Dolutegravir 50 mg, Lamivudine 300 mg, Tenofovir Alafenamide 25 mg Tablets

DOVATO is a fixed-dose combination of the HIV‑1 antiretroviral agents, dolutegravir and lamivudine [see Microbiology (12.4)].

The Cmax, Ctrough, and AUCtau parameters of the components of DOVATO are provided in Table 6.

The absorption, distribution, and elimination pharmacokinetic parameters of the components of DOVATO are provided in Table 7.

Specific Populations — No clinically significant differences in the pharmacokinetics of the components of DOVATO were observed based on age, sex, or race. Pharmacokinetic data for dolutegravir and lamivudine in subjects 65 years of age and older are limited.

Patients with Renal Impairment: The pharmacokinetics for the individual components of DOVATO have been evaluated in patients with renal impairment. See the U.S. prescribing information for the individual components, TIVICAY (dolutegravir) and EPIVIR (lamivudine).

Patients with Hepatic Impairment: The pharmacokinetics for the individual components of DOVATO have been evaluated in patients with varying degrees of hepatic impairment. See the U.S. prescribing information for the individual components, TIVICAY (dolutegravir) and EPIVIR (lamivudine).

Pediatric Subjects: In adolescents receiving DOVATO, dolutegravir and lamivudine exposures were higher as compared to adults; however, the differences in exposure were not considered clinically significant. Lamivudine and dolutegravir exposures were within the observed ranges at the recommended doses in adults and pediatrics receiving the individual components of DOVATO (Table 8).

Pregnant women: Lamivudine: Lamivudine pharmacokinetics were studied in 36 pregnant women during 2 clinical trials conducted in South Africa. Lamivudine pharmacokinetics in pregnant women were similar to those seen in non-pregnant adults and in postpartum women. Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples.

Drug Interaction Studies — Clinical Studies: No drug interaction studies were conducted with DOVATO. The drug interaction studies described below were conducted with dolutegravir or lamivudine when used alone. Table 9 summarizes the effects of dolutegravir on the pharmacokinetics of coadministered drugs. Table 10 summarizes the effect of other drugs on the pharmacokinetics of dolutegravir when used alone and Table 11 summarizes the effect of sorbitol on the pharmacokinetics of lamivudine when used alone.

No clinically significant differences in the pharmacokinetics of tenofovir (organic anion transporter [OAT]1 and OAT3 substrates) or para-amino hippurate (OAT1 and OAT3 substrates) were observed when coadministered with dolutegravir.

No clinically significant differences in the pharmacokinetics of trimethoprim/sulfamethoxazole were observed when coadministered with lamivudine.

No clinically significant differences in the pharmacokinetics of lamivudine were observed when coadministered with trimethoprim (MATE1, MATE2-K, and OCT2 inhibitor)/sulfamethoxazole, interferon alfa, or ribavirin.

In Vitro Studies Where Drug Interaction Potential Was Not Further Evaluated Clinically: Dolutegravir: Dolutegravir does not inhibit CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A. Dolutegravir does not induce CYP1A2, CYP2B6, or CYP3A4.

Dolutegravir is a substrate of UGT1A3 and UGT1A9. Dolutegravir does not inhibit UGT1A1 or UGT2B7.

Dolutegravir is a substrate of BCRP and P-gp. Dolutegravir does not inhibit P‑gp, BCRP, bile salt export pump (BSEP), organic anion transporter polypeptide (OATP)1B1, OATP1B3, OCT1, multidrug resistance protein (MRP)2, or MRP4. Dolutegravir is not a substrate of OATP1B1 or OATP1B3.

Lamivudine: Lamivudine is a substrate of P-gp and BCRP. Lamivudine does not inhibit OATP1B1/3, BCRP, P-gp, MATE1, MATE2-K, OCT1, OCT2, or OCT3.

Tenofovir alafenamide is an antiviral drug against the hepatitis B virus [see Microbiology (12.4)].

The pharmacokinetic properties of VEMLIDY are provided in Table 5. The multiple dose PK parameters of tenofovir alafenamide and its metabolite tenofovir are provided in Table 6.

[see Drug Interactions (7)] — The effects of coadministered drugs on the exposure of tenofovir alafenamide are shown in Table 9. The effects of tenofovir alafenamide on the exposure of coadministered drugs are shown in Table 10 [For information regarding clinical recommendations, see Drug Interactions (7)]. Information regarding potential drug-drug interactions with HIV antiretrovirals is not provided (see the prescribing information for emtricitabine/tenofovir alafenamide for interactions with HIV antiretrovirals).