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Kisunla ™ (donanemab-azbt) injection, for intravenous infusion
350 mg/20 mL (17.5 mg/mL)
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
How should ARIA be managed in patients treated with Kisunla™ (donanemab-azbt)?
Suspend donanemab dosing in radiographically moderate or severe ARIA-E or ARIA-H of any clinical symptom severity, radiographically mild ARIA-E with moderate or severe clinical symptom severity, and radiographically mild symptomatic ARIA-H.
See important safety information, including boxed warning, in the attached prescribing information.
Management of Amyloid-Related Imaging Abnormalities
Dosing Recommendations for Patients With ARIA-E and Dosing Recommendations for Patients With ARIA-H provide recommendations for dosing interruptions for patients with amyloid-related imaging abnormalities-edema (ARIA-E) and amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H), respectively.
The Appendix shows the severity of amyloid-related imaging abnormalities (ARIA) classified by radiographic criteria.
Dosing Recommendations for Patients With ARIA-E
Dosing Recommendations for Patients With ARIA-E provides recommendations for dosing interruptions for patients with ARIA-E.
Clinical Symptom Severitya |
ARIA-E Severity on MRI (ARIA MRI Classification Criteria) |
||
Mild |
Moderate |
Severe |
|
Asymptomatic |
May continue dosing at current dose and schedule |
Suspend dosingb |
Suspend dosingb |
Mild |
May continue dosing based on clinical judgment |
Suspend dosingb |
|
Moderate or severe |
Suspend dosingb |
||
Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; MRI = magnetic resonance imaging.
aMild: discomfort noticed, but no disruption of normal daily activity. Moderate: discomfort sufficient to reduce or affect normal daily activity. Severe: incapacitating, with inability to work or to perform normal daily activity.
bSuspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification. Resumption of dosing should be guided by clinical judgment.
There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E.1
Dosing Recommendations for Patients With ARIA-H
Dosing Recommendations for Patients With ARIA-H provides recommendations for dosing interruptions for patients with ARIA-H.
Clinical Symptom Severity |
ARIA-H Severity on MRI (ARIA MRI Classification Criteria) |
||
Mild |
Moderate |
Severe |
|
Asymptomatic |
May continue dosing at current dose and schedule |
Suspend dosinga |
Suspend dosingb |
Symptomatic |
Suspend dosinga |
Suspend dosinga |
|
Abbreviations: ARIA-H = amyloid-related imaging abnormalities-hemosiderin deposition (includes microhemorrhage and superficial siderosis); MRI = magnetic resonance imaging.
aSuspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; resumption of dosing should be guided by clinical judgment; consider a follow-up MRI to assess for stabilization 2 to 4 months after initial identification.
bSuspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. Use clinical judgment when considering whether to continue treatment or permanently discontinue donanemab.
In patients who develop intracerebral hemorrhage greater than 1 cm in diameter during treatment with donanemab, suspend dosing until magnetic resonance imaging (MRI) demonstrates radiographic stabilization and symptoms, if present, resolve. Resumption of dosing should be guided by clinical judgment.1
Medication Management of ARIA-E in Clinical Trials
The double-blind, placebo-controlled studies allowed for the use of oral or intravenous corticosteroids to treat ARIA-E (ARIA-E Corticosteroid Dosing Considerations Guidance in Placebo-Controlled Studies).2,3 For asymptomatic or mild symptoms, the participant could be observed. For moderate symptoms, the use of oral or intravenous steroids were considered. In the case of severe symptoms associated with ARIA-E, investigators could hospitalize the participant for close observation and consider the use of intravenous steroids. Final management decisions were at the discretion of the investigator.4
Route of Administration |
Dexamethasone |
Methylprednisolone |
IV doses |
10 mg loading dose, then 4 mg every 6 hours |
1000 mg IV each day |
Oral doses |
4 mg × 2 (8 mg) first dose, then 4 mg every 8 hours, taper over week |
24-48 mg first day, then taper over week. Example consideration:
|
Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; IV = intravenous; MRI = magnetic resonance imaging.
aThe choice of steroids was based on high anti-inflammatory action and no mineralocorticoid action.
