Rifabutin (Mycobutin)

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).

References

  1. Maslo C et al. Clinical and bacteriologic impact of rifabutin prophylaxis for Mycobacterium avium complex infection in patients with human immunodeficiency virus infection. Clin Infect Dis 24: 344-349, 1997
  2. Nightingale SD et al. Two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex infection in AIDS. N Engl J Med 329: 828-833, 1993
  3. Fichtenbaum C et al. Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection. AIDS 14: 2889-2893, 2000
  4. Shafran SD et al. Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. J Infect Dis 177: 252-255, 1998
  5. Frank MO et al. Rifabutin and uveitis. N Engl J Med 330: 868, 1994
  6. Kelleher P et al. Uveitis associated with rifabutin and macrolide therapy for Mycobacterium avium intracellulare infection in AIDS patients. Genitourin Med 72: 419-421, 1996
  7. Burman W et al. Use of antiretroviral therapy during treatment of active tuberculosis with a rifabutin-based regimen. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 136, 2003
  8. Agarwala S et al. Pharmacokinetic effect of rifabutin on atazanavir with and without ritonavir in healthy subjects. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 445-W, 2002
  9. Hamzeh FM et al. Steady-state pharmacokinetic interaction of modified-dose indinavir and rifabutin. Clin Pharmacol Ther 73: 159-169, 2003
  10. Cato A et al. The effect of multiple doses of ritonavir on the pharmacokinetics of rifabutin. Clin Pharmacol Ther 63: 414-421, 1998
  11. Bonora S et al. Pharmacokinetics (PKs) of rifabutin (RIF) coadministered with lopinavir / ritonavir (LPV / r) in HIV patients affected by tuberculosis (TB). Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 863, 2003
  12. Moyle G et al. Interaction between saquinavir soft-gel and rifabutin in patients infected with HIV. Br J Clin Pharmacol 54: 178-182, 2002
  13. Gallicano K et al. A pharmacokinetic study of intermittent rifabutin dosing with a combination of ritonavir and saquinavir in patients infected with human immunodeficiency virus. Clin Pharmacol Ther 70: 149-158, 2001
  14. Weiner M et al. Evaluation of the drug interaction between rifabutin and efavirenz in patients with HIV infection and tuberculosis. Clin Infect Dis 41: 1343-1349, 2005
  15. Maldonad S et al. Pharmacokinetic interaction between nevirapine and rifabutin. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract 341, 1999
  16. Marzolini C et al. Impaired absorption of rifabutin by concomitant administration of didanosine. AIDS 15: 2203-2204, 2001

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.