Rifabutin dosing

Rifabutin Dose reduction of rifabutin to half the standard dose and a dose increase of indinavir to 1000 mg (three 333 mg capsules) every 8 hours are recommended when rifabutin and indinavir are coadministered. 

RIFABUTIN EFAVIRENZ Possible 1 efficacy of rifabutin i bioavailability t rifabutin dose by 50% for daily treatment, or double the dose if the patient is on treatment two or three times a week... 

RIFABUTIN PROTEASE INHIBITORS t efficacy and t adverse effects of rifabutin Inhibition of CYP3A4-mediated metabolism. Nelfinavir also competitively inhibits 2C19 1 rifabutin dose by at least 50% when given with amprenavir, indinavir or nelfinavir, and by 75% with atazanavir, ritonavir (with or without lopinavir) or tipranavir... 

UNTOWARD EFFECTS Rifabutin generally is well tolerated in persons with HIV infection primary reasons for discontinuation of therapy include rash (4%), GI intolerance (3%), and neutropenia (2%). Overall, neutropenia occurred in 25% of patients with severe HIV infection who received rifabutin. Uveitis and arthralgias have occurred in patients receiving rifabutin doses >450 mg daily in combination with clarithromycin or fluconazole. Patients should be cautioned to discontinue the drug if visual symptoms occur. Like rifampin, the drug causes an orange-tan discoloration. Rarely, thrombocytopenia, a flu-like syndrome, hemolysis, myositis, chest pain, and hepatitis have occurred. 

The manufacturer of ketoconazole suggests that the levels of both drugs may be affected if rifabutin is also taken. They suggest that the rifabutin dose may need to be reduced. ... 

The CDC in the US state that the combination is probably clinically useful, and they suggest increasing the dose of rifabutin to 450 mg or 600 mg daily, or 600 mg two to three times weekly. In one study doubling the rifabutin dose from 300 mg twice weekly to 600 mg twice weekly when starting efavirenz resulted in rifabutin AUCs that were 20% higher than baseline values. However, in one analysis, 8 of 35 patients (23%) taking efavirenz and given rifabutin 450 mg once daily were found to have sub-therapeutic rifabutin levels, and they were switched to isoniazid. Concurrent use should therefore be closely monitored. 

Rifabutin. The AUC of saquinavir 600 mg three times daily was reduced by about 40% by rifabutin 300 mg daily, in 12 HIV-positive subjects. Similarly, the AUC of saquinavir (soft capsules) 1.2 g three times daily was decreased by 47% by rifabutin 300 mg once daily in 14 HIV-positive patients. In addition, the rifabutin AUC was increased by 44% by saquinavir. " However, combined use of ritonavir and saquinavir (hard capsules), both 400 mg twice daily, with intermittent rifabutin dosing (300 mg weekly or 150 mg every 3 days) for 8 weeks was reported to be safe and manageable. Rifabutin did not significantly alter the protease inhibitor levels, and the rifabutin pharmacokinetics were similar to those usually seen with rifabutin 300 mg daily alone. ... 

Established interactions of clinical importance. The protease inhibitors increase the levels of rifabutin, with a consequent increase in adverse effects unless the rifabutin dose is reduced. Ritonavir is the most potent protease inhibitor in this regard, and the combination has been considered contraindicated. However, the CDC in the US say that the combination may be used if the dose of rifabutin is markedly reduced. In addition, rifabutin decreases the levels of some protease inhibitors, particularly saquinavir, increasing the risk of treatment failure. Rifabutin should not be used when saquinavir is the sole protease inhibitor (no longer recommended). However, there is some evidence that rifabutin can be used with ritonavir-boosted saquinavir. Table 21.5 , (p.827) summarises the clinical recommendations for the concurrent use of protease inhibitors and rifabutin. Therapy should be well monitored. Note that, in one analysis, the use of rifabutin 150 mg twice weekly with low-dose ritonavir and a second protease inhibitor was associated with low rifabutin levels. " Recommended doses of rifabutin in patients taking ritonavir-boosted protease inhibitors are 150 mg every other day or three times per week. ... 

Amprenavir Rifabutin dose at least halved (150 mg daily or every other day, or 300 mg three times per week). Amprenavir dose unchanged. Not recommended (amprenavir levels markedly reduced). 1-3... 

Ritonavir alone Rifabutin dose reduced by at least 75% (150 mg every other day or three times per week). Further dose reductions may be necessary. Ritonavir dose unchanged. May be used at usual doses, although limited data (ritonavir levels reduced). May lead to loss of virologic response. 3, 11... 

Darunavir/ritonavir Rifabutin dose reduced to 150 mg every other day. Not recommended (darunavir levels predicted to be markedly reduced). 14, 15... 

Gallicano K, Khaliq Y, Carignan G, Tsei A Walmsley S, CameronDW. A pharmacokinetic stu< of intermittent rifabutin dosing witii a combination of ritonavir and saquinavir in patients infected with human immunodeficiency virus. Clin Pharmacol Ther (2001) 70, 149-58. 

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