Product Information
Registration Status: ActiveVEMLIDY FILM COATED TABLET 25MG is approved to be sold in Singapore with effective from 2017-12-11. It is marketed by GILEAD SCIENCES SINGAPORE PTE LTD, with the registration number of SIN15392P.
This product contains Tenofovir Alafenamide 25mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Patheon Inc. in CANADA.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Tenofovir alafenamide fumarate (TAF) is a nucleotide reverse transcriptase inhibitor (NRTI) and a novel ester prodrug of the antiretroviral tenofovir. Following oral administration, TAF is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Tenofovir mimics normal DNA building blocks but is lacking a 3'-OH molecule required for phosphodiester bond linkage. By competing with regular nucleotides for incorporation into proviral DNA and prevention of the formation of the 5' to 3' phosphodiester linkage required for DNA elongation, tenofovir causes early chain termination and prevents proviral DNA transcription. Although tenofovir (available as tenofovir disoproxil fumarate) has a good safety profile and efficacy, and is currently a cornerstone of HIV antiviral treatment, its use has been associated with nephrotoxicity and reduced bone mineral density. In comparison, TAF has been shown to have improved antiviral efficacy, enhanced delivery of TFV into peripheral blood mononuclear cells (PBMCs) and lymphatic tissues, a higher barrier to resistance, and an improved safety profile. Improved renal safety is likely attributable to lower circulating plasma concentrations of tenofovir and therefore less exposure and damage to bone and the kidneys, where tenofovir is metabolized. Because HIV antiretroviral therapy is usually life-long, reduced toxicity and improved efficacy results in better patient outcomes and improved adherence in the long term. Tenofovir alafenamide fumarate is currently available in two fixed dose combination products: Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide), and Descovy (emtricitabine and tenofovir alafenamide). Both products are indicated for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older.
Indication
For use in the treatment of HIV infection and chronic hepatitis B.
Mechanism of Action
Tenofovir alafenamide fumarate (TAF) is a nucleotide reverse transcriptase inhibitor (NRTI) and a novel ester prodrug of the antiretroviral tenofovir. Following oral administration, TAF is converted in vivo to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. Tenofovir mimics normal DNA building blocks but is lacking a 3'-OH molecule required for phosphodiester bond linkage. By competing with regular nucleotides for incorporation into proviral DNA and prevention of the formation of the 5' to 3' phosphodiester linkage required for DNA elongation, tenofovir causes early chain termination and prevents proviral DNA transcription.
Pharmacokinetics
- Absorption
- Tmax is observed at 1 hour post oral administration.
- Distribution
- Metabolism
- In vivo, TAF is hydrolyzed within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate. In vitro studies have shown that TAF is metabolized to tenofovir by cathepsin A (also known as Lysosomal Protective Protein) in peripheral blood mononuclear cells (PBMCs) and macrophages; and by Carboxylesterase 1 (CES1) in hepatocytes.
- Elimination
Active Ingredient/Synonyms
Tenofovir alafenamide | Tenofovir alafenamide |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.