Uses of Alfavir: - HIV infection - Chronic hepatitis B virus (HBV) infection Chronic Hepatitis B Infection Hypersensitivity

Hepatic viral infections (Hepatitis B)

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.

How to use Tenofovir Alafenamide: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Tenofovir Alafenamide is to be taken empty stomach. Administration: Take with food 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 Renal Dose: Renal impairment Mild, moderate, or severe: No dosage adjustment required ESRD (CrCl <15 mL/min): Use not recommended

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

Hypersensitivity

Common - Headache 1-10% Headache (9%) ALT >5 x ULN (8%) Abdominal pain (7%) Fatigue (6%) Cough (6%) Glycosuria >3+ (5%) Nausea (5%) Back pain (5%)

Before you take Tenofovir Alafenamide, tell your healthcare provider about all of your medical conditions, including if you are pregnant or plan to become pregnant. It is not known if Tenofovir Alafenamide will harm your unborn baby. Tell your healthcare provider if you become pregnant during treatment with Tenofovir Alafenamide. Pregnancy Registry: There is a pregnancy registry for women who take antiviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk with your healthcare provider about how you can take part in this registry.

Precaution: 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

If overdose occurs, monitor patient for evidence of toxicity. Treatment of overdosage with Tenofovir alafenamide consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Tenofovir is efficiently removed by hemo- dialysis with an extraction coefficient of approximately 54%.

Store below 30°C. Keep it in its original container. protect from light. Keep out of children’s reach.

Hepatic viral infections (Hepatitis B)

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

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