“Is This Normal?”: Understanding and Managing Adverse Reactions

The International Conference on Harmonisation of Technical Requirements for Registration for Pharmaceuticals for Human Use, of which the World Health Organization and the FDA are members, defines an adverse drug reaction (ADR) as "a response to a drug which is noxious and unintended, and which occurs at doses normally used for prophylaxis, diagnosis, or therapy of disease or the modification of physiologic function.”¹

In 2025, there were almost 1.1 million serious adverse drug reactions reported (excluding deaths) and 150,000 deaths in the US.² Early recognition and management of ADRs is critical to preventing long-term disability or death. Effective adverse reaction management requires a combined effort from patients and health care providers.

Types of ADRs

Although ADRs are categorized using various classification systems, the most common is the ABCDEF classification (Table³). This system categorizes adverse reactions by their mechanism and predictability.

Recognizing ADRs

ADRs are a leading cause of preventable harm and hospitalization; therefore, recognition is crucial for patient safety. Recognition efforts should be intensified for high-risk groups (eg, pediatric and geriatric populations) and high-risk medications (eg, anticoagulants, antibiotics, antineoplastics, and nonsteroidal anti-inflammatory agents).

• Temporal relationship: Determine whether the symptoms began shortly after starting a new medication, increasing the dose, or restarting a medication.
• Common signs: Evaluate nonspecific symptoms such as fever, fatigue, skin rash, itching, hives, or swelling. Serious reactions may present with anaphylaxis, sudden weight changes, or organ-specific symptoms.⁴
• Dechallenge assessment: Evaluate symptom relief upon discontinuation of medication.⁴
• Review known risks: Consult drug information resources to determine if symptoms match known adverse effects or toxicity profiles.⁴

Risk Factors

Adverse drug reactions result from a complex association between patient-specific vulnerabilities and drug characteristics.

• Polypharmacy: Polypharmacy, defined as the concurrent use of 5 or more medications, contributes to ADRs through elevated drug-drug interactions, prescribing cascades, and cumulative pharmacological burden.⁵
• Age-related vulnerabilities: Patients 65 years and older may be at higher risk of ADRs due to reduced hepatic and renal clearance, increased comorbidities, and frailty. Infants and neonates have immature hepatic and renal systems, making drug metabolism less predictable.
• Genetic variation: Genetic variation can increase an individual’s risk of ADRs. Approximately 9% of ADRs are linked to medications where genetic information could have resulted in safer prescribing practices. Of these, 75% are associated with just 3 genes: CYP2C19, CYP2D6, and SLCO1B1.⁶
• Organ dysfunction: Organ dysfunction alters how the body metabolizes, distributes, and eliminates medications, potentially leading to toxic accumulation and/or heightened sensitivity.
• Biological sex: As of 2026, biological sex is recognized as a major determinant of drug safety. Females experience ADRs 1.5 to 1.7 times more frequently than males. This disparity is driven by distinct physiological differences that alter pharmacokinetics.⁷

Prevention Strategies

The prevention of ADRs is achieved through a combination of clinical vigilance, patient-centered care, and the incorporation of advanced technology.

Clinical Vigilance

Modern guidelines mandate the use of standardized dosing metrics. When liquid medications are dispensed, the directions must be in metric units (mL). Weight-based dosing requires the patient’s weight to verify calculations. High-alert medications require enhanced safeguards, and foundational safety continues to rely on verifying the “5 rights” (right patient, right drug, right dose, right route, and right time). Comprehensive medication reconciliation should be performed at every transition point.

Patient-Centered Care

Patients should be encouraged to fill all prescriptions at a single pharmacy, as this enables more effective screening for drug-drug interactions. Pharmacy staff should verify demographic and allergy information at each visit. Patients should be counseled on why and how they take their medication, as well as given a general overview of therapy expectations. A well-informed patient is much more likely to recognize adverse reactions early and take appropriate action before real harm occurs.

Advanced Technology

Technology can provide proactive, personalized safeguards against ADRs by predicting risks before administration. Clinical decision support systems analyze patient-specific data, including age, weight, and kidney function, and apply that information to large drug databases. Genetic testing reveals how a patient’s DNA affects their drug metabolism. Pharmacometabolomics, a branch of metabolomics, uses technology to identify and quantify drugs in a patient’s circulation, helping guide dosing and avoid drug interactions.⁸

Management Strategies

Adverse drug reaction management requires a swift, coordinated effort between the patient and the provider to identify the cause and prevent harm. The speed and intensity of ADR management are dictated by severity.

