aducanumab (Rx)

>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%)

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

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.

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

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

• 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