Total Cost
Free shipping on all orders

Powered by GeniusRx

brand vemlidy 25 mg tablet

In stock Manufacturer GILEAD SCIENCES 61958230101
$40.22 / Tablet

Select Quantity

Prescription is required

Uses

Tenofovir alafenamide fumarate is used for the treatment of chronic hepatitis B virus (HBV) infection.

Tenofovir alafenamide fumarate also is used for the treatment of human immunodeficiency virus (HIV) infection. For information on use of the drug as an antiretroviral agent, see section 8:18.08.

Chronic Hepatitis B Virus Infection

Tenofovir alafenamide fumarate is used for the treatment of HBV infection in adults with compensated liver disease. Safety and efficacy of tenofovir alafenamide fumarate have not been established in patients with decompensated cirrhosis (Child-Pugh class B or C), and the drug is not recommended for treatment of HBV infection in such patients.

The goal of antiviral therapy in patients with chronic HBV infection is to decrease the morbidity and mortality related to the infection (e.g., cirrhosis, hepatic failure, hepatocellular carcinoma). Sustained suppression of HBV replication has been associated with normalization of serum ALT concentrations, loss of hepatitis B e antigen (HBeAg) with or without detection of antibody to HBeAg (anti-HBe), and improvement in liver histology. Currently available therapies for chronic HBV infection (e.g., adefovir, entecavir, lamivudine, telbivudine, tenofovir alafenamide, tenofovir disoproxil fumarate [tenofovir DF], interferon alfa, peginterferon alfa) are used in an attempt to provide an immunologic cure (HBsAg loss and sustained HBV DNA suppression), but cannot provide a virologic cure (eradication of HBV).

Treatment of chronic HBV infection is complex and evolving, and specialized references and experts should be consulted. Information from the American Association for the Study of Liver Diseases (AASLD) regarding management of HBV infection, including recommendations for initial treatment, is available at https://www.aasld.org.

Clinical Experience

Efficacy and safety of tenofovir alafenamide fumarate for the treatment of HBV infection were evaluated in 2 randomized, double-blind, active-controlled studies in treatment-naive (have not previously received nucleoside or nucleotide antivirals) and previously treated adults with compensated liver disease (study 108 and study 110). The primary efficacy end point in both studies was the proportion of patients with plasma HBV DNA levels less than 29 IU/mL at week 48.

In study 108, 425 adults with chronic HBV infection who were negative for serum HBeAg (mean age 46 years, 61% male; 72% Asian, 25% White, 2% Black; 24% HBV genotype B infection, 38% HBV genotype C infection, 31% HBV genotype D infection; 21% previously treated; mean baseline plasma HBV DNA level 5.8 log10 IU/mL; mean serum ALT concentration 94 units/L, 9% with history of cirrhosis) were randomized in a 2:1 ratio to receive tenofovir alafenamide fumarate (25 mg of tenofovir alafenamide once daily) or tenofovir DF (300 mg once daily) for 48 weeks. Concomitant use of other nucleoside or nucleotide antivirals or interferons was not permitted. At 48 weeks, 94 or 93% of patients receiving tenofovir alafenamide or tenofovir DF, respectively, had plasma HBV DNA levels less than 29 IU/mL. In patients with baseline serum ALT concentrations above the upper limit of normal (based on AASLD criteria), normalized ALT concentrations were achieved by 50% of those treated with tenofovir alafenamide and 32% of those treated with tenofovir DF.

In study 110, 873 adults with chronic HBV infection who were positive for serum HBeAg (mean age 38 years, 64% male; 82% Asian, 17% White, 1% Black or other races; 17% HBV genotype B infection, 52% HBV genotype C infection, 23% HBV genotype D infection; 26% previously treated; mean baseline plasma HBV DNA level 7.6 log10 IU/mL; mean serum ALT concentration 120 units/L, 7% with history of cirrhosis) were randomized in a 2:1 ratio to receive tenofovir alafenamide fumarate (25 mg of tenofovir alafenamide once daily) or tenofovir DF (300 mg once daily) for 48 weeks. Concomitant use of other nucleoside or nucleotide antivirals or interferons was not permitted. At 48 weeks, 64 or 67% of patients receiving tenofovir alafenamide or tenofovir DF, respectively, had plasma HBV DNA levels less than 29 IU/mL. In patients with baseline serum ALT concentrations above the upper limit of normal (based on AASLD criteria), normalized ALT concentrations were achieved by 45% of those treated with tenofovir alafenamide and 36% of those treated with tenofovir DF .