Severe Adverse Reactions

When a severe or life-threatening ADR is identified, the drug must be immediately discontinued. This includes severe allergic reactions, including anaphylaxis, angioedema, and severe shortness of breath; serious dermatological reactions, such as Stevens-Johnson syndrome or toxic epidermal necrosis; and organ toxicity. Patients must seek immediate medical attention in the event of a severe adverse reaction.

Moderate Adverse Reactions

Moderate reactions cause significant distress but are not life-threatening. These require a change in therapy: discontinuation, a change in dose if the reaction is dose-dependent, or substitution with a therapeutically equivalent medication.

Pharmacotherapy may be used in these situations to reduce inflammation and/or rash (corticosteroids) and to manage itching, rash, and swelling (antihistamines). Patients should be monitored for 24 to 48 hours to ensure the reaction does not progress to a severe one.

Mild Adverse Reactions

Mild reactions cause minimal discomfort, and medications do not need to be discontinued if the benefits outweigh the risks. If the reaction is intolerable, a minor dose reduction may be considered. Symptomatic relief can include antihistamines for minor itching or rhinitis, antiemetics for nausea, and topical treatments for localized skin irritation.

Conclusion

The effective identification and management of ADRs is paramount for patient safety. As the medical community strives for a patient-centered approach, integrating technologies such as pharmacogenomics and clinical decision support systems prevents adverse reactions before medications are even administered. This, coupled with vigilant clinical observations, documentation, and transparency, culminates in fewer adverse drug reactions and improved patient safety.

Managing ADRs requires a swift, coordinated, tiered response that prioritizes lifesaving interventions for severe ADRs and dose adjustments coupled with symptomatic treatment for more moderate or mild reactions.

REFERENCES

1. International drug monitoring: the role of national centres. Report of a WHO meeting. World Health Organ Tech Rep Ser. 1972;498:1-25.

2. FDA Adverse Event Reporting System (FAERS) public dashboard for drugs and biologics. FDA. Accessed January 9, 2026. https://fis.fda.gov/sense/app/95239e26-e0be-42d9-a960-9a5f7f1c25ee/sheet/7a47a261-d58b-4203-a8aa-6d3021737452/state/analysis

3. Adverse drug reactions: a guide for general practice nurses. Practice Nurse website. April 6, 2025. Accessed January 9, 2026. https://practicenurse.co.uk/modules/prescribing/adverse-drug-reactions-a-guide-for-general-practice-nurses

4. Kommu S, Carter C, Whitfield P. Adverse Drug Reactions. In: StatPearls. StatPearls Publishing; January 10, 2024. Accessed January 9, 2026. https://www.ncbi.nlm.nih.gov/books/NBK599521/

5. Alhumaidi, Reham M., et al. Risk of polypharmacy and its outcome in terms of drug interaction in an elderly population: a retrospective cross-sectional study. Journal of clinical medicine. 2023;12(12):3960.

6. PGx Testing for Three Genes Could Prevent Three-Quarters of Avoidable Adverse Drug Reactions. Inside Precision Medicine website. March 28, 2025. https://www.insideprecisionmedicine.com/topics/precision-medicine/pgx-testing-for-three-genes-could-prevent-three-quarters-of-avoidable-adverse-drug-reactions/#:~:text=The%20study%20analyzed%20ADR%20reports,systems%2C%E2%80%9D%20the%20researchers%20wrote. Accessed January 9, 2026.

7. O'Mahony D, Cruz-Jentoft AJ, Gudmundsson A, et al. Sex differences in patterns of potentially inappropriate prescribing and adverse drug reactions in hospitalized older people: Findings from the SENATOR trial. J Am Geriatr Soc. 2024; 72(11): 3476-3483. doi:10.1111/jgs.19071.

8. Beger RD, Schmidt MA, Kaddurah-Daouk R. Current concepts in pharmacometabolomics, biomarker discovery, and precision medicine. Metabolites. 2020;10(4):129. doi:10.3390/metabo10040129