Usage
- Tenofovir alafenamide (TAF) is prescribed for the treatment of chronic hepatitis B virus (HBV) infection in adults and adolescents (12 years and older weighing at least 35 kg) with compensated liver disease. It is an antiviral medication, specifically a nucleoside analog reverse transcriptase inhibitor (NRTI).
- Pharmacological Classification: Antiviral, Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI).
- Mechanism of Action: Tenofovir alafenamide is a prodrug of tenofovir. It is intracellularly metabolized to tenofovir diphosphate, which inhibits HBV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and by causing DNA chain termination after incorporation into viral DNA.
Alternate Names
- International Nonproprietary Name (INN): Tenofovir alafenamide
- Brand Names: Vemlidy, HepBest (India)
How It Works
- Pharmacodynamics: TAF inhibits HBV replication by being incorporated into viral DNA, thus terminating its production. This leads to decreased levels of HBV DNA in the blood.
- Pharmacokinetics:
- Absorption: TAF is rapidly absorbed after oral administration, ideally with food to improve absorption. It is a prodrug that is hydrolyzed to tenofovir.
- Metabolism: Primarily metabolized intracellularly by carboxylesterase-1 and cathepsin A to its active form tenofovir diphosphate. It does not depend on CYP enzymes for conversion.
- Elimination: Tenofovir, the major circulating metabolite, is primarily eliminated by the kidneys via glomerular filtration and active tubular secretion.
Dosage
Standard Dosage
Adults:
- 25 mg once daily taken orally with food.
Children:
- 12 years and older weighing at least 35 kg: 25 mg once daily taken orally with food.
- Children younger than 12 years or weighing less than 35 kg: Use and dose must be determined by a doctor as safety and efficacy have not been established.
Special Cases:
- Elderly Patients: No dose adjustment is needed for patients 65 years and older.
- Patients with Renal Impairment: No dose adjustment is needed for patients with creatinine clearance (CrCl) ≥ 15 mL/min, including those on hemodialysis (administer after hemodialysis). Not recommended for patients with CrCl < 15 mL/min not on hemodialysis.
- Patients with Hepatic Dysfunction: No dose adjustment is required for mild hepatic impairment (Child-Pugh A). Not recommended for patients with decompensated hepatic impairment (Child-Pugh B or C).
Clinical Use Cases
TAF is not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, or emergency situations. Its use is specific to chronic HBV infection.
Dosage Adjustments
Dose modifications are not typically made based on comorbidities, genetic polymorphisms or other metabolic disorders except as outlined in the ‘Special Cases’ above.
Side Effects
Common Side Effects
- Headache
- Abdominal pain/discomfort
- Fatigue
- Nausea
- Diarrhea
Rare but Serious Side Effects
- Lactic acidosis (build-up of lactic acid in the blood)
- Severe hepatomegaly with steatosis (enlarged liver with fat accumulation)
- New onset or worsening renal impairment
- Acute exacerbations of hepatitis B after treatment discontinuation
Long-Term Effects
- Reduced bone mineral density
- Renal dysfunction
Adverse Drug Reactions (ADR)
- Any signs of lactic acidosis (rapid breathing, cold sweats, blueish skin tint, etc.)
- Signs of liver problems (jaundice, yellowing of eyes, dark urine, pale colored stools, swelling in ankles, etc.)
- Signs of kidney problems (changes in urination, swelling, weight gain, etc.)
Contraindications
- Hypersensitivity to tenofovir alafenamide or any component of the formulation.
Drug Interactions
- Drugs that strongly affect P-gp and BCRP activity (e.g., rifampin, St. John’s Wort, carbamazepine) may reduce tenofovir alafenamide plasma concentrations.
- Co-administration with other nephrotoxic drugs may increase the risk of renal impairment.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B3 (Australia); Not Assigned (US FDA), but animal studies indicate no fetal harm at exposures equivalent to human doses, and limited human data shows no association between TAF use and birth defects.
- Fetal risks: Low placental transfer. However, monitor for potential adverse effects.
- Breastfeeding: Unknown if present in human milk. Use with caution, weighing risks/benefits.
Drug Profile Summary
- Mechanism of Action: NRTI inhibiting HBV reverse transcriptase.
- Side Effects: Headache, fatigue, nausea, abdominal pain, rare but serious: lactic acidosis, hepatomegaly with steatosis, acute hepatitis B exacerbation after treatment discontinuation.
- Contraindications: Hypersensitivity.
- Drug Interactions: P-gp and BCRP inducers.
- Pregnancy & Breastfeeding: Limited data, use with caution and weigh the potential benefits against the potential risks.
- Dosage: Adults and adolescents ≥12 years and ≥35 kg: 25 mg once daily with food.
- Monitoring Parameters: Renal function (serum creatinine, urine protein, urine glucose), liver function tests (LFTs), HBV DNA levels, HIV testing (prior to initiation).
Popular Combinations
TAF is often used as monotherapy for HBV. Its fixed-dose combination with emtricitabine is used for HIV PrEP and treatment.
Precautions
- Test for HIV before initiating therapy as TAF alone is not effective against HIV.
- Closely monitor renal function.
- Monitor for signs/symptoms of lactic acidosis and hepatic steatosis.
- Patients with pre-existing renal or hepatic issues require careful monitoring.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Tenofovir Alafenamide?
A: 25 mg once daily with food for adults and adolescents 12 years and older weighing at least 35 kg.
Q2: How does Tenofovir Alafenamide differ from Tenofovir Disoproxil Fumarate (TDF)?
A: TAF is a prodrug of tenofovir that results in higher intracellular drug levels and lower plasma drug levels compared to TDF. This translates into improved renal and bone safety profiles with TAF.
Q3: Can Tenofovir Alafenamide be used during pregnancy?
A: While categorized as B3 in Australia and not formally assigned a US pregnancy category, animal data and limited human data suggest low risk. The decision to use TAF during pregnancy should weigh the potential benefits against the unknown risks.
Q4: What are the key monitoring parameters for patients on Tenofovir Alafenamide?
A: Monitor renal function, liver function tests, HBV DNA levels, and perform an HIV test before starting TAF.
Q5: What should be done if a patient misses a dose of Tenofovir Alafenamide?
A: If less than 18 hours have passed since the missed dose, the patient should take it as soon as possible and resume their normal schedule. If more than 18 hours have passed, they should skip the missed dose and continue with the next scheduled dose.
Q6: Is Tenofovir Alafenamide effective against HIV?
A: No, Tenofovir Alafenamide is not indicated for use as monotherapy for the treatment of HIV. Patients must be tested for HIV before starting TAF and, if positive, should receive a combination regimen that is active against HIV.
Q7: Are there any dietary restrictions while taking Tenofovir Alafenamide?
A: It is recommended to take Tenofovir Alafenamide with food to enhance its absorption. No other specific dietary restrictions are associated with its use. However, concurrent use of St. John’s Wort can decrease the levels of Tenofovir Alafenamide in the blood.
Q8: What are the potential long-term side effects of Tenofovir Alafenamide?
A: Long-term use of TAF may be associated with a decrease in bone mineral density and the potential for renal dysfunction, though generally less so than with Tenofovir Disoproxil Fumarate (TDF).
Q9: Can Tenofovir Alafenamide be used in patients with hepatic impairment?
A: It can be used in patients with mild hepatic impairment (Child-Pugh A) without dose adjustment. However, TAF is not recommended for those with moderate to severe (Child-Pugh B or C) hepatic impairment.
