Product Information
Registration Status: ActiveSIN14147P
TRUVADA TABLET 200MG/300MG is approved to be sold in Singapore with effective from 2012-05-14. It is marketed by GILEAD SCIENCES SINGAPORE PTE LTD, with the registration number of SIN14147P.
This product contains Emtricitabine 200mg, and Tenofovir Disoproxil 300mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Takeda GmbH in IRELAND, andGilead Sciences Ireland UC in GERMANY.
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.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}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
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
Tenofovir disoproxil fumarate (a prodrug of tenofovir), marketed by Gilead Sciences under the trade name Viread, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. In vivo tenofovir disoproxil fumarate is converted to tenofovir, an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5'-monophosphate.
Indication
Tenofovir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 2 years of age and older. It is also indicated for the treatment of chronic hepatitis B in adults and pediatric patients 12 years of age and older.
Mechanism of Action
Tenofovir inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination. Specifically, the drugs are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NTRTIs (nucleoside/tide reverse transcriptase inhibitors) lack a 3'-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors.
Pharmacokinetics
- Absorption
- Tenofovir disoproxil fumarate is the water soluble diester prodrug of the active ingredient tenofoir. The oral bioavailability in fasted patients is approximately 25%. When a single oral dose (300 mg) is given to HIV-1 infected subjects in the fasted state, the maximum serum concentration was achieved in 1.0 ± 0.4 hours (Tmax). Cmax and AUC values are 0.30 ± 0.09 µg/mL and 2.29 ± 0.69 µg∙hr/mL. Administration of food (high fat meal containing 40 to 50% fat) increases the oral bioavailability, with an increase in the AUC of approximately 40%. Cmax is lower in the oral powder, compared to the tablet formulation. However, the mean AUC is similar between the two formulations.
- Distribution
- * 1.3 ± 0.6 L/kg [tenofovir 1.0 mg/kg IV] * 1.2 ± 0.4 L/kg [tenofovir 3.0 mg/kg IV]
- Metabolism
- The cytochrome P450 enzyme system is not involved with the metabolism of tenofovir disoproxil or tenofovir.
- Elimination
Clearance
The following are renal clearance (CL renal) parameters for subjects with varying degrees of renal function: * 243.5 ± 33.3 mL/min [baseline creatinine clearance >80 mL/min] * 168.6 ± 27.5 mL/min [baseline creatinine clearance 50-80 mL/min] * 100.6 ± 27.5 mL/min [baseline creatinine clearance 30-49 mL/min] * 43.0 ± 31.2 mL/min [baseline creatinine clearance 12-29 mL/min] The following are clearance (CL/F) parameters for subjects with varying degrees of renal function: * 1043.7 ± 115.4 [baseline creatinine clearance >80 mL/min] * 807.7 ± 279.2 [baseline creatinine clearance 50-80 mL/min] * 444.4 ± 209.8 [baseline creatinine clearance 30-49 mL/min] * 177.0 ± 97.1 [baseline creatinine clearance 12-29 mL/min]
Toxicity
Limited clinical experience at doses higher than the therapeutic dose of tenofovir 300 mg is available. In Study 901 tenofovir disoproxil fumarate 600 mg was administered to 8 patients orally for 28 days. No severe adverse reactions were reported. The effects of higher doses are not known.
Active Ingredient/Synonyms
Bis(POC)PMPA | Tenofovir bis(isopropyloxycarbonyloxymethyl) ester | Tenofovir disoproxil |
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.