Donanemab (Kisunla): Alzheimer's Treatment Guide

Donanemab-azbt (Kisunla) represents a significant advancement in Alzheimer disease (AD) treatment, particularly for early-stage patients. Below are key clinical pearls for healthcare professionals:

Indications & Patient Selection

Approved for early symptomatic Alzheimer disease, including mild cognitive impairment and mild dementia stages with confirmed amyloid pathology via PET or CSF biomarkers[1][6].
Most effective in patients with low-to-medium tau pathology (35% disease progression slowing vs. 22% in mixed tau populations)[1][6].

Dosing Protocol

Initial phase: 700 mg IV every 4 weeks × 3 doses[2][6]
Maintenance: 1400 mg IV every 4 weeks thereafter[2][6]
Stopping criteria: Therapy can be discontinued once amyloid plaques are reduced to minimal levels on PET imaging (achieved in 17-69% of patients by 76 weeks)[1][6].

Administration Essentials

Requires 30-minute IV infusion with 0.9% NaCl dilution to 4-10 mg/mL[2][7].
Pre-infusion checks:
- Baseline brain MRI[6][7]
- APOE ε4 genotyping (higher ARIA risk in homozygotes)[6]
- Amyloid confirmation[2][6]
Infusion reactions: Monitor for fever, chills, hypotension, or dyspnea. Pre-medication with antihistamines/steroids may be considered[4][5].

Safety Monitoring

ARIA (Amyloid-Related Imaging Abnormalities):
- MRI required before 2nd, 3rd, 4th, and 7th infusions[2][6]
- 24% incidence of ARIA-Edema (ARIA-E) in trials[6]
- Suspend dosing for symptomatic ARIA; permanent discontinuation for severe cases[6][7]
Other risks: Microhemorrhages (19.1%), superficial siderosis (15.5%)[6]

Efficacy Evidence

TRAILBLAZER-ALZ 2 trial (N=1,736):
- 35.1% slower decline on iADRS vs placebo (low/medium tau group)[1]
- 39% reduced risk of progressing to next disease stage[6]
- Amyloid plaque reduction: 61% at 6 months, 84% at 18 months[6]

Patient Education Points

Emphasize disease modification rather than cure[4][5]
Discuss infusion commitment: Monthly visits for ≥6 months[4][8]
Review ARIA symptoms: Headache, confusion, visual changes[5][8]
Highlight stopping potential: Reduced treatment burden if plaques clear[1][6]

Practice Considerations

Use shared decision-making tools to weigh benefits vs risks (ARIA, cost, infusion logistics)[3]
Coordinate with radiologists for standardized MRI monitoring[3]
Consider amyloid PET availability and insurance coverage barriers[3]

This monoclonal antibody offers a unique stop-and-monitor treatment paradigm, but requires careful patient selection and multidisciplinary management to optimize safety outcomes[3][6].

Citations:

[1] https://www.pharmacytimes.com/view/fda-approves-donanemab-azbt-for-early-symptomatic-alzheimer-disease

[2] https://www.drugs.com/monograph/donanemab-azbt.html

[3] https://www.neurologylive.com/view/guidance-safe-use-donanemab-ad-clinical-settings-gil-rabinovici

[4] https://www.veteranshealthlibrary.va.gov/medicationsva/203,a624048

[5] https://www.saintlukeskc.org/health-library/donanemab-azbt-injection

[6] https://www.pharmacytimes.com/view/kisunla-from-eli-lilly

[7] https://www.medcentral.com/drugs/monograph/189031-324037/donanemab-azbt-intravenous

[8] https://medlineplus.gov/druginfo/meds/a624048.html

[9] https://assets.ctfassets.net/plyq12u1bv8a/5WKR7TZgj7toZ2QWorcsXB/4453f5006ecdcb350caf0b3e124cd748/PG238_Kisunla__donanemab-azbt__v1.pdf

[10] https://medicalpolicy.bcbstx.com/content/dam/bcbs/medicalpolicy/pdf/rx/RX501.177_2025-03-15.pdf

[11] https://hhs.iowa.gov/media/14833/download?inline