a reduced daily dose of 150mg rifabutin or the standard 300mg dose twice a week should be used.8
- Fosamprenavir (Telzir): the dose of rifabutin should be halved when unboosted fosamprenavir is used. If ritonavir (Norvir)-boosted fosamprenavir is being used, patients should take the standard 300mg dose but only every two to three days.
- Indinavir (Crixivan): 1000mg every eight hours with a reduced daily dose of 150mg rifabutin or the standard 300mg dose twice a week.9
- Nelfinavir (Viracept): a reduced daily dose of 150mg rifabutin is recommended.
- Full-dose ritonavir: United States authorities recommend 500mg ritonavir twice daily with a reduced daily dose of 150mg rifabutin or the standard 300mg dose twice a week. However, European regulators recommend that rifabutin not be taken by patients taking full-dose ritonavir.10
- Ritonavir as a ‘booster’ of other protease inhibitors should be used with a reduced daily dose of 150mg rifabutin or the standard 300mg dose twice a week.
- Ritonavir-boosted lopinavir (Kaletra): a reduced dose of 150mg rifabutin once a day should be used.11
- Saquinavir (Invirase) should not be taken with rifabutin unless boosted with low-dose ritonavir.12 Rifabutin dosage should be reduced to 150mg two to three times a week if taken concurrently with ritonavir-boosted saquinavir.13
- Tipranavir (Aptivus): a reduced daily dose of 150mg rifabutin or the standard 300mg dose twice a week should be used.
- Efavirenz (Sustiva): an increased dose of 450 or 600mg rifabutin a day or 600mg twice a week.14 No dose adjustment is required for nevirapine (Viramune).15
The nucleoside reverse transcriptase inhibitors (NRTIs) do not have any significant drug interactions with rifabutin. However, the tablet version of ddI (didanosine, Videx), which includes an antacid buffer, may reduce absorption of rifabutin.16
Other drugs known to interact with rifabutin include oral contraceptives, warfarin, dapsone, phenytoin, methadone hydrochloride (Methadose), fluconazole (Diflucan), clarithromycin (Clarosip / Klaricid / Klaricid XL) and itraconazole (Sporanox).