Can Trazodone, Cyclobenzaprine, Amlodipine, Ezetimibe, Alendronate, or Bupropion cause impaired renal function (low Glomerular Filtration Rate, GFR)?

Medication-Induced Renal Impairment Assessment

Among the medications listed, amlodipine is the only agent with documented potential to cause acute GFR decline, though this effect is typically modest and less pronounced than with ACE inhibitors or ARBs; the remaining medications (trazodone, cyclobenzaprine, ezetimibe, alendronate, and bupropion) are not recognized causes of reduced GFR.

Amlodipine and Kidney Function

Amlodipine does not directly cause nephrotoxicity but may be associated with acute GFR declines when initiated, particularly in combination with other antihypertensive agents. 1

• In the ACCOMPLISH trial, patients treated with benazepril plus amlodipine experienced acute eGFR declines >15% in some cases, though these declines were less frequent and less severe compared to benazepril plus hydrochlorothiazide 1
• Importantly, amlodipine is inferior to ACE inhibitors and ARBs for renoprotection in chronic kidney disease, though it effectively controls blood pressure without significantly worsening renal function in most cases 2
• The American Society of Nephrology indicates that amlodipine does not improve impaired kidney function and should not be first-line therapy for CKD patients with proteinuria 2
• In diabetic nephropathy trials (IDNT and RENAAL), amlodipine was inferior to angiotensin receptor blockers for preventing progressive loss of kidney function 3

Medications Without Direct Renal Effects

The remaining medications in your list do not cause reduced GFR through direct nephrotoxic mechanisms:

Bupropion

• Bupropion and its metabolites are cleared renally and may accumulate in patients with pre-existing renal impairment (GFR <90 mL/min), but the drug does not cause kidney injury 4
• Dose reduction is recommended in renal impairment to prevent drug accumulation and adverse effects, not because bupropion damages the kidneys 4

Trazodone

• Trazodone is nearly completely metabolized hepatically with no documented nephrotoxic effects 5
• The drug has minimal cardiovascular side effects and no reported renal toxicity in clinical trials 5

Cyclobenzaprine

• No evidence in the provided literature suggests cyclobenzaprine causes GFR reduction
• This muscle relaxant is not recognized as a nephrotoxic agent

Ezetimibe

• No evidence in the provided literature links ezetimibe to reduced GFR
• This lipid-lowering agent does not have known nephrotoxic properties

Alendronate

• No evidence in the provided literature suggests alendronate causes GFR reduction
• Bisphosphonates are not typically associated with decreased GFR in standard dosing

Clinical Context: Medications That DO Cause GFR Reduction

For comparison, medications with well-documented effects on GFR include:

• NSAIDs: Widely nephrotoxic with both acute and chronic effects on kidney function; NSAID prescribing decreased significantly after eGFR reporting implementation, with subsequent improvements in renal function when NSAIDs were discontinued 6
• Cyclosporine: Can precipitate acute renal failure when combined with ACE inhibitors due to vasoconstrictor effects 3
• ACE inhibitors/ARBs: Cause predictable acute GFR declines of 10-20% through hemodynamic effects (efferent arteriolar vasodilation), which is expected and not an indication to discontinue therapy 3

Practical Recommendation

If your patient has low GFR, investigate other causes before attributing it to these medications. Focus on:

• Volume depletion or diuretic overuse 3
• Concurrent NSAID use 3, 6
• Renal artery stenosis 3
• Systemic hypotension 3
• Pre-existing chronic kidney disease progression 3

Monitor renal function when initiating amlodipine, but do not discontinue it solely for modest GFR declines unless accompanied by other concerning features. 1