Dosage and Administration

General

Prior to initiation of tenofovir alafenamide fumarate for the treatment of chronic hepatitis B virus (HBV) infection, patients should be tested for human immunodeficiency virus type 1 (HIV-1) infection. The drug should not be used alone in patients with HBV and HIV coinfection.(See Individuals with HBV and HIV Coinfection under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)

Serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose, and urine protein should be assessed prior to initiation of tenofovir alafenamide fumarate and monitored as clinically indicated during treatment with the drug.(See New Onset or Worsening Renal Impairment under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)

Administration

Tenofovir alafenamide fumarate is administered orally once daily with food.

Dosage

Dosage of tenofovir alafenamide fumarate is expressed in terms of tenofovir alafenamide.

Adult Dosage

Treatment of Chronic HBV Infection

For the treatment of chronic HBV infection in adults, the recommended dosage of tenofovir alafenamide is 25 mg once daily.

Special Populations

Hepatic Impairment

Dosage adjustments are not necessary if tenofovir alafenamide is used in patients with mild hepatic impairment (Child-Pugh class A).

Tenofovir alafenamide is not recommended in patients with decompensated hepatic impairment (Child-Pugh class B or C).(See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Renal Impairment

Dosage adjustments are not necessary if tenofovir alafenamide is used in patients with mild, moderate, or severe renal impairment.

Tenofovir alafenamide is not recommended in patients with end-stage renal disease (creatinine clearance less than 15 mL/minute).(See Renal Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

Geriatric Patients

Limited data suggest that there are no clinically important differences in the pharmacokinetics of tenofovir alafenamide or tenofovir in geriatric patients compared with younger adults.(See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Cautions

Contraindications

The manufacturer states that there are no contraindications to the use of tenofovir alafenamide fumarate.

Warnings/Precautions

Warnings

Severe Acute Exacerbation of HBV Infection after Discontinuance of Treatment

Severe acute exacerbations of hepatitis B virus (HBV) infection may occur following discontinuance of HBV treatment, including tenofovir alafenamide.

Hepatic function should be closely monitored with clinical and laboratory follow-up for at least several months after tenofovir alafenamide is discontinued. If appropriate, resumption of HBV treatment may be warranted.

Other Warnings/Precautions

Individuals with HBV and HIV Coinfection

Safety and efficacy of tenofovir alafenamide have not been established in patients with HBV and human immunodeficiency virus type 1 (HIV-1) coinfection.

Tenofovir alafenamide is not used alone for the treatment of HIV-1 infection and should not be used alone for treatment of HBV infection in patients with HBV and HIV-1 coinfection because of the risk of development of HIV-1 resistance.

Prior to initiation of tenofovir alafenamide for the treatment of chronic HBV infection, all patients should be offered HIV antibody testing and, if positive, an appropriate antiretroviral regimen recommended for patients with HBV and HIV-1 coinfection should be used.

New Onset or Worsening Renal Impairment

Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported in HIV-infected patients receiving tenofovir prodrugs (e.g., tenofovir DF) and similar effects have been reported in animal toxicology studies.

No cases of Fanconi syndrome or proximal renal tubulopathy (PRT) were reported in clinical trials evaluating tenofovir alafenamide for treatment of chronic HBV infection.

In a pooled analysis of 2 clinical studies in adults with chronic HBV infection (studies 108 and 110), the median baseline estimated glomerular filtration rate (eGFR) was 106 or 105 mL/minute prior to treatment with tenofovir alafenamide or tenofovir DF, respectively. Mean serum creatinine concentrations increased by less than 0.1 mg/dL and median serum phosphorus concentrations decreased by 0.1 mg/dL in both treatment groups. The median change in eGFR from baseline was -1.2 mL/minute in patients treated with tenofovir alafenamide compared with -5.4 mL/minute in those treated with tenofovir DF. The long-term clinical importance of these renal laboratory changes on the incidence of adverse effects reported with these tenofovir prodrugs is not known.

Patients receiving a tenofovir prodrug who have impaired renal function or are receiving nephrotoxic agents (e.g., nonsteroidal anti-inflammatory agents [NSAIAs]) are at increased risk of developing adverse renal effects.(See Drug Interactions: Nephrotoxic Drugs or Drugs Eliminated by Renal Excretion.)

