Drug Interaction Report

MONITOR: Coadministration with bictegravir may increase the plasma concentrations of drugs that are substrates of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1). The mechanism is inhibition of OCT2- and MATE1-mediated renal tubular secretion by bictegravir. In healthy volunteers, coadministration of metformin 500 mg twice daily with bictegravir/tenofovir alafenamide 50 mg/25 mg once daily increased mean metformin peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) by 28%, 39% and 36%, respectively, compared to administration of metformin alone.

MANAGEMENT: Caution is advised when bictegravir is used with drugs that are substrates of OCT2 or MATE1, particularly those with a narrow therapeutic range. Close monitoring is particularly recommended in patients with moderate renal impairment (CrCl 30 to 59 mL/min) who are to be administered bictegravir and metformin, due to the increased risk of lactic acidosis. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever bictegravir is added to or withdrawn from therapy.

GENERALLY AVOID: Varenicline may enhance the effects of alcohol as well as alter the way an individual reacts to alcohol. During postmarketing use, some patients have reported experiencing increased intoxicating effects of alcohol while taking varenicline. In addition, some reported cases of neuropsychiatric events, including unusual and sometimes aggressive behavior directed toward oneself or others, may have been worsened by concomitant use of alcohol. These events were often accompanied by amnesia.

MANAGEMENT: Patients should be advised to limit their consumption of alcohol until they know whether varenicline affects their tolerance for alcohol, and to exercise caution driving or operating machinery until they know how quitting smoking and/or varenicline may affect them. Patients should immediately stop taking varenicline and contact their physician if they develop agitation, hostility, aggressive behavior, depressed mood, or changes in behavior or thinking that are not typical for them, or if they develop suicidal ideation or behavior.

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.