Is Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide) nephrotoxic?

Nephrotoxicity of Odefsey (Emtricitabine, Rilpivirine, and Tenofovir Alafenamide)

Odefsey has significantly lower nephrotoxicity risk compared to older tenofovir formulations, but renal monitoring is still recommended as rare cases of nephrotoxicity can occur with tenofovir alafenamide (TAF).

Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate

Odefsey contains tenofovir alafenamide (TAF), which was specifically developed to improve the renal safety profile compared to tenofovir disoproxil fumarate (TDF). The key differences are:

• TAF produces lower plasma tenofovir concentrations than TDF, reducing exposure to kidneys 1
• TAF is more efficiently delivered to HIV target cells, allowing for a lower dose (25mg vs 300mg with TDF)
• TAF demonstrates better renal outcomes in clinical trials compared to TDF-containing regimens 2

Renal Safety Profile of TAF in Odefsey

While TAF has improved renal safety compared to TDF, it's important to understand:

• TAF is not completely free of nephrotoxic potential - rare cases of renal impairment have been reported 3
• The FDA label for tenofovir alafenamide notes that "postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products" 4
• These cases typically involve patients with confounding factors that may have contributed to renal events 4

Risk Factors for TAF-Associated Nephrotoxicity

Patients with the following characteristics require closer monitoring:

• Pre-existing kidney disease (eGFR <50 mL/min/1.73m²) 5
• Concomitant use of other nephrotoxic medications 5
• Comorbid conditions like hypertension or diabetes 1
• Co-infection with hepatitis B or C 1
• Use of TAF with ritonavir-boosted protease inhibitors 5, 1

Monitoring Recommendations

For patients on Odefsey:

• Assess renal function at baseline before starting therapy 4
• Monitor serum creatinine, estimated GFR, urine glucose, and urine protein at 1-3 months after initiation and then every 6-12 months if stable 1
• More frequent monitoring (every 3-6 months) is recommended for patients with risk factors for kidney disease 1
• Consider testing for tubular dysfunction if there are concerns (protein/albumin:creatinine ratio) 1

When to Consider Discontinuation

Discontinue Odefsey if:

• Patient develops clinically significant decreases in renal function 4
• eGFR drops by >25% from baseline and decreases to <50 mL/min/1.73m² 5
• Evidence of Fanconi syndrome develops (proximal tubular dysfunction) 4
• New onset or worsening proteinuria or albuminuria occurs 5

Clinical Manifestations of TAF Nephrotoxicity

Though rare, potential signs of TAF-related nephrotoxicity include:

• Acute kidney injury 3
• Proximal tubular dysfunction 4
• Fanconi syndrome (characterized by phosphate wasting, glycosuria, aminoaciduria) 4
• Proteinuria 5

Conclusion

While Odefsey (containing TAF) represents a significant improvement in renal safety compared to older TDF-containing regimens, it is not completely devoid of nephrotoxic potential. Appropriate monitoring of renal function is still necessary, particularly in patients with risk factors for kidney disease. The overall nephrotoxicity risk with Odefsey is low but not zero.