Note: Confirm the presence of amyloid beta pathology prior to treatment initiation.
Alzheimer disease: IV: Initial: Dosing based on actual body weight: 1 mg/kg once every 4 weeks for infusions 1 and 2; 3 mg/kg once every 4 weeks for infusions 3 and 4; 6 mg/kg once every 4 weeks for infusions 5 and 6; maintenance dose: 10 mg/kg once every 4 weeks starting with infusion 7. Administer infusions at least 21 days apart.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, aducanumab is not expected to undergo renal elimination.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, aducanumab is not expected to undergo hepatic metabolism.
Refer to adult dosing.
|
Severity of clinical symptoms |
ARIA-E severity on MRI | ||
|---|---|---|---|
|
Mild |
Moderate |
Severe | |
|
Asymptomatic |
Continue current aducanumab dose and schedule. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
|
Mild |
Continue aducanumab dosing based on clinical judgement. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
|
Moderate or severe |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
|
Clinical symptom severity |
ARIA-H severity on MRI | ||
|---|---|---|---|
|
Mild |
Moderate |
Severe | |
|
Asymptomatic |
Continue current aducanumab dose and schedule. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
Withhold aducanumab until MRI shows radiographic stabilization and symptoms (if present) resolve. Use clinical judgement to determine whether to continue treatment or permanently discontinue aducanumab. |
|
Symptomatic |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume at same dose and titration prior to withholding therapy, as guided by clinical judgement. |
Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. May resume dose at same and titration prior to withholding therapy, as guided by clinical judgement. |
Withhold aducanumab until MRI shows radiographic stabilization and symptoms (if present) resolve. Use clinical judgement to determine whether to continue treatment or permanently discontinue aducanumab. |
Intracerebral hemorrhage >1 cm in diameter: Withhold aducanumab until MRI shows radiographic resolution and symptoms (if present) resolve. Use clinical judgement to determine whether to continue treatment or permanently discontinue aducanumab; in some studies, aducanumab was permanently discontinued in patients who developed intracerebral hemorrhage >1 cm in diameter (Budd Haeberlein 2022).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Aduhelm: Aducanumab-avwa 300 mg/3 mL (3 mL); Aducanumab-avwa 170 mg/1.7 mL (1.7 mL) [contains polysorbate 80]
No
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761178s000lbl.pdf#page=21, must be dispensed with this medication.
IV: Dilution required prior to administration. Administer by IV infusion over 60 minutes through an IV line containing a sterile, low-protein binding, 0.2 or 0.22 micron in-line filter. Discard unused portion.
Alzheimer disease: Treatment of Alzheimer disease in patients with mild cognitive impairment or mild dementia stage of disease, with confirmed presence of amyloid beta pathology prior to treatment initiation.
Limitations of use: Safety and effectiveness of initiating treatment at earlier or later stages of Alzheimer disease have not been studied.
Aducanumab may be confused with adalimumab.
Amyloid-related imaging abnormalities-edema (ARIA-E) consistent with vasogenic edema and/or sulcal effusions (Ref) or amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H) characterized by superficial siderosis and microhemorrhages (Ref) commonly occur with aducanumab therapy. Patients may develop ARIA-H with concomitant ARIA-E. In patients who developed ARIA-E during clinical trials, most cases were mild to moderate in severity; recurrent episodes have also been described and were less symptomatic than initial episodes. Clinical symptoms suggesting ARIA (-E and/or -H) may include altered mental status, confusion, delirium, disorientation, dizziness, headache, nausea, seizure, vertigo, and visual disturbance. Resolution of ARIA (-E and/or -H) occurred within 12 to 20 weeks in the majority of cases in clinical trials.
Mechanism: It is speculated that increased clearance of amyloid from parenchymal plaques into perivascular space may result in excess fluid shifts. This movement of amyloid into cerebral vessel walls may also increase vascular friability and permeability, thus impairing vessel wall integrity to permit small amounts of blood passage. Increased vascular permeability at which both fluid and red blood cells cross the vessel wall may suggest a common pathophysiologic mechanism for both ARIA-E and ARIA-H (Ref).
ARIA-E: Dose-related; related to the pharmacologic action. Increased cerebrovascular permeability due to antibody binding to deposited amyloid-beta results in an increase in extracellular fluid volume and vasogenic edema (Ref).
ARIA-H: Dose-related; related to the pharmacologic action. Small leakage of blood from a vessel into adjacent tissue parenchyma or subarachnoid space/periadvential compartments leaves small residual deposits of iron in the form of hemosiderin, resulting in microhemorrhage and/or superficial siderosis (Ref).
