Tenofovir is a nucleotide analogue.
Tenofovir has activity against HIV-1, including non-clade B strains, HIV-2 and hepatitis B virus.
Tenofovir disoproxil fumarate is hydrolyzed to tenofovir, which is then phosphorylated to tenofovir diphosphate. Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the natural substrate, deoxyadenosine 5'-triphosphate, and by DNA chain termination.
Resistance to nucleotide analogues occurs through two mechanisms; decreased incorporation of the nucleotide analogue into the viral DNA and increased excision of the nucleotide from the viral DNA.
In two phase I randomized, double blind, placebo-controlled trials, a dose-proportional increase in drug exposure was associated with incremental decreases of plasma HIV-1 RNA (viral load). The maximum effect was seen at an oral dose of 300 mg once daily. The antiviral effect of tenofovir may persist following drug discontinuation.
The oral bioavailability of a 300 mg dose of TDF is 25% in the fasted state. Administration with high fat meal increases tenofovir AUC and Cmax by 40% and 14%, respectively. Protein binding in vitro is less than 7%. It is not appreciably metabolized by the liver and the renal route is the primary elimination pathway.
Adverse effects include nausea, vomiting, diarrhea, asthenia, headache, flatulence, abdominal pain and anorexia.
Adults and Adolescents:
300 mg orally once daily with a meal
Children: dose has not been established
Disease state based dosing:
CrCl 30-49 ml/min – 300 mg every 48 hours
CrCl 10-29 ml/min – 300 mg twice per week
Hemodialysis – 300 mg every 7 days OR 300mg following a total of approximately 12
hours of dialysis
No dose adjustment necessary
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleotide analogues.
Tenofovir slightly inhibits CYP1A2. However, this is not expected to lead to any clinically significant drug interactions.
Category B: No evidence of risk in humans but studies inadequate.
LFTs, baseline serum creatinine/BUN, serum phosphate
Viread®/Gilead Sciences Inc