Voriconazole interactions

Many experts now consider voriconazole as the initial drug of choice for invasive aspergillosis in patients without significant contraindications (e.g., drug interactions or preexisting liver dysfunction) to azole therapy. 

Is voriconazole an acceptable option in this patient Are there any drug interaction concerns ... 

Voriconazole 6 mg/kg IV loading dose every 12 hours on day 1 followed by 4 mg/kg PO/IV every 12 hours Dosage adjustment in hepatic dysfunction IV formulation contraindicated if creatinine clearance less than 50 mDminute multiple drug interactions. 

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. 

Etravirine is a substrate as well as an inducer of CYP3A4 and an inhibitor of CYP2C9 and CYP2C19 it has many therapeutically significant drug-drug interactions (Tables 49-3 and 49-4). Some of the interactions are difficult to predict. For example, etravirine may decrease itraconazole and ketoconazole concentrations but increase voriconazole... 

Voriconazole is predominantly metabolized by CYP2C19, and although it is an inhibitor of CYP3A4 its inhibitory effects are much less than those of itraconazole, as shown in this case, in which it appeared not to interact with beclomethasone, while itraconazole did. 

BARBITURATES FLUCONAZOLE, ITRACONAZOLE, KETOCONAZOLE, VORICONAZOLE 1 azole levels with risk of therapeutic failure Barbiturates induce CYP3A4, which metabolizes itraconazole and the active metabolite of itraconazole. Primidone is metabolized to phenobarbitone Watch for inadequate therapeutic effects and t dose of azole if effect due to interaction... 

CARBAMAZEPINE ANTIFUNGALS - ITRACONAZOLE, KETOCONAZOLE, MICONAZOLE, POSACONAZOLE, VORICONAZOLE 1 plasma concentrations of itraconazole and of its active metabolite, ketoconazole, posaconazole and voriconazole, with risk of therapeutic failure, t carbamazepine plasma concentrations These azoles are highly lipophilic, and clearance is heavily dependent upon metabolism by CYP isoenzymes. Carbamazepine is a powerful inducer of CYP3A4 and other CYP isoenzymes (CYP2C18/19, CYP1A2), and the result is very low or undetectable plasma levels. Inhibition of P-gp t bioavailability of carbamazepine Avoid co-administration of posaconazole or voriconazole with carbamazepine. Watch for inadequate therapeutic effects, and t dose of itraconazole. Higher doses of itraconazole may not overcome this interaction. Consider use of the less lipophilic fluconazole, which is less dependent on CYP metabolism. Necessary to monitor carbamazepine levels... 

ITRACONAZOLE, FLUCONAZOLE, MICONAZOLE, VORICONAZOLE SULPHONYLUREAS t risk of hypoglycaemic episodes Inhibition of CYP2C9-mediated metabolism of these sulphonylureas Watch for and warn patients about symptoms of hypoglycaemia >- For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

ITRACONAZOLE VORICONAZOLE 1 levels of itraconazole and of its active metabolite, and significant risk of therapeutic failure Voriconazole is an inducer of CYP3A4 Watch for inadequate therapeutic effects, and t dose of itraconazole if due to interaction. Higher doses of itraconazole may not overcome this interaction, so consider the use of less lipophilic fluconazole, which is less dependent on CYP metabolism... 

Micafungin Topical 0.1% solution 1 drop ql h while awake Side effects include pulmonary edema, blood dyscrasias, hypercalcemia, hepatotoxicity (rare), gastrointestinal symptoms, headache, fever, chills, anemia, eosinophilia, hypokalemia, liver function test elevations, infusion site reactions. Drug interaction with cyclosporine and additional voriconazole. Pregnancy category C lactation safety unknown. Coadministration of caspofungin is contraindicated with multiple antiretrovirals (refer to Table 11-3) Topical not commercially available... 

Voriconazole is contraindicated in patients with known hypersensitivity to voriconazole or its components. There is no information regarding cross-sensitivity between voriconazole and other azole antifungal agents. Caution should be used when prescribing voriconazole to patients with hypersensitivity to other azoles. Refer to Table 11-14 for drug interactions. 

For details of interactions with individual antifungal azoles, see individual monographs (fluconazole, itraconazole, ketoconazole, miconazole, and voriconazole). 

Voriconazole has a half-life of about 6 hours and undergoes complex hepatic metabolism. There is wide intersubject variability in the disposition of voriconazole, which is at least partly related to a CYP2C19 polymorphism. Voriconazole has the potential for drug-drug interactions mediated by CYP3A4, CYP2C9, and CYP2C19. 

Ullmann AJ. Review of the safety, tolerability, and drug interactions of the new antifungal agents caspofungin and voriconazole. Curr Med Res Opin 2003 19(4) 263-71. 

Clinically important, potentially hazardous interactions with amiodarone, azithromycin, bepredil, bosentan, bretylium, cisapride, clarithromycin, disopyramide, erythromycin, erythromycin fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, miconazole, nefazodone, nilotinib, paroxetine, pimozide, probucol, procainamide, quinidine, quinine, ritonavir, saquinavir, sertraline, sotalol, SSRIs, terfenadine, troleandomycin, voriconazole, zileuton, ziprasidone... 

Clinically important, potentially hazardous interactions with acetylcysteine, adenosine, aprepitant, aripiprazole, buprenorphine, caffeine, charcoal, clarithromycin, clobazam, dorazepate, clozapine, darunavir, dasatinib, delavirdine, dexamethasone, diltiazem, doxacurium, erythromycin, felodipine, fesoterodine, fosamprenavir, imatinib, influenza vaccines, lacosamide, lapatinib, levetiracetam, lopinavir, methylprednisolone, midazolam, nelfinavir, nilotinib, piracetam, prednisolone, propoxyphene, ritonavir, rivaroxaban, rufinamide, solifenacin, St John s wort, telithromycin, temsirolimus, terbinafine, tolvaptan, troleandomycin, verapamil, voriconazole... 

---