Liverpool HIV Interactions

Start a new interaction query Switch to Table View

Generate a personalised report in PDF format

Potential Interaction

Bictegravir/ Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF)

Metformin

Quality of Evidence: Moderate

Summary:

Coadministration of multiple dose of metformin (850 mg once daily followed by 500 mg twice daily and 500 mg once daily) was studied with bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg once daily) in 32 subjects. Coadministration increased metformin Cmax and AUC by 28% and 39% due to inhibition of renal OCT2 and MATE1 transporters by bictegravir. The pharmacodynamic characteristics of metformin (including glucose reduction, increases in active GLP-1 and plasma lactate) were not affected by coadministration with bictegravir, emtricitabine and tenofovir alafenamide relative to placebo. In addition, no significant differences were observed in fasted blood glucose or HbA1c values before and after initiating bictegravir in HIV+ people with either normal or mildly impaired renal function receiving metformin at daily doses of 500-3000 mg. The US product label for Biktarvy refers to the Prescribing Information of metformin for assessing the benefit and risk of concomitant use of Biktarvy and metformin. This is particularly important in patients with renal impairment. The European product label for Biktarvy indicates that no dose adjustment is required upon coadministration in patients with normal renal function, but for patients with moderate renal impairment, close monitoring should be considered when starting coadministration of bictegravir with metformin, due to increased risk for lactic acidosis in these patients and a dose adjustment of metformin should be considered if required.

Description:

Coadministration of metformin (500 mg twice daily) and bictegravir/emtricitabine/tenofovir alafenamide increased metformin AUC and Cmin by 39% and 36% (due to inhibition of OCT1/MATE1), but had no significant effect on Cmax. No dose adjustment is required upon co-administration in patients with normal renal function. In patients with moderate renal impairment, close monitoring should be considered when starting coadministration of bictegravir with metformin, due to the increased risk for lactic acidosis in these patients. A dose adjustment of metformin should be considered if required.

Biktarvy Summary of Product Characteristics, Gilead Sciences Ltd, June 2019.

Coadministration may increase metformin concentrations. Refer to the prescribing information of metformin for assessing the benefit and risk of concomitant use of Biktarvy and metformin. Coadministration of metformin (500 mg twice daily) and bictegravir/tenofovir alafenamide (50/25 mg once daily) increased metformin Cmax, AUC and Cmin by 28%, 39% and 36%.

Biktarvy Prescribing Information, Gilead Sciences Inc, August 2019.

Glycemic control under metformin treatment before and after the initiation of a bictegravir containing regimen was evaluated retrospectively in 20 people living with HIV. The mean metformin dose was 1455 + 726 mg daily (ranging from 500 to 3000 mg daily). No clinically significant differences were observed in the glucose fasting values when comparing values pre- versus post- bictegravir initiation (fasting blood glucose 134+33 versus 128+24 mg/dL, mean difference -2.2%; P=0.311). Similarly, no differences were observed for HbA1c (48+11 versus 50+10 mmol/mol, mean difference +2%; P=0.907). The same observation applied when comparing fasted glucose or HbA1c values before and after initiation of bictegravir in individuals receiving metformin daily doses >1000 mg (fasting blood glucose 130+33 versus 124+24 mg/L; P=0.504 and HbA1c 49+12 versus 52+10 mmol/mol; P=0.863). No individuals experienced episodes of hypoglycaemia or lactic acidosis after initiating bictegravir. All individuals included in the study had a normal renal function or mild renal dysfunction. In conclusion, this study provides evidence from a real-life setting that coadministration of bictegravir and metformin did not result in statistically and/or clinically relevant effects on glycaemic control. This was confirmed also for daily doses of metformin >1000 mg.

Lack of clinically relevant interactions between bictegravir and metformin in persons with diabetes and HIV. Cattaneo D, Fromenti T, Minisci D, et al. J Antimicrob Chemother 2021;76(7):1945-1946.

Coadministration of bictegravir/emtricitabine/tenofovir alafenamide and metformin (850 mg followed by 500 mg twice daily) was studied in healthy subjects. Inhibition of renal transporters OCT2 and/or MATE1 by bictegravir led to a modest increase (~39%) of metformin plasma exposure following coadministration with bictegravir/emtricitabine/tenofovir alafenamide. The pharmacodynamics responses for metformin (such as glucose reduction, and active GLP-1 and lactate increases after OGTT) were not significantly affected by bictegravir/emtricitabine/tenofovir alafenamide relative to placebo.

Lack of clinically relevant effect of bictegravir on metformin pharmacokinetics and pharmacodynamics. Zhang H, West S, Vu A, et al. 18th International Workshop on Clinical Pharmacology of Antiviral Therapy, Chicago, June 2017, abstract P_50.