Gabapentin and Metolazone – Prescribing Cascade

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In this case scenario with gabapentin and metolazone, I lay out how the prescribing cascade can rear its ugly head.

SK is a 74-year-old male with a past medical history significant for chronic kidney disease stage 3, type 2 diabetes, hypertension, peripheral neuropathy, and heart failure with preserved ejection fraction. His medication list includes lisinopril 20 mg daily, amlodipine 10 mg daily, furosemide 40 mg twice daily, atorvastatin 40 mg nightly, aspirin 81 mg daily, insulin glargine 20 units at bedtime, and metformin 500 mg twice daily. Recently, his primary care provider started gabapentin 300 mg three times daily for neuropathic pain in his feet.

Two weeks later, SK presented to the clinic with worsening bilateral lower extremity edema and an increase in shortness of breath. His weight was up four pounds since his last visit, and his blood pressure remained controlled. Labs showed stable renal function with an eGFR of 32 mL/min/1.73m², and potassium and sodium levels were within normal range. Given the concern for fluid retention, the clinician added metolazone (Zaroxolyn) 2.5 mg daily as needed to be taken 30 minutes before furosemide to help augment diuresis.

While this strategy may provide symptomatic relief, it also introduces additional risks. Using metolazone on top of loop diuretics like furosemide significantly increases the chance of electrolyte disturbances, particularly hypokalemia, hyponatremia, and worsening renal function. In this case, it is important to recognize the gabapentin and metolazone connection and that gabapentin itself can cause or worsen peripheral edema (excellent board exam question), especially in older adults and in those with kidney impairment, where drug clearance is reduced. Simply adding more diuretics without addressing the underlying culprit could expose the patient to unnecessary risks. Dose reduction or discontinuation of gabapentin should be strongly considered as part of the overall management plan.

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