Emtricitabine and tenofovir alafenamide

Consult the Full Prescribing Information prior to and during use for potential drug interactions. ( 7 , 12.3 )

7.1 Potential for Other Drugs to Affect One or More Components of DESCOVY TAF, a component of DESCOVY, is a substrate of P-gp, BCRP, OATP1B1, and OATP1B3. Drugs that strongly affect P-gp and BCRP activity may lead to changes in TAF absorption (see Table 6 ). Drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentration of TAF, which may lead to loss of therapeutic effect of DESCOVY and development of resistance. Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF. TAF is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or UGT1A1.

TAF is a weak inhibitor of CYP3A in vitro . TAF is not an inhibitor or inducer of CYP3A in vivo .

7.2 Drugs Affecting Renal Function Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of DESCOVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs [see Warnings and Precautions (5.4) ] .

7.3 Established and Other Potentially Significant Interactions Table 6 provides a listing of established or potentially clinically significant drug interactions with recommended steps to prevent or manage the drug interaction (the table is not all inclusive). The drug interactions described are based on studies conducted with either DESCOVY, the components of DESCOVY (emtricitabine and tenofovir alafenamide) as individual agents, or are predicted drug interactions that may occur with DESCOVY. For magnitude of interaction, see Clinical Pharmacology (12.3) . Table 6 Established and Other Potentially Significant This table is not all inclusive.

Drug Interactions Concomitant Drug Class: Drug Name Effect on Concentration ↓=Decrease Clinical Comment ↑= Increase Antiretroviral Agents: Protease Inhibitors (PI) tipranavir/ritonavir ↓ TAF Coadministration with DESCOVY is not recommended. atazanavir/cobicistat ↑ TAF Coadministration with DESCOVY in pediatric patients weighing 14 to < 35 kg is not recommended [see Use in Specific Populations (8.4) ] . Other Agents Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ TAF Consider alternative anticonvulsant. Antimycobacterials: rifabutin rifampin rifapentine ↓ TAF Coadministration of DESCOVY with rifabutin, rifampin, or rifapentine is not recommended. Herbal Products: St.

John’s wort (Hypericum perforatum) ↓ TAF Coadministration of DESCOVY with St. John’s wort is not recommended.

7.4 Drugs without Clinically Significant Interactions with DESCOVY Based on drug interaction studies conducted with the components of DESCOVY, no clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following antiretroviral agents: atazanavir with ritonavir, atazanavir with cobicistat (in those weighing ≥35 kg), darunavir with ritonavir or cobicistat, dolutegravir, efavirenz, ledipasvir, lopinavir/ritonavir, maraviroc, nevirapine, raltegravir, rilpivirine, and sofosbuvir.

No clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following drugs: buprenorphine, itraconazole, ketoconazole, lorazepam, methadone, midazolam, naloxone, norbuprenorphine, norgestimate/ethinyl estradiol, and sertraline.

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to DESCOVY during pregnancy. Healthcare providers are encouraged to register individuals by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no statistically significant difference in the overall risk of major birth defects for emtricitabine (FTC) or tenofovir alafenamide (TAF) compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ) .

The rate of miscarriage for individual drugs is not reported in the APR. The estimated background rate of miscarriage in the clinically recognized pregnancies in the U.S. general population is 15–20%. In animal studies, no adverse developmental effects were observed when the components of DESCOVY were administered separately during the period of organogenesis at exposures 60 and 108 times (mice and rabbits, respectively) the FTC exposure and at exposure equal to or 53 times (rats and rabbits, respectively) the TAF exposure at the recommended daily dose of DESCOVY (see Data ).

Likewise, no adverse developmental effects were seen when FTC was administered to mice through lactation at exposures up to approximately 60 times the exposure at the recommended daily dose of DESCOVY. No adverse effects were observed in the offspring when TDF was administered through lactation at tenofovir exposures of approximately 14 times the exposure at the recommended daily dosage of DESCOVY. Data Human Data Prospective reports from the APR of overall major birth defects in pregnancies exposed to the components of DESCOVY are compared with a U.S. background major birth defect rate. Methodological limitations of the APR include the use of MACDP as the external comparator group.

The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. Emtricitabine (FTC): Based on prospective reports to the APR of over 7300 exposures to FTC-containing regimens during pregnancy resulting in live births (including over 5400 exposed in the first trimester and over 1800 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.0% (95% CI: 2.5% to 3.5%) and 2.7% (95% CI: 2.0% to 3.6%) following first and second/third trimester exposure, respectively, to FTC-containing regimens.…