VEMLIDY is a tablet containing tenofovir alafenamide for oral administration. Tenofovir alafenamide, a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor, is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Each tablet contains 25 mg of tenofovir alafenamide (equivalent to 28 mg of tenofovir alafenamide fumarate). The tablets include the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The tablets are film coated with a coating material containing: iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. 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). It has an empirical formula of C 21 H 29 O 5 N 6 P∙½(C 4 H 4 O 4 ) and a formula weight of 534.50. It 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

VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients 6 years of age and older and weighing at least 25 kg with compensated liver disease . VEMLIDY is a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor and is indicated for the treatment of chronic hepatitis B virus infection in adults and pediatric patients 6 years of age and older and weighing at least 25 kg with compensated liver disease.

Tablets: 25 mg of tenofovir alafenamide (equivalent to 28 mg of tenofovir alafenamide fumarate) — yellow, round, film-coated tablets, debossed with "GSI" on one side of the tablet and "25" on the other side. Tablets: 25 mg of tenofovir alafenamide.

Testing: Prior to initiation of VEMLIDY, test patients for HIV infection. VEMLIDY alone should not be used in patients with HIV infection. Prior to or when initiating VEMLIDY, and during treatment on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. Also assess serum phosphorus in patients with chronic kidney disease. Recommended dosage: 25 mg (one tablet) taken orally once daily with food. Renal Impairment: VEMLIDY is not recommended in patients with estimated creatinine clearance below 15 mL per minute who are not receiving chronic hemodialysis. In patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after hemodialysis. Hepatic Impairment: VEMLIDY is not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment

Testing Prior to Initiation of VEMLIDY Prior to initiation of VEMLIDY, patients should be tested for HIV-1 infection. VEMLIDY alone should not be used in patients with HIV-1 infection . Prior to or when initiating VEMLIDY, and during treatment with VEMLIDY on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus

Recommended Dosage in Adults and Pediatric Patients 6 Years of Age and Older and Weighing at Least 25 kg The recommended dosage of VEMLIDY in adults and pediatric patients 6 years of age and older and weighing at least 25 kg is one 25 mg tablet taken orally once daily with food

Dosage in Patients with Renal Impairment No dosage adjustment of VEMLIDY is required in patients with estimated creatinine clearance greater than or equal to 15 mL per minute, or in patients with end stage renal disease (ESRD; estimated creatinine clearance below 15 mL per minute) who are receiving chronic hemodialysis. On days of hemodialysis, administer VEMLIDY after completion of hemodialysis treatment. VEMLIDY is not recommended in patients with ESRD who are not receiving chronic hemodialysis . No data are available to make dose recommendations in pediatric patients with renal impairment

Dosage in Patients with Hepatic Impairment No dosage adjustment of VEMLIDY is required in patients with mild hepatic impairment (Child-Pugh A). VEMLIDY is not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment .

HBV and HIV-1 coinfection: VEMLIDY alone is not recommended for the treatment of HIV-1 infection. HIV-1 resistance may develop in these patients. New onset or worsening renal impairment: Prior to or when initiating VEMLIDY, and during treatment on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. Also assess serum phosphorus in patients with chronic kidney disease. Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. 5.1 Severe Acute Exacerbation of Hepatitis B after Discontinuation of Treatment Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Patients who discontinue VEMLIDY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, resumption of anti-hepatitis B therapy may be warranted

Risk of Development of HIV-1 Resistance in Patients Coinfected with HBV and HIV-1 Due to the risk of development of HIV-1 resistance, VEMLIDY alone is not recommended for the treatment of HIV-1 infection. The safety and efficacy of VEMLIDY have not been established in patients coinfected with HBV and HIV-1. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for patients coinfected with HIV-1 should be used

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 . Patients 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 VEMLIDY, and during treatment with VEMLIDY on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome

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 tenofovir disoproxil fumarate (TDF), another prodrug of tenofovir, alone or in combination with other antiretrovirals. Treatment with VEMLIDY should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

VEMLIDY is a substrate of P-glycoprotein (P-gp) and BCRP. Drugs that strongly affect P-gp and BCRP activity may lead to changes in VEMLIDY absorption. Consult the full prescribing information prior to and during treatment for potential drug-drug interactions

Potential for Other Drugs to Affect VEMLIDY VEMLIDY is a substrate of P-glycoprotein (P-gp) and BCRP. Drugs that strongly affect P-gp and BCRP activity may lead to changes in tenofovir alafenamide absorption . Drugs that induce P-gp activity are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentrations of tenofovir alafenamide, which may lead to loss of therapeutic effect of VEMLIDY. Coadministration of VEMLIDY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of tenofovir alafenamide

Drugs Affecting Renal Function Because tenofovir is primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of 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 4 provides a listing of established or potentially clinically significant drug interactions. The drug interactions described are based on studies conducted with tenofovir alafenamide or are predicted drug interactions that may occur with VEMLIDY [For magnitude of interaction, see Clinical Pharmacology ] . Information regarding potential drug-drug interactions with HIV antiretrovirals is not provided . The table includes potentially significant interactions but is not all inclusive. Table 4 Established and Other Potentially Significant Drug Interactions This table is not all inclusive. Concomitant Drug Class: Drug Name Effect on Concentration ↓ = decrease. Clinical Comment Anticonvulsants: ↓ tenofovir alafenamide When coadministered with carbamazepine, the tenofovir alafenamide dose should be increased to two tablets once daily. Coadministration of VEMLIDY with oxcarbazepine, phenobarbital, or phenytoin is not recommended. Carbamazepine Indicates that a drug interaction study was conducted. P-gp inducer Oxcarbazepine Phenobarbital Phenytoin Antimycobacterials: ↓ tenofovir alafenamide Coadministration of VEMLIDY with rifabutin, rifampin or rifapentine is not recommended. Rifabutin Rifampin Rifapentine Herbal Products: ↓ tenofovir alafenamide Coadministration of VEMLIDY with St. John's wort is not recommended. St. John's wort (Hypericum perforatum) 7.4 Drugs without Clinically Significant Interactions with VEMLIDY Based on drug interaction studies conducted with VEMLIDY, no clinically significant drug interactions have been observed with: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.