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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 the active moiety.
## 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
* **HIV-1 Infection (Age 2 to <12 years or weight ≥ 17 kg):** 10 mg/kg orally once daily, not to exceed 300 mg daily.
* **HIV-1 Infection (Age 12 to <18 years or weight ≥ 35 kg):** 300 mg orally once daily.
* **Chronic Hepatitis B (Age 10 to <18 years or weight ≥ 35 kg):** 300 mg orally once daily.
* *Dosing in pediatric patients younger than 2 years or weighing less than 17 kg for HIV-1, or younger than 10 years or weighing less than 35 kg for HBV is not established by FDA.*
## Dose Adjustments
* **Renal Impairment (Adults):** Dose adjustment is required 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.
* Hemodialysis: 300 mg every 7 days after a total of 5 doses in the first week.
* *Dose adjustments for pediatric patients with renal impairment are not well established and should be based on expert consultation and close monitoring.*
## Contraindications
* Hypersensitivity to tenofovir disoproxil fumarate or any component of the formulation.
## Adverse Effects
* **Common:** Diarrhea, nausea, vomiting, headache, rash, abdominal pain.
* **Serious:**
* **Renal toxicity:** Proximal tubulopathy, Fanconi syndrome, acute kidney injury, and renal failure. Risk is increased with concomitant nephrotoxic agents.
* **Bone toxicity:** Decreased bone mineral density (osteomalacia, osteoporosis), leading to fractures.
* **Lactic acidosis and severe hepatomegaly with steatosis:** Potentially fatal.
* **Immune reconstitution inflammatory syndrome (IRIS):** Can occur in HIV-infected patients.
## Key Drug Interactions
* **Nephrotoxic agents (e.g., aminoglycosides, NSAIDs, certain antivirals like adefovir):** Increased risk of renal toxicity.
* **Didanosine (ddI):** TDF increases ddI plasma concentrations, potentially increasing the risk of ddI-related toxicities. Concomitant use is generally not recommended, or requires dose adjustment of ddI and close monitoring.
* **Lopinavir/ritonavir:** No dose adjustment of TDF is needed, but monitoring for renal toxicity is advised.
## Monitoring
* **Baseline and periodic renal function:** Serum creatinine, BUN, urine glucose, urine protein, electrolytes.
* **Baseline and periodic bone mineral density:** Especially in patients with risk factors for fractures.
* **Liver function tests:** In patients with HBV.
* **HIV viral load and CD4 count:** In patients with HIV.
## Clinical Pearls
* TDF is a component of many fixed-dose combination antiretroviral therapies.
* The risk of renal and bone toxicity is a significant concern with long-term use of TDF.
* Consider TAF (tenofovir alafenamide) in patients with pre-existing renal impairment or those at high risk for bone or renal complications, as TAF has a more favorable safety profile in these aspects.
* Ensure adequate hydration.
* Discontinue if significant renal impairment or bone toxicity occurs.
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*This information is intended for healthcare professionals. Always consult the most current prescribing information and local guidelines before making clinical decisions.*
