What is the recommended dosage of tenofovir disoproxil fumarate (TDF) for an adult patient with chronic hepatitis B and compensated liver disease?

Tenofovir Dosing for Chronic Hepatitis B

For adults with chronic hepatitis B and compensated liver disease, the recommended dose of tenofovir disoproxil fumarate (TDF) is 300 mg once daily, taken orally without regard to food. 1, 2

Standard Dosing by Patient Population

Adults and Adolescents ≥12 Years

• TDF 300 mg once daily is the standard dose for patients weighing ≥35 kg 3, 1, 2
• The medication can be taken with or without food 2
• Tenofovir alafenamide (TAF) 25 mg once daily is an alternative formulation with improved renal and bone safety profile 1, 4

Adolescents (12-18 years)

• For patients ≥12 years and ≥35 kg: TDF 300 mg once daily 3, 1
• Alternative dosing: 8 mg/kg daily (up to maximum 300 mg) 3
• At week 72,89% of adolescents achieved virological response (HBV DNA <400 copies/mL) with no resistance development 3

Pediatric Patients <12 Years

• TDF is not approved for chronic hepatitis B in children under 12 years of age 3, 2
• Safety and efficacy have not been established in this population for hepatitis B treatment 2

Dose Adjustments for Renal Impairment

Renal function monitoring is critical as tenofovir is primarily renally eliminated. 1, 2

Baseline Assessment Required

• Measure creatinine clearance, serum phosphorus, urine glucose, and urine protein before initiating therapy 1, 2

Dosing by Creatinine Clearance (CrCl)

• CrCl ≥50 mL/min: TDF 300 mg every 24 hours (standard dose) 3, 2
• CrCl 30-49 mL/min: TDF 300 mg every 48 hours 3, 2
• CrCl 10-29 mL/min: TDF 300 mg every 72-96 hours 3, 2
• CrCl <10 mL/min without dialysis: TDF is not recommended 3
• Hemodialysis patients: TDF 300 mg every 7 days or after approximately 12 hours of dialysis 3, 2

A recent study demonstrated that more aggressive dose reduction (every 72 hours vs every 48 hours) in patients with moderate renal impairment did not affect virological control and resulted in better renal function recovery 5

Preferred Alternatives for High-Risk Patients

For patients with risk factors for renal dysfunction or bone disease, consider TAF, entecavir, or besifovir over TDF. 3

Risk Factors Warranting Alternative Agents

• Baseline eGFR <60 mL/min 3
• Proteinuria or albuminuria >0.5 mg/dL (urine albumin:creatinine ratio >30 mg/g) 3
• Hypophosphatemia <2.5 mg/dL 3
• Uncontrolled diabetes or hypertension 3
• Osteopenia, osteoporosis, or chronic steroid use 3
• Advanced age 3

Comparative Safety Data

• In a 96-week trial comparing TAF vs TDF, patients with risk factors on TDF had median eGFR decline of -5.0 mL/min vs -0.3 mL/min with TAF 3
• Bone mineral density changes were -3.29% with TDF vs +1.23% with TAF 3
• TAF is not recommended if CrCl <15 mL/min 3, 4

Switching from TDF to Alternative Agents

Patients who develop renal dysfunction or decreased bone density on TDF can improve these parameters by switching to TAF. 3

• After switching from TDF to TAF at week 96, eGFR improved from -4.6 mL/min decline to -0.06 mL/min by week 144 3
• Bone mineral density significantly improved after switching to TAF 3
• Long-term TAF treatment through 5 years showed median eGFR decline <2.5 mL/min and mean bone density declines <1% 6

Treatment Duration

The optimal duration of treatment for chronic hepatitis B is unknown. 2

• For HBeAg-positive patients: minimum 1 year, continuing at least 1 year after HBeAg seroconversion 3
• For HBeAg-negative patients: longer than 1 year, but optimal duration not established 3
• Treatment is typically long-term or indefinite for most patients with compensated liver disease 1

Critical Safety Warnings

Post-Treatment Hepatitis Exacerbation

Severe acute exacerbations of hepatitis can occur after discontinuing tenofovir. 1, 2

• Monitor hepatic function closely with clinical and laboratory follow-up for at least several months after discontinuation 1, 2
• Resumption of anti-hepatitis B therapy may be warranted if exacerbation occurs 2

Monitoring Requirements

• Renal function: Monitor creatinine clearance, serum phosphorus, urine glucose, and urine protein regularly 1, 2
• Bone density: Consider monitoring in patients with risk factors for osteoporosis 3
• Liver function: Monitor ALT, AST, and HBV DNA levels during treatment 1

Common Pitfalls to Avoid

• Failing to adjust dose for renal impairment: Always calculate creatinine clearance before initiating therapy and monitor regularly 1, 2
• Using TDF in high-risk patients: Consider TAF or entecavir in patients with baseline renal or bone disease 3
• Abrupt discontinuation: Never stop tenofovir without close monitoring due to risk of severe hepatitis flare 1, 2
• Inadequate monitoring: Long-term safety requires consistent renal and bone monitoring, particularly with TDF 1
• Combining with other tenofovir products: Do not use TDF with other tenofovir-containing products (TRUVADA, VEMLIDY, etc.) 2