Tenofoviralafenamide

Products

Various drugs containing tenofoviralafenamide are on the market worldwide. In many countries, tenofoviralafenamide was first approved in 2016 (United States: 2015).

• Biktarvy: bictegravir, emtricitabine, and tenofoviralafenamide (HIV).
• Genvoya: elvitegravir, cobicistat, emtricitabine, and tenofoviralafenamide (HIV).
• Descovy: emtricitabine and tenofoviralafenamide (HIV).
• Odefsey: emtricitabine, rilpivirine and tenofoviralafenamide (HIV).
• Symtuza: darunavir + cobicistat + emtricitabine + tenofoviralafenamide.
• Vemlidy: tenofoviralafenamide (hepatitis B).

Vemlidy for chronic hepatitis B therapy was first approved in 2016 (Switzerland: 2017).

Structure and properties

Tenofoviralafenamide (C₂₃H₃₁O₇N₆P, M_r = 534.5 g/mol) is an alanine derivative and a phosphonamidate prodrug of tenofovir. It exists as a fumarate salt and is hydrolyzed intracellularly by the lysosomal carboxypeptidase cathepsin A to tenofovir. Unlike tenofovirdisoproxil (TDF), tenofoviralafenamide (TAF) is more stable in plasma. This increases selectivity for target cells, increases intracellular concentrations, increases efficacy, and decreases adverse effects (renal, bone).

Effects

Tenofovir (ATC J05AF07) has antiviral properties against HIV and HBV. The effects are due to inhibition of the viral enzyme reverse transcriptase, which transcribes viral RNA into DNA and is important in viral replication. The activated agent is incorporated into DNA and leads to chain termination.

Indications

• For the treatment of infection with HIV-1 (combination therapy).
• For the treatment of chronic hepatitis B.

Dosage

According to the professional information. The drugs are administered perorally. TAF is administered at a lower dose than TDF.

Interactions

Tenofoviralafenamide is a substrate of P-glycoprotein and a weak inhibitor of CYP3A4. It undergoes renal tubular secretion via OAT1, OAT3, and MRP4.

Adverse effects

Tenofovir may rarely cause renal damage, including nephritis, renal insufficiency, and renal failure. Decreases in bone density and, rarely, osteonecrosis are also possible. Tenofoviralafenamide was developed with the goal of increasing the tolerability of tenofovir and improving its efficacy.