Tenofovir Alafenamide

Indications

Tenofovir Alafenamide is used for: Chronic Hepatitis B Infection

Adult Dose

Chronic Hepatitis B Infection Indicated for treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease 25 mg PO qDay with food Hepatic impairment Mild (Child-Pugh A): No dosage adjustment required Decompensated (Child-Pugh B or C) hepatic impairment: Use not recommended

Child Dose

Renal Dose

Renal impairment Mild, moderate, or severe: No dosage adjustment required ESRD (CrCl <15 mL/min): Use not recommended

Administration

Take with food

Contra Indications

Hypersensitivity

Precautions

Lactic acidosis and severe hepatomegaly with steatosis, including fatalities, reported with nucleoside analogs, including tenofovir disoproxil fumarate in combination with other antiretrovirals; most were reported in women; obesity and prolonged nucleoside exposure may be risks factors Discontinuation of antihepatitis B drugs may result in severe acute exacerbations of hepatitis B Owing to the risk of development of HIV-1 resistance, tenofovir AF alone is not recommended for the treatment of HIV-1 infection; test for HIV-1 before initiating treatment Lactation Unknown if distributed in human breast milk Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy-Lactation

Pregnancy There are no human data on use in pregnant women to inform a drug-associated risks of adverse fetal developmental outcome In animal studies, no adverse developmental effects were observed when tenofovir alafenamide was administered during the period of organogenesis at exposure equal to or 51 times (rats and rabbits, respectively) the tenofovir alafenamide exposure at the recommended daily dose Lactation Unknown if distributed in human breast milk Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Drugs that induce P-gp result in decreased tenofovir AF absorption and plasma concentrations, which may lead to loss of therapeutic effect (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St John’s wort) Drugs that inhibit P-gp and BCRP may increase tenofovir AF absorption and plasma concentration. Coadministration of tenofovir AF 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 include acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, high-dose or long-term NSAD use

Adverse Effects

Side effects of Tenofovir Alafenamide : 1-10% Headache (9%) ALT >5 x ULN (8%) Abdominal pain (7%) Fatigue (6%) Cough (6%) Glycosuria >3+ (5%) Nausea (5%) Back pain (5%)

Mechanism of Action

Tenofovir alafenamide (AF) is a nucleotide reverse transcriptase inhibitor (NRTI) and a phosphonamidate prodrug of tenofovir Compared with tenofovir disoproxil fumarate (tenofovir DF, Viread), tenofovir AF is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile Tenofovir AF as a lipophilic cell-permeant compound enters primary hepatocytes by passive diffusion and by the hepatic uptake transporters OATP1B1 and OATP1B3 and is converted to tenofovir diphosphate Tenofovir diphosphate inhibits HBV replication through incorporation into viral DNA by the HBV reverse transcriptase, which results in DNA chain-termination