Serum creatinine, serum phosphorous, estimated creatinine clearance, urine glucose, and urine protein should be assessed in all patients prior to initiating tenofovir alafenamide and monitored as clinically appropriate during treatment with the drug.

Tenofovir alafenamide should be discontinued in patients who develop clinically important decreases in renal function or evidence of Fanconi syndrome.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have been reported in patients receiving nucleoside or nucleotide analogs (e.g., the tenofovir prodrug tenofovir disoproxil fumarate [tenofovir DF]) alone or in conjunction with other antiretroviral agents.

Tenofovir alafenamide should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (signs of hepatotoxicity may include hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).

Bone Effects

In animal studies and clinical trials, tenofovir prodrugs (tenofovir alafenamide, tenofovir DF) have been associated with decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism, suggestive of increased bone turnover. The long-term clinical importance of these BMD changes is not known.

In a pooled analysis of 2 clinical studies in adults with chronic HBV infection (study 108 and study 110), the mean percentage change in BMD from baseline to week 48 was assessed by dual-energy X-ray absorptiometry (DXA). At the lumbar spine, the mean percentage change in BMD was -0.6% in patients treated with tenofovir alafenamide compared with -2.4% in those treated with tenofovir DF; 6% of those treated with tenofovir alafenamide and 20% of those treated with tenofovir DF had lumbar spine BMD declines that were 5% or more. At the total hip, the mean percentage change in BMD was -0.2% in patients treated with tenofovir alafenamide compared with -1.9% in those treated with tenofovir DF. At the femoral neck, 3% of patients treated with tenofovir alafenamide and 6% of those treated with tenofovir DF had BMD declines that were 7% or greater.

Specific Populations

Pregnancy

Data are not available regarding use of tenofovir alafenamide in pregnant women.

In animal studies, there was no evidence of impaired fertility or harm to the fetus. Adverse developmental effects were not observed when tenofovir alafenamide was administered during organogenesis to rats or rabbits in dosages that resulted in exposures equal to or 51 times higher, respectively, than human exposures reported with the recommended daily dosage of tenofovir alafenamide.

If tenofovir alafenamide is used during pregnancy or the patient becomes pregnant while receiving the drug, the patient should be enrolled in the Antiretroviral Pregnancy Registry (APR) at 800-258-4263.

Lactation

It is not known whether tenofovir alafenamide and its metabolites are distributed into human milk, affect human milk production, or have effects on the breast-fed infant. Tenofovir is distributed into milk of lactating rats and rhesus monkeys receiving tenofovir DF.

The benefits of breast-feeding and the importance of tenofovir alafenamide to the woman should be considered along with the potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Pediatric Use

Safety and efficacy of tenofovir alafenamide have not been established in pediatric patients younger than 18 years of age.

Geriatric Use

Clinical trials of tenofovir alafenamide did not include sufficient numbers of patients 65 years of age and older to determine if they respond differently than younger adults.

Hepatic Impairment

Safety and efficacy of tenofovir alafenamide have not been established in patients with decompensated cirrhosis (Child-Pugh class B or C), and the drug is not recommended in such patients.

Dosage adjustments are not necessary if tenofovir alafenamide is used in patients with mild hepatic impairment (Child-Pugh class A). In individuals with mild hepatic impairment, tenofovir alafenamide and tenofovir plasma exposures are 7.5 and 11% lower, respectively, compared with exposures reported in those with normal hepatic function.

Renal Impairment

Pharmacokinetics of tenofovir alafenamide have not been studied in patients with end-stage renal disease (estimated creatinine clearance less than 15 mL/minute), and the drug is not recommended in such patients.

Dosage adjustments are not necessary if tenofovir alafenamide is used in patients with mild, moderate, or severe renal impairment. In individuals with severe renal impairment, tenofovir alafenamide and tenofovir plasma exposures are 1.9- and 5.7-fold higher, respectively, compared with exposures reported in those with normal renal function.

Common Adverse Effects

Adverse effects reported in 5% or more of patients with compensated liver disease receiving tenofovir alafenamide for the treatment of HBV infection include headache, abdominal pain, fatigue, cough, nausea, and back pain.

