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# Tenofovir Disoproxil Fumarate (TDF)
## Overview
Tenofovir disoproxil fumarate (TDF) is a nucleoside reverse transcriptase inhibitor (NRTI) used in the treatment of HIV-1 infection and chronic Hepatitis B virus (HBV) infection. It is a prodrug of tenofovir, which is phosphorylated intracellularly to its active diphosphate form, tenofovir diphosphate.
## Primary Indications
* Treatment of HIV-1 infection in combination with other antiretroviral agents.
* Treatment of chronic Hepatitis B virus (HBV) infection.
## Adult Dosing
* **HIV-1 Infection:** 300 mg orally once daily.
* **Chronic HBV Infection:** 300 mg orally once daily.
## Pediatric Dosing
Dosing in pediatric patients is weight-based and depends on age and indication. Consult specific pediatric guidelines or the product monograph for precise dosing.
* **HIV-1 Infection (6 years and older, weighing at least 17 kg):** 10 mg/kg orally once daily, not to exceed 300 mg/day.
* **Chronic HBV Infection:** Information is limited. Consult specific pediatric guidelines.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is required based on creatinine clearance (CrCl).
* CrCl 50 mL/min or greater: No adjustment.
* CrCl 30 to 49 mL/min: 300 mg every 24 hours.
* CrCl 10 to 29 mL/min: 300 mg every 48 hours.
* CrCl less than 10 mL/min or on hemodialysis: 300 mg every 72 hours (or after 12 hours of hemodialysis).
* **Hepatic Impairment:** No dose adjustment is generally recommended.
## Contraindications
* Hypersensitivity to tenofovir disoproxil fumarate or any component of the formulation.
## Adverse Effects
* **Renal:** Proximal tubulopathy (Fanconi syndrome), acute kidney injury, elevated creatinine.
* **Bone:** Decreased bone mineral density (osteopenia, osteoporosis), bone fractures.
* **Gastrointestinal:** Nausea, diarrhea, vomiting, abdominal pain.
* **Metabolic:** Lactic acidosis, hyperlipidemia, hyperglycemia.
* **Other:** Headache, fatigue, rash.
## Key Drug Interactions
* **Nephrotoxic Agents:** Concomitant use with other nephrotoxic drugs (e.g., aminoglycosides, NSAIDs, certain antivirals like adefovir) may increase the risk of renal adverse effects. Consider alternatives or increased monitoring.
* **Didanosine (ddI):** Coadministration with ddI increases ddI plasma concentrations and risk of pancreatitis and peripheral neuropathy. TDF should be used with caution or avoided with ddI.
* **Aspirin, NSAIDs, Ibuprofen:** Concurrent use may increase serum creatinine and the risk of renal toxicity.
## Monitoring
* **Renal Function:** Baseline serum creatinine, estimated CrCl, and urinalysis. Monitor regularly during therapy, especially in patients with pre-existing renal impairment or those taking concomitant nephrotoxic drugs.
* **Bone Mineral Density:** Baseline and periodic monitoring, particularly in patients with a history of fractures or other risk factors for osteoporosis.
* **Liver Function Tests:** Baseline and periodic monitoring in patients with HBV.
* **Viral Load and CD4 Count:** For HIV-1 treatment.
* **Serum Phosphate:** Monitor for hypophosphatemia, especially in patients with renal impairment.
## Clinical Pearls
* TDF is associated with renal and bone toxicity. Careful patient selection and monitoring are crucial.
* Consider alternative agents (e.g., tenofovir alafenamide) in patients at high risk for renal or bone adverse effects.
* TDF should be taken orally with a full glass of water, preferably with a meal.
* Discontinuation of TDF in patients with HBV may lead to severe exacerbations of hepatitis; monitor liver function closely upon discontinuation.
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*This information is intended for healthcare professionals. It is essential to consult the most current prescribing information and relevant clinical guidelines before initiating or modifying therapy.*
