Alenvir 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 with compensated liver disease.
Tenofovir alafenamide is a phosphonamidate prodrug of tenofovir (2’-deoxyadenosine monophosphate analog). Tenofovir alafenamide as a lipophilic cell-permeant compound enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3. Tenofovir alafenamide is then converted to tenofovir through hydrolysis primarily by carboxylesterase 1 (CES1) in primary hepatocytes. Intracellular tenofovir is subsequently phosphorylated by cellular kinases to the pharmacologically active metabolite tenofovir diphosphate. Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases that include mitochondrial DNA polymerase γ and there is no evidence of toxicity to mitochondria in cell culture.
Testing Prior to Initiation of Tenofovir alafenamide: Prior to initiation of Tenofovir alafenamide, patients should be tested for HIV-1 infection. Tenofovir alafenamide alone should not be used in patients with HIV-1 infection.
Recommended Dosage in Adults: The recommended dosage of Tenofovir alafenamide is 25 mg (one tablet) taken orally once daily with food.
Dosage in Patients with Renal Impairment: No dosage adjustment of Tenofovir alafenamide 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 Tenofovir alafenamide after completion of hemodialysis treatment. Tenofovir alafenamide is not recommended in patients with ESRD who are not receiving chronic hemodialysis.
Dosage in Patients with Hepatic Impairment: No dosage adjustment of Tenofovir alafenamide is required in patients with mild hepatic impairment (Child-Pugh A). Tenofovir alafenamide is not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.
Pediatric Use: Safety and effectiveness of Tenofovir alafenamide in pediatric patients less than 18 years of age have not been established.
Geriatric Use: In clinical trials, Tenofovir alafenamide was administered to 89 subjects aged 65 and over. No clinically significant differences in safety or efficacy have been observed between elderly subjects and subjects between 18 and less than 65 years of age.
Potential for Other Drugs to Affect Alenvir: Alenvir is a substrate of P-glycoprotein (P-gp) and BCRP. Drugs that strongly affect P-gp and BCRP activity may lead to changes in Alenvir absorption. Drugs that induce P-gp activity are expected to decrease the absorption of Alenvir resulting in decreased plasma concentrations of Alenvir which may lead to loss of therapeutic effect of Alenvir. Coadministration of Alenvir with other drugs that inhibit P-gp and BCRP may increase the absorption & plasma concentration of Alenvir.
Drugs Affecting Renal Function: Alenvir is primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of Alenvir 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.
The following adverse reactions are discussed in other sections of the labeling:
Lactic Acidosis/Severe Hepatomegaly with Steatosis
Severe Acute Exacerbation of Hepatitis B
New Onset or Worsening of Renal Impairment
The most common side effects are headache, stomach pain, tiredness, cough, nausea, back pain
