DESCOVY

Indications and Usage ( 1.1 ) 06/2025 Dosage and Administration, Recommended Dosage for Treatment of HIV-1 Infection in Pediatric Patients Weighing at Least 14 kg to Less than 35 kg ( 2.4 ) 06/2025

1 INDICATIONS AND USAGE HIV-1 Treatment ( 1.1 ): DESCOVY is a two-drug combination of emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV nucleoside analog reverse transcriptase inhibitors (NRTIs), and is indicated: in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and adolescent patients weighing at least 35 kg. for the treatment of HIV-1 infection in pediatric patients weighing at least 14 kg to less than 35 kg in combination with other antiretroviral agents, including darunavir and cobicistat but not other protease inhibitors that require a CYP3A inhibitor. HIV-1 PrEP ( 1.2 ): DESCOVY is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of HIV-1 infection from sexual acquisition, excluding individuals at risk from receptive vaginal sex. Individuals must have a negative HIV-1 test immediately prior to initiating DESCOVY for HIV-1 PrEP. Limitations of Use ( 1.2 ): The indication does not include use of DESCOVY in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated. 1.1 Treatment of HIV-1 Infection DESCOVY is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and adolescent patients weighing at least 35 kg. DESCOVY is indicated for the treatment of HIV-1 infection in pediatric patients weighing at least 14 kg to less than 35 kg in combination with other antiretroviral agents, including darunavir and cobicistat but not other protease inhibitors that require a CYP3A inhibitor. 1.2 HIV-1 Pre-Exposure Prophylaxis (PrEP) DESCOVY is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of HIV-1 infection from sexual acquisition, excluding individuals at risk from receptive vaginal sex. Individuals must have a negative HIV-1 test immediately prior to initiating DESCOVY for HIV-1 PrEP [see Dosage and Administration (2.2) and Warnings and Precautions (5.2) ]. Limitations of Use: The indication does not include use of DESCOVY in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated [see Clinical Studies (14.3) ].

2 DOSAGE AND ADMINISTRATION Testing: Prior to or when initiating DESCOVY, test for hepatitis B virus infection. Prior to or when initiating DESCOVY, and during use on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all individuals. In individuals with chronic kidney disease, also assess serum phosphorus. ( 2.1 ) HIV-1 Screening: Screen all individuals for HIV-1 infection immediately prior to initiating DESCOVY for HIV-1 PrEP and at least once every 3 months while taking DESCOVY, and upon diagnosis of any other sexually transmitted infections (STIs). ( 2.2 ) Recommended dosage: Treatment of HIV-1 Infection: Adult and pediatric patients weighing at least 35 kg: One 200 mg/25 mg tablet once daily with or without food. ( 2.3 ) Pediatric patients receiving DESCOVY with other antiretroviral agents, including darunavir and cobicistat but not other protease inhibitors administered with either ritonavir or cobicistat, and weighing: at least 25 to less than 35 kg: One 200 mg/25 mg tablet once daily with or without food. ( 2.4 ) at least 14 to less than 25 kg: One 120 mg/15 mg tablet once daily with or without food. ( 2.4 ) HIV-1 PrEP: One 200 mg/25 mg tablet once daily with or without food in individuals with body weight at least 35 kg. ( 2.5 ) Renal impairment: DESCOVY is not recommended in individuals with estimated creatinine clearance of 15 to below 30 mL per minute, or below 15 mL per minute who are not receiving chronic hemodialysis. ( 2.6 ) 2.1 Testing When Initiating and During Use of DESCOVY for Treatment of HIV-1 Infection or for HIV-1 PrEP Prior to or when initiating DESCOVY, test individuals for hepatitis B virus infection [see Warnings and Precautions (5.1) ] . Prior to or when initiating DESCOVY, and during use of DESCOVY on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all individuals. In individuals with chronic kidney disease, also assess serum phosphorus [see Warnings and Precautions (5.4) ]. 2.2 HIV-1 Screening for Individuals Receiving DESCOVY for HIV-1 PrEP Screen all individuals for HIV-1 infection immediately prior to initiating DESCOVY for HIV-1 PrEP and at least once every 3 months while taking DESCOVY, and upon diagnosis of any other sexually transmitted infections (STIs) [see Indications and Usage (1.2) , Contraindications (4) , and Warnings and Precautions (5.2) ]. If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection [see Warnings and Precautions (5.2) , Use in Specific Populations (8.4) , and Clinical Studies (14.3) ]. 2.3 Recommended Dosage for Treatment of HIV-1 Infection in Adults and Pediatric Patients Weighing at Least 35 kg DESCOVY is a two-drug fixed dose combination product containing emtricitabine (FTC) and tenofovir alafenamide (TAF). The recommended dosage of DESCOVY for treatment of HIV-1 is one tablet containing 200 mg FTC and 25 mg of TAF taken orally once daily with or without food in: adults and pediatric patients with body weight at least 35 kg and estimated creatinine clearance greater than or equal to 30 mL per minute; or adults with creatinine clearance below 15 mL per minute who are receiving chronic hemodialysis. On days of hemodialysis, administer the daily dose of DESCOVY after completion of hemodialysis treatment [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . The safety and effectiveness of DESCOVY coadministered with an HIV-1 protease inhibitor that is administered with either ritonavir or cobicistat have not been established in adults with creatinine clearance below 15 mL per minute, with or without hemodialysis. For specific dosing recommendations for coadministered antiretroviral drugs, refer to their respective presc …

