Viranz Drug Interactions

Efavirenz is an inducer of CYP3A4. Other compounds that are substrates of CYP3A4 may have decreased plasma concentrations when coadministered with Efavirenz.
Concomitant Antiretroviral Agents: Amprenavir: when amprenavir (1200 mg every 12 hours) was given with efavirenz (600 mg once daily) in HIV-infected subjects. While the clinical significance of decreased amprenavir concentrations has not been established, the magnitude of the observed pharmacokinetic interaction should be taken into consideration when choosing a regimen containing both efavirenz and amprenavir.
Fosamprenavir calsium: For coadministration with fosamprenavir and ritonavir, the prescribing information for fosamprenavir calcium should be consulted.
Atazanavir: Coadministration of efavirenz 600mg with atazanavir resulted in substantial decreases in atazanavir exposure, necessitating dosage adjustment of atazanavir in combination with ritonavir. Efavirenz concentrations when co-administered with atazanavir and low-dose ritonavir were similar to efavirenz alone, based on comparison with historical data.
Indinavir: The optimal dose of indinavir, when given in combination with efavirenz, is not known. Increasing the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to efavirenz.
Ritonavir: When Efavirenz 600 mg (given once daily at bedtime) and ritonavir 500 mg (given every 12 hours) was studied the combination was not well tolerated and was associated with a higher frequency of adverse clinical experiences (e.g., dizziness, nausea, paraesthesia) and laboratory abnormalities (elevated liver enzymes). Monitoring of liver enzymes is recommended when Efavirenz is used in combination with ritonavir.
Saquinavir: Use of Efavirenz in combination with sequinavir as the sole protease inhibitor is not recommended.
Antimicrobial Agents: Rifamycins: Rifamycins reduced efavirenz. The dose of Efavirenz should be increased to 800 mg/day when taken with rifampin. No dose adjustment of rifampin is recommended when given with Efavirenz. Rifabutin had no significant effect on the pharmacokinetics of efavirenz. The daily dose of rifabutin should be increased by 50% when administered with efavirenz and that the rifabutin dose may be doubled for regimens in which rifabutin is given two or three times a week in combination with efavirenz.
Clarithromycin: Coadministration of 400 mg of Efavirenz once daily with clarithromycin given as 500 mg every 12 hours for seven days resulted in a significant effect of efavirenz. Develop rash while receiving Efavirenz and clarithromycin. No dose adjustment of Efavirenz is recommended when given with clarithromycin. Alternative to clarithromycin should be considered.
Antifungal agents: Voriconazole: Coadministration of 400 mg of Efavirenz (400 mg orally once daily) with voriconazole (200 mg orally every 12 hours) in uninfected volunteers resulted in a 2 way interaction.
Itraconazole: Coadministration of efavirenz (600 mg orally once daily) with itraconazole (200 mg orally every 12 hours). Since no dose recommendation for itraconazole can be made, alternative antifungal treatment should be considered.
Lipid-lowering agents: Coadministration of efavirenz with the HMG-CoA reductase inhibitors atorvastatin, pravastatin, or simvastatin has been shown to reduce the plasma concentration of the statin in uninfected volunteers. Cholesterol levels should be periodically monitored. Dosage adjustments of statins may be required.
Anticonvulsants: Carbamazepine: Coadministration of efavirenz (600 mg orally once daily) with carbamazepine (400 mg once daily) in uninfected volunteers resulted in a two-way interaction. There are no data with coadministration of higher doses of either medicinal product; therefore, no dose recommendation can be made, and alternative anticonvulsant treatment should be considered.
Other anticonvulsants: No data are available on the potential interactions of efavirenz with phenytoin, Phenobarbital, or other anticonvulsants that are substrates of CYP450 isozymes.
Other Drug Interactions: Oral Contraceptives: Because the potential interaction of efavirenz with oral contraceptives has not been fully characterized, a reliable method of barrier contraception should be used in addition to oral contraceptives.
Methadone: Patients should be monitored for signs of withdrawal and their methadone dose increased as required to alleviate withdrawal symptoms.
St.John's wort (Hypericum perforatum): Patients on efavirenz should not concomitantly use products containing St. John's wort (Hypericum perforatum) since it may be expected to result in reduced plasma concentrations of efavirenz. This effect is due to an induction of CYP3A4 and may result in loss of therapeutic effect and development of resistance.
Antidepressants: There were no clinically significant effects on pharmacokinetic parameters when paroxetine and efavirenz were coadministered. No dose adjustments are necessary for either efavirenz or paroxetine when these drugs are coadministered. The dose of sertraline should be increased when administered with efavirenz to compensate for the induction of sertraline metabolism by efavirenz. Sertraline dose increases should be guided by clinical response.
Cetirizine: No dose adjustments are necessary for either efavirenz or cetirizine when these drugs are coadministered.
Lorazepam: No dose adjustment is necessary for either efavirenz or lorazepam when these drugs are co-administered.
Calcium channel blockers: Diltiazem dose adjustments should be guided by clinical response (refer to the product circular for diltiazem).
No data are available on the potential interactions of efavirenz with other calcium channel blockers that are substrates of the CYP3A4 enzyme (eg, verapamil, felodepine, nifedipine, nicardipine). When efavirenz is administered concomitantly with one of these agents, there is a potential for reduction in the plasma concentrations of the calcium channel blocker. Dose adjustments should be guided by clinical response (refer to the corresponding manufacturer's product circular for the calcium channel blocker).
Cannabinoid Test Interaction: Efavirenz does not bind to cannabinoid receptors. False positive urine cannabinoid test results have been reported in uninfected volunteers who received Efavirenz. False positive test result have only been observed with the CEDIA DAU Multi-level THC assay, which is used for screening, and have not been observed with other cannabinoid assays tested including tests used for confirmation of positive results.