Voriconazole Protease inhibitors

Azalides azithromycin Azoles fluconazole, itraconazole, ketoconazole, and voriconazole Macrolides erythromycin, clarithromycin Protease inhibitors amprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, and saquinavir Quinolones ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin. 

Pimozide Drugs that prolong the QT interval - CYP3A inhibitors (eg, clarithromycin, dirithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, protease inhibitors, sertraline, telithromycin, troleandomycin, voriconazole)... 

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. 

PROTEASE INHIBITORS VORICONAZOLE 1 efficacy of voriconazole L plasma levels Avoid co-administration if the dose of ritonavir is 400 mg twice a day or greater. Avoid combining low-dose ritonavir (100 mg once a day) unless benefits outweigh risks... 

Protease inhibitors HfV protease is essential for virus infectivity because protease is needed for viral replication. Protease inhibitors bind reversibly to the active site of HfV protease preventing protease from cleaving the viral precursor polypeptide and blocking viral maturation. Immature viral particles are noninfectious. Amprenavir (APV) Agenerase 50 mg capsule 15 mg/ml solutions Itraconazole, fluconazole, ketoconazole, voriconazole,... 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Clinically important, potentially hazardous interactions with aspirin, carbamazepine, clarithromycin, enoxaparin, HIV protease inhibitors, itraconazole, ketoconazole, phenobarbital, phenytoin, posaconazole, ritonavir, St John s wort, voriconazole... 

The current use of protease inhibitors and voriconazole is predicted to interfere with the metabolism of both drugs. Studies suggest that ritonavir decreases voriconazole levels, but no interaction was seen between indinavir and voriconazole in one study. 

In a study in 18 healthy subjects, the pharmacokinetics of hoth indinavir 800 mg three times daily and voriconazole 200 mg twice daily were unaffected hy at least a week of concurrent use. However, in vitro studies suggest that the metaholism of HfV-protease inhihitors may he inhihited hy voriconazole, and the metaholism of voriconazole may he inhihited hy HTV-protease inhibitors. The manufacturer therefore suggests that patients should be carefully monitored for evidence of drug toxicity and/or loss of efficacy during concurrent use of other HIV-protease inhibitors (amprenavir, neliinavir and saquinavir are specifically mentioned). ... 

Voriconazole is an inhibitor and a substrate of the cytochrome P450 isoenzyme CYP3A4 protease inhibitors are also metabolised by this route, and can, to varying degrees, also inhibit this isoenzyme. 

The manufacturers of voriconazole say that the concurrent use of ritonavir (at doses of400 mg and above twice daily) is contraindicated, presumably because the efficacy of the voriconazole is expected to be markedly reduced. The manufacturer of ritonavir also recommends that when it is used as a pharmacokinetic enhancer (usually 100 mg twice daily) voriconazole should only be given if the benefits outweigh the risks. Most protease inhibitors are given with ritonavir as a pharmacokinetic enhancer however, caution is also warranted if they are given alone, as all the protease inhibitors can inhibit CYP3A4 to some extent and may therefore also increase voriconazole levels. Voriconazole may also affect protease inhibitor levels, but other than ritonavir and indinavir, which are not affected this does not appear to have been studied. Be aware that some increase in their levels is theoretically possible if voriconazole is given. 

The oral dose of voriconazole does not have to be adjusted in patients who have renal impairment. However, intravenous administration of voriconazole should be avoided in these patients as the carrier vehicle sulfobu-tyl ether P-cyclodextrin sodium can accumulate in these patients. Dosage adjustment is required in patients who have chronic hepatic impairment. As voriconazole is a substrate for a number of cytochrome P450 enzymes, a number of clinically important dmg interactions occur with dmgs including ciclospotin, tacrolimus, phenytoin, warfarin, HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors. 

---