At what eGFR level does acamprosate become contraindicated due to Impaired Renal Function?

Acamprosate Contraindication in Renal Impairment

Acamprosate is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m² (CKD Stage 4-5).

Mechanism and Renal Considerations

Acamprosate (calcium acetylhomotaurinate) is a medication used for maintaining abstinence in alcohol use disorder (AUD) by modulating glutamatergic neurotransmission. It has several important pharmacokinetic properties that make renal function a critical consideration:

• Acamprosate is not metabolized by the liver but is primarily eliminated unchanged through the kidneys 1
• The drug has limited absorption but moderate distribution (volume of distribution ~20L)
• In patients with normal renal function, approximately 50% of the drug is excreted unchanged in urine 1

Contraindication Threshold

The evidence clearly indicates that acamprosate is contraindicated in patients with severe renal impairment. According to pharmacokinetic studies:

• Renal insufficiency significantly influences the elimination of acamprosate 1
• The drug is contraindicated in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) 1, 2

Clinical Application to This Case

For the 55-year-old man with:

• AUD seeking medication to support abstinence
• CKD Stage 4 (eGFR 25 mL/min/1.73 m²)
• Hypertension and regular monitoring

Acamprosate would be contraindicated due to his eGFR of 25 mL/min/1.73 m², which falls below the threshold of 30 mL/min/1.73 m².

Alternative Approaches for AUD Treatment in Renal Impairment

Since acamprosate is contraindicated in this patient, alternative FDA-approved medications for AUD should be considered:

1. Naltrexone: Can be used with caution in renal impairment as it's primarily metabolized by the liver
2. Disulfiram: Use with caution in patients with renal impairment, but no specific contraindication based on eGFR

Importance of Appropriate Medication Selection in CKD

Inappropriate medication use in CKD patients is common and problematic:

• Studies show that 15-67% of medications prescribed to patients with renal insufficiency may not align with dosing recommendations 3, 4
• Nephrotoxic drugs are frequently prescribed to CKD patients, potentially accelerating renal function deterioration 5

Conclusion

The correct answer is C. eGFR 30 mL/min/1.73 m² (CKD Stage 3). Acamprosate becomes contraindicated when eGFR falls below 30 mL/min/1.73 m². Since this patient has an eGFR of 25 mL/min/1.73 m², acamprosate would be contraindicated, and alternative treatments for AUD should be considered.