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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.
Can Kisunla™ (donanemab-azbt) be used with anticoagulants or antiplatelet therapy?
Symptoms of ARIA-E can resemble an ischemic stroke. Be cautious with use of antithrombotics or thrombolytics (e.g., tissue plasminogen activator) in patients treated with donanemab.
See important safety information, including boxed warning, in the attached prescribing information.
Amyloid-related imaging abnormalities-edema (ARIA-E) can cause focal neurologic deficits that can mimic an ischemic stroke; treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with donanemab.
Concomitant Antithrombotic Medication Use in TRAILBLAZER-ALZ 2
A phase 3, placebo-controlled 72-week study evaluated the safety and efficacy of donanemab in adults aged 60 to 85 years with early symptomatic Alzheimer's disease.1
Participants were randomized at the beginning of double-blind treatment in a 1:1 ratio to receive intravenous infusions every 4 weeks of either
Participants were excluded from enrollment if they had
Severe white matter disease was consistent with a score of 3 in any of the brain regions rated on a modified age-related white matter changes (ARWMC) scale, across both hemispheres.4
Antithrombotic medications were allowed in the TRAILBLAZER-ALZ 2 study, including antiplatelet and anticoagulant medications.1 The majority of exposures to antithrombotic medications were to aspirin, with reported use in 80% of donanemab-treated participants.3,5 Other antithrombotic medications included thrombolytics, non-aspirin antiplatelets, and anticoagulants including heparins, warfarin, and direct oral anticoagulants (Concomitant Antithrombotic Medication Use: TRAILBLAZER-ALZ 2).5
The number of events and the limited exposure to non-aspirin antithrombotic medications limit definitive conclusions about the risk of amyloid-related imaging abnormalities (ARIA) or intracerebral hemorrhage in participants taking antithrombotic medications.3
Frequency of ARIA Based on Safety MRI by Concomitant Antithrombotic Use: TRAILBLAZER-ALZ 2 provides the incidence of ARIA-E, amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H), and macrohemorrhage in participants using antithrombotic medications and those not using antithrombotic medications.
Placebo |
Donanemab |
|
ARIA-E Incidence, n/N (%) |
||
No antithrombotic use |
9/512 (1.8) |
124/504 (24.6) |
≥1 antithrombotic use |
7/362 (1.9) |
72/349 (20.6) |
Aspirin |
6/286 (2.1) |
56/280 (20.0) |
Non-aspirin antiplatelet |
0/33 (0.0) |
9/50 (18.0) |
Anticoagulant |
1/86 (1.2) |
16/83 (19.3) |
Thrombolytic |
0/2 (0.0) |
0/1 (0.0) |
ARIA-H Incidence, n/N (%) |
||
No antithrombotic use |
63/512 (12.3) |
148/504 (29.4) |
≥1 antithrombotic use |
47/362 (13.0) |
106/349 (30.4) |
Aspirin |
38/286 (13.3) |
87/280 (31.1) |
Non-aspirin antiplatelet |
7/33 (21.2) |
11/50 (22.0) |
Anticoagulant |
11/86 (12.8) |
20/83 (24.1) |
Thrombolytic |
0/2 (0.0) |
0/1 (0.0) |
Macrohemorrhage Incidence,b n/N (%) |
||
No antithrombotic use |
2/512 (0.4) |
2/504 (0.4) |
≥1 antithrombotic use |
0/362 (0.0) |
2/349 (0.6) |
Aspirin |
0/286 (0.0) |
0/280 (0.0) |
Non-aspirin antiplatelet |
0/33 (0.0) |
1/50 (2.0) |
Anticoagulant |
0/86 (0.0) |
0/83 (0.0) |
Thrombolytic |
0/2 (0.0) |
0/1 (0.0) |
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 including microhemorrhage and superficial siderosis; MRI = magnetic resonance imaging.
aThis analysis set includes participant data from the first dose of treatment to the last dose plus 57 days.
bMacrohemorrhage is defined as an intracerebral hemorrhage greater than 1 cm.