Drug Interactions

The following drug interactions are based on studies that used tenofovir alafenamide fumarate or are predicted to occur.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Tenofovir alafenamide is a weak inhibitor of cytochrome P-450 (CYP) isoenzyme 3A in vitro; tenofovir alafenamide does not induce or inhibit other CYP isoenzymes, including CYP1A2, 2B6, 2C8, 2C9, 2C19, or 2D6.

Drugs Affecting or Affected by P-glycoprotein Transport System and Breast Cancer Resistance Protein

Tenofovir alafenamide is a substrate of the P-glycoprotein (P-gp) transport system and breast cancer resistance protein (BCRP). Drugs that strongly affect P-gp transport or BCRP activity may lead to changes in tenofovir alafenamide absorption.

Concomitant use of tenofovir alafenamide and P-gp inducers is expected to decrease absorption of tenofovir alafenamide and may result in decreased plasma concentrations and loss of therapeutic effect of tenofovir alafenamide.

Concomitant use of tenofovir alafenamide and inhibitors of P-gp or BCRP may increase absorption of tenofovir alafenamide resulting in increased plasma concentrations of the drug.

Nephrotoxic Drugs or Drugs Eliminated by Renal Excretion

Tenofovir is principally excreted by a combination of glomerular filtration and active tubular secretion. Concomitant use of tenofovir alafenamide with drugs that reduce renal function or compete for active tubular secretion (e.g., acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, gentamicin, high-dose or multiple nonsteroidal anti-inflammatory agents [NSAIAs]) may increase concentrations of tenofovir and other drugs that are renally eliminated, which may increase the risk of adverse effects.

Anticonvulsants

Carbamazepine

Concomitant use of carbamazepine (300 mg twice daily) and the fixed combination of emtricitabine and tenofovir alafenamide (emtricitabine/tenofovir alafenamide) substantially decreases tenofovir alafenamide plasma concentrations and AUC.

If tenofovir alafenamide and carbamazepine are used concomitantly, dosage of tenofovir alafenamide should be increased to 50 mg once daily.

Oxcarbazepine, Phenobarbital, and Phenytoin

Concomitant use of tenofovir alafenamide and oxcarbazepine, phenobarbital, or phenytoin is expected to decrease tenofovir alafenamide plasma concentrations.

Concomitant use of tenofovir alafenamide and oxcarbazepine, phenobarbital, or phenytoin is not recommended.

Antifungal Agents

No clinically important pharmacokinetic interactions were reported when tenofovir alafenamide was used concomitantly with itraconazole or ketoconazole.

Antimycobacterial Agents

Concomitant use of tenofovir alafenamide and rifabutin, rifampin, or rifapentine is expected to decrease plasma concentrations of tenofovir alafenamide.

Concomitant use of tenofovir alafenamide and rifabutin, rifampin, or rifapentine is not recommended.

Cobicistat

Concomitant use of cobicistat (150 mg once daily) and tenofovir alafenamide (8 mg once daily) results in increased peak plasma concentrations and AUC of tenofovir alafenamide.

Estrogens and Progestins

No clinically important pharmacokinetic interactions were reported when tenofovir alafenamide was used concomitantly with ethinyl estradiol or norgestimate.

HBV Antivirals

There is no in vitro evidence of antagonistic anti-HBV effects between tenofovir and other HBV nucleoside or nucleotide reverse transcriptase inhibitor antivirals (e.g., entecavir, lamivudine, telbivudine).

HCV Antivirals

HCV Polymerase Inhibitors

Sofosbuvir

No clinically important pharmacokinetic interactions were reported when tenofovir alafenamide was used concomitantly with sofosbuvir.

HCV Replication Complex Inhibitors

Ledipasvir and Sofosbuvir

No clinically important pharmacokinetic interactions were reported when tenofovir alafenamide was used concomitantly with the fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir).

Midazolam

No clinically important pharmacokinetic interactions were reported when tenofovir alafenamide was used concomitantly with midazolam.

Sertraline

No clinically important pharmacokinetic interactions were reported when tenofovir alafenamide was used concomitantly with sertraline.

St. John's Wort

Concomitant use of St. John's wort (Hypericum perforatum) and tenofovir alafenamide is expected to decrease plasma concentrations of tenofovir alafenamide.

Concomitant use of tenofovir alafenamide and St. John's wort is not recommended.

Write Your Own Review

Your meds on autopilot. Forever.