tenofovir alafenamide 25 MG Oral Tablet [Vemlidy]

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) ].

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 prescribing information [see Drug Interactions (7) ] . 2.4 Recommended Dosage for Treatment of HIV-1 Infection in Pediatric Patients Weighing at Least 14 kg to Less than 35 kg The recommended dosage of DESCOVY for treatment of HIV-1 in pediatric patients is based on body weight and is provided in Table 1 . This dosing information is applicable to pediatric patients with estimated creatinine clearance greater than or equal to 30 mL per minute [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] who are receiving DESCOVY with other antiretroviral agents, including darunavir (DRV) and cobicistat (COBI) but not including other HIV-1 protease inhibitors that are administered with either ritonavir or cobicistat. Table 1 Dosing for Treatment of HIV-1 Infection in Pediatric Patients Weighing 14 to Less than 35 kg Body Weight (kg) DESCOVY Dosage 25 kg to less than 35 kg One tablet containing 200 mg of FTC and 25 mg of TAF taken orally once daily 14 kg to less than 25 kg One tablet containing 120 mg of FTC and 15 mg of TAF taken orally once daily For specific dosing recommendations for coadministered antiretroviral drugs, refer to their respective prescribing information [see Drug Interactions (7) ] . 2.5 Recommended Dosage for HIV-1 PrEP in Adults and Adolescents Weighing at Least 35 kg The dosage of DESCOVY for HIV-1 PrEP is one tablet (containing 200 mg of FTC and 25 mg of TAF) once daily taken orally with or without food in: adults and adolescents without HIV-1 weighing at least 35 kg and with a creatinine clearance greater than or equal to 30 mL per minute; or adults without HIV-1 and 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 Indications and Usage (1.2) and Clinical Pharmacology (12.3) ]. 2.6 Not Recommended in Individuals with Severe Renal Impairment for Treatment of HIV-1 Infection or for HIV-1 PrEP DESCOVY is not recommended in individuals with: severe renal impairment (estimated creatinine clearance of 15 to below 30 mL per minute); or end stage renal disease (ESRD; estimated creatinine clearance below 15 mL per minute) who are not receiving chronic hemodialysis [see Dosage and Administration (2.3 , 2.5) and Use in Specific Populations (8.6) ] .

WARNINGS AND PRECAUTIONS Comprehensive management to reduce the risk of sexually transmitted infections (STIs), including HIV-1, when DESCOVY is used for HIV-1 PrEP: Counsel on adherence to daily dosing and safer sex practices, including condoms, to reduce the risk of STIs. ( 5.2 ) Management to reduce the risk of acquiring HIV-1 drug resistance when DESCOVY is used for HIV-1 PrEP: refer to full prescribing information for additional detail. ( 5.2 ) Immune reconstitution syndrome during treatment of HIV-1 infection: May necessitate further evaluation and treatment. ( 5.3 ) New onset or worsening renal impairment: Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein when initiating DESCOVY and during use on a clinically appropriate schedule in all individuals. Also assess serum phosphorus in individuals with chronic kidney disease. ( 5.4 ) Lactic acidosis/severe hepatomegaly with steatosis: Discontinue DESCOVY in individuals who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. ( 5.5 ) 5.1 Severe Acute Exacerbation of Hepatitis B in Individuals with HBV All individuals should be tested for the presence of hepatitis B virus (HBV) before or when initiating DESCOVY [see Dosage and Administration (2.1) ] . Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in individuals with HBV who have discontinued products containing FTC and/or tenofovir disoproxil fumarate (TDF) and may occur with discontinuation of DESCOVY. Individuals with HBV who discontinue DESCOVY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, anti-hepatitis B therapy may be warranted, especially in individuals with advanced liver disease or cirrhosis, since post-treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure. Individuals without HBV should be offered vaccination. 5.2 Comprehensive Management to Reduce the Risk of Sexually Transmitted Infections, Including HIV-1, and Development of HIV-1 Resistance When DESCOVY Is Used for HIV-1 PrEP Use DESCOVY for HIV-1 PrEP to reduce the risk of HIV-1 infection as part of a comprehensive prevention strategy, including adherence to daily administration and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). The time from initiation of DESCOVY for HIV-1 PrEP to maximal protection against HIV-1 infection is unknown. Risk for HIV-1 acquisition includes behavioral, biological, or epidemiologic factors including but not limited to condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Counsel individuals on the use of other prevention measures (e.g., consistent and correct condom use, knowledge of partner(s)’ HIV-1 status, including viral suppression status, regular testing for STIs that can facilitate HIV-1 transmission). Inform individuals without HIV-1 about, and support their efforts in, reducing sexual risk behavior . Use DESCOVY to reduce the risk of acquiring HIV-1 only in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undetected HIV-1 infection who are taking only DESCOVY, because DESCOVY alone does not constitute a complete regimen for HIV-1 treatment [see Microbiology (12.4) ]; therefore, care should be taken to minimize the risk of initiating or continuing DESCOVY before confirming the individual is HIV-1 negative. Some HIV-1 tests only detect anti-HIV antibodies and may not identify HIV-1 during the acute stage of infection. Prior to initiating DESCOVY for HIV-1 PrEP, ask seronegative individuals about recent (in past month) potential exposure events (e.g., condomless sex or condom breaking during sex with a partner of unknown HIV-1 status or unknown viremic status, or a recent STI), and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash). 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. 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 . If an HIV-1 test indicates possible HIV-1 infection, or if symptoms consistent with acute HIV-1 infection develop following a potential exposure event, convert the HIV-1 PrEP regimen to an HIV treatment regimen until negative infection status is confirmed using a test approved or cleared by the FDA as an aid in the diagnosis of acute or primary HIV-1 infection. Counsel individuals without HIV-1 to strictly adhere to the once daily DESCOVY dosing schedule. The effectiveness of DESCOVY in reducing the risk of acquiring HIV-1 is strongly correlated with adherence, as demonstrated by measurable drug levels in a clinical trial of DESCOVY for HIV-1 PrEP. Some individuals, such as adolescents, may benefit from more frequent visits and counseling to support adherence [see Use in Specific Populations (8.4) , Microbiology (12.4) , and Clinical Studies (14.3) ]. 5.3 Immune Reconstitution Syndrome Immune reconstitution syndrome has been reported in patients with HIV-1 treated with combination antiretroviral therapy, including FTC, a component of DESCOVY. During the initial phase of combination antiretroviral treatment, patients with HIV-1 whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment. Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment. 5.4 New Onset or Worsening Renal Impairment Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products; while most of these cases were characterized by potential confounders that may have contributed to the reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse events [see Adverse Reactions (6.1 , 6.2) ] . DESCOVY is not recommended in individuals with estimated creatinine clearance of 15 to below 30 mL per minute, or in individuals with estimated creatinine clearance below 15 mL per minute who are not receiving chronic hemodialysis. Individuals taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions. Prior to or when initiating DESCOVY, and during treatment with 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. Discontinue DESCOVY in individuals who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. 5.5 Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of DESCOVY, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals. Treatment with DESCO

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 )

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