Descovy Drug Information

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 . 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 the femoral neck were experienced by 7% of FTC+TAF with EVG+COBI participants.

The long-term clinical significance of these BMD changes is not known. In 799 virologically-suppressed TDF-treated adult participants with HIV-1 that switched to FTC+TAF with EVG+COBI, at Week 48 mean BMD increased (1.86% lumbar spine, 1.95% total hip). BMD declines of 5% or greater at the lumbar spine were experienced by 1% of FTC+TAF with EVG+COBI participants. BMD declines of 7% or greater at the femoral neck were experienced by 1% of FTC+TAF with EVG+COBI participants.

Adverse Reactions in a Clinical Trial of FTC+TAF with EVG+COBI in Virologically-Suppressed Adults with HIV-1 and End Stage Renal Disease (ESRD) Receiving Chronic Hemodialysis In a 48-week trial of virologically-suppressed adult participants with HIV-1 and end stage renal disease (ESRD) (estimated creatinine clearance of less than 15 mL/min) on chronic hemodialysis treated with FTC+TAF with EVG+COBI (N=55), the most commonly reported adverse reaction (adverse event assessed as causally related by investigator and all grades) was nausea (7%). Serious adverse events were reported in 53% of participants and the most common serious adverse events were pneumonia (13%), fluid overload (7%), hyperkalemia (7%) and osteomyelitis (7%). Overall 5% of participants permanently discontinued treatment due to an adverse event. Adverse Reactions in Clinical Trials in Pediatric Participants with HIV-1 Study 106: Adverse Reactions in a Clinical Trial of FTC+TAF with EVG+COBI in Pediatric Participants Weighing at Least 25 kg The safety profile of FTC+TAF in pediatric participants weighing at least 25 kg is informed by an open-label trial of antiretroviral treatment-naïve pediatric participants with HIV-1 between the ages of 12 to less than 18 years weighing at least 35 kg through 48 weeks (N=50; cohort 1) and virologically-suppressed participants with HIV-1 between the ages of 6 to less than 12 years weighing at least 25 kg (N=52; cohort 2). Participants received FTC+TAF with EVG+COBI through 48 weeks. With the exception of a decrease in the mean CD4+ cell count observed in cohort 2, the safety of this combination was similar to that in adults.

