What is the investigation and management of severe vomiting post amivantamab administration?

Management of Severe Vomiting Post-Amivantamab Administration

For patients experiencing severe vomiting after amivantamab administration, a three-drug antiemetic regimen consisting of a 5-HT3 receptor antagonist, dexamethasone, and an NK1 receptor antagonist (aprepitant) should be used for both immediate management and future prophylaxis.

Initial Assessment and Workup

When a patient presents with severe vomiting after amivantamab administration:

1. Evaluate severity and complications:

   • Assess for signs of dehydration (dry mucous membranes, decreased skin turgor, hypotension)
   • Check vital signs, including orthostatic measurements
   • Evaluate for electrolyte abnormalities, particularly hypokalemia
   • Rule out infusion-related reaction vs. delayed emesis

2. Laboratory investigations:

   • Complete blood count
   • Comprehensive metabolic panel (electrolytes, renal function, liver function)
   • Serum lactate if severe symptoms or signs of dehydration

Immediate Management

1. Hydration:

   • Aggressive IV hydration with dextrose-containing fluids 1
   • Correct electrolyte abnormalities, particularly potassium

2. Antiemetic Therapy:

   • First-line combination therapy:

     • 5-HT3 receptor antagonist (ondansetron 8 mg IV or palonosetron 0.25 mg IV)
     • Dexamethasone 12 mg IV
     • Aprepitant 125 mg orally (if not previously administered) 2

   • For refractory vomiting, add one of the following:

     • Haloperidol 0.5-2 mg IV/PO every 4-6 hours 2, 1
     • Metoclopramide 10-20 mg IV every 6 hours 2
     • Olanzapine 5-10 mg PO daily 1

Prevention for Future Amivantamab Administrations

Based on the high emetogenic potential demonstrated with amivantamab in some patients:

1. Pre-medication regimen:

   • 5-HT3 receptor antagonist (palonosetron 0.25 mg IV preferred due to longer half-life)
   • Dexamethasone 12 mg IV
   • Aprepitant 125 mg orally on day 1, followed by 80 mg on days 2 and 3 2

2. Alternative approach if aprepitant is contraindicated:

   • Palonosetron 0.25 mg IV
   • Dexamethasone 20 mg IV
   • Consider olanzapine 10 mg orally 2

Special Considerations

• Infusion modifications: Consider slower infusion rate for future amivantamab administrations, as infusion-related reactions including vomiting are common with this bispecific antibody 2

• Drug interactions: Be aware that aprepitant is a moderate inhibitor of CYP3A4 and can alter the metabolism of certain drugs, potentially increasing their plasma concentrations. These interactions are more significant with oral medications due to first-pass metabolism 2

• Contraindications: Aprepitant should not be used with pimozide, terfenadine, astemizole, or cisapride due to potentially dangerous drug interactions 2

• Pediatric patients: For pediatric patients, the three-drug combination (5-HT3 antagonist, dexamethasone, and aprepitant) is also recommended for high-emetic risk agents 2

Follow-up and Monitoring

• Monitor hydration status and electrolyte balance
• Assess effectiveness of antiemetic regimen
• Consider prophylactic antiemetics for 2-3 days after amivantamab administration
• Document severity of vomiting to guide future antiemetic prophylaxis

By implementing this comprehensive approach to managing severe vomiting post-amivantamab administration, clinicians can significantly reduce morbidity and improve quality of life for patients receiving this important targeted therapy for NSCLC with EGFR exon 20 insertion mutations.