Tudofovir (Tenofovir 300mg)
(Tenofovir Disoproxil Fumarate Tablets IP)
Each film coated tablet contains:
Tenofovir Disoproxil Fumarate IP 300 mg
Colours: Indigo Carmine & Titanium Dioxide.
Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine 5`-triphosphate and, after incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases alpha and beta, and mitochondrial DNA polymerase gamma.
The pharmacokinetics of tenofovir disoproxil fumarate has been evaluated in healthy volunteers and HIV-1 infected individuals. Tenofovir pharmacokinetics is similar between these populations.
Absorption: Tenofovir disoproxil fumarate is a water-soluble diester prodrug of the active ingredient tenofovir. The oral bioavailability of tenofovir from tenofovir disoproxil fumarate in fasted patients is approximately 25%. Following oral administration of a single dose of tenofovir disoproxil fumarate 300 mg to HIV-1 infected patients in the fasted state, maximum serum concentrations (C max ) are achieved in 1.0 ± 0.4 hrs. C max and AUC values are 296 ± 90 ng/mL and 2287 ± 685 ng·hr/mL, respectively.
The pharmacokinetics of tenofovir are dose proportional over a tenofovir disoproxil fumarate dose range of 75 to 600 mg and are not affected by repeated dosing.
Effects of Food on Oral Absorption: Administration of tenofovir disoproxil fumarate following a high-fat meal (~700 to 1000 kcal containing 40 to 50% fat) increases the oral bioavailability, with an increase in tenofovir AUC of approximately 40% and an increase in C max of approximately 14%. However, administration of tenofovir disoproxil fumarate with a light meal did not have a significant effect on the pharmacokinetics of tenofovir when compared to fasted administration of the drug. Food delays the time to tenofovir C max by approximately 1 hour.
Distribution: In vitro binding of tenofovir to human plasma or serum proteins is less than 0.7 and 7.2%, respectively, over the tenofovir concentration range 0.01 to 25 μg/mL. The volume of distribution at steady state is 1.3 ± 0.6 L/kg and 1.2 ± 0.4 L/kg, following intravenous administration of tenofovir 1.0 mg/kg and 3.0 mg/kg.
Metabolism and Elimination: In vitro studies indicate that neither tenofovir disoproxil nor tenofovir are substrates of CYP450 enzymes.
Following IV administration of tenofovir, approximately 70-80% of the dose is recovered in the urine as unchanged tenofovir within 72 hours of dosing. Following a single dose, oral administration of tenofovir disoproxil fumarate, the terminal elimination half-life of tenofovir is approximately 17 hours. After multiple oral doses of tenofovir disoproxil fumarate 300 mg once daily (under fed conditions), 32 ± 10% of the administered dose is recovered in urine over 24 hours.
Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion.
INDICATIONS: TUDOFOVIR is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.