Bone Mineral Density Effects Cohort 1: Treatment-naïve adolescents (12 to less than 18 years; at least 35 kg) Among the participants in cohort 1 receiving FTC+TAF with EVG+COBI, mean BMD increased from baseline to Week 48, +4.2% at the lumbar spine and +1.3% for the total body less head (TBLH). Mean changes from baseline BMD Z-scores were −0.07 for lumbar spine and −0.20 for TBLH at Week 48. One participant had significant (at least 4%) lumbar spine BMD loss at Week 48. Cohort 2: Virologically-suppressed children (6 to less than 12 years; at least 25 kg) Among the participants in cohort 2 receiving FTC+TAF with EVG+COBI, mean BMD increased from baseline to Week 48, +3.9% at the lumbar spine and +4.2% for TBLH. Mean changes from baseline BMD Z-scores were -0.24 for lumbar spine and -0.19 for TBLH at Week 48. Six participants had significant (at least 4%) lumbar spine BMD loss at Week 48 and 2 participants also had at least 4% TBLH BMD loss at Week 48. Change from Baseline in CD4+ cell counts Cohort 2: Virologically-suppressed children (6 to less than 12 years; at least 25 kg) Cohort 2 evaluated pediatric participants (N=52) who were virologically-suppressed and who switched from their antiretroviral regimen to FTC+TAF with EVG+COBI. Although all participants had HIV-1 RNA < 50 copies/mL, there was a decrease from baseline in CD4+ cell count at Weeks 24 and 48. The mean baseline and mean change from baseline in CD4+ cell count and in CD4% from Week 2 to Week 48 are presented in Table 2. All participants maintained their CD4+ cell counts above 400 cells/mm 3. Table 2 Mean Change in CD4+ Count and CD4 Percentage from Baseline to Week 48 in Virologically-Suppressed Pediatric Participants from 6 to <12 Years Who Switched to FTC+TAF with EVG+COBI Mean Change from Baseline Baseline Week 2 Week 4 Week 12 Week 24 Week 32 Week 48 CD4+ Cell Count (cells/mm 3 ) 961 Mean (SD) -117 -114 -112 -118 -62 -66 CD4% 38 +0.3% -0.1% -0.8% -0.8% -1.0% -0.6% Study 1474: Adverse Reactions in a Clinical Trial of FTC+TAF with Bictegravir in Pediatric Participants Weighing at Least 14 to Less Than 25 kg In a separate open-label trial of virologically-suppressed participants at least 2 years of age and weighing at least 14 to less than 25 kg (N=22; cohort 3) who received FTC+TAF with bictegravir through 24 weeks, no new adverse reactions or laboratory abnormalities were identified compared to those observed in adults. In this trial, the mean (SD) change from baseline to Week 24 in CD4+ cell count was −126 cells per mm 3 and the mean (SD) change in CD4% from baseline to Week 24 was 0.2% (4.4%). Study 128: Adverse Reactions in a Clinical Trial of DESCOVY in combination with Darunavir+Cobicistat (DRV+COBI) in Pediatric Participants Weighing at Least 14 kg The safety profile of DESCOVY is also informed by a separate open-label trial of virologically-suppressed pediatric participants between the ages of 6 to less than 12 years and weighing at least 25 to less than 40 kg (N=9; cohort 2), and virologically-suppressed pediatric participants at least 2 years of age and weighing at least 14 to less than 25 kg (N=11; cohort 3) who received DESCOVY in combination with DRV+COBI through Week 48. In this study, the safety profile of DESCOVY was similar to that in adults. Bone Mineral Density Effects Cohort 2: Pediatric Participants Weighing at Least 25 to Less Than 40 kg Among the participants in cohort 2 who had both baseline and Week 48 measurements (n=8 and 9 for lumbar spine and TBLH, respectively), mean BMD increased from baseline to Week 48, +6.1% at lumbar spine and +4.4% for TBLH. Cohort 3: Pediatric Participants Weighing at Least 15 to less Than 25 kg Among the participants in cohort 3 who had both baseline and Week 48 measurements (n=7 and 10 for lumbar spine and TBLH, respectively), mean BMD increased from baseline to Week 48, +8.7% at lumbar spine and +6.9% for TBLH. Adverse Reactions from Clinical Trial Experience in Individuals without HIV-1 Taking DESCOVY for HIV-1 PrEP The safety profile of DESCOVY for HIV-1 PrEP was comparable to that observed in clinical trials of participants with HIV based on a double-blind, randomized, active-controlled trial (DISCOVER) in which a total of 5,387 adult men and transgender women without HIV-1 who have sex with men received DESCOVY (N=2,694) or TRUVADA (N=2,693) once daily for HIV-1 PrEP . Median duration of exposure was 86 and 87 weeks, respectively.

The most common adverse reaction in participants who received DESCOVY (incidence greater than or equal to 5%, all grades) was diarrhea (5%). Table 3 provides a list of the most common adverse reactions that occurred in 2% or more of participants in either treatment group. The proportion of participants who discontinued treatment with DESCOVY or TRUVADA due to adverse events, regardless of severity, was 1.3% and 1.8%, respectively. Table 3 Adverse Reactions (All Grades) Reported in ≥2% in Either Arm in the DISCOVER Trial of Participants without HIV-1 DESCOVY (N=2,694) TRUVADA (N=2,693) Diarrhea 5% 6% Nausea 4% 5% Headache 2% 2% Fatigue 2% 3% Abdominal pain Includes the following terms: abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, and abdominal discomfort 2% 3% Renal Laboratory Tests Changes from baseline to Week 48 in renal laboratory data are presented in Table 4. The long-term clinical significance of these renal laboratory changes on adverse reaction frequencies between DESCOVY and TRUVADA is not known.