An analysis of ARIA was conducted using data from the placebo-controlled portions of the phase 2 TRAILBLAZER-ALZ and phase 3 TRAILBLAZER-ALZ 2 studies, and an open-label addendum to the TRAILBLAZER-ALZ 2 study. In this analysis, 240 events of ARIA-E were reported in participants who received donanemab the placebo-controlled trials and 207 in the open-label addendum.4
In this analysis, 42 donanemab-treated participants received supportive therapy for ARIA-E; of those, 21 received corticosteroids (Summary of Corticosteroid Use in Participants With ARIA-E). The median duration of corticosteroid treatment was 17 days.4
Route of Administration |
Dexamethasone |
Methylprednisolone |
Prednisone |
Intravenous, n |
7 |
4 |
0 |
Oral, n |
7 |
8 |
5 |
Abbreviations: ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; MRI = magnetic resonance imaging.
Corticosteroids were most often prescribed to participants with severe ARIA-E. Donanemab-treated participants that were prescribed corticosteroids included
- 25.9% of those with severe ARIA-E
- 3.6% of those with moderate ARIA-E, and
- 1.0% of those with mild ARIA-E.4
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Kisunla [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
2Sims JR, Zimmer JA, Evans CD, et al; TRAILBLAZER-ALZ 2 Investigators. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA. 2023;330(6):512-527. https://doi.org/10.1001/jama.2023.13239
3Mintun MA, Lo AC, Evans CD, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. 2021;384(18):1691-1704. https://doi.org/10.1056/NEJMoa2100708
4Zimmer JA, Ardayfio P, Wang H, et al. Amyloid-related imaging abnormalities with donanemab in early symptomatic Alzheimer disease: secondary analysis of the TRAILBLAZER-ALZ and ALZ 2 randomized clinical trials. JAMA Neurol. Published online March 10, 2025. https://doi.org/10.1001/jamaneurol.2025.0065
5Cogswell PM, Andrews TJ, Barakos JA, et al; ASNR Alzheimer’s, ARIA, and Dementia Study Group. Alzheimer's disease anti-amyloid immunotherapies: imaging recommendations and practice considerations for ARIA monitoring. AJNR Am J Neuroradiol. 2025;46(1):24-32. https://doi.org/10.3174/ajnr.A8469
Appendix
ARIA MRI Classification Criteria shows the ARIA radiographic severity classification criteria.1
ARIA Type |
Radiographic Severity |
||
Mild |
Moderate |
Severe |
|
ARIA-E |
FLAIR hyperintensity confined to sulcus and/or cortex/subcortex white matter in 1 location <5 cm. |
FLAIR hyperintensity 5 to 10 cm in single greatest dimension, or more than 1 site of involvement, each measuring <10 cm. |
FLAIR hyperintensity >10 cm with associated gyral swelling and sulcal effacement. One or more separate/independent sites of involvement may be noted. |
ARIA-H microhemorrhagea |
≤4 new incident microhemorrhages |
5 to 9 new incident microhemorrhages |
≥10 new incident microhemorrhages |
ARIA-H superficial siderosisa |
1 newb focal area of superficial siderosis |
2 new focal areas of superficial siderosis |
>2 new focal areas of superficial siderosis |
Abbreviations: ARIA = amyloid-related imaging abnormalities; ARIA-E = amyloid-related imaging abnormalities-edema observed on MRI as vasogenic cerebral edema or sulcal effusions; ARIA-H = amyloid-related imaging abnormalities-hemosiderin deposition which includes microhemorrhage and superficial siderosis; FLAIR = fluid attenuation inversion recovery; MRI = magnetic resonance imaging.
aHemosiderin deposits (microhemorrhage and superficial siderosis) are seen on T2* gradient-recalled echo sequence on MRI. ARIA-H severity score is based on cumulative numbers of treatment-emergent microhemorrhages and regions of superficial siderosis compared with the baseline MRI.
bIncludes new or worsening superficial siderosis.
Date of Last Review: April 17, 2025