Tenofovir Disoproxil Fumarate

Indications

Tenofovir Disoproxil Fumarate is used for: HIV-1 infection, Chronic hepatitis B

Adult Dose

Oral Chronic hepatitis B; HIV infection (Indicated in combination with other antiretroviral agents for treatment of HIV-1 infection) Adult: 300 mg once daily.

Child Dose

HIV Infection <2 years: Safety and efficacy not established >2 years: 8 mg/kg PO qDay; not to exceed 300 mg/day Hepatitis B Infection <12 years: Safety and efficacy not established >12 years; <35 kg: Safety and efficacy not established >12 years; >35 kg: 300 mg PO qDay

Renal Dose

Renal impairment: Haemodialysis patients: 300 mg once every 7 days or after a cumulative total of 12 hr of dialysis. CrCl (ml/min) Dosage Recommendation 10-29 300 mg 72-96 hrly. 30-49 300 mg 48 hrly.

Administration

May be taken with or without food. Take consistently either always w/ or always w/o food.

Contra Indications

Tenofovir is contraindicated in patients with previously demonstrated hypersensitivity to Tenofovir or any component of the product.

Precautions

Patient w/ hepatomegaly or other risk factors for liver disease. Renal impairment. Pregnancy. Patient Counselling This drug may cause dizziness, if affected, do not drive or operate machinery. Monitoring Parameters Monitor renal function and serum phosphate concentrations before start of therapy, 4 wkly during the 1st wk, and then 3 mthly; hepatic function for several mth following discontinuation. Determine HIV status in all hepatitis B virus (HBV) infected patients prior to treatment. Lactation: HIV+ women are advised not to breastfeed

Pregnancy-Lactation

Pregnancy Human data Available prospective reported data from the APR shows no increase in the overall risk of major birth defects with first trimester exposure for tenofovir DF compared with US rate for major birth defects Data from 3 controlled clinical trials in 327 pregnant women with chronic HBV infection did not observe an increased risk of adverse pregnancy related outcomes with tenofovir DF use during the third trimester Animal data In animal reproduction studies, no adverse developmental effects were observed when tenofovir DF was administered at doses >14 (TDF) and 2.7 (tenofovir) times those of the recommended daily dose Lactation Based on published data, tenofovir shown to be present in human breast milk Unknown if tenofovir DF affects milk production or has effects on the breastfed child HIV-infected mothers: Breastfeeding in HIV-1 infected mothers is not recommended owing to potential for HIV-1 transmission HBV-infected mothers: The developmental and health benefits of breastfeeding should be considered 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 In a study of 50 HIV-uninfected, breastfeeding women on a tenofovir-containing regimen initiated between 1 and 24 weeks postpartum (median 13 weeks), drug was undetectable in plasma of most infants after 7 days of treatment in mothers

Interactions

Decreased atazanavir concentration with tenofovir unless also co-administered with ritonavir. Increased serum concentration of tenofovir or co-administered drug if taken with drugs that are eliminated by active tubular secretion. Potentially Fatal: Increased risk of renal impairment with recent or concurrent use of nephrotoxic agents (e.g. aminoglycosides, amphotericin B, foscarnet, ganciclovir, pentamidine, vancomycin, cidofovir or interleukin-2); monitor renal function wkly if unavoidable. Increased didanosine levels and thereby increasing risk of pancreatitis and peripheral neuropathy, with a high treatment failure rate with concurrent use; avoid concurrent use.

Adverse Effects

Side effects of Tenofovir Disoproxil Fumarate : >10% Asthenia (11%), Diarrhea (16%), Nausea (11%), Pain (12%) 1-10% Anorexia, Depression, Myalgia, Peripheral neuropathy, Dyspepsia, Rash, Headache, Vomiting, Flatulence, Abdominal pain, Neutropenia, Increased transaminases

Mechanism of Action

Tenofovir disoproxil fumarate, a diester prodrug of tenofovir, is a nucleotide reverse transcriptase inhibitor. After oral absorption, tenofovir disoproxil fumarate is rapidly converted to tenofovir and then undergo subsequent phosphorylation by cellular enzymes to the active tenofovir diphosphate, which inhibits the activity of HIV-1 reverse transcriptase.