Pharmacodynamics: Viread™ 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.

Pharmacokinetics:Absorption: The oral bioavailability of tenofovir from Viread™ in fasted patients is approximately 25%. The pharmacokinetics of tenofovir are dose proportional over a Viread™ dose range of 75 to 600 mg and are not affected by repeated dosing. Effects of Food on Oral Absorption: Viread™ should be taken with a meal to enhance bioavailability. Administration following a high-fat meal (~ 700 to 1000 kcal containing 40-50% fat) increases the oral bioavailability, with an increase in Viread™ of approximately 40%.  Distribution: In-vitro binding of tenofovir to human plasma or serum proteins is less than 7.2%. Metabolism and Elimination: In-vitro studies indicate that neither tenofovir disoproxil nor tenofovir are substrates of CYP450 enzymes. Tenofovir is eliminated by a combination of glomerular filtration and active tubular secretion. There may be competition for elimination with other compounds that are also renally eliminated.

Drug Interactions: Changes in pharmacokinetic parameters for tenofovir occur in the presence of the following co-administered drugs: Lamivudine, Didanosine, Indinavir, Lopinavir/Ritonavir, and Efavirenz. Warning: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals.

Precautions: Fat redistribution: Redistribution/ accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy.

Adverse Reactions:Treatment related: nausea, diarrhea, asthenia, vomiting, and anorexia. Laboratory abnormalities: increased: triglyceride, creatine kinase, amylase, AST, ALT, glucose. Use of tenofovir may also result in bone toxicity or impairment, most likely caused by a phosphorus deficiency. 

Other Considerations:Nursing Mothers: Mothers should be instructed NOT to breast-feed if they are receiving Viread™.

Nutrient-Herb Interactions: Patients should also avoid the use of St. John’s Wort and Milk Thistle (Silymarin) to limit possible nutrient-herb interactions.

Source

• Viread™ (tenofovir disoproxil fumarate). Package insert. Gilead Sciences: Foster City, CA. October 2001.