Voriconazole Rifabutin

RIFABUTIN VORICONAZOLE t plasma concentrations of rifabutin, with risk of toxic effects of rifabutin (nausea, vomiting). Dangerous toxic effects such as leukopenia and thrombocytopenia may occur Due to inhibition of metabolism of rifabutin by the CYP3A4 isoenzymes by voriconazole Avoid concomitant use. If absolutely necessaiy, close monitoring of FBC and liver enzymes and examination of eyes for uveitis and corneal opacities is necessary... 

Drugs that affect voriconazole include the following barbiturates (long acting), cimetidine, nonnucleoside reverse transcriptase inhibitors (NNRIs), phenytoin, protease inhibitors, proton pump inhibitors, rifampin, rifabutin. 

Drugs affected by voriconazole include the following benzodiazepines, calcium channel blockers, cisapride, coumarin anticoagulants, cyclosporine, ergot alkaloids, HMG-CoA reductase inhibitors, NNRTIs, phenytoin, protease inhibitors, pimozide, proton pump inhibitors, quinidine, prednisolone, rifabutin, sirolimus, sulfonylureas, tacrolimus, vinca alkaloids. 

Drugs that may be affected by atazanavir include the following antiarrhythmics, atenolol, benzodiazepines, calcium channel blockers, cisapride, clarithromycin, ergot derivatives, HMG-CoA reductase inhibitors, immunosuppressants, indinavir, irinotecan, itraconazole, ketoconazole, oral contraceptives, PDE5 inhibitors, pimozide, rifabutin, saquinavir, tenofovir, tricyclic antidepressants, voriconazole, warfarin. 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Significant drug interactions include cyclosporins (increased cyclosporine levels), phenytoin, rifampin, and rifabutin (decreased voriconazole levels). Because of its low toxicity profile, this drug may gain importance in the chronic treatment of infections with invasive dimorphic fungi and resistant Candida spp. 

RIFAMPICIN, RIFABUTIN, RIFAPENTINE ITRACONAZOLE, KETOCONAZOLE, POSACONAZOLE, VORICONAZOLE i levels of these azoles, with significant risk of therapeutic failure. Rifampicin is a very potent inducer that can produce undetectable concentrations of ketoconazole Rifampicin is a powerful inducer of CYP3A4 and other CYP isoenzymes. Rifabutin is a less powerful inducer but more potent than rifapentine. Rifapentine is an inducer of CYP3A4 and CYP2C8/9. Rifampicin is also a powerful inducer of P-gp, thus 1 bioavailability of itraconazole Avoid co-administration of ketoconazole or voriconazole with these drugs. Watch for inadequate therapeutic effects of itraconazole. Higher doses of itraconazole may not overcome this interaction, so consider the use of less lipophilic fluconazole, which is less dependent on CYP metabolism. Avoid co-administration of posaconazole with rifabutin... 

Clinically important, potentially hazardous interactions with atazanavir, carbamazepine, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, ritonavir, saquinavir, St John s wort, troleandomycin, voriconazole, warfarin... 

Clinically important, potentially hazardous interactions with alfentanil, alfuzosin, alprazolam, amiodarone, amprenavir, aprepitant, astemizole, atazanavir, bepridil, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, ciclesonide, clozapine, conivaptan, cyclosporine, cyproterone, dasatinib, diazepam, dihydroergotamine, ergot alkaloids, estazolam, eszopidone, etravirine, ezetimibe, fentanyl, fesoterodine, flecainide, flurazepam, fluticasone, halazepam, ivabradine, ixabepilone, ketoconazole, lapatinib, levothyroxine, meperidine, meptazinol, methysergide, midazolam, nifedipine, nilotinib, oral contraceptives, phenytoin, pimozide, piroxicam, propafenone, propoxyphene, quazepam, quinidine, ranolazine, rifabutin, rifampin, rifapentine, rimonabant, rivaroxaban, saquinavir, sildenafil, silodosin, simvastatin, solifenacin, St John s wort, tadalafil, temsirolimus, trabectedin, triazolam, vardenafil, voriconazole, zolpidem... 

Coadministration with rifampin, rifabutin, or ritonavir is contraindicated because of accelerated voriconazole metabolism. Efavirenz and perhaps other normucleoside reverse transcriptase inhibitors (NNRTIs) significantly increase voriconazole metabolism and slow the metabolism of the NNRTI. When given with phenytoin, the voriconazole dose should be doubled. Drugs that significantly accumulate in patients receiving voriconazole include cyclosporine,... 

Rifabutin levels are increased by fluconazole, posaconazole, voriconazole, and possibly itraconazole. Patients taking this combination are at increased risk of rifabutin toxicity, specifically uveitis, and should be closely monitored. Rifabutin markedly reduces the plasma levels of itraconazole, posaconazole, and voriconazole. These azoles should be used cautiously with rifabutin, if at all Rifabutin does not affect the metabolism of fluconazole. 

Rifabutin 300 mg daily decreased the AUC and maximum plasma levels of voriconazole 200 mg twice daily by 79% and 67%, respectively. Increasing the dose of voriconazole to 350 mg twice daily in tire presence of ri-... 

Rifabutin increases the metabolism of itraconazole, posaconazole and voriconazole, probably, at least in part, by inducing their metabolism by the cytochrome P450 CYP3A subfamily. Fluconazole is largely excreted unchanged in the urine and so it is not affected. The azoles apparently increase rifabutin levels by inhibiting its metabolism, probably by CYP3A4. Raised rifabutin levels can cause uveitis. 

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). 

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