Section 05 · Monograph

Donanemab

Reviewed Nov 2026FDA label

KisunlaAnti-amyloid mAb

Black Box Warning

Amyloid Related Imaging Abnormalities (ARIA): seen radiographically as ARIA-E (edema/effusion) and ARIA-H (hemosiderin deposition, including microhemorrhage and superficial siderosis)
ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events can occur; ARIA can be fatal
Serious intracerebral hemorrhages greater than 1 cm have occurred, including fatal cases
ApoE ε4 homozygotes have a higher incidence of ARIA, including symptomatic and serious ARIA (~15% of AD patients are homozygotes)
Test for ApoE ε4 status prior to initiation of treatment to inform ARIA risk
Obtain a recent baseline brain MRI before initiating treatment; enhanced clinical vigilance for ARIA recommended during the first 24 weeks
Additional caution advised with antithrombotic or thrombolytic agents given a reported fatal intracerebral hemorrhage after thrombolytic administration in a treated patient

Treatment of Alzheimer's disease, in patients with mild cognitive impairment (MCI) or mild dementia stage of disease with confirmed presence of amyloid beta pathologyFDA-labeled

Humanized IgG1 monoclonal antibody directed against an insoluble, modified, N-terminal truncated pyroglutamate form of amyloid beta (N3pG) deposited specifically in brain amyloid plaques
Selectively targets aggregated plaque-form amyloid beta rather than soluble monomeric forms
Binding triggers microglial-mediated clearance of amyloid plaques, resulting in significant reduction of amyloid PET signal
Uses a 'treat-to-target' dosing strategy allowing potential treatment discontinuation once amyloid clearance is achieved

Confirm amyloid beta pathology and obtain ApoE ε4 genotype testing before initiating treatment
Obtain a recent baseline brain MRI prior to the first infusion
Administered as an IV infusion over approximately 30 minutes, once every 4 weeks
Titration: Infusion 1 = 350 mg; Infusion 2 = 700 mg; Infusion 3 = 1050 mg; Infusion 4 and onward = 1400 mg
Obtain MRI prior to the 2nd, 3rd, 4th, and 7th infusions to screen for ARIA
Consider discontinuing treatment once amyloid plaques have been reduced to minimal levels on amyloid PET imaging (treat-to-target approach)

No dosage adjustment necessary for mild-to-moderate renal or hepatic impairment; not studied in severe impairment

Known serious hypersensitivity to donanemab-azbt or to any excipients; reactions have included anaphylaxis

No formal drug-drug interaction studies have been conducted
Concomitant antithrombotic therapy may increase risk of intracerebral hemorrhage, particularly in the setting of ARIA
Use of thrombolytic agents carries increased hemorrhagic risk; a fatal case has been reported
As a monoclonal antibody, no CYP450-mediated interactions are expected

ARIA-H microhemorrhage (~25% of treated patients)
ARIA-E edema/effusion (~24% of treated patients, vs ~2% placebo)
ARIA-H superficial siderosis (~15%)
Headache (~13%)
Infusion-related reactions (9-16%), generally mild to moderate, most common with earlier infusions
Hypersensitivity reactions, including anaphylaxis
Intracerebral hemorrhage >1 cm (rare), including fatal cases
Intestinal obstruction reported at low frequency

ApoE ε4 genotype testing prior to treatment initiation
Baseline brain MRI required before starting therapy
Follow-up MRIs prior to the 2nd, 3rd, 4th, and 7th infusions to screen for ARIA
Additional MRI at any time new neurological symptoms suggestive of ARIA occur
Periodic amyloid PET imaging to assess plaque clearance and evaluate candidacy for treatment discontinuation
Clinical monitoring for infusion-related and hypersensitivity reactions
Review of concomitant antithrombotic/anticoagulant medication use

No adequate data available on use in pregnant women to evaluate drug-associated risk of major birth defects or miscarriage
No animal reproductive or developmental toxicity studies have been conducted
Alzheimer's disease occurs almost exclusively outside of reproductive age
No data on presence in human milk, effects on breastfed infants, or on milk production