3 DOSAGE FORMS AND STRENGTHS DESCOVY tablets are available in two dose strengths: 200 mg/25 mg tablets: 200 mg of emtricitabine (FTC) and 25 mg of tenofovir alafenamide (TAF) (equivalent to 28 mg of tenofovir alafenamide fumarate). These tablets are blue, rectangular-shaped, film-coated, debossed with “GSI” on one side and “225” on the other side. 120 mg/15 mg tablets: 120 mg of FTC and 15 mg of TAF (equivalent to 16.8 mg of tenofovir alafenamide fumarate). These tablets are white, round-shaped, film coated, debossed with “GSI” on one side and “15” on the other side. Tablets: 200 mg/25 mg and 120 mg/15 mg of FTC and TAF respectively ( 3 )

4 CONTRAINDICATIONS DESCOVY for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status [see Warnings and Precautions (5.2) ]. DESCOVY for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status. ( 4 )

6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B [see Warnings and Precautions (5.1) ] . Immune Reconstitution Syndrome [see Warnings and Precautions (5.3) ] . New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.4) ] . Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.5) ]. In participants with HIV-1, the most common adverse reaction (incidence greater than or equal to 10%, all grades) was nausea. ( 6.1 ) In adults without HIV-1 in a PrEP trial, the most common adverse reaction (incidence greater than or equal to 5%, all grades) was diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug (or a drug given in various combinations with other concomitant therapy) cannot be directly compared to rates in the clinical trials of another drug (or drug given in the same or different combination therapy) and may not reflect the rates observed in practice. Adverse Reactions in Clinical Trials of FTC+TAF with Elvitegravir (EVG) plus Cobicistat (COBI) in Treatment-Naïve Adults with HIV-1 In pooled 48-week trials of antiretroviral treatment-naïve adult participants with HIV-1, the most common adverse reaction in participants treated with FTC+TAF with EVG+COBI (N=866) (incidence greater than or equal to 10%, all grades) was nausea (10%). In this treatment group, 0.9% of participants discontinued FTC+TAF with EVG+COBI due to adverse events during the 48-week treatment period [see Clinical Studies (14.2) ] . The safety profile was similar in virologically-suppressed adults with HIV-1 who were switched to FTC+TAF with EVG+COBI (N=799). Antiretroviral treatment-naïve adult participants with HIV-1 treated with FTC+TAF with EVG+COBI experienced mean increases of 30 mg/dL of total cholesterol, 15 mg/dL of LDL cholesterol, 7 mg/dL of HDL cholesterol, and 29 mg/dL of triglycerides after 48 weeks of use. Renal Laboratory Tests In two 48-week trials in antiretroviral treatment-naïve adults with HIV-1 treated with FTC+TAF with EVG+COBI (N=866) with a median baseline eGFR of 115 mL per minute, mean serum creatinine increased by 0.1 mg per dL from baseline to Week 48. Median urine protein-to-creatinine ratio (UPCR) was 44 mg per gram at baseline and at Week 48. In a 48-week trial in virologically-suppressed