What is the recommended approach to diagnose and manage infusion‑related or hypersensitivity reactions to Kisunla (donanemab‑azbt)?

Management of Kisunla (Donanemab) Infusion Reactions

For Kisunla infusion reactions, immediately stop the infusion upon first observation of any signs or symptoms, maintain IV access with normal saline, and manage based on reaction severity using a graded approach with antihistamines and corticosteroids for mild-to-moderate reactions and epinephrine for anaphylaxis. 1

Immediate Recognition and Initial Response

Prompt recognition is critical—stop the infusion immediately at the first sign of any reaction. 2, 1

• Maintain IV access with normal saline for medication administration and potential fluid resuscitation 2
• Assess the ABCs (Airway, Breathing, Circulation) and level of consciousness 2
• Position the patient appropriately: Trendelenburg for hypotension, sitting upright for respiratory distress, or recovery position if unconscious 2
• Administer supplemental oxygen if needed 2
• Call for medical assistance immediately 2

Early warning signs matter: Patients who feel odd, uncomfortable, or express urgency to urinate or defecate should be taken seriously—immediately measure blood pressure and pulse rate. 2

Clinical Presentation of Kisunla Infusion Reactions

Infusion-related reactions occur in 9% of Kisunla-treated patients, with 70% occurring within the first 4 infusions. 1

Common signs and symptoms include: 1

• Chills and erythema
• Nausea and vomiting
• Difficulty breathing or dyspnea
• Sweating
• Elevated or low blood pressure
• Headache
• Chest pain

Reactions typically occur during infusion or within 30 minutes post-infusion. 1

Graded Management Algorithm

Grade 1 (Mild) Reactions

Severity: Pruritus, flushing, urticaria, chest tightness, back pain, joint pain 2

Management: 2, 1

• Slow the infusion rate to 50% of current rate
• Monitor vital signs continuously for ≥15 minutes
• Maintain IV normal saline at keep-vein-open (KVO) rate
• Once symptoms resolve, restart infusion at 50% of original rate and titrate upward as tolerated

Grade 2 (Moderate) Reactions

Severity: Mild reaction symptoms plus transient cough, shortness of breath, tachycardia, or hypotension (SBP drop ≥30 mmHg from baseline or SBP ≤90 mmHg) 2

Management: 2, 1

• Stop or temporarily cease the infusion
• Administer H1/H2 antagonists: diphenhydramine 50 mg IV plus ranitidine 50 mg IV (combined H1/H2 blockade is superior to H1 alone) 2
• Administer corticosteroids: methylprednisolone 1-2 mg/kg IV every 6 hours 2
• If hypotensive: place patient supine in Trendelenburg position and administer normal saline bolus 1000-2000 mL 2
• If hypoxemic: provide oxygen by mask or nasal cannula 2
• After complete symptom resolution (~15 minutes), restart infusion at 50% of previous rate and titrate slowly 2
• If symptoms recur upon rechallenge, permanently discontinue the infusion for that session 2

Pre-treatment consideration: For subsequent infusions after a Grade 2 reaction, consider prophylactic antihistamines, acetaminophen, or corticosteroids. 1

Grade 3-4 (Severe/Life-Threatening) Reactions

Severity: Sudden onset with rapid intensification, loss of consciousness, severe hypotension, angioedema of tongue/airway, or involvement of ≥2 organ systems (cardiovascular, skin, respiratory, gastrointestinal) 2

Management—Treat as Anaphylaxis: 2, 1

Primary intervention:

• Epinephrine 0.2-0.5 mg (1 mg/mL) IM into the lateral thigh—repeat every 5-15 minutes as needed 2
• This is the only life-saving medication in true anaphylaxis—do not delay administration 2

Aggressive fluid resuscitation:

• Normal saline 1-2 L IV at 5-10 mL/kg in first 5 minutes 2
• Follow with crystalloid or colloid boluses of 20 mL/kg, then slow infusion 2

Adjunctive medications:

• H1/H2 antagonists: diphenhydramine 50 mg IV plus ranitidine 50 mg IV 2
• Corticosteroids: methylprednisolone 1-2 mg/kg IV every 6 hours 2

For specific complications:

• Bradycardia: atropine 600 μg IV 2
• Refractory hypotension despite epinephrine and fluids: dopamine 400 mg in 500 mL at 2-20 μg/kg/min or vasopressin 25 units in 250 mL (0.1 U/mL) at 0.01-0.04 U/min 2
• Patients on β-blockers: glucagon 1-5 mg IV infusion over 5 minutes (followed by infusion if needed) 2
• Bronchospasm: β2-agonist nebulizer (albuterol 0.083% via nebulizer) 2

Rechallenge is discouraged in severe reactions. 2, 1

Distinguishing Anaphylaxis from Other Hypersensitivity Reactions

Anaphylaxis criteria—administer epinephrine immediately when ANY of the following are present: 2

1. Acute onset with skin/mucosal involvement (urticaria or angioedema) plus respiratory compromise or hypotension
2. Involvement of ≥2 organ systems after Kisunla exposure (cardiovascular, skin, respiratory, gastrointestinal)
3. Isolated hypotension after exposure (SBP <90 mmHg or >30% drop from baseline)

Cytokine-release syndrome/non-IgE-mediated reactions present similarly but typically respond to infusion rate reduction and antihistamines without requiring epinephrine. 2, 3

Post-Reaction Monitoring and Documentation

• Monitor vital signs continuously until complete symptom resolution 2
• Observe for minimum 24 hours after severe (Grade 3-4) reactions to detect biphasic anaphylaxis 2
• Document reaction grade, specific symptoms, time of onset, interventions performed, and patient response 2
• For severe reactions, obtain serum tryptase levels 30-120 minutes after reaction onset to help confirm IgE-mediated mechanism 3

Special Considerations for Kisunla

ARIA (Amyloid-Related Imaging Abnormalities) vs. Infusion Reactions:

• ARIA is a separate safety concern with Kisunla, occurring in 24% of patients (mostly radiographic, often asymptomatic) 1
• ARIA typically presents with headache, confusion, visual disturbances, or seizures—distinct from acute infusion reactions 1
• Enhanced clinical vigilance for ARIA is recommended during the first 24 weeks of treatment 1

Hypersensitivity reactions (including anaphylaxis and angioedema) are contraindications:

• Kisunla is contraindicated in patients with history of serious hypersensitivity to donanemab-azbt or excipients 1
• Promptly discontinue upon first observation of hypersensitivity signs 1

Critical Pitfalls to Avoid

Do not delay epinephrine in suspected anaphylaxis—it is the only life-saving medication. 2

Never restart infusion at full original rate after a reaction—always resume at 50% rate if rechallenge is appropriate. 2

Do not discharge patients prematurely after severe reactions—24-hour observation is mandatory to capture biphasic events. 2

Corticosteroids prevent biphasic reactions but provide no acute benefit in anaphylaxis—never use as sole therapy. 2

Do not confuse ARIA symptoms (headache, confusion) with infusion reactions—ARIA requires different management and MRI evaluation. 1

Most Kisunla infusion reactions (70%) occur within the first 4 infusions—maintain heightened vigilance during this period. 1

Infusion reactions resulted in discontinuation in 4% of Kisunla-treated patients—proper management can prevent unnecessary treatment cessation. 1