What to do for a patient with impaired renal function on fluoxetine (Prozac), lamotrigine (Lamictal), gabapentin, topiramate (Topamax), buspirone (Buspar), apixaban (Eliquis), lorazepam (Ativan), levothyroxine, montelukast (Singulair), and pantoprazole (Protonix) with a history of seizures and asthma?

Management of Worsening Renal Function in a Patient on Multiple Medications

Immediate medication adjustments are required: reduce gabapentin and topiramate doses by 50%, discontinue or dose-reduce apixaban to 2.5 mg twice daily if creatinine ≥1.5 mg/dL, and discontinue lorazepam or use with extreme caution given the anticholinergic burden and renal impairment. 1, 2, 3, 4

Critical Medication Adjustments Required

Antiepileptic Drugs Requiring Dose Reduction

• Gabapentin requires significant dose reduction in renal impairment, as it is eliminated entirely by renal excretion as unchanged drug, with plasma clearance directly proportional to creatinine clearance. 4, 5

  • For creatinine clearance <30 mL/min, reduce the dose by approximately 50% or more depending on the degree of impairment. 4, 6
  • Gabapentin can be removed by hemodialysis, requiring supplemental dosing if dialysis becomes necessary. 4, 7

• Topiramate requires dose reduction to half the usual adult dose when creatinine clearance is less than 70 mL/min/1.73m². 3

  • Patients with renal impairment will require a longer time to reach steady-state at each dose. 3
  • Topiramate is cleared by hemodialysis at 4-6 times the normal rate, necessitating supplemental doses during dialysis. 3

Anticoagulation Management

• Apixaban (Eliquis) requires dose reduction from 5 mg twice daily to 2.5 mg twice daily if the patient meets criteria for severe renal impairment (serum creatinine ≥1.5 mg/dL, age ≥80 years, or body weight <60 kg). 2
  • Full-dose apixaban with severe renal impairment significantly increases major bleeding risk. 2
  • Close monitoring for bleeding complications is essential after dose adjustment. 2

Benzodiazepine Considerations

• Lorazepam (Ativan) should be minimized or discontinued to reduce anticholinergic burden in patients with renal impairment, particularly those with cognitive symptoms or risk factors. 8
  • If anxiolysis is required, consider alternatives with no dose adjustment needed, though lorazepam can be used cautiously if necessary. 8
  • Enhanced receptor sensitivity secondary to accumulation of endogenous uremic toxins increases the risk of adverse effects from benzodiazepines in renal failure. 9

Medications Requiring Monitoring But No Immediate Dose Change

• Lamotrigine (Lamictal) is less affected by renal impairment and does not require routine dose adjustment, though monitoring is prudent. 6

• Fluoxetine (Prozac) is primarily hepatically metabolized and does not require dose adjustment for renal impairment alone. 9

• Buspirone (Buspar) does not require specific renal dose adjustment but should be monitored for increased side effects. 9

• Levothyroxine requires no adjustment for renal function. 9

• Montelukast (Singulair) and pantoprazole (Protonix) do not require renal dose adjustments. 9

Critical Monitoring Parameters

• Recheck serum creatinine, potassium, and sodium within 3-7 days after medication changes to assess response and detect electrolyte abnormalities. 1, 2

• Monitor for signs of drug toxicity, particularly neurotoxicity from antiepileptic drugs, which can manifest as altered mental status, increased seizure frequency, or new-onset seizures. 10, 5

  • Supratherapeutic dosing of renally-cleared medications can lead to significant neurotoxic effects, potentiated by older age, pre-existing CNS conditions, and renal failure. 10

• Assess renal function every 1-3 months given progressive kidney disease, and more frequently if creatinine continues to rise. 1, 2

• Consider therapeutic drug monitoring for antiepileptic drugs to ensure levels remain in therapeutic range while avoiding toxicity. 10, 5

Nephroprotective Strategies

• Avoid nephrotoxic medications, particularly NSAIDs, which should be strictly avoided in patients with impaired renal function. 11, 1

  • NSAIDs reduce renal function and increase the risk of acute kidney injury, especially when combined with other medications affecting renal perfusion. 11

• Ensure adequate hydration to support remaining renal function and reduce the risk of further deterioration. 1, 3

• Review all medications for potential drug-drug interactions that could worsen renal function or increase toxicity risk. 9, 5

Common Pitfalls to Avoid

• Do not continue full doses of gabapentin and topiramate without adjustment, as accumulation leads to neurotoxicity, encephalopathy, and paradoxical seizure worsening. 4, 10, 5

• Do not use full-dose apixaban if severe renal impairment criteria are met, as this dramatically increases bleeding risk. 2

• Avoid combining multiple CNS depressants (lorazepam, gabapentin, topiramate) at full doses in renal impairment, as uremic toxins enhance receptor sensitivity and increase sedation risk. 3, 9

• Do not assume all antiepileptic drugs require the same adjustments—gabapentin and topiramate are renally cleared and require significant dose reduction, while lamotrigine is less affected. 5, 6

Preparation for Progressive Renal Decline

• Consider nephrology referral given GFR decline, as patients with CKD and declining function benefit from specialized management. 1

• Begin discussions about renal replacement therapy options if GFR approaches 15 mL/min, including hemodialysis, peritoneal dialysis, or conservative management. 1

  • Preparation for kidney failure should begin when patients reach CKD stage 4 (GFR <30 mL/min). 1

• Plan for supplemental dosing of gabapentin and topiramate if hemodialysis becomes necessary, as both are significantly cleared by dialysis. 3, 4, 7