Table 4 Laboratory Assessments of Renal Function Reported in Participants without HIV-1 Receiving DESCOVY or TRUVADA in the DISCOVER Trial DESCOVY (N=2,694) TRUVADA (N=2,693) eGFR CG =estimated Glomerular Filtration Rate by Cockcroft-Gault; UPCR=urine protein/creatinine ratio Serum Creatinine (mg/dL) Mean (SD). Change at Week 48 −0.01 0.01 eGFR CG (mL/min) Median (Q1, Q3). Change at Week 48 1.8 (−7.2, 11.1) −2.3 (−10.8, 7.2) Percentage of Participants who Developed UPCR >200 mg/g Based on N who had normal UPCR (≤ 200 mg/g) at baseline. At Week 48 0.7% 1.5% Bone Mineral Density Effects In the DISCOVER trial, mean increases from baseline to Week 48 of 0.5% at the lumbar spine (N=159) and 0.2% at the total hip (N=158) were observed in participants receiving DESCOVY, compared to mean decreases of 1.1% at the lumbar spine (N=160) and 1.0% at the total hip (N=158) in participants receiving TRUVADA. BMD declines of 5% or greater at the lumbar spine and 7% or greater at the total hip were experienced by 4% and 1% of participants, respectively, in both treatment groups at Week 48. The long-term clinical significance of these BMD changes is not known. Serum Lipids Changes from baseline to Week 48 in total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and total cholesterol to HDL ratio are presented in Table 5. Table 5 Fasting Lipid Values, Mean Change from Baseline, Reported in Participants without HIV-1 Receiving DESCOVY or TRUVADA in the DISCOVER Trial Excludes participants who received lipid lowering agents during the treatment period.

DESCOVY (N=2,694) TRUVADA (N=2,693) Baseline Week 48 Baseline Week 48 mg/dL Change The baseline and change from baseline are for participants with both baseline and Week 48 values. mg/dL Change Total Cholesterol (fasted) 176 N=1,098 0 176 N=1,124 -12 HDL-Cholesterol (fasted) 51 -2 51 -5 LDL-Cholesterol (fasted) 103 N=1,079 0 103 N=1,107 -7 Triglycerides (fasted) 109 +9 111 -1 Total Cholesterol to HDL ratio 3.7 0.2 3.7 0.1

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of products containing TAF. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and Subcutaneous Tissue Disorders Angioedema, urticaria, and rash Renal and Urinary Disorders Acute renal failure, acute tubular necrosis, proximal renal tubulopathy, and Fanconi syndrome

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.

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 .

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 . 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 . 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.

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.

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 ) 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 before birth ( in utero ) through sexual maturity at daily exposures (AUC) of approximately 60-fold higher than human exposures at the recommended daily dose. Tenofovir Alafenamide: TAF was administered orally to pregnant rats (25, 100, or 250 mg/kg/day) and rabbits (10, 30, or 100 mg/kg/day) through organogenesis (on gestation days 6 through 17, and 7 through 20, respectively). No adverse embryo-fetal effects were observed in rats and rabbits at TAF exposures approximately similar to (rats) and 53 (rabbits) times higher than the exposure in humans at the recommended daily dose of DESCOVY. TAF is rapidly converted to tenofovir; the observed tenofovir exposures in rats and rabbits were 59 (rats) and 93 (rabbits) times higher than human tenofovir exposures at the recommended daily dose.

Since TAF is rapidly converted to tenofovir and a lower tenofovir exposure in rats and mice was observed after TAF administration compared to tenofovir disoproxil fumarate (TDF, another prodrug for tenofovir) administration, a pre/postnatal development study in rats was conducted only with TDF. Doses up to 600 mg/kg/day were administered through lactation; no adverse effects were observed in the offspring on gestation day 7 (and lactation day 20) at tenofovir exposures of approximately 14 times higher than the exposures in humans at the recommended daily dose of DESCOVY.

