What is the appropriate approach to manage a patient with a suspected drug reaction, considering their medical history, age, sex, weight, and potential severity of the reaction?

Approach to Drug Reaction Management

Stop the suspected drug immediately and assess for anaphylaxis using the ABC approach (Airway, Breathing, Circulation), positioning the patient appropriately based on symptoms, and administering intramuscular epinephrine 0.01 mg/kg (maximum 0.5 mg) into the lateral thigh if any criteria for anaphylaxis are met. 1

Immediate Assessment and Stabilization

Stop Drug Administration and Maintain IV Access

• Immediately discontinue the suspected medication while maintaining intravenous access for potential resuscitation 1
• Assess vital signs including blood pressure, pulse rate, oxygen saturation, and level of consciousness 1
• Any patient complaint of feeling "odd," uncomfortable, or expressing need to urinate/defecate during infusion should trigger immediate vital sign measurement 1

Patient Positioning Based on Clinical Presentation

• Hypotension: Place patient in Trendelenburg position 1
• Respiratory distress: Position sitting upright 1
• Unconscious: Place in recovery position 1
• Administer oxygen if needed and call for medical assistance immediately 1

Distinguish Reaction Severity and Type

Anaphylaxis Recognition and Treatment

Administer epinephrine 0.01 mg/kg (1 mg/mL dilution, maximum 0.5 mL) intramuscularly into the lateral thigh muscle immediately if the patient meets any anaphylaxis criteria 1

• Repeat epinephrine every 5-15 minutes if needed 1
• Initiate rapid fluid resuscitation with 1-2 liters normal saline at 5-10 mL/kg in first 5 minutes 1
• Give crystalloids or colloids in 20 mL/kg boluses followed by slow infusion 1
• Administer combined H1/H2 antihistamines: diphenhydramine 50 mg IV plus ranitidine 50 mg IV (superior to either alone) 1
• Give corticosteroids equivalent to 1-2 mg/kg IV methylprednisolone every 6 hours 1

Special Considerations for Refractory Cases

• Bradycardia: Treat with atropine 600 mcg IV 1
• Patients on beta-blockers: Administer glucagon 1-5 mg IV infusion over 5 minutes, followed by infusion at 5-15 mg/min titrated to response 1
• Persistent hypotension despite epinephrine and fluids: Add dopamine 400 mg in 500 mL at 2-20 mcg/kg/min, or vasopressin 25 units in 250 mL (0.1 U/mL) at 0.01-0.04 U/min 1

Mild-to-Moderate Hypersensitivity or Cytokine-Release Reactions

For Grade 1-2 reactions without anaphylaxis criteria 1:

• Grade 1: Slow the infusion rate 1
• Grade 2: Slow rate or temporarily stop infusion, treat with H1/H2 antihistamines and corticosteroids, then restart at 50% rate and titrate to tolerance 1
• Grade 3-4: Stop infusion permanently, give H1/H2 antihistamines and corticosteroids, and discourage rechallenge 1

Infusion Reactions (Non-Allergic)

• Symptoms (flushing, rash, chills) typically resolve quickly after stopping or slowing infusion 1
• More common with taxanes (paclitaxel 27% incidence) during first few cycles 1
• For mild taxane infusion reactions, rechallenge may be attempted at much slower rate if patient, physician, and nursing staff agree, patient is counseled, and emergency equipment is available 1

Detailed History and Risk Factor Assessment

Pre-Administration Screening

Before any drug administration, obtain 1:

• Complete medical history including previous allergic disorders and atopic status 1
• All medications taken in previous 2 months including over-the-counter and complementary therapies, with exact dates started and stopped 1
• Previous drug allergies with specific reaction details 1
• Concomitant medications that increase anaphylaxis risk: beta-blockers, ACE inhibitors 1
• Chronic conditions increasing risk: respiratory disease, cardiovascular disease, mastocytosis 1

Reaction Timing Patterns

• Taxane reactions: Typically occur during first few cycles but can occur at any time 1
• Platinum drug reactions: Usually occur after reexposure or at completion of initial chemotherapy (e.g., cycle 6) 1
• Anaphylaxis during anesthesia: Manifests within minutes to one hour, not 12 hours later 2
• Reactions can occur during infusion, after completion, or even days later 1

Diagnostic Workup

Immediate Laboratory Testing

For suspected anaphylaxis, obtain serum mast cell tryptase at specific timepoints 1, 3, 2:

• First sample: As soon as feasible during resuscitation (within 5 minutes to 3 hours) 1, 3
• Second sample: 1-2 hours after symptom onset 1, 3
• Third sample: 24 hours later or during convalescence to establish baseline 1, 3
• Serial measurements are more useful than single measurements 1
• Critical caveat: Normal tryptase does not rule out anaphylaxis 1

Additional Testing

• Allergen-specific IgE can be drawn during acute reaction but should be repeated 4-6 weeks later if initially negative, as IgE may be temporarily consumed 3
• Approximately 23.6% of allergic reactions are non-IgE-mediated and will have negative blood tests despite true clinical allergy 3
• Never diagnose allergy based solely on positive specific IgE without clinical correlation 3

For Severe Cutaneous Reactions (Stevens-Johnson Syndrome/TEN)

If blistering and mucosal involvement present 1:

• Full blood count, ESR, CRP, electrolytes, liver function, coagulation studies 1
• Chest X-ray 1
• Skin biopsy from lesional skin for histopathology 1
• Second perilesional biopsy for direct immunofluorescence to exclude immunobullous disorders 1
• Bacteriology swabs from lesional skin 1
• Document extent of erythema and epidermal detachment separately on body map using Lund and Browder chart 1

Documentation and Reporting

Essential Documentation Elements

Record the following 1, 2:

• Index date (date of first symptom or sign: sore throat, rash, skin pain, sore eyes/mouth) 1
• Exact timing of symptom onset relative to drug administration 1, 2
• All drugs taken with dates started, dose escalations, and dates stopped 1
• Vital signs and treatment administered with patient response 2
• Progression of eruption if cutaneous reaction 1

Reporting Requirements

• Report serious known reactions and all reactions to newly released drugs to FDA, even if certainty is low 4
• Inform the patient about the adverse drug reaction and document appropriately in medical record 4

Monitoring and Follow-Up

Observation Period

• Monitor vital signs until complete resolution 1
• 24-hour observation required for severe reactions 1
• Corticosteroids prevent biphasic reactions but are not critical in immediate management 1

Prevention of Recurrence

• If previous life-threatening reaction occurred, never use the implicated drug again 1
• For mild previous platinum reactions, exercise great caution with desensitization and consider allergist consultation 1
• Desensitization can be considered for patients with prior reactions (more common after allergic reactions but can be used after severe infusion reactions) 1

Critical Pitfalls to Avoid

• Do not delay epinephrine administration while waiting for IV access or other interventions—intramuscular epinephrine is first-line 1
• Avoid inserting IV catheters through lesional skin in severe cutaneous reactions 1
• Do not use catheter tie-in technique for epinephrine infusions as obstruction causes drug stasis and increased local concentration 5
• Avoid leg veins in elderly or those with occlusive vascular disease 5
• Do not attribute delayed symptoms (>12 hours post-anesthesia) to anaphylaxis without systemic features 2
• Ensure premedications were actually taken orally before drug administration 1
• Have updated resuscitation protocol and equipment immediately available before any high-risk drug administration 1