ADVERSE DRUG REACTIONS AND DRUG–DRUG INTERACTIONS ASSOCIATED WITH CIMETIDINE: AN ADR STUDY AND PHARMACOVIGILANCE REVIEW

Background: Cimetidine, a first-generation histamine H₂-receptor antagonist, has been widely used for the management of acid-related gastrointestinal disorders for several decades. Despite its long-standing clinical use and perceived safety, accumulating evidence indicates that cimetidine is associated with a broad spectrum of adverse drug reactions (ADRs) and clinically relevant drug–drug interactions. Objective: This narrative review aims to comprehensively summarize the pharmacological basis, clinical manifestations, and mechanistic pathways underlying adverse reactions and drug–drug interactions associated with cimetidine. Methods: A narrative synthesis of published clinical reports, case studies, pharmacokinetic analyses, and mechanistic investigations was undertaken to evaluate hepatic, renal, neurological, metabolic, immunological, and hypersensitivity-related adverse effects of cimetidine, along with its interaction potential. Results: Cimetidine-induced toxicity is mediated through both pharmacokinetic mechanisms—primarily cytochrome P450 inhibition—and immunomodulatory effects. Rare but serious complications include autoimmune-like hepatitis, ANCA-associated acute tubulointerstitial nephritis, acute dystonic reactions, metabolic derangements such as lactic acidosis, and severe drug–drug interactions involving agents with narrow therapeutic indices. Emerging evidence challenges the traditional view of cimetidine as a benign therapy, particularly in vulnerable populations. Conclusion: Although most cimetidine-associated adverse effects are uncommon, several can be severe or life-threatening. Increased clinical awareness, careful patient selection, and vigilant monitoring are essential to mitigate risks, especially given its continued over-the-counter availability.