What is the interaction between Truvada (emtricitabine and tenofovir disoproxil fumarate) and fenofibrate regarding renal function?

Interaction Between Truvada and Fenofibrate: Renal Function Concerns

Patients taking Truvada (emtricitabine and tenofovir disoproxil fumarate) with fenofibrate require close renal monitoring due to potential additive nephrotoxic effects, as both medications can independently impact kidney function.

Mechanism of Interaction

The interaction between Truvada and fenofibrate primarily concerns their combined effects on renal function:

1. Tenofovir disoproxil fumarate (TDF) effects:

   • Causes increased tenofovir plasma exposure
   • Associated with proximal tubular dysfunction
   • Can lead to decreased glomerular filtration rate (GFR)
   • May cause Fanconi syndrome in rare cases 1

2. Fenofibrate effects:

   • Causes rapid increases in serum creatinine (within weeks)
   • Associated with declined estimated GFR
   • Approximately 27% of patients experience creatinine increases ≥0.3 mg/dL within 6 months 2
   • Effects may be reversible without treatment discontinuation 3

Risk Factors for Nephrotoxicity

The risk of renal impairment is higher in patients with:

• Pre-existing renal disease 2
• Chronic kidney disease 2
• Diabetes 2
• Older age 3
• Concomitant use of medications affecting renal hemodynamics:
  • Calcium channel blockers (especially dihydropyridines) 2
  • ACE inhibitors 2
  • Angiotensin receptor blockers 3
  • Furosemide 2
• Higher doses of fenofibrate 2

Monitoring Recommendations

For patients on both Truvada and fenofibrate:

• Baseline assessment:

  • Serum creatinine
  • Estimated GFR
  • Urinalysis for proteinuria and glycosuria

• Follow-up monitoring:

  • Frequent renal function monitoring 1
  • Monitor for signs of proximal tubular dysfunction:
    • Euglycemic glycosuria
    • Hypophosphatemia
    • Proteinuria
    • Increased urinary phosphorus excretion 1

Management Strategies

1. Consider alternative medications:

   • Replace Truvada with tenofovir alafenamide (TAF)-containing regimens when possible, as TAF has less renal toxicity 1, 4
   • Switch to entecavir if treating hepatitis B 1

2. Dose adjustments:

   • Adjust tenofovir dose for creatinine clearance <50 ml/min 1
   • Consider lower doses of fenofibrate in high-risk patients 2

3. Discontinuation criteria:

   • Discontinue tenofovir if GFR decreases >25% from baseline and to <60 ml/minute/1.73 m² 1
   • Consider discontinuing fenofibrate if serum creatinine increases ≥30% 3
   • Discontinue tenofovir if there is evidence of proximal tubular dysfunction 1

Clinical Pearls

• Fenofibrate-associated increases in creatinine may not always reflect true renal function deterioration but could involve altered creatinine secretion 3
• The interaction between tenofovir and fenofibrate is not mitigated by staggering administration by 12 hours 1
• Tenofovir alafenamide (TAF) gives much reduced plasma tenofovir exposure compared to tenofovir disoproxil fumarate (TDF), making it a safer alternative 1, 4
• Renal effects of fenofibrate may be reversible even without discontinuation 3
• Long-term fenofibrate use may actually be associated with slower progression of renal function impairment and albuminuria 3, 5

This interaction requires vigilance but can be managed with appropriate monitoring and medication adjustments when necessary.