Product Information
Registration Status: ActiveODEFSEY FILM-COATED TABLET 200MG/25MG/25MG is approved to be sold in Singapore with effective from 2020-09-25. It is marketed by JOHNSON & JOHNSON PTE LTD, with the registration number of SIN16015P.
This product contains Emtricitabine 200mg,Rilpivirine 25mg, and 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,Rottendorf Pharma GmbH in GERMANY, andRottendorf Pharma GmbH in GERMANY, and.
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
Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) for the treatment of HIV infection in adults. Emtricitabine is an analogue of cytidine. The drug works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA.
Indication
Indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults and for postexposure prophylaxis of HIV infection in health care workers and others exposed occupationally or nonoccupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with risk for transmission of the virus.
Mechanism of Action
Emtricitabine works by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA. Emtricitabine is a synthetic nucleoside analogue of cytidine. It is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate, which is responsible for the inhibition of HIV-1 reverse transcriptase. It competes with the natural substrate deoxycytidine 5'-triphosphate and incorporates into nascent viral DNA, resulting in early chain termination. Therefore emtricitabine inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate deoxycytidine 5'-triphosphate and by its incorporation into viral DNA. By inhibiting HIV-1 reverse transcriptase, emtricitabine can help to lower the amount of HIV, or "viral load", in a patient's body and can indirectly increase the number of immune system cells (called T cells or CD4+ T-cells). Both of these changes are associated with healthier immune systems and decreased likelihood of serious illness.
Pharmacokinetics
- Absorption
- Rapidly absorbed (mean absolute bioavailability of 93% for capsules, and 75% for solution). Food does not effect absorption.
- Distribution
- Metabolism
- Minimally transformed (13%), most appears unchanged in urine (86%). The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3′-sulfoxide diastereomers (~ 9% of dose) and conjugation with glucuronic acid to form 2′-O-glucuronide (~ 4% of dose). In vitro studies indicate emtricitabine is not an inhibitor or cytochrome P450 enzymes.
- Elimination
Clearance
* 302 +/- 94 mL/min [Renal Function Creatinine Clearance>80 ml/min] * 168 +/- 10 mL/min [Renal Function Creatinine Clearance 50-80 ml/min] * 138 +/- 28 mL/min [Renal Function Creatinine Clearance 30-49 ml/min] * 99 +/- 6 mL/min [Renal Function Creatinine Clearance<30 ml/min] * 64 +/- 12 mL/min [ESRD patients requiring dialysis]
Toxicity
Symptoms of overdose include serious liver problems (hepatotoxicity, with liver enlargement and fat in the liver called steatosis) or a lactic acidosis (buildup of an acid in the blood).
Active Ingredient/Synonyms
(−)-(2R,5S)-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine | (−)-2'-deoxy-5-fluoro-3'-thiacytidine | (−)-cis-4-amino-5-fluoro-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one | (−)-FTC | (−)-β-2',3'-dideoxy-5-fluoro-3'-thiacytidine | (2R-cis)-4-amino-5-fluoro-1-(2-(hydroxymethyl)-1,3-oxathiolan-5-yl)-2(1H)-pyrimidinone | 4-amino-5-fluoro-1-((2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl)pyrimidin-2(1H)-one | 4-Amino-5-fluoro-1-((2R,5S)-2-hydroxymethyl-[1,3]oxathiolan-5-yl)-1H-pyrimidin-2-one | 5-fluoro-1-((2R,5S)-2-(hydroxymethyl)-1,3-oxathiolan-5-yl)cytosine | Emtricitabin | Emtricitabina | Emtricitabine | Emtricitabinum | Emtricitabine |
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.
Description
Rilpivirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) which is used for the treatment of HIV-1 infections in treatment-naive patients.[A31328] It is a diarylpyrimidine derivative, a class of molecules that resemble pyrimidine nucleotides found in DNA.[A31329] The internal conformational flexibility of rilpivirine and the plasticity of it interacting binding site gives it a very high potency and an unlikely generation of resistance compared to other NNRTI's.[A31331] Rilpivirine was developed by Tilbotec, Inc. and FDA approved on May 20, 2011.[L1030] On November 21, 2017, Rilpivirine, in combination with dolutegravir, was approved as part of the first complete treatment regimen with only two drugs for the treatment of adults with HIV-1 named Juluca.[L1031]
Indication
Rilpivirine, in combination with other agents, is indicated for the treatment of HIV-1 infections in antiretroviral treatment-naive patients with HIV-1 RNA ≤100,000 copies/mL and CD4+ cell count >200 cells/mm3.[L1030] The FDA combination therapy approval of rilpivirine and dolutegravir is indicated for adults with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.[L1031]
Mechanism of Action
Rilpivirine is a non-competitive NNRTI that binds to reverse transcriptase. Its binding results in the blockage of RNA and DNA- dependent DNA polymerase activities, like HIV-1 replication. It does not present activity against human DNA polymerases α, β and γ.[L1032] Rilpivirine binds to the HIV-1 reverse transcriptase (RT) and its flexible structure around the aromatic rings allows the adaptation to changes in the non-nucleoside RT binding pocket.[A31335]
Pharmacokinetics
- Absorption
- Absorption of rilpivirine is characterized by a lag time followed by a linear increase in plasma concentration. Under fasting conditions, the Cmax of rilpivirine can be decreased even by 46% while its AUC can be reduced by 43%. When given with a protein-rich drink the Cmax and AUC of rilpivirine is decreased by 50%. Therefore, it is recommended to consume rilpiviridine with a non-protein-rich meal. The average Tmax of various rilpivirine concentrations is 3-4 h.[A31331] The reported AUC in patients from clinical studies is 2235 ng h/ml.[FDA label]
- Distribution
- In VIH-1 patients, the apparent volume of distribution in the central compartment was determined to be 152-173 L.[L1032]
- Metabolism
- Mainly hepatically metabolized by CYP3A. Because it is highly protein bound, its free plasma concentration is very small thus is unlikely to inhibit cytochrome proteins to a clinically relevant degree despite being an inhibitor of CYP3A4, CYP2C19, and CYP2B6.[A7414]
- Elimination
Clearance
In HIV-1 patients, the apparent oral clearance is estimated to be 10.5-11.8 L/h.[L1032]
Toxicity
Rilpivirine did not induce chromosomal damage in vivo. It did not show any effect on mating or fertility in animal studies. On the other hand, mice studies have result positive for the formation of hepatocellular neoplasms which can be rodent-specific.[FDA label]
Active Ingredient/Synonyms
4-{[4-({4-[(E)-2-cyanovinyl]-2,6-dimethylphenyl}amino)pyrimidin-2-yl]amino}benzonitrile | Rilpivirine |
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.
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.