Liverpool HIV Interactions

Potential Interaction

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

Ciclosporin (Cyclosporine)

Quality of Evidence: Very Low

Summary:

Coadministration has not been studied. Coadministration of ciclosporin, a potent P-gp inhibitor, is expected to increase bictegravir concentrations but to a modest extent. Coadministration of bictegravir with darunavir/cobicistat (a strong CYP3A4 and P-gp inhibitor) increased bictegravir exposure by 74%. This increase is unlikely to be clinically significant; available dose exposure data, as well as data from phase 2 and phase 3 studies (48 weeks treatment), have shown a good safety profile with up to a 2.4 fold increase in bictegravir AUC. However, tenofovir alafenamide (the prodrug of tenofovir) is a substrate of P-gp and inhibitors of P-gp such as ciclosporin are expected to increase the absorption of tenofovir alafenamide and thereby increase the systemic concentration. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile. Note, the European product label for Biktarvy does not recommend coadministration with ciclosporin. If the combination is needed, clinical and biological monitoring, notably renal function, is recommended.

Description:

Co-administration of ciclosporin (IV or oral use) is not recommended. If the combination is needed, clinical and biological monitoring, notably renal function, is recommended. The interaction has not been studied with any of the components of Biktarvy. Co-administration of ciclosporin (IV or oral use) is expected to increase plasma concentrations of both bictegravir and tenofovir alafenamide due to inhibition of P-gp.

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

The antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir was evaluated in a phase 1b, randomized, double-blinded, adaptive, sequential cohort, placebo-controlled study. HIV-infected adults not taking antiretroviral therapy were randomized to receive BIC (5, 25, 50, or 100 mg) or placebo once daily for 10 days. Steady-state plasma exposure was approximately dose-proportional up to a 100 mg dose. Bictegravir AUCs on day 10 were 87538 ng.h/ml in the 50 mg group and 178.902 ng.h/ml in the 100 mg group. Bictegravir was safe and well tolerated at all dose levels.

Antiviral activity, safety, and pharmacokinetics of bictegravir as 10-day monotherapy in HIV-1-Infected Adults. Gallant JE, Thompson M, DeJesus E, et al. J Acquir Immune Defic Syndr. 2017, 75(1): 61-66.

The efficacy and safety of bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine was assessed in a double-blind, multicentre, active-controlled, randomised controlled non-inferiority trial. 631 participants were randomly assigned to receive coformulated bictegravir, emtricitabine, and tenofovir alafenamide (n=316) or coformulated dolutegravir, abacavir, and lamivudine (n=315), of whom 314 and 315 patients, respectively, received at least one dose of study drug. At 48 weeks, coformulated bictegravir, emtricitabine, and tenofovir alafenamide achieved virological suppression in 92% of previously untreated adults and was non-inferior to coformulated dolutegravir, abacavir, and lamivudine, with no treatment-emergent resistance. Bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated with better gastrointestinal tolerability than dolutegravir, abacavir, and lamivudine

Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Gallant J, Lazzarin A, Mills A, et al. Lancet. 2017, 390(10107):2063-2072.

In a randomised, double-blind, multicentre, placebo-controlled, non-inferiority trial, HIV-infected adults were randomly assigned to receive oral fixed-dose combination bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg (n=320)or dolutegravir 50 mg with coformulated emtricitabine 200 mg and tenofovir alafenamide 25 mg, with matching placebo (n-325), once a day for 144 weeks. The fixed-dose combination of bictegravir, emtricitabine, and tenofovir alafenamide was safe and well tolerated compared with the dolutegravir regimen. Incidence and severity of adverse events were similar between groups, and few participants discontinued treatment due to adverse events (5 [2%] of 320 in the bictegravir group and 1 [<1%] 325 in the dolutegravir group).

Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Sax PE, Pozniak A, Montes ML, et al. Lancet. 2017,390(10107):2073-2082.

View all available interactions with Bictegravir/ Emtricitabine/Tenofovir alafenamide (BIC/FTC/TAF) by clicking here.