Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 100mg/mL (1.7-mL, 3-mL single-dose vials)
Alzheimer Disease
Indicated for treatment of Alzheimer disease
Administered as IV infusion every 4 weeks and at least 21 days apart
Initiate treatment in patients with mild cognitive impairment or mild dementia stage of disease, the population studied in clinical trials
Safety or effectiveness data are not available on initiating treatment at earlier or later stages of the disease than were studied
Dosing titration schedule
Infusions 1-2: 1 mg/kg IV q4Weeks
Infusions 3-4: 3 mg/kg IV q4Weeks
Infusions 5-6: 6 mg/kg IV q4Weeks
Infusion 7 and beyond: 10 mg/kg IV q4Weeks
Dosage Modifications
Renal or hepatic impairment
- No studies were conducted to evaluate pharmacokinetics in patients with renal or hepatic impairment
- Not expected to undergo renal elimination or metabolism by hepatic enzymes
Dosing Considerations
Magnetic resonance imaging (MRI)
- Prior to initiation: Obtain recent (ie, within at least 1 year) brain MRI
- Before 7th infusion (1st dose of 10 mg/kg) and 12th infusion (6th dose of 10 mg/kg)
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Enhanced clinical vigilance recommended if radiographic severe ARIA-H observed
- If ≥10 new incident microhemorrhages or >2 focal areas of superficial siderosis (radiographic severe amyloid-related imaging abnormalities due to hemosiderin deposition [ARIA-H]) is observed, continue treatment with caution only after a clinical evaluation and a follow-up MRI demonstrating radiographic stabilization (eg, no increase in size or number of ARIA-H)
Safety and efficacy not established
Adverse Effects
>10%
Amyloid-related imaging abnormalities-edema (ARIA-E) (35%)
Headache (21%)
ARIA-H microhemorrhage (19%)
ARIA-H superficial siderosis (15%)
Falls (15%)
1-10%
Diarrhea (9%)
Confusion/delirium/altered mental status/disorientation (8%)
Warnings
Amyloid-related imaging abnormalities
Monoclonal antibodies directed against aggregated forms of beta-amyloid, including this drug, can cause amyloid-related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H)
Incidence and timing of ARIA vary among treatments; ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events rarely can occur
Serious intracerebral hemorrhages, some of which have been fatal, have been observed in patients treated with this class of medications
ApoE epsilon 4 Homozygotes
- Patients who are apolipoprotein E epsilon 4 (ApoE epsilon 4) homozygotes (approximately 15% of Alzheimer’s disease patients) treated with this class of medications, including this drug, have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers
- Testing for ApoE epsilon 4 status should be performed prior to initiation of treatment to inform risk of developing ARIA; prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results
- Prescribers should inform patients that if genotype testing is not performed they can still be treated with this drug; however, it cannot be determined if they are ApoE epsilon 4 homozygotes and at higher risk for ARIA
- Consider benefit of this drug for treatment of Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment
Contraindications
None
Cautions
Angioedema and urticaria reported; promptly discontinue infusion upon first observation of any signs or symptoms consistent with a hypersensitivity reaction, and initiate appropriate therapy
Amyloid-related imaging abnormalities (ARIA)
- May cause ARIA-E; observed on MRI as brain edema, sulcal effusions, and ARIA-H, which includes microhemorrhage and superficial siderosis
- ARIA most commonly presents as temporary swelling in areas of the brain that usually resolves over time; other symptoms include headache, confusion, dizziness, seizures, vision changes, or nausea
- Majority of ARIA observed during first 8 doses, particularly during titration; enhanced clinical vigilance recommended
- Safety in patients with any pretreatment localized superficial siderosis, ≥10 brain microhemorrhages, and/or with a brain hemorrhage >1 cm within 1 year of treatment initiation has not been established
- For ARIA-E or mild/moderate ARIA-H, continue treatment
- If dosing is temporarily suspended, resume at same dose and titration schedule
- There are no systematic data on continued dosing following detection of radiographically moderate or severe ARIA
- Refer to prescribing information for ARIA MRI classification criteria
Monitoring and management guidelines
- Recommendations for dosing in patients with ARIA-E depend on clinical symptoms and radiographic severity
- Recommendations for dosing in patients with ARIA-H depend on
- type of ARIA-H and radiographic severity
- Use clinical judgment in considering whether to continue dosing in patients with recurrent ARIA-E
- Baseline brain MRI and periodic monitoring with MRI are recommended
- If patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated
- If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment
- There is limited experience in patients who continued dosing through symptomatic ARIA-E or through asymptomatic moderate or severe ARIA-E
- There are limited data on dosing patients who experienced recurrent ARIA-E
- The Alzheimer’s Network for Treatment and Diagnostics (ALZ-NET) is a voluntary provider-enrolled patient registry that collects information on treatments for Alzheimer’s disease, including this drug; providers may obtain information about registry at www.alz-net.orgor contact alz-net@acr.org
Pregnancy & Lactation
Pregnancy
There are no adequate data on use in pregnant females to evaluate for drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
Lactation
No data are available on presence of aducanumab in human milk, effects on the breastfed infants, or effects on milk production; published data from other monoclonal antibodies generally indicate low passage of monoclonal antibodies into human milk and limited systemic exposure in the breastfed infant; the effects of this limited exposure are unknown
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
High affinity, fully human IgG1 monoclonal antibody that targets beta amyloid and binds to aggregated forms of beta-amyloid; preferentially binds to parenchymal over vascular amyloid; reduces plaque formation on neurons
Administration
IV Incompatibilities
Do not use other diluents besides 0.9% NaCl to prepare diluted solution
IV Compatibilities
0.9% NaCl
IV Preparation
Calculate dose, total drug volume required, and number of vials needed; each vial contains a drug concentration of 100 mg/mL
Visually inspect solution in vial(s); solution is clear to opalescent and colorless to yellow; discard if opaque particles, discoloration, or other foreign particles are present
Using aseptic technique, withdraw required volume from vial(s) and add into a 0.9% NaCl 100-mL infusion bag; do not use other IV diluents to prepare diluted solution
Gently invert infusion bag to mix completely; do not shake
After dilution, immediate use is recommended
If not used immediately, refrigerate diluted solution at 2-8ºC (36-46ºF) for up to 3 days, or store at room temperature up to 30ºC (86ºF) for up to 12 hr
IV Administration
Before infusion if diluted solution was refrigerated, allow it to warm to room temperature
Infuse IV over 1 hr through an IV–line containing a sterile, low–protein binding, 0.2– or 0.22–micron in–line filter
Promptly discontinue infusion upon first observation of any signs or symptoms consistent with a hypersensitivity-type reaction
Missed dose
- Resume administration at the same dose as soon as possible
- Infusions are administered q4Weeks and at least 21 days apart
Storage
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF) in original carton until use to protect from light; do not freeze or shake
- If no refrigeration is available, may store in its original carton to protect from light at room temperature up to 25ºC (77ºF) for up to 3 days
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Prior to dilution
- Unopened vials may be removed from and returned to refrigerator, if necessary, when kept in the original carton; not to exceed a total of 24 hr at room temperature (up to 25ºC [77ºF])
Diluted solutions
- After dilution, immediate use is recommended
- If not used immediately, refrigerate diluted solution at 2-8ºC (36-46ºF) for up to 3 days, or store at room temperature up to 30ºC (86ºF) for up to 12 hr
Images
Formulary
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