Table 4.
The main drugs interacting with voriconazole
| Drug | Interaction with voriconazole and management strategy |
|---|---|
| Drugs contraindicated | |
| Astemizole, cisapride, ergot alkaloids, quinidine, sirolimus, terfenadine | Their levels are increased by voriconazole, avoid co-administration. Switch to a drug with no or with predictable interactions (for example, cyclosporine) |
| Carbamazepine, long-acting barbiturates, rifampicin | They decrease voriconazole levels, avoid co-administration. Switch to a drug with no interactions (for example, levetiracetam) |
| Rifabutin | Co-administration decreases voriconazole levels and increases rifabutin levels (contraindicated according to FDA, not according to EMA, see below), avoid co-administration |
| Drugs not contraindicated but if co-administered the dose of voriconazole must be modified (increased) | |
| Phenytoin | Increase voriconazole oral maintenance dose from 200 mg to 400 mg every 12 hours (100–200 mg every 12 hours if <40 kg) and intravenous maintenance dose to 5 mg/kg every 12 hours; monitor for phenytoin toxicity |
| Efavirenz | Increase voriconazole oral maintenance dose from 200 mg to 400 mg every 12 hours (100–200 mg every 12 hours if <40 kg) and reduce efavirenz dose by 50% to 300 mg/day |
| Rifabutin (according to FDA contraindicated as rifampicin) | According to EMA, increase oral voriconazole maintenance dose from 200 to 350 mg every 12 hours (100–200 mg every 12 hours if <40 kg) and intravenous maintenance dose to 5 mg/kg every 12 hours; monitor for rifabutin toxicity |
| Other drugs (apart from ritonavir, their levels are increased by voriconazole) | |
| Low dose ritonavir (100 mg every 12 hours) | Co-administration decreases levels of both voriconazole and ritonavir; better avoided |
| Cyclosporine, omeprazole, tacrolimus and warfarin | Their blood levels are increased by voriconazole and their dose should be reduced (by half for cyclosporine and by two-thirds for tacrolimus). Monitor serum levels of cyclosporine and tacrolimus or INR for warfarin |
| Other drugs such as benzodiazepines, opioid analgesics (for example, oxycodone or fentanyl), sulfonylureas, statins, vinca alkaloids, calcium channel blockers | Their levels are increased by voriconazole co-administration. Monitor closely for their side effects, discontinue if toxicity is suspected or consider decreasing dosage immediately when voriconazole is started |
EMA, European Medicines Agency; FDA, Food and Drug Administration; INR, international normalized ratio.