TDF-treated adults with HIV-1 who switched to FTC+TAF with EVG+COBI (N=959) with a mean baseline eGFR of 112 mL per minute, mean serum creatinine was similar to baseline at Week 48; median UPCR was 61 mg per gram at baseline and 46 mg per gram at Week 48. Across these trials, renal serious adverse events or discontinuations due to renal adverse reactions were encountered in less than 1% of participants treated with FTC+TAF with EVG+COBI. In a 24-week trial in adults with HIV-1 and renal impairment (baseline eGFR 30 to 69 mL per minute) who received FTC+TAF with EVG+COBI (N=248), mean serum creatinine was 1.5 mg per dL at both baseline and Week 24. Median UPCR was 161 mg per gram at baseline and 93 mg per gram at Week 24. FTC+TAF with EVG+COBI was permanently discontinued due to worsening renal function in two of 80 (3%) participants. Bone Mineral Density Effects In the pooled analysis of two 48-week trials of antiretroviral treatment-naïve adult participants with HIV-1, bone mineral density (BMD) from baseline to Week 48 was assessed by dual-energy X-ray absorptiometry (DXA). Mean BMD decreased from baseline to Week 48 −1.30% with FTC+TAF with EVG+COBI at the lumbar spine and −0.66% at the total hip. BMD declines of 5% or greater at the lumbar spine were experienced by 10% of FTC+TAF with EVG+COBI participants. BMD declines of 7% or greater at t …

7 DRUG INTERACTIONS 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 USE IN SPECIFIC POPULATIONS Pediatrics: Treatment of HIV-1 Infection: Not recommended for patients weighing less than 14 kg. ( 8.4 ) HIV-1 PrEP: Not recommended for individuals weighing less than 35 kg. ( 8.4 ) 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. Tenofovir Alafenamide (TAF): Based on prospective reports to the APR of over 1600 exposures to TAF-containing regimens during pregnancy resulting in live births (including over 1300 exposed in the first trimester and over 300 exposed in the second/third trimester), the prevalence of birth defects in live births was 3.9% (95% CI: 2.9% to 5.2%) and 4.7% (95% CI: 2.6% to 7.7%) following first and second/third trimester exposure, respectively, to TAF-containing regimens. Animal Data Emtricitabine: FTC was administered orally to pregnant mice (250, 500, or 1000 mg/kg/day) and rabbits (100, 300, or 1000 mg/kg/day) through organogenesis (on gestation days 6 through 15, and 7 through 19, respectively). No significant toxicological effects were observed in embryo-fetal toxicity studies performed with FTC in mice at exposures (area under the curve [AUC]) approximately 60 times higher and in rabbits at approximately 108 times higher than human exposures at the recommended daily dose. In a pre/postnatal development study with FTC, mice were administered doses up to 1000 mg/kg/day; no significant adverse effects directly related to drug were observed in the offspring exposed daily from bef …

12.1 Mechanism of Action DESCOVY is a fixed dose combination of antiretroviral drugs emtricitabine (FTC) and tenofovir alafenamide (TAF) [see Microbiology (12.4) ] .

