Rifabutin adverse effects

The manufacturer in the US contraindicates the combination of voriconazole and rifabutin. However, the UK manufacturer permits concurrent use if the benefits outweigh the risks. If used together, it is recommended that the oral dose of voriconazole be increased from 200 mg twice daily to 350 mg twice daily (and from 100 to 200 mg twice daily in patients under 40 kg). The intravenous dose should also be increased from 4 to 5 mg/kg twice daily. Importantly, the manufacturer advises careful monitoring for rifabutin adverse effects (e.g. check full blood counts, monitor for uveitis). 

Rifabutin and rifampicin (rifampin) cause a very marked fall in delavirdine plasma levels rifabutin levels are raised when the delavirdine dose is increased to compensate for this. Rifabutin does not affect efavirenz levels, whereas efavirenz decreases rifabutin levels. There is usually no important interaction between rifabutin and nevirapine, although some patients may have a higher risk of rifabutin adverse effects. 

The adverse effects that most frequently result in discontinuation of rifabutin include GI intolerance, rash, and neutropenia. Rifabutin levels will be increased with concurrent administration of fluconazole and clarithromycin, resulting in anterior uveitis, polymyalgia syndrome, and a yellowish-tan discoloration of the skin (pseudojaundice). Other adverse reactions are similar to those of rifampin, such as hepatitis, red-orange discoloration of body fluids, and drug interactions due to effects on the hepatic P450 cytochrome enzyme system. 

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. 

T effects OF amiodarone, astemizole, atorvastadn, barbiturates, bepridil, bupropion, cerivastatin, cisapride, clorazepate, clozapine, clarithromycin, desipramine, diazepam, encainide, ergot alkaloids, estazolam, flecainide, flurazepam, indinavir, ketoconazole, lovastatin, meperidine, midazolam, nelfinavir, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, simvastatin, SSRIs, TCAs, terfenadine, triazolam, troleandomycin, zolpidem X effects W/ barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, St. John s wort, tobacco X effects OF didanosine, hypnotics, methadone, OCPs, sedatives, theophylline, warfarin EMS T Effects of amiodarone, diazepam, midazolam and BBs, may need X- doses concurrent use of Viagra-type drugs can lead to hypotension X- effects of warfarin concurrent EtOH use can T adverse effects T glucose ODs May cause an extension of adverse SEs symptomatic and supportive Rivasrigmine (Exelon) [Cholinesterase Inhibitor/Anri ... 

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... 

The adverse effects of amprenavir in patients treated with combination therapy included nausea, vomiting, diarrhea, epigastric pain, flatulence, paresthesia, headache, rash, and fatigue (4). The contribution of a single drug to the observed adverse effects is difficult to establish. Amprenavir inhibits CYP3A4 to a greater extent than saquinavir, and to a much lesser extent than ritonavir (5). Co-administration with rifampicin and rifabutin should be avoided. Those who take... 

The effects of fluconazole and clarithromycin on the pharmacokinetics of rifabutin and 25-O-desacetylrifabu-tin have been studied in ten HIV-infected patients who were given rifabutin 300 mg qds in addition to fluconazole 200 mg qds and clarithromycin 500 mg qds (73). There was a 76% increase in the plasma AUC of rifabutin when either fluconazole or clarithromycin was given alone and a 152% increase when both drugs were given together. The authors concluded that patients should be monitored for adverse effects of rifabutin when it is co-administered with fluconazole or clarithromycin. 

A 300 mg dose of rifabutin is usually well tolerated. Adverse effects include neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances (nausea, flatulence). Myositis (12) and uveitis (13) are rarely observed. The drug-induced lupus-like syndrome has been linked in a few cases with rifampicin and rifabutin. 

In a multicenter study from the National Institute of Allergy and Infectious Diseases in the USA, azithromycin (600 mg/day) plus rifabutin (300 mg/day) was poorly tolerated by 31 patients with or without HIV infection (14). Gastrointestinal symptoms and neutropenia were the major adverse effects. There was no significant pharmacokinetic interaction between the two drugs. 

Rifabutin. In one study, the pharmacokinetics of nevirapine were only minimally affected by rifabutin in 19 patients, when compared with historical data. The manufacturer notes that the concurrent use of rifabutin with nevirapine caused a minor 9% increase in nevirapine clearance and a 17% increase in its AUC, and a 28% increase in maximum steady-state rifabutin levels. They say that because of the high intersubject variability, some patients may experience large increases in rifabutin exposure and may be at higher risk of adverse effects. Concurrent use should be well monitored and undertaken cautiously. The CDC in the US state that the combination of nevirapine and rifabutin can be used. ... 

Rifampicin (Rifampin). The manufacturer states that the AUC of nevirapine was reduced by 58% by rifampicin in 14 subjecls, when compared with historical data. There was no change in steady-state rifampicin pharmacokinetics. Based on these pharmacokinetic data, the manufacturer suggests that the concurrent use of rifampicin with nevirapine is not recommended, and that rifabutin may be considered instead, with close monitoring of adverse effects. ... 

The pharmacokinetics of rifabutin are not affected by the concurrent use of zidovudine in AIDS patients, " and rifabutin does not affect the pharmacokinetics of zidovudine in HIV-positive patients, although one review found a trend towards increased zidovudine clearance. No increase in adverse effects appears to occur when rifabutin is given with zidovudine."... 

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. ... 

Drug-drug interactions Tipranavir + ritonavir In some studies co-administration of rifabutin and tipranavir + ritonavir increased the concentrations of rifabutin and its main metabolite 25-O-desacetyl-rifabutin this combination should be used with caution and adverse effects should be monitored pOS", 209 =, 210 =]. 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

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