Rifabutin dosage

Dosage adjustments in comhination therapy Amprenavir. Amprenavir 1,200 mg and ritonavir 200 mg once a day or amprenavir 600 mg and ritonavir 100 mg twice a day. Am-penavirandefavirenz. Amprenavir 1,200 mg twice a day and ritonavir 200 mg twice a day with standard dose of efavirenz. Indinavir. Indinavir 800 mg twice a day and ritonavir 100-200 mg twice a day or indinavir400 mg twice a day and ritonavir 400 mg twice a day. Nelfinavirorsaquinavir. Ritonavir 400 mg twice a day. Rifabutin. Decrease rifabutin dosage to 150 mg every other day. 

Drug-drug interactious Lopinavir - - ritonavir The steady-state pharmacokinetics of rifabutin and its active metabolite 25-desacetyl-rifabutin have been examined before and after the addition of lopinavir - -ritonavir in 10 patients with HIV infection and active tuberculosis [79 ]. Samples were collected at 2-4 weeks after starting rifabutin 300 mg thrice weekly without lopinavir -I- ritonavir, 2 weeks after the addition of lopinavir -I- ritonavir 400/100 mg bd to rifabutin 150 mg thrice weekly, and (if rifabutin plasma concentrations were below the target range) 2 weeks after an increase in rifabutin dosage to 300 mg thrice weekly with lopinavir + ritonavir. Lopinavir - -ritonavir reduced the Cmax of total rifabutin and most unbound rifabutin C ax values were below the tuberculosis MIC. For most patients, the AUC was low or lower than associated with treatment failure or relapse and with acquired rifampicin resistance. The authors concluded that the recommended doses of rifabutin for use with lopinavir -I- ritonavir may be inadequate in many patients and recommended monitoring of plasma concentrations. 

HIV infection (in combination with other antiretrovirals) PO 800 mg (two 400-mg capsules) q8h. Dosage adjustments when given concomitantly Delavirdine, itraconazole, ketoconazok Reduce dose to 600 mg q8h. Efavirenz-. Increase dose to 1,000 mg q8h. Lopinavir/ritonavir Reduce dose to 600 mg twice a day. Nevirapine-. Increase dose to 1,000 mgqSh. Rifabutin-. Reduce rifabutin by lA and increase indinavir to 1,000 mg q8h. Ritonavir 100-200 mg twice a day and indinavir 800 mg twice a day or ritonavir 400 mg twice a day and indinavir 400 mg twice a day. 

The most common adverse effects associated with nelfinavir are diarrhea and flatulence. Diarrhea often responds to antidiarrheal medications but can be dose-limiting. Nelfinavir is an inhibitor of the CYP3A system, and multiple drug interactions may occur (Tables 49-3 and 49-4). An increased dosage of nelfinavir is recommended when co-administered with rifabutin (with a decreased dose of rifabutin), whereas a decrease in saquinavir dose is suggested with concurrent nelfinavir. Co-administration with efavirenz should be avoided due to decreased indinavir levels. Nelfinavir has a favorable safety and pharmacokinetic profile for pregnant women compared with that of other Pis (Table 49-5) there is no evidence of human teratogenicity. 

The use of rifampicin with the protease inhibitors indinavir, nelfinavir, and amprenavir is contraindicated. However, these agents can be used with rifabutin after appropriate dosage reduction. Failure to reduce the dosage of rifabutin can result in toxic manifestations, such arthralgia and uveitis. 

The oral administration of 300 mg of rifabutin produces a peak plasma concentration of approximately 0.4 pg/mL at 2 to 3 hours. The drug is metabolized by hepatic CYPs and eliminated in a biphasic manner with a mean terminal half-life of 45 hours (range of 16 to 96 hours). Because rifabutin is a lipophilic drug, concentrations are substantially higher (five- to tenfold) in tissue than in plasma. Following absorption from the GI tract, rifabutin is eliminated in the urine and bile. Adjustment of dosage is not necessary in patients with impaired renal function. Rifabutin is a weaker inducer of hepatic CYPs than is rifampin. 

A study in 24 HI V-positive patients taking methadone found that after taking rifabutin 300 mg daily for 13 days the pharmacokinetics of the methadone were minimally changed. However 75% of the patients reported at least one mild symptom of methadone withdrawal, but this was not enough for any of them to withdraw from the study. Only 3 of them asked for and received an increase in their methadone dosage. The authors offered the opinion that over-reporting of withdrawal symptoms was likely to be due to the warnings that the patients had received. ... 

Rifabutin appears to interact to a very mueh lesser extent so that fewer, if any, patients are likely to need a methadone dosage inerease. 

The effect of rifabutin is less than rifampicin, and the authors of the above report suggested that no atovaquone dosage adjustment is needed. However, in the UK, the manufacturer of atovaquone still considers that rifabutin use could result in subtherapeutic atovaquone levels in some patients, and they also advise against the concurrent use of this combination. ... 

Information on the interaction between itraconazole and rifabutin is very limited, but monitor for reduced antifungal activity, raising the itraconazole dosage as necessary, and watch for increased rifabutin levels and toxicity (in particular uveitis). More study is needed. Note that the manufacturers recommend that the combination should be avoided. "... 

Although there is less information, rifabutin appears to interact similarly to rifampicin. When dapsone is given with rifabutin, the dosage of dapsone may need to be increased, but this may increase exposure to the potentially toxic hydroxylamine metabolite. ... 

The eSM in the UK has warned about the need to be aware of the increased risk of uveitis with clarithromycin and rifabutin and of the raised rifabutin levels. If uveitis occurs the CSM recommends that rifabutin should be stopped and the patient should be referred to an ophthalmologist. Because of the increased risk of uveitis they also say that consideration should be given to reducing the dosage of rifabutin to 300 mg daily in the presence of maerolides. Later review and a case-control study suggest that this dose is associated with a redueed risk of uveitis and maintains efficacy. ... 

Rifabutin bioavailability is increased by amprenavir, atazanavir, fosamprenavir/ritonavir, indinavir, lopinavir/ritonavir, nelfinavir, tipranavir/ritonavir, and especially ritonavir, with an increased risk of toxicity. Rifabutin modestiy decreases the bioavailability of indinavir, neifinavir, and particuiarly saquinavir (with an increased risk of therapeutic faiiure), but has no effect on amprenavir, atazanavir, and ritonavir-boosted fosamprenavir. The combination of rifabutin with protease inhibitors may be used, but dosage adjustments of rifabutin or both drugs are often necessary. 

A number of liver transplant patients have needed markedly increased tacrolimus dosages when rifampicin (rifampin) was added. A pharmacokinetic study has shown that rifampicin increases the clearance and decreases the bioavailability of intravenous and oral tacrolimus. Rifabutin is unlikely to interact to the same extent, but given the magnitude of the interaction with rifampicin, caution is still warranted. 

Direct information about rifabutin seems to be lacking, but any interaction with tacrolimus is likely to be much less marked than with rifampicin because its enzyme-inducing effects are considerably less. Nevertheless until the situation is clear it would be prudent to closely monitor concurrent use with any rifamycin, being alert for the need to raise the tacrolimus dosage. 

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