What are the side effects of tenofovir?

Side Effects of Tenofovir

Tenofovir is associated with significant renal toxicity and bone mineral density loss, particularly with long-term use of tenofovir disoproxil fumarate (TDF), while tenofovir alafenamide (TAF) has improved safety profile for these specific concerns. 1

Major Side Effects by System

Renal Effects

• Proximal renal tubular dysfunction:
  • Can progress to Fanconi syndrome (renal failure, hypokalemia, hypophosphatemia, metabolic acidosis, albuminuria/proteinuria) 1
  • Concentration-dependent accumulation in proximal tubule cells 1
  • Risk factors: pre-existing renal dysfunction, concomitant nephrotoxic medications
  • More common with TDF than TAF formulation 1
  • Monitoring: Regular assessment of creatinine clearance, electrolytes, urinalysis

Bone Effects

• Decreased bone mineral density:
  • Associated with increased risk of osteoporosis and fractures 2
  • Long-term TDF use (>24 months) significantly increases fracture risk in elderly patients 3
  • In a study of elderly patients with chronic hepatitis B, TDF increased fracture risk by 80% after 24 months compared to entecavir (sHR 1.80) 3
  • More pronounced with TDF than TAF formulation 1
  • Monitoring: Consider baseline and follow-up bone density scans in at-risk patients

Gastrointestinal Effects

• Nausea
• Vomiting
• Diarrhea 4, 5

Metabolic Effects

• Lactic acidosis (rare but serious) 1

Formulation Differences

Tenofovir Disoproxil Fumarate (TDF)

• Higher risk of renal dysfunction
• Greater reduction in eGFR (-7.8 mL/min at 48 weeks in one study) 1
• More significant bone mineral density loss 1, 2

Tenofovir Alafenamide (TAF)

• Improved renal safety profile
• Minimal eGFR reduction (-0.06 mL/min) 1
• Less impact on bone mineral density 1
• May increase low-density lipoprotein cholesterol 1

Special Considerations

Drug Interactions

• With ritonavir/cobicistat-boosted regimens:
  • Increased tenofovir concentrations requiring careful monitoring 1
  • Ritonavir may block MRP-2 transporter in kidneys, potentially increasing tenofovir levels 1

Dose Adjustments

• Required for patients with renal impairment 6
• TDF not recommended for creatinine clearance <10 mL/min without renal replacement therapy 1
• TAF not recommended for creatinine clearance <15 mL/min 1

Monitoring Recommendations

1. Baseline assessment of renal function before starting therapy
2. Regular monitoring of creatinine clearance, serum phosphate, urinalysis
3. Consider bone mineral density testing in patients with risk factors
4. More frequent monitoring when used with boosted antiretroviral regimens 1

Risk Mitigation

• Consider TAF instead of TDF in patients with or at risk of renal dysfunction or bone disease 1
• Switch from TDF to TAF, besifovir, or entecavir if renal dysfunction or bone mineral density loss develops 1
• Ensure adequate hydration
• Avoid concomitant nephrotoxic medications when possible

Common Pitfalls

• Failing to recognize early signs of renal dysfunction
• Not adjusting dosage in patients with renal impairment
• Overlooking bone health in long-term therapy
• Not considering drug interactions with boosted antiretroviral regimens

When initiating tenofovir therapy, the formulation choice should be based on patient-specific factors including age, renal function, bone health, and concomitant medications to minimize adverse effects while maintaining therapeutic efficacy.