A fatal intracranial hemorrhage occurred in a participant treated with donanemab in the setting of focal neurological symptoms of ARIA and the use of a thrombolytic agent (eg, tissue plasminogen activator). Focal neurologic symptoms of ARIA-E can mimic an ischemic stroke and treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with donanemab.3
Caution should be exercised when considering the use of donanemab in patients with factors that indicate an increased risk for intracerebral hemorrhage and in particular for patients who need to be on anticoagulant therapy or patients with findings on magnetic resonance imaging that are suggestive of cerebral amyloid angiopathy.3
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Sims 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
2Solomon PR. TRAILBLAZER-ALZ 2: clinical background and study design. Abstract presented at: Alzheimer's Association International Conference (AAIC); July 16-20, 2023; Amsterdam, Netherlands.
3Kisunla [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
4Wahlund LO, Barkhof F, Fazekas F, et al. A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke. 2001;32(6):1318-1322. https://doi.org/10.1161/01.STR.32.6.1318
5Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Appendix
Concomitant Medication |
Placebo |
Donanemab |
Total |
Antithrombotics |
363 (41.5) |
348 (40.8) |
711 (41.2) |
Aspirin |
286 (32.7) |
279 (32.7) |
565 (32.7) |
Acetylsalicylic acid |
273 (31.2) |
271 (31.8) |
544 (31.5) |
Acetylsalicylic acid; aluminium glycinate; magnesium carbonate |
2 (0.2) |
0 (0.0) |
2 (0.1) |
Acetylsalicylic acid; ascorbic acid |
1 (0.1) |
0 (0.0) |
1 (0.1) |
Acetylsalicylic acid; butalbital; caffeine |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Acetylsalicylic acid; caffeine |
1 (0.1) |
1 (0.1) |
2 (0.1) |
Acetylsalicylic acid; caffeine; paracetamol |
8 (0.9) |
6 (0.7) |
14 (0.8) |
Acetylsalicylic acid; dipyridamole |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Acetylsalicylic acid; glycine |
2 (0.2) |
1 (0.1) |
3 (0.2) |
Acetylsalicylic acid; lansoprazole |
1 (0.1) |
0 (0.0) |
1 (0.1) |
Acetylsalicylic acid; methocarbamol |
1 (0.1) |
0 (0.0) |
1 (0.1) |
Non-aspirin antiplatelets |
33 (3.8) |
52 (6.1) |
85 (4.9) |
Alprostadil |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Cilostazol |
5 (0.6) |
4 (0.5) |
9 (0.5) |
Clopidogrel |
27 (3.1) |
44 (5.2) |
71 (4.1) |
Dipyridamole |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Eptifibatide |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Prasugrel |
2 (0.2) |
2 (0.2) |
4 (0.2) |
Sarpogrelate |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Ticagrelor |
2 (0.2) |
2 (0.2) |
4 (0.2) |
Anticoagulants |
88 (10.1) |
84 (9.8) |
172 (10.0) |
Apixaban |
39 (4.5) |
35 (4.1) |
74 (4.3) |
Bivalirudin |
0 (0.0) |
2 (0.2) |
2 (0.1) |
Dabigatran |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Dalteparin |
1 (0.1) |
0 (0.0) |
1 (0.1) |
Edoxaban |
1 (0.1) |
0 (0.0) |
1 (0.1) |
Enoxaparin |
16 (1.8) |
9 (1.1) |
25 (1.4) |
Heparin |
11 (1.3) |
12 (1.4) |
23 (1.3) |
Low molecular weight heparin |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Nadroparin |
0 (0.0) |
1 (0.1) |
1 (0.1) |
Rivaroxaban |
23 (2.6) |
26 (3.0) |
49 (2.8) |
Warfarin |
7 (0.8) |
4 (0.5) |
11 (0.6) |
Thrombolytics |
2 (0.2) |
1 (0.1) |
3 (0.2) |
Alteplase |
2 (0.2) |
1 (0.1) |
3 (0.2) |
Date of Last Review: January 24, 2025