| Coadministered drugs | Effect on rifabutin | Effect on co-administered drug | Comments |
| ANTIVIRALS |
| Amprenavir
| 2.9-fold ↑ AUC, 2.2-fold ↑ Cmax
| No significant change in kinetics.
| A 50% reduction in the rifabutin dose is
recommended when combined with amprenavir. Increased monitoring for adverse reactions is warranted.
|
| Fosamprenavir/ritonavir
| 64% ↑ AUC **
| 35% ↑ AUC and 36% ↑ Cmax, no effect Ctrough (amprenavir)
| Dosage reduction of rifabutin by at least 75% (to 150 mg every other day or three times per week) is recommended when combined with fosamprenavir
|
| Indinavir
| 20% increase in AUC.
| 32% decrease in AUC.
| |
| Lopinavir/ritonavir
| 5.7-fold ↑ AUC, 3.4 fold ↑ Cmax**
| No significant change in lopinavir kinetics
| Dosage reduction of rifabutin by at least 75% of the usual dose of 300 mg/day is recommended (i.e., a maximum dose of 150 mg every other day or three times per week).
Increased monitoring for adverse reactions is warranted. Further dosage reduction of rifabutin may be necessary.
|
| Saquinavir
| No data.
| 40% decrease in AUC.
| |
| Ritonavir
| 4-fold increase in AUC, 2.5-fold increase in Cmax
| No data
| Due to this multifold increase in rifabutin concentrations and the subsequent risk of side effects, patients requiring both rifabutin and a protease inhibitor, other protease inhibitors should be considered.
|
| Tipranavir/ritonavir
| 2.9-fold ↑ AUC, 1.7-fold ↑ Cmax
| No significant change in tipranavir kinetics
| Therapeutic drug monitoring of rifabutin is recommended.
Coadministration of tipranavir with rifabutin may increase concentrations of rifabutin and its metabolite. Reduce rifabutin dose 75% (eg, 150 mg every other day) and increase monitoring |
| Zidovudine
| No significant change in kinetics
| Approx. 32% decrease in Cmax and AUC.
| A large clinical study has shown that these changes are of no clinical relevance.
|
| ANTIFUNGALS |
| Fluconazole
| 82% increase in AUC.
| No significant change in steady-state plasma concentrations
| |
| Itraconazole
| No data.
| 70-75% decrease in Cmax and AUC.
| A case report indicates an increase in rifabutin serum levels in the presence of itraconazole.
|
| Posaconazole
| 31%↑ Cmax, 72%↑ AUC
| 43% Cmax, 49% AUC
| Co-administration of posaconazole with rifabutin increases rifabutin plasma concentrations and decreases posaconazole plasma concentrations. Concomitant use of rifabutin and posaconazole should be avoided unless the benefit to the patient outweighs the risk. However, if concomitant administration is required, close monitoring of breakthrough fungal infections as well as frequent monitoring for adverse reactions due to increased rifabutin plasma concentrations (e.g., uveitis, leukopenia) are recommended.
|
| Voriconazole
| 195%↑ Cmax, 331%↑ AUC ***
| Rifabutin (300 mg once daily) decreased the Cmax and AUC of voriconazole at 200 mg twice daily by 69% and 78%, respectively.
During co-administration with rifabutin, the Cmax and AUC of voriconazole at 350 mg twice daily were 96% and 68% of the levels when administered alone at 200 mg twice daily. At a voriconazole dose of 400 mg twice daily Cmax and AUC were 104% and 87% higher, respectively, compared with voriconazole alone at 200 mg twice daily.
| If the benefit outweighs the risk, rifabutin may be coadministered with voriconazole if the maintenance dose of voriconazole is increased to 5 mg/kg intravenously every 12 hours or from 200 mg to 350 mg orally, every 12 hours (100 mg to 200 mg orally, every 12 hours in patients less than 40 kg). Careful monitoring of full blood counts and adverse events to rifabutin (e.g. uveitis) is recommended when rifabutin is coadministered with voriconazole
|
| Ketoconazole/miconazole
| No data.
| No data.
| Co-administered medications, sucha s ketoconazole, that competitively inhibit the Cyt P450IIIA activity may increase circulating drug levels of rifabutin.
|
| ANTI-PCP (Pneumocystis carinii pneumonia) |
| Dapsone
| No data.
| Approximately 27%-40% decrease in AUC.
| Study conducted in HIV infected patients (rapid and slow acetylators)
|
| Sulfamethoxazole-Trimethoprim
| No significant change in Cmax and AUC.
| Approx. 15-20% decrease in AUC.
| In another study, only trimethoprim (not sulfamethoxazole had 14% decrease in AUC and 6% in Cmax but were not considered clinically significant.
|
| ANTI-MAC (Mycobacterium avium intracellulare complex) |
| Azithromycin
| No PK interaction
| No PK interaction
| |
| Clarithromycin
| Approx. 77% increase in AUC.
| Approx. 50% decrease in AUC.
| Study conducted in HIV infected patients
|
| OTHER |
| Methadone
| No data.
| No significant effect.
| No apparent effect of rifabutin on either peak levels of methadone or systemic exposure based upon AUC. Rifabutin kinetics not evaluated.
|
| Oral contraceptives
| No data.
| No data.
| Contraceptive cover may not be adequate during concomitant therapy with rifabutin, therefore, patients should be advised to use other methods of contraception.
|
| Tacrolimus
| No data.
| No data.
| Rifabutin decreases tacrolimus trough blood levels.
|
