(see also table below).
Bictegravir inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro. Co-administration of Biktarvy with the OCT2 and MATE1 substrate metformin did not result in a clinically significant increase in metformin exposure. Biktarvy may be co-administered with substrates of OCT2 and MATE1.
Bictegravir is not an inhibitor or inducer of CYP in vivo.
Emtricitabine
In vitro and clinical pharmacokinetic drug-drug interaction studies have shown that the potential for CYP-mediated interactions involving emtricitabine with other medicinal products is low. Co-administration of emtricitabine with medicinal products that are eliminated by active tubular secretion may increase concentrations of emtricitabine, and/or the co-administered medicinal product. Medicinal products that decrease renal function may increase concentrations of emtricitabine.
Tenofovir alafenamide
Tenofovir alafenamide is transported by P-glycoprotein (P –gp) and breast cancer resistance protein (BCRP). Co-administration of Biktarvy with medicinal products that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption. Medicinal products that induce P-gp activity (e.g. rifabutin, carbamazepine, phenobarbital) are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentration of tenofovir alafenamide, which may lead to loss of therapeutic effect of Biktarvy and development of resistance. Co-administration of Biktarvy with other medicinal products that inhibit P-gp and BCRP may increase the absorption and plasma concentration of tenofovir alafenamide.
Tenofovir alafenamide is not an inhibitor or inducer of CYP3A in vivo.
Other interactions
Interactions between Biktarvy or its individual component(s) and co-administered medicinal products are listed in Table 1 below (increase is indicated as “↑”, decrease as “↓” and no change as “↔”; all No Effect Boundaries are 70%-143%).
Table 1: Interactions between Biktarvy or its individual component(s) and other medicinal products
Medicinal product by therapeutic areas/Possible Mechanism of Interaction
Effects on medicinal product levels.
Mean percent change in AUC, Cmax, Cmin
Recommendation concerning co-administration with Biktarvy
HERBAL PRODUCTS
St. John's wort (Hypericum perforatum)
(Induction of CYP3A, UGT1A1, and P-gp)
Interaction not studied with any of the components of Biktarvy.
Co-administration may decrease bictegravir and tenofovir alafenamide plasma concentrations.
Co-administration with St John's wort is contraindicated, due to the effect of St John's wort on the bictegravir component of Biktarvy.
ANTI-INFECTIVES
Antimycobacterials
Rifampicin (600 mg once daily), Bictegravir1
(Induction of CYP3A, UGT1A1, and P-gp)
Bictegravir:
AUC: ↓ 75%
Cmax: ↓ 28%
Interaction not studied with tenofovir alafenamide.
Co-administration of rifampicin may decrease tenofovir alafenamide plasma concentrations.
Co-administration is contraindicated due to the effect of rifampicin on the bictegravir component of Biktarvy.
Rifabutin (300 mg once daily), Bictegravir1
(Induction of CYP3A and P-gp)
Bictegravir:
AUC: ↓ 38%
Cmin: ↓ 56%
Cmax: ↓ 20%
Interaction not studied with tenofov |
