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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 chronic Hepatitis B virus (HBV) infection in adults and pediatric patients.
* Part of combination antiretroviral therapy (ART) for the treatment of HIV-1 infection in adults and pediatric patients.
## Adult Dosing
* **Chronic Hepatitis B:** 300 mg orally once daily.
* **HIV-1 Infection:** 300 mg orally once daily, typically in combination with other antiretroviral agents.
## Pediatric Dosing
* **Chronic Hepatitis B:**
* **Ages 12 years to <17 years:** 300 mg orally once daily.
* **Ages 7 years to <12 years:** 10 mg/kg orally once daily, not to exceed 300 mg.
* **Ages 2 years to <7 years:** 16 mg/kg orally once daily, not to exceed 300 mg.
* **HIV-1 Infection:** Dosing varies by age, weight, and indication (e.g., treatment-naive vs. treatment-experienced). Specific pediatric dosing for HIV requires consultation with a specialist and adherence to established guidelines, as it is weight-based and complex. Consult current pediatric HIV treatment guidelines.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is required based on creatinine clearance (CrCl).
* CrCl > 50 mL/min: 300 mg once daily.
* CrCl 30-49 mL/min: 300 mg every 48 hours.
* CrCl 10-29 mL/min: 300 mg every 72 hours.
* CrCl < 10 mL/min or on hemodialysis: 300 mg every 7 days after a full weekly dose.
* **Hepatic Impairment:** No dose adjustment is generally recommended. However, TDF should be discontinued if clinical jaundice occurs.
## Contraindications
* Hypersensitivity to TDF or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, abdominal pain, headache, dizziness, asthenia, rash.
* **Serious:**
* **Nephrotoxicity:** Acute kidney injury, Fanconi syndrome (proximal renal tubulopathy), interstitial nephritis. Risk is increased with concurrent use of other nephrotoxic agents.
* **Bone Abnormalities:** Decreased bone mineral density (osteomalacia, osteoporosis), fractures.
* **Lactic Acidosis/Hepatomegaly with Steatosis:** Potentially fatal.
* **Immune Reconstitution Inflammatory Syndrome (IRIS):** Can occur in patients with advanced HIV and IRIS.
* **Hepatitis B Flare:** Exacerbation of hepatitis B upon discontinuation.
## Key Drug Interactions
* **Nephrotoxic Drugs:** Concomitant use with other drugs that are nephrotoxic (e.g., aminoglycosides, NSAIDs, certain antivirals like adefovir) can increase the risk of renal toxicity.
* **Tenofovir-Activating Drugs:** TDF is a prodrug; its activity is dependent on conversion to tenofovir diphosphate.
* **Didanosine:** Concomitant use is generally not recommended due to increased risk of pancreatitis and peripheral neuropathy. If used, consider dose reduction of didanosine.
* **Lopinavir/Ritonavir:** Increased tenofovir exposure may occur; monitor renal function.
* **Atazanavir:** Concomitant use without ritonavir may increase the risk of hyperbilirubinemia and renal-related adverse events. If coadministered with atazanavir without ritonavir, a dose of TDF may be needed.
## Monitoring
* **Renal Function:** Serum creatinine and estimated glomerular filtration rate (eGFR) at baseline and regularly during treatment (e.g., every 3-6 months, or more frequently in patients with risk factors for renal impairment or concurrent nephrotoxic agents). Urine tests for proteinuria and glucosuria should also be performed.
* **Bone Mineral Density:** Baseline and periodically, especially in patients with a history of fractures or other risk factors for bone disease.
* **Liver Function Tests:** For patients with chronic HBV, monitor ALT and HBV DNA levels.
* **Complete Blood Count:** Monitor for anemia.
* **Electrolytes:** Monitor for hypophosphatemia, which can be indicative of Fanconi syndrome.
## Clinical Pearls
* TDF is associated with a higher risk of renal and bone toxicity compared to tenofovir alafenamide (TAF). Consider TAF in patients with pre-existing renal or bone disease, or those at high risk.
* Discontinuation of TDF in patients with chronic HBV may lead to severe hepatitis B exacerbation. Monitor liver function closely after discontinuation.
* Ensure adequate hydration to minimize the risk of renal adverse events.
* For pediatric patients, adherence to weight-based dosing is crucial.
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This information is intended for healthcare professionals and does not replace professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines for definitive guidance.