Pediatric Use The safety and effectiveness of DESCOVY for the treatment of HIV-1 infection have been established in pediatric patients weighing at least 14 kg . Treatment of HIV-1 Infection Adolescent Patients Weighing at Least 35 kg: The safety and effectiveness of DESCOVY in combination with other antiretroviral agents for the treatment of HIV-1 infection was established in adolescent patients weighing at least 35 kg. Use of DESCOVY in adolescent patients is supported by adequate and well controlled trials of FTC+TAF with EVG+COBI in adults and by an open-label trial in antiretroviral treatment-naïve pediatric participants with HIV-1 aged 12 to less than 18 years and weighing at least 35 kg through Week 48 (N=50; Study 106 ) administered FTC+TAF with EVG+COBI. The safety and effectiveness of FTC+TAF with EVG+COBI in adolescent participants was similar to that in adults on this regimen . Pediatric Patients Weighing at least 14 kg and Less than 35 kg: The safety and effectiveness of DESCOVY in combination with other antiretroviral agents, including darunavir and cobicistat (DRV+COBI) but not including other protease inhibitors that require a CYP3A inhibitor, for the treatment of HIV-1 infection was established in pediatric patients weighing at least 14 kg to less than 35 kg . Use of DESCOVY in pediatric patients weighing at least 14 kg to less than 35 kg is supported by: adequate and well controlled trials of FTC+TAF with EVG+COBI in adults; an open-label trial in virologically-suppressed pediatric participants aged 6 to less than 12 years and weighing at least 25 kg (N=52; Study 106 ) administered FTC+TAF with EVG+COBI through Week 48; an open-label trial of DESCOVY administered in combination with DRV+COBI in virologically-suppressed pediatric participants at least 2 years of age and weighing at least 14 kg to less than 40 kg (n=20; Study 128 ) through Week 48; an open-label trial of FTC+TAF with bictegravir in virologically-suppressed pediatric participants at least 2 years of age and weighing at least 14 to less than 25 kg through Week 24 (N=22; Study 1474 ). Overall, the safety and effectiveness of FTC+TAF in pediatric participants in these trials were similar to that observed in adults. Specifically, the safety and efficacy of FTC+TAF with EVG+COBI in participants 6 to 12 years of age and weighing at least 25 kg were similar to that in antiretroviral treatment-naïve adults and adolescents receiving this regimen, with the exception of a decrease from baseline in CD4+ cell count.

The safety and effectiveness of DESCOVY when administered with DRV+COBI in pediatric participants weighing at least 14 kg to less than 40 kg were similar to that in adults. Use of DESCOVY with Other Protease Inhibitors that Require CYP3A Inhibition in Pediatric Patients Weighing at least 14 kg to Less than 35 kg: The use of DESCOVY with atazanavir and cobicistat (ATV+COBI) is not recommended in pediatric patients weighing at least 14 kg to less than 35 kg. The use of DESCOVY with ATV+COBI was studied in pediatric patients weighing at least 14 kg to less than 35 kg.

In Study 128, participants who received ATV+COBI in cohort 2 (25 kg to <40 kg, n=14) and cohort 3 (14 kg to <25 kg, n=15) showed TAF exposures (C max and AUC) that exceeded adult exposures by 4–5-fold in cohort 2, and 2–3-fold in cohort 3. Limited safety data were available to support the increased TAF exposures. Therefore, the use of DESCOVY with ATV+COBI is not recommended in pediatric patients weighing at least 14 kg to less than 35 kg. Safety and effectiveness of DESCOVY in combination with protease inhibitors that require ritonavir in pediatric patients weighing at least 14 kg to less than 35 kg have not been established.

Pediatric Patients Weighing less than 14 kg: Safety and effectiveness of DESCOVY for treatment of HIV-1 infection in pediatric patients weighing less than 14 kg have not been established. HIV-1 PrEP Safety and effectiveness of DESCOVY for HIV-1 PrEP in at-risk adolescents weighing at least 35 kg, excluding individuals at risk from receptive vaginal sex, is supported by data from an adequate and well-controlled trial of DESCOVY for HIV-1 PrEP in adults with additional data from safety and pharmacokinetic studies in previously conducted trials with the individual drug products, FTC and TAF, with EVG+COBI, in adults and pediatric participants with HIV-1. While using DESCOVY for HIV-1 PrEP, HIV-1 testing should be repeated at least every 3 months, and upon diagnosis of any other STIs. Previous studies in at-risk adolescents indicated waning adherence to a daily oral PrEP regimen once visits were switched from monthly to quarterly visits.

Adolescents may therefore benefit from more frequent visits and counseling. Safety and effectiveness of DESCOVY for HIV-1 PrEP in pediatric individuals weighing less than 35 kg have not been established.

for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status. DESCOVY for HIV-1 PrEP is contraindicated in individuals with unknown or positive HIV-1 status.

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%.