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# Tenofovir Disoproxil Fumarate (TDF)
## Overview
Tenofovir disoproxil fumarate (TDF) is a nucleotide analog reverse transcriptase inhibitor (NtRTI) used in the treatment of HIV-1 infection and chronic Hepatitis B virus (HBV) infection.
## 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 Hepatitis B:** 300 mg orally once daily.
## Pediatric Dosing
Dosing is weight-based and varies by age and indication. Consult specific pediatric guidelines or product labeling.
* **HIV-1 Infection (ages 2-17 years):** Dosing varies based on weight. For example, children weighing 17 kg to <22 kg may receive 150 mg once daily, and those weighing 22 kg to <28 kg may receive 200 mg once daily. The maximum dose is 300 mg once daily.
* **Chronic Hepatitis B (ages 12-17 years):** 300 mg orally once daily.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is necessary based on creatinine clearance (CrCl).
* CrCl 30-49 mL/min: 300 mg every 48 hours.
* CrCl <30 mL/min (and not on hemodialysis): 300 mg every 72 hours.
* On hemodialysis: 300 mg every 7 days after a full weekly dose.
## Contraindications
* Hypersensitivity to tenofovir disoproxil fumarate or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, headache, rash, abdominal pain.
* **Serious:**
* Lactic acidosis and severe hepatomegaly with steatosis (rare, but potentially fatal).
* Fanconi syndrome (proximal renal tubulopathy).
* Acute renal failure.
* Bone mineral density decrease (osteomalacia).
* Exacerbations of Hepatitis B upon discontinuation.
## Key Drug Interactions
* **Nephrotoxic Agents:** Concomitant use with drugs that are nephrotoxic (e.g., aminoglycosides, NSAIDs, certain antivirals like cidofovir, high-dose or prolonged use of acyclovir/ganciclovir) may increase the risk of renal adverse events.
* **Didanosine:** Concomitant use can increase didanosine plasma concentrations and lead to increased toxicity. Coadministration is generally not recommended.
* **Lopinavir/Ritonavir:** May require dose adjustment of TDF in patients with renal impairment.
## Monitoring
* **Renal Function:** Serum creatinine and estimated CrCl should be assessed at baseline and periodically throughout therapy. Urinalysis for proteinuria and glucosuria should also be performed.
* **Liver Function:** Liver enzymes (AST, ALT) should be monitored, especially in patients with HBV.
* **Bone Mineral Density:** Consider monitoring bone density in patients with a history of fractures or other risk factors for bone disease.
* **Viral Load and CD4 Count:** For HIV-1 treatment, monitor HIV RNA levels and CD4+ T-cell counts.
* **Hepatitis B Viral Load (HBV DNA):** Monitor HBV DNA levels for efficacy in chronic Hepatitis B treatment.
## Clinical Pearls
* TDF is a prodrug; it is hydrolyzed to tenofovir, the active moiety.
* Renal toxicity and bone demineralization are significant concerns, particularly with long-term use or in patients with pre-existing renal dysfunction.
* Discontinuation of therapy in patients with chronic HBV may lead to severe exacerbations of hepatitis. Continued monitoring of liver function is recommended after discontinuation.
* Consider switching to tenofovir alafenamide (TAF) in patients with renal impairment or bone density concerns, as TAF has a more favorable renal and bone safety profile.
**Educational Disclaimer:** This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for complete and up-to-date details before making any treatment decisions.
