Abstract
The rising prevalence of multimorbidity, defined as the coexistence of two or more chronic health conditions, is particularly pronounced among older adults and often necessitates polypharmacy. This increases the risk of adverse drug reactions (ADRs) and drug-drug interactions (DDIs), yet multimorbid individuals remain underrepresented in clinical trials. This narrative review synthesizes evidence from 55 recent sources, including randomized controlled trials, observational studies, systematic reviews, and real-world data, to evaluate the burden, risk factors, and management strategies for ADRs and DDIs in this vulnerable population. The findings highlight that ADRs and DDIs contribute substantially to hospitalizations, therapeutic failures, and morbidity. Common ADRs include gastrointestinal bleeding, hypoglycemia, nephrotoxicity, and central nervous system depression, while high-risk interactions frequently involve drugs such as warfarin, non-steroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors, and selective serotonin reuptake inhibitors (SSRIs). Key areas of focus include geriatric multimorbidity, organ dysfunction, and the clustering of comorbidities. The review underscores the utility of deprescribing protocols, electronic decision support systems, and interdisciplinary care approaches. Persistent challenges, such as inappropriate prescribing and the complexity of polypharmacy, call for targeted interventions, including personalized dosing, the incorporation of artificial intelligence for risk prediction, and long-term pharmacovigilance frameworks. Advancing safer pharmacotherapy in patients with multiple conditions (multimorbid patients) requires holistic, evidence-informed, and patient-centered strategies.