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Transcript
RIFABUTIN
Usual Dose
Adult (150 mg capsules): Prophylaxis 300 mg Q24H PO (UWHC cost/day $22.07).
Treatment 150-450 mg Q24H PO (UWHC cost/day $11.03-33.10).
Indications
1. Mycobacterium avium complex
a. prophylaxis in AIDS patients with CD4 cell counts <100 cells/mm3. Third-line after azithromycin and
clarithromycin due to potential for multiple drug interactions.
b. treatment – as part of a multi-drug regimen
2. Mycobacterium tuberculosis in HIV infected individuals who require protease inhibitor or non-nucleoside reverse
transcriptase inhibitor therapy.
Comments
Side effects similar in type and incidence to rifampin. Side effects are less with the doses used for prophylaxis. Uveitis has
been reported in patients receiving rifabutin therapy (600 mg/day, NEJM 1994;330:438-9). Although prophylaxis reduces
the incidence of MAC infections, its use has not been associated with prolonged survival. In HIV- positive patients
requiring tuberculosis and antiretroviral therapy, consult Infectious Diseases for dose adjustments. Use as single agent
may lead to rifabutin/rifampin resistance.
Drug Interactions
Rifabutin, like all rifamycins, induces cytochrome P450 enzymes in the liver and uridine 5-diphosphate transferases.
However, its effects are not as potent as rifampin, and interacting drugs may be stronger inhibitors, resulting in increases
in rifabutin blood levels and potentially increasing its toxicity. With some drugs, both effects may be seen. The following
drugs have blood levels reduced by rifabutin as a result of induction of metabolic enzymes:
• Atovaquone
• Indinavir
• Romidepsin
• Clarithromycin
• Irinotecan (& active metabolite)
• Saquinavir
• Cyclosporine
• Itraconazole
• Sirolimus
• Dapsone
• Ixabepilone
• Sunitinib
• Dasatanib
• Lapatinib
• Tacrolimus
• Delavirdine
• Maraviroc
• Temsirolimus (↓ levels of active metabolite)
• Efavirenz
• Nelfinavir
• Tolvaptan
• Erlotinib
• Nilotinib
• Trimetrexate
• Etravirine
• Oral Contraceptives
• Voriconazole*
• Everolimus
• Posaconazole
• Warfarin
• Imatinib
• Ranolazine*
• Zidovudine
* - indicates drug is contraindicated to administer concurrently with rifabutin
The following drugs may increase blood levels of rifabutin and also increase the risk of rifabutin toxicity:
• Amprenavir/Fosamprenavir
• Didanosine (buffered powder)
• Nevirapine
• Atazanavir
• Fluconazole
• Posaconazole
• Azithromycin
• Fosamprenavir
• Ritonavir
• Clarithromycin
• Indinavir
• Tipranivir
• Darunavir
• Lopinavir
• Voriconazole*
• Delavirdine
• Nelfinavir
• - indicates drug is contraindicated to administer concurrently with rifabutin
Rifabutin also interacts with sulfamethoxazole to increase exposure to the toxic sulfamethoxazole hydroxylamine
metabolite, increasing the risk of rash, thrombocytopenia, leukopenia and liver enzyme increases.