An 84-year-old male on famotidine (Pepcid) 40 mg at bedtime for reflux presents with 3 days of new confusion and mild lethargy. His baseline serum creatinine last month was 1.6 mg/dL with an estimated CrCl of 38 mL/min. Which assessment finding best explains his presentation?

Question

Accepted Answer

✅ D. H2-receptor antagonists are cleared renally, and an unadjusted dose in CrCl under 50 can produce delirium in older adults
Famotidine and all H2 blockers are predominantly renally cleared. When CrCl drops below 50 mL/min, the standard dose must be reduced (famotidine typically cut by 50% for CrCl 30–50, or given every 36–48 hours for CrCl <30). Accumulation in the elderly crosses the blood-brain barrier and causes CNS adverse effects — confusion, delirium, hallucinations, agitation. The 2023 AGS Beers Criteria list H2 blockers as potentially inappropriate in older adults with delirium or at high risk of delirium.

❌ A. Famotidine commonly causes a serotonin syndrome-like picture
Famotidine does not cause serotonin syndrome. Serotonin syndrome arises from serotonergic drugs (SSRIs, SNRIs, MAOIs, tramadol, triptans, linezolid) and features hyperthermia, clonus, and autonomic instability — not this presentation.

❌ B. H2 blockers directly suppress the hypothalamic-pituitary axis, causing cortisol-driven confusion
H2 blockers do not suppress the HPA axis. This is a distractor with plausible-sounding vocabulary and no basis in pharmacology.

❌ C. Famotidine is a potent CYP3A4 inhibitor, producing drug-interaction-mediated delirium
Cimetidine (Tagamet) is the H2 blocker with significant CYP450 inhibition. Famotidine has minimal CYP effect, which is why it replaced cimetidine for most uses. The correct mechanism for confusion here is renal accumulation, not CYP interaction.

:::important
H2 blockers in the elderly with reduced kidney function are a classic Beers-listed cause of delirium. Cut famotidine dose by half for CrCl 30–50, extend interval for CrCl <30. New confusion + renal decline + H2 blocker = check the dose first.
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Famotidine

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