What are the basics in managing Adverse Drug Reactions (ADRs)?

Basics of Adverse Drug Reaction (ADR) Management

The cornerstone of managing adverse drug reactions (ADRs) is prompt recognition, accurate classification, and implementation of appropriate interventions based on reaction severity, with observation periods following severe reactions to monitor for biphasic responses. 1

Definition and Classification of ADRs

ADRs are defined by several major health organizations:

• WHO: Noxious, unintended reactions occurring at doses normally used in humans
• FDA: Any undesirable experience associated with medicinal product use
• EMA: Noxious, unintended responses occurring at normal doses 1, 2

ADRs are classified into several types (with mnemonics):

• Type A (Augmented): Dose-dependent, predictable, high morbidity but low mortality
• Type B (Bizarre): Non-dose related, unpredictable, idiosyncratic, low morbidity but high mortality
• Type C (Chronic): Dose and time-related effects
• Type D (Delayed): Time-related effects
• Type E (End of use): Withdrawal reactions
• Type F (Failure): Unexpected failure of therapy
• Type G (Genetic): Genetically determined reactions 1, 3

Risk Factors for ADRs

Several factors increase susceptibility to ADRs:

• Age: Elderly patients have altered pharmacokinetics
• Polypharmacy: Increases risk of drug interactions
• Genetic polymorphisms: Affect drug metabolism
• Comorbidities: Especially renal or hepatic impairment
• Previous history of ADRs 2

Recognition and Diagnosis

When evaluating a suspected ADR:

1. Establish accurate clinical diagnosis of the adverse event
2. Document drug exposure timeline in relation to symptoms
3. Consider alternative causes for the reaction
4. Assess causality based on:
   • Timing of drug administration and reaction onset
   • Pattern of illness
   • Results of investigations
   • Response to drug withdrawal (dechallenge)
   • Response to rechallenge (if ethically appropriate) 4

Management Approach

Immediate Management

1. Assess severity of the reaction
2. Discontinue the offending drug if possible
3. Provide supportive care based on symptoms
4. Treat specific reactions according to manifestations:
   • For anaphylaxis: Administer epinephrine 0.3-0.5mg IM (adults) or 0.01mg/kg up to 0.3mg (children) into anterolateral thigh 5
   • For mild infusion reactions: Slow or temporarily stop infusion 1

Follow-up Management

1. Observation period after anaphylactic reactions due to risk of biphasic reactions
   • Longer observation for patients with severe initial symptoms
   • Consider hospital admission for severe or refractory symptoms 1
2. Allergist/immunologist consultation for suspected anaphylactic reactions 1
3. Psychological support for patients experiencing ADRs 1
4. Documentation of the reaction in medical records
5. Reporting to appropriate pharmacovigilance systems 6

Prevention Strategies

1. Medication reconciliation at care transitions
2. Start low, go slow dosing approach for high-risk medications
3. Computerized order entry systems with drug interaction alerts
4. Standardized protocols and "five rights" verification
5. Patient education about potential side effects and when to seek medical attention
6. Genetic testing when appropriate for medications with known pharmacogenetic associations 2

Special Considerations for Specific Drug Classes

Chemotherapeutic Agents

• Platinum agents (carboplatin, cisplatin): Reactions typically occur after reexposure
• Taxanes (paclitaxel, docetaxel): Reactions typically occur during first few cycles
• Desensitization protocols may be considered for patients who have had reactions but require continued treatment 1

Considerations for Rechallenge

• For mild infusion reactions to taxanes: May rechallenge with slower infusion rate if:
  1. Patient and healthcare team are comfortable with plan
  2. Patient has been appropriately counseled
  3. Emergency equipment is available 1
• For severe reactions: The implicated drug should not be used again 1

Reporting ADRs

Spontaneous reporting is crucial for post-marketing surveillance despite limitations of under-reporting. Healthcare professionals should report ADRs to local or national pharmacovigilance systems to improve drug safety 6.

Common Pitfalls to Avoid

1. Failure to recognize ADRs as cause of new symptoms
2. Treating ADR symptoms without addressing the causative drug
3. Inappropriate rechallenge after severe reactions
4. Inadequate observation after anaphylactic reactions
5. Failure to report ADRs to pharmacovigilance systems

Remember that while Type A reactions (80% of serious ADRs) are potentially preventable through careful medication management, Type B reactions are largely unpredictable and require vigilance and prompt intervention when they occur 2.