1. Clinical Overview
Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor (NRTI). It is designed to deliver the active metabolite, tenofovir diphosphate, more efficiently to target cells (lymphocytes and macrophages) while minimizing systemic exposure. This results in potent antiviral activity against HIV-1 and HBV at a significantly lower dose (25mg) compared to the older prodrug tenofovir disoproxil fumarate (TDF, 300mg), leading to an improved renal and bone safety profile. It is a cornerstone of modern antiretroviral therapy (ART) and hepatitis B treatment in India.
| Onset | Duration | Bioavailability |
|---|---|---|
| Rapid absorption with a median Tmax of 0.48 hours. Antiviral effect begins within hours, but full virological suppression for HIV/HBV typically takes weeks to months of continuous therapy. | Intracellular half-life of the active metabolite (tenofovir diphosphate) in peripheral blood mononuclear cells is >150 hours, allowing for once-daily dosing and providing a long duration of antiviral action. | Approximately 40% when administered with a high-fat meal. Bioavailability in the fasted state is lower (~25-30%). It is recommended to be taken with food for optimal and consistent absorption. |
2. Mechanism of Action
TAF is a phosphonamidate prodrug of tenofovir. It is more stable in plasma than TDF, leading to lower circulating tenofovir levels. It enters target cells (CD4+ cells, hepatocytes) efficiently via passive diffusion and potentially specific transporters. Intracellularly, it is cleaved by cathepsin A to release tenofovir, which is then phosphorylated by cellular kinases to its active form, tenofovir diphosphate (TFV-DP). TFV-DP acts as a competitive inhibitor of viral reverse transcriptase (HIV) and DNA polymerase (HBV). It is incorporated into the growing viral DNA chain, causing chain termination due to the lack of a 3'-OH group, thereby inhibiting viral replication.
3. Indications & Uses
- Treatment of HIV-1 infection in adults and pediatric patients (weighing at least 25 kg) in combination with other antiretroviral agents.
- Treatment of chronic hepatitis B virus (HBV) infection in adults and adolescents (aged 12 years and older with compensated liver disease).
4. Dosage & Administration
Adult Dosage: HIV-1 Treatment: One tablet containing TAF 25mg once daily with food, as part of a complete ART regimen (e.g., TAF 25mg + Emtricitabine 200mg). HBV Treatment: One tablet containing TAF 25mg once daily with food. Note: Dosage is based on the FDC; TAF 25mg is rarely available as a standalone tablet.
Administration: Must be taken orally with food to enhance bioavailability. Swallow whole; do not crush, split, or chew. Maintain strict adherence to the prescribed schedule. If a dose is missed, take it as soon as remembered unless it is almost time for the next dose. Do not double the dose.
5. Side Effects
Common side effects may include:
- Nausea
- Headache
- Fatigue
- Diarrhea
- Abdominal pain
- Flatulence
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Rifabutin, Rifampicin, Rifapentine (strong CYP inducers) | Significantly decrease TAF plasma concentrations, leading to loss of virological response and possible resistance. | Major - Contraindicated or requires alternative agent. |
| Carbamazepine, Phenytoin, Phenobarbital (anticonvulsants) | May decrease TAF levels. Use alternative anticonvulsant or monitor virological response closely. | Major |
| St. John's Wort (Hypericum perforatum) | Decreases TAF plasma concentration. Contraindicated. | Major |
| Nephrotoxic drugs (e.g., Aminoglycosides, Amphotericin B, Ganciclovir, NSAIDs like Ibuprofen, Diclofenac) | May increase risk of renal impairment. Monitor renal function. | Moderate |
| Drugs that inhibit renal transporters (e.g., Cidofovir, High-dose or multiple NSAIDs) | May increase tenofovir concentrations. Monitor for renal effects. | Moderate |
| Antacids containing Aluminium/Magnesium Hydroxide | May be taken simultaneously with TAF if taken with food. No significant interaction when administered with food. | Minor |
7. Patient Counselling
- DO take this medicine exactly as prescribed, at the same time every day.
- DO take it with food (a meal or snack).
- DO NOT stop taking this medicine without consulting your doctor, especially if you have Hepatitis B.
- DO NOT share your medicine with anyone.
- DO use additional barrier protection (condoms) to prevent HIV transmission, as ART may not prevent all risks.
8. Toxicology & Storage
Overdose: Limited experience. Potential symptoms may include nausea, vomiting, diarrhea, and lactic acidosis. Renal and hepatic toxicity are possible at very high doses.
Storage: Store at room temperature (15°C to 30°C). Protect from moisture. Keep in the original blister pack or container. Keep out of reach of children. Do not use after the expiry date printed on the pack.