Onset: Varied; ARIA may occur at any time during treatment, but most events occur within the first 8 doses.
Risk factors:
ARIA-E:
• Apolipoprotein E ε4 carriers (Ref)
• Dose; risk increases with higher doses (Ref) and during dose titration (Ref)
ARIA-H: Microhemorrhages:
• Apolipoprotein E ε4 carriers (Ref)
• Increasing age (Ref)
• Greater number of microhemorrhages at baseline (Ref)
• Older adults with cardiovascular risk factors and/or evidence of prior cerebrovascular event (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults. ARIA-E: amyloid related imaging abnormalities-edema; ARIA-H: amyloid related imaging abnormalities-hemosiderin deposition.
>10%:
Hematologic & oncologic: Hemosiderosis (CNS: ARIA-H superficial siderosis: 15%) (table 1), microhemorrhage (CNS: ARIA-H: 19%) (table 2)
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|
|
15% |
2% |
1,105 |
1,087 |
ARIA-H superficial siderosis |
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|
|
19% |
7% |
1,105 |
1,087 |
ARIA-H microhemorrhage |
Nervous system: Brain edema (ARIA-E, including sulcal effusion: 20% to 64%; higher in apolipoprotein E ε4 carriers) (table 3), falling (15%), headache (21%) (table 4)
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|
|
64% |
N/A |
N/A |
N/A |
ARIA-E; apolipoprotein E ε4 carriers; homozygotes |
|
35% |
3% |
1,105 |
1,087 |
ARIA-E; apolipoprotein E ε4 carriers; heterozygotes |
|
20% |
N/A |
N/A |
N/A |
ARIA-E; apolipoprotein E ε4 non-carriers |
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
|---|---|---|---|
|
21% |
16% |
1,105 |
1,087 |
1% to 10%:
Gastrointestinal: Diarrhea (9%)
Nervous system: Altered mental status (≤8%) (table 5), confusion (≤8%) (table 6), delirium (≤8%) (table 7), disorientation (≤8%) (table 8)
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|
|
≤8% |
≤4% |
1,105 |
1,087 |
Defined as "confusion, delirium, altered mental status, disorientation" |
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|
|
≤8% |
≤4% |
1,105 |
1,087 |
Defined as "confusion, delirium, altered mental status, disorientation" |
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|
|
≤8% |
≤4% |
1,105 |
1,087 |
Defined as "confusion, delirium, altered mental status, disorientation" |
|
Drug (Aducanumab) |
Placebo |
Number of Patients (Aducanumab) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|
|
≤8% |
≤4% |
1,105 |
1,087 |
Defined as "confusion, delirium, altered mental status, disorientation" |
<1%:
Dermatologic: Urticaria
Hypersensitivity: Angioedema
Immunologic: Antibody development
Nervous system: Seizure (associated with ARIA)
Postmarketing: Nervous system: Status epilepticus
There are no contraindications listed in the manufacturer's labeling.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.
Other warning/precautions:
• Appropriate use: Safety and effectiveness of initiating treatment at stages other than mild cognitive impairment/mild dementia (eg, earlier or later stages of Alzheimer disease) have not been studied. Confirm the presence of amyloid beta pathology prior to treatment initiation.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Adverse events were not observed in animal reproduction studies. The pharmacologic target of aducanumab (amyloid beta) is not present in rats, which may limit the relevance of animal data.
Aducanumab is a humanized monoclonal antibody (IgG1). Human IgG is known to cross the placenta; exposure is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
It is not known if aducanumab is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
PET or lumbar puncture to confirm presence of amyloid beta pathology (prior to initiation); brain MRI (prior to initiation [within 1 year], prior to infusion 5 [first dose of 6 mg/kg], infusion 7 [first dose of 10 mg/kg], infusion 9 [third dose of 10 mg/kg], and infusion 12 [sixth dose of 10 mg/kg]); monitor closely for clinical and MRI changes; monitor for symptoms suggestive of amyloid-related imaging abnormalities (ARIA) (eg, headache, altered mental status, dizziness, visual disturbance, seizure, nausea); MRI as indicated if ARIA symptoms present or asymptomatic ARIA observed (Hameed 2020; manufacturer’s labeling).
Aducanumab is a monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. Aducanumab reduces amyloid beta plaques, the accumulation of which is a defining pathophysiological feature of Alzheimer disease.
Distribution: Vd: 9.63 L.
Metabolism: Degraded via catabolic pathways into small peptides and amino acids.
Half-life elimination: 24.8 days.
Solution (Aduhelm Intravenous)
170 mg/1.7 mL (per mL): $338.40
300 mg/3 mL (per mL): $338.40
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