Donanemab Administration: Safety Protocol Guide

To minimize adverse reactions when administering Donanemab-azbt (Kisunla), follow these evidence-based protocols:

Baseline Assessments:
1. Perform APOE ε4 genotyping (higher ARIA risk in homozygotes).
2. Obtain a brain MRI to rule out pre-existing microhemorrhages/superficial siderosis.
3. Confirm amyloid pathology via PET or CSF biomarkers.
Pre-Medication (if needed):
1. Consider acetaminophen (650 mg PO), antihistamines (e.g., diphenhydramine 25–50 mg IV), or corticosteroids (e.g., dexamethasone 4 mg IV) for patients with prior infusion reactions.

Dilution: Use 0.9% NaCl to dilute to 4–10 mg/mL (e.g., 350 mg vial in 100 mL NaCl for 3.5 mg/mL).
Infusion Rate: Administer over 30 minutes via IV pump.
Line Flush: Use 0.9% NaCl only post-infusion.

Vital Signs: Check every 15 minutes (watch for hypotension, fever, or hypoxia).
Reaction Signs:
- Early (0–30 min): Chills, flushing, nausea, chest tightness.
- Severe: Anaphylaxis (angioedema, stridor).
Action for Reactions:
- Mild: Slow infusion rate by 50%.
- Moderate/Severe: Stop infusion and administer epinephrine (0.3 mg IM) or IV fluids as needed.

Monitor for ≥30 minutes for delayed hypersensitivity.
Educate patients to report ARIA symptoms within 24–72 hours (headache, confusion, visual changes).

MRI Surveillance: Schedule scans before 2nd, 3rd, 4th, and 7th infusions.
ARIA Management:
- Asymptomatic ARIA-E: Continue dosing with closer MRI monitoring.
- Symptomatic ARIA: Suspend treatment until resolved; restart only if benefits outweigh risks.

Absolute: History of severe hypersensitivity to donanemab or excipients.
Relative:
- ApoE ε4 homozygotes (higher ARIA risk).
- Anticoagulant use (may increase hemorrhage risk).

By adhering to these steps, clinicians can balance efficacy with reduced adverse event risks.

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