Efavirenz with voriconazole

In a study in healthy subjects, efavirenz 400 mg daily decreased the steady-state maximum plasma levels and the AUC of voriconazole 200 mg twice daily by 61% and 77%, respectively. At the same time, the steady-state maximum plasma levels and the AUC of efavirenz were increased by 38% and 44%, respectively. In a dose-adjustment study, when voriconazole 300 mg twice daily and efavirenz 300 mg daily were used together, the AUC of voriconazole was 55% lower than that seen with the standard dose of voriconazole 200 mg twice daily alone, and the efavirenz AUC was equivalent to that seen with efavirenz 600 mg daily alone. " In a further dose-adjustment study, when voriconazole 4(X) mg twice daily was given with efavirenz 300 mg once daily, the AUC of voriconazole was just 7% lower than that seen with voriconazole 200 mg twice daily alone. The AUC of efavirenz was increased by 17% and the maximum plasma concentration was equivalent, when compared with efavirenz 600 mg once daily alone. " ... 

IMATINIB 1. ANTIBIOTICS - clarithromycin, erythromycin 2. ANTIFUNGALS -fluconazole, itraconazole, ketoconazole voriconazole 3. ANTIVIRALS -efavirenz, ritonavir 4. GRAPEFRUIT JUICE 5. H2 RECEPTOR BLOCKERS - cimetidine t imatinib levels with t risk of toxicity (e.g. abdominal pain, constipation, dyspnoea) and of neurotoxicity (e.g. taste disturbances, dizziness, headache, paraesthesia, peripheral neuropathy) Due to inhibition of CYP3A4-mediated metabolism of imatinib Monitor for clinical efficacy and for the signs of toxicity listed, along with convulsions, confusion and signs of oedema (including pulmonary oedema). Monitor electrolytes and liver function, and for cardiotoxicity... 

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,... 

There is one case of a patient taking a variety of antiretrovirals and antibacterials who developed oral candidiasis while taking voriconazole 200 mg twice daily, which was attributed to an interaction with efavirenz. The dose of voriconazole was titrated upwards to 350 mg twice daily to achieve higher trough levels. The candidiasis was eventually found to be resistant to voriconazole, and it was postulated that this developed because of under-dosing in the presence of efavirenz. ... 

Carbonara S, Regazzi M, Cirad E, Villani P, Stano F, Cusato M, Heichen M, Monno L. Long-term efficacy and safety of TDM-assisted combination of voriconazole plus efavirenz in an AIDS patient with cryptococcosis and liver cirrhosis. Ann Pharmacother 2009 43 978-84. 

Voriconazole is not recommended for use in combination with efavirenz however, if they are co-administered, the dosage of voriconazole should be increased to 400 mg 12-hourly and the dosage of efavirenz reduced to 300 mg/day, in order to provide systemic exposure similar to standard-dose monotherapy [SEDA-32, 498]. The combination of voriconazole and efavirenz in doses adjusted according to steady-state plasma concentrations has been studied in a 40-year-old man with AIDS, cryptococcosis, and mild liver cirrhosis [154 ]. Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dosage adjustment (oral voriconazole 200 mg bd plus oral efavirenz 300 mg/day). There was stable suppression of cryptococcosis and plasma HIV viremia at long-term follow-up (66 weeks), with no significant adverse events. 

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