11 DESCRIPTION DESCOVY (emtricitabine and tenofovir alafenamide) is a fixed dose combination tablet containing emtricitabine (FTC) and tenofovir alafenamide (TAF) for oral administration. FTC, a synthetic nucleoside analog of cytidine, is an HIV nucleoside analog reverse transcriptase inhibitor (HIV NRTI). TAF, an HIV NRTI, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. DESCOVY tablets are available in two dose strengths: 200 mg/25 mg tablets: 200 mg of FTC and 25 mg of TAF (equivalent to 28 mg of tenofovir alafenamide fumarate). 120 mg/15 mg tablets: 120 mg of FTC and 15 mg of TAF (equivalent to 16.8 mg of tenofovir alafenamide fumarate). Both dose strengths of DESCOVY tablets include the following inactive ingredients: croscarmellose sodium, magnesium stearate, and microcrystalline cellulose. The 200 mg/ 25 mg tablets are film-coated with a coating material containing indigo carmine aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. The 120 mg/15 mg tablets are film-coated with a coating material containing polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. Emtricitabine: The chemical name of FTC is 4-amino-5-fluoro-1-(2 R -hydroxymethyl-1,3-oxathiolan-5 S -yl)-(1H)-pyrimidin-2-one. FTC is the (-)enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5 position. FTC has a molecular formula of C 8 H 10 FN 3 O 3 S and a molecular weight of 247.24 and has the following structural formula: FTC is a white to off-white powder with a solubility of approximately 112 mg per mL in water at 25 °C. Chemical Structure Tenofovir Alafenamide: The chemical name of tenofovir alafenamide fumarate drug substance is L-alanine, N -[( S )-[[(1 R )-2-(6-amino-9 H -purin-9-yl)-1-methylethoxy]methyl]phenoxyphosphinyl]-, 1-methylethyl ester, (2 E )-2-butenedioate (2:1). Tenofovir alafenamide fumarate has an empirical formula of C 21 H 29 O 5 N 6 P•1⁄2(C 4 H 4 O 4 ) and a formula weight of 534.50 and has the following structural formula: Tenofovir alafenamide fumarate is a white to off-white or tan powder with a solubility of 4.7 mg per mL in water at 20 °C. Chemical Structure

10 OVERDOSAGE No data are available on overdose of DESCOVY in patients. If overdose occurs, monitor the individual for evidence of toxicity. Treatment of overdose with DESCOVY consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the individual. Emtricitabine (FTC): Limited clinical experience is available at doses higher than the recommended dose of FTC in DESCOVY. In one clinical pharmacology study, single doses of FTC 1200 mg (6 times the FTC dose in DESCOVY) were administered to 11 participants. No severe adverse reactions were reported. The effects of higher doses are not known. Hemodialysis treatment removes approximately 30% of the FTC dose over a 3-hour dialysis period starting within 1.5 hours of FTC dosing (blood flow rate of 400 mL per minute and a dialysate flow rate of 600 mL per minute). It is not known whether FTC can be removed by peritoneal dialysis. Tenofovir Alafenamide (TAF) : Limited clinical experience is available at doses higher than the recommended dose of TAF. A single dose of 125 mg TAF (5 times the TAF dose in 200/25 mg DESCOVY) was administered to 48 healthy participants; no serious adverse reactions were reported. The effects of higher doses are unknown. Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%.

16 HOW SUPPLIED/STORAGE AND HANDLING DESCOVY tablets are available in bottles and blister packs containing 30 tablets: Bottles 200 mg/25 mg tablets each contain 200 mg of emtricitabine (FTC) and 25 mg of tenofovir alafenamide (TAF). These tablets are blue, rectangular-shaped, and film-coated with “GSI” debossed on one side and “225” on the other side (NDC 61958-2002-1). 120 mg/15 mg tablets each contain 120 mg of FTC and 15 mg of TAF. These tablets are white, round-shaped, and film coated with “GSI” debossed on one side and “15” on the other side (NDC 61958-2005-1). Bottles contain a silica gel desiccant, polyester coil, and child resistant closure. Keep bottle tightly closed. The bottle containing 200 mg/25 mg tablets (NDC 61958-2002-1) may have a tamper-evident seal over the cap. If a tamper-evident seal is present, do not use if the seal is opened or damaged. Blister Pack 200 mg/25 mg tablets each contain 200 mg of FTC and 25 mg of TAF. These tablets are blue, rectangular-shaped, and film-coated with “GSI” debossed on one side and “225” on the other side (NDC 61958-2002-2). Blister packs are sealed with a child-resistant laminated foil lidding material (peel-push) and each blister cavity contains a die-cut desiccant film which is heat staked to the foil lidding material. Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) (see USP Controlled Room Temperature). Dispense only in original container.