What are the immediate steps to take if a patient experiences shaking and wheezing one hour after Darzalex (daratumumab) Faspro treatment?

Immediate Management of Delayed Infusion Reaction to Darzalex Faspro

Stop the infusion immediately and administer intravenous epinephrine 50 mcg (0.5 mL of 1:10,000 solution) for this Grade 2-3 infusion reaction presenting with shaking (rigors/chills) and wheezing (bronchospasm) one hour post-treatment. 1, 2

Initial Assessment and Stabilization

This presentation represents a delayed infusion-related reaction (IRR) to daratumumab, which can occur up to one hour after administration. 1 The combination of shaking and wheezing indicates respiratory involvement requiring immediate intervention.

Immediate Actions (First 5 Minutes)

• Stop any ongoing infusion if the patient is still connected to IV access 1
• Assess airway, breathing, and circulation using the ABC approach 1, 2
• Administer 100% oxygen via face mask or nasal cannula 1, 2
• Obtain vital signs including blood pressure, heart rate, oxygen saturation, and respiratory rate 2
• Establish or maintain IV access for medication administration 1
• Call for help and note the exact time of symptom onset 1, 2

Pharmacological Management

Primary Treatment: Epinephrine

For bronchospasm with wheezing, administer IV epinephrine 50 mcg (0.5 mL of 1:10,000 solution) immediately. 1, 2 This addresses both the bronchospasm and any potential hypotension. Repeat doses every few minutes as needed if symptoms persist or worsen. 2

• If multiple doses are required, start a continuous epinephrine infusion: prepare 1 mg (1 mL of 1:1000) in 100 mL normal saline and infuse at 30-100 mL/hour (5-15 mcg/min), titrating to response 2, 3
• Epinephrine has a short half-life, making continuous infusion preferable to repeated boluses for sustained effect 2, 3

Adjunctive Medications

Administer the following secondary medications: 1, 2

• Diphenhydramine 50 mg IV (H1 antihistamine) for symptomatic relief 1
• Hydrocortisone 200 mg IV (or methylprednisolone 125 mg IV) 1, 2
• Ranitidine 50 mg IV or famotidine 20 mg IV (H2 antihistamine) for additional histamine blockade 1

Bronchospasm-Specific Treatment

For persistent wheezing despite epinephrine: 1, 2

• Albuterol (salbutamol) nebulizer 2.5-5 mg or metered-dose inhaler with spacer 1, 2
• Consider IV salbutamol infusion if nebulized therapy is insufficient 2
• Consider magnesium sulfate 2 g IV over 20 minutes for refractory bronchospasm 1, 2
• Consider aminophylline loading dose (5-6 mg/kg IV over 20 minutes) for severe, persistent bronchospasm 2

Grading and Decision Algorithm

Grade 1-2 (Mild to Moderate)

• Mild wheezing without respiratory distress, chills without rigors
• Management: Slow or stop infusion, administer antihistamines and corticosteroids, monitor closely 1
• May resume at slower rate after symptom resolution 1

Grade 3 (Severe) - This Patient's Presentation

• Symptomatic bronchospasm with wheezing requiring treatment, rigors/shaking 1
• Management: Stop infusion permanently for this dose, administer epinephrine, aggressive symptomatic treatment 1
• After complete resolution, may attempt rechallenge at future infusions with enhanced premedication and slower infusion rate 1

Grade 4 (Life-Threatening)

• Respiratory compromise requiring intubation, hemodynamic instability
• Management: Stop infusion, aggressive resuscitation with epinephrine, consider ICU admission, permanently discontinue daratumumab 1

Monitoring and Observation

This patient requires extended observation of at least 4-6 hours after complete symptom resolution. 4 Delayed reactions occurring one hour post-infusion carry risk for biphasic reactions, which can occur up to 72 hours later (most commonly around 8 hours). 4

Observation Criteria

• Continuous monitoring of vital signs every 15 minutes for the first hour, then every 30 minutes 2
• Continuous pulse oximetry to detect desaturation 2
• Cardiac monitoring if any hemodynamic instability occurred 2
• Assess for biphasic reaction risk factors: severity of initial reaction, requirement for multiple epinephrine doses (increases odds ratio to 4.82) 4

Discharge Planning and Follow-Up

Patient may be discharged only after: 4

• Complete resolution of all symptoms (wheezing, shaking, any respiratory distress)
• Hemodynamic stability without ongoing interventions
• Completion of minimum 4-6 hour observation period
• Normal oxygen saturation on room air

Post-Discharge Medications

Prescribe the following for 2-3 days: 4

• H1 antihistamine (diphenhydramine 25-50 mg every 6 hours or cetirizine 10 mg daily)
• H2 antihistamine (famotidine 20 mg twice daily)
• Corticosteroid (prednisone 40-60 mg daily, then taper)

Note: Corticosteroids do not prevent biphasic reactions but may reduce symptom severity. 4

Future Daratumumab Administration

Premedication Enhancement

For subsequent doses, enhance premedication regimen: 1, 5

• Methylprednisolone 100 mg IV (or equivalent) 1 hour before infusion 1
• Acetaminophen 650-1000 mg PO 1
• Diphenhydramine 25-50 mg IV or PO 1
• Consider adding montelukast 10 mg PO 1 hour before infusion (reduces IRR incidence from 45% to 27%) 5

Administration Modifications

• Slower infusion rate for subsequent doses 1
• Consider desensitization protocol if daratumumab is essential and no alternatives exist 1
• Most IRRs occur with first infusion (82-95%); subsequent infusions have much lower risk 1

Critical Pitfalls to Avoid

• Do not delay epinephrine administration for bronchospasm—it is the definitive treatment with bronchodilator, vasopressor, and mediator-release inhibition properties 1, 2
• Do not assume the reaction is over after initial symptom resolution—biphasic reactions can occur up to 72 hours later 4
• Do not discharge prematurely—patients with respiratory symptoms require minimum 4-6 hours observation 4
• Do not rely solely on corticosteroids for acute management—they have slow onset of action and no role in acute treatment 4
• Do not use IM epinephrine when IV access is available—IV route allows precise titration and faster onset 2
• Do not assume all reactions occur during infusion—daratumumab reactions can be delayed up to one hour post-administration 1