1. Clinical Overview
Tenofovir disoproxil fumarate (TDF) is an oral prodrug of tenofovir, a nucleotide reverse transcriptase inhibitor (NRTI). It is a cornerstone of antiretroviral therapy (ART) for HIV-1 infection and a first-line agent for chronic Hepatitis B virus (HBV) infection. In the Indian context, it is widely used, cost-effective, and available under the National AIDS Control Programme (NACP). It requires careful monitoring of renal function and bone mineral density due to potential adverse effects.
| Onset | Duration | Bioavailability |
|---|---|---|
| Antiviral effect begins within hours, but significant virological suppression (HIV/HBV) is typically observed within 2-4 weeks of initiation. | Approximately 24 hours, supporting once-daily dosing. | Approximately 25% in fasted state. Increases to ~39% with a high-fat meal. |
2. Mechanism of Action
Tenofovir disoproxil fumarate is a diester prodrug of tenofovir. After oral administration, it is converted to tenofovir, which is taken up by cells and phosphorylated by cellular enzymes to its active form, tenofovir diphosphate. Tenofovir diphosphate is a competitive inhibitor of viral reverse transcriptase (HIV) and DNA polymerase (HBV). It acts as a chain terminator after incorporation into the growing viral DNA chain, thereby inhibiting viral replication.
3. Indications & Uses
- Treatment of HIV-1 infection in adults and pediatric patients (≥2 years, ≥10 kg) in combination with other antiretroviral agents.
- Treatment of chronic Hepatitis B virus (HBV) infection in adults and pediatric patients (≥12 years, ≥35 kg) with compensated liver disease.
4. Dosage & Administration
Adult Dosage: HIV-1 or HBV: 300 mg orally once daily, with or without food (better with food).
Administration: Swallow tablet whole with water. Can be taken with or without food, but a high-fat meal increases bioavailability. For PrEP, must be confirmed HIV-negative before initiation and regularly during use. Do not use as monotherapy for HIV.
5. Side Effects
Common side effects may include:
- Nausea
- Diarrhea
- Flatulence
- Headache
- Fatigue
- Dizziness
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Didanosine (ddI) | Increases ddI concentration; may increase ddI-associated adverse effects (pancreatitis, neuropathy). Should be administered separately. | Major |
| Adefovir dipivoxil | Additive nephrotoxicity; concurrent use not recommended. | Major |
| NSAIDs (e.g., Ibuprofen, Diclofenac) | May increase risk of nephrotoxicity. Monitor renal function closely. | Moderate |
| Aminoglycosides, Vancomycin | Increased risk of nephrotoxicity. Avoid concurrent use if possible. | Major |
| Probenecid | May increase tenofovir concentration by competing for renal tubular secretion. Monitor for adverse effects. | Moderate |
| Lopinavir/ritonavir | May increase tenofovir plasma levels. Monitor for renal effects. | Moderate |
| Hepatitis B antivirals (e.g., Entecavir) | No significant interaction, but used in combination for HBV may increase risk of resistance if not fully suppressive. | Minor |
7. Patient Counselling
- DO take the tablet exactly as prescribed, once daily.
- DO take it with food for better absorption and reduced stomach upset.
- DO get your kidney function and bone density tests done as advised by your doctor.
- DO inform all your healthcare providers you are taking this medicine.
- DONT stop taking this medicine without consulting your doctor, especially for HBV, as it can cause a dangerous flare-up of hepatitis.
- DONT use it for HIV PrEP if you are already HIV positive.
- DONT share your medication with others.
8. Toxicology & Storage
Overdose: Limited data. Highest dose ingested in clinical trials was 1200 mg. Potential symptoms may include nausea, vomiting, lactic acidosis, and renal impairment.
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.