Introduction

CNS agent, an amyloid beta-directed monoclonal antibody.

Uses for Aducanumab

Alzheimer's Disease

Treatment of Alzheimer’s disease; limit use of drug to patients with mild cognitive impairment or mild dementia stage of the disease, the population that was evaluated in clinical trials.

Accelerated approval based on reduction in amyloid beta plaques (a surrogate marker of response). Continued approval may be contingent upon verification of clinical benefit (e.g., long-term cognitive changes) in confirmatory studies.

Reduction of amyloid beta plaques with aducanumab-avwa was clearly and consistently demonstrated across trials. However, there is controversy regarding whether this is an appropriate surrogate end point to predict clinical benefit; several organizations and expert panels have published appropriate use criteria or position statements expressing concerns over the available evidence supporting use.

Aducanumab Dosage and Administration

General

Pretreatment Screening

• Obtain a recent (within 1 year) brain MRI.

Patient Monitoring

• Discontinue the infusion if signs or symptoms of a hypersensitivity reaction (e.g., angioedema, urticaria) occur.

• Monitor for amyloid-related imaging abnormalities by obtaining an MRI prior to the 7th and 12th infusions. (See Therapy Interruption for Toxicity under Dosage and Administration.)

Administration

Administer by IV infusion once every 4 weeks. Use a 0.2- or 0.22-micron inline filter.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

If an infusion is missed, resume administration at the same dosage as soon as possible; separate doses by at least 21 days.

Vials are for single use only; discard unused portions.

Dilution

Must dilute prior to IV infusion.

Determine the number of vials needed based on the patient’s actual body weight and recommended dosage.

Withdraw the required volume of aducanumab and add to infusion bag containing 100 mL of 0.9% sodium chloride injection; do not use any other diluents.

Mix the final diluted solution for infusion by gentle inversion; do not shake. Allow the diluted solution to warm up to room temperature prior to infusion.

Administer immediately. If immediate administration is not possible, the diluted solution may be stored at 2–8°C for up to 3 days or at room temperature (up to 30°C) for up to 12 hours.

Rate of Administration

Administer by IV infusion over approximately 1 hour.

Dosage

Calculate dose based on actual body weight.

Adults

Alzheimer's Disease

Initial Titration

Titrate dosage according to the following schedule; administer IV infusions every 4 weeks:

• Infusion 1 (at week 0) and infusion 2 (at week 4): 1 mg/kg

• Infusion 3 (at week 8) and infusion 4 (at week 12): 3 mg/kg

• Infusion 5 (at week 16) and infusion 6 (at week 20): 6 mg/kg

Maintenance Dosing

Recommended maintenance dosage starting with infusion 7 (week 24) is 10 mg/kg every 4 weeks.

Therapy Interruption for Toxicity

Discontinue if radiographic severe ARIA-H is observed. May resume with caution after clinical evaluation and a follow-up MRI documents radiographic stabilization. For amyloid related imaging abnormalities-edema (ARIA-E) or mild/moderate ARIA-H, treatment may continue with caution. If dosing is temporarily suspended, dosing may resume at that same dose and titration schedule. There are no systematic data on continued dosing following detection of radiographically moderate or severe ARIA.

Special Populations

Hepatic Impairment

No special population dosage recommendations at this time.

Renal Impairment

No special population dosage recommendations at this time.

Geriatric Patients

No special population dosage recommendations at this time.

Contraindications

• None.

Warnings/Precautions

Amyloid Related Imaging Abnormalities (ARIA)

ARIA-edema (ARIA-E; brain edema or sulcal effusions) and ARIA-hemosiderin deposition (ARIA-H; microhemorrhage and superficial siderosis) reported in clinical studies. Can occur at any time during treatment; most likely to occur within the first 8 doses.

Obtain a baseline brain MRI prior to starting aducanumab. Safety not established in patients with any pretreatment localized superficial siderosis, ≥10 brain microhemorrhages, and/or brain hemorrhage >1 cm within 1 year of treatment initiation.

May not present with symptoms. Screen for asymptomatic ARIA with brain MRI prior to the 7th infusion (first maintenance dose) and 12th infusion of aducanumab. Clinical symptoms of ARIA include headache, confusion/delirium/altered mental status/disorientation, dizziness/vertigo, visual disturbance, and nausea.

Temporary dose suspension or permanent discontinuation may be required in patients with radiographic findings of ARIA.

Hypersensitivity

Hypersensitivity reactions (e.g., angioedema, urticaria) reported.

Discontinue IV infusion promptly and initiate appropriate medical treatment if hypersensitivity reaction occurs.

Immunogenicity

Development of anti-drug antibodies reported.

Specific Populations

Pregnancy

Not known whether aducanumab is associated with risk if used during pregnancy.

Lactation

Not known whether aducanumab is distributed into milk, affects milk production, or affects the breast-fed infant.

Consider known benefits of breast-feeding along with mother's clinical need for aducanumab and any potential adverse effects of the drug or disease on the infant.

Pediatric Use

Not studied in pediatric patients.

Geriatric Use

No safety differences noted between patients ≥65 years of age and patients ≥75 years of age, or in older versus younger patients.

Hepatic Impairment

Not studied; not expected to be metabolized by hepatic enzymes.

Renal Impairment

Not studied; not expected to be eliminated renally.

Common Adverse Effects

Adverse effects occurring in ≥2% of patients include ARIA-E, headache, ARIA-H microhemorrhage, ARIA-H superficial siderosis, falls, diarrhea, and confusion/delirium/altered mental status/disorientation.

General

Pretreatment Screening

• Obtain a recent (within 1 year) brain MRI.

Patient Monitoring

• Discontinue the infusion if signs or symptoms of a hypersensitivity reaction (e.g., angioedema, urticaria) occur.

• Monitor for amyloid-related imaging abnormalities by obtaining an MRI prior to the 7th and 12th infusions. (See Therapy Interruption for Toxicity under Dosage and Administration.)

Administration

Administer by IV infusion once every 4 weeks. Use a 0.2- or 0.22-micron inline filter.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

If an infusion is missed, resume administration at the same dosage as soon as possible; separate doses by at least 21 days.

Vials are for single use only; discard unused portions.

Dilution

Must dilute prior to IV infusion.

Determine the number of vials needed based on the patient’s actual body weight and recommended dosage.

Withdraw the required volume of aducanumab and add to infusion bag containing 100 mL of 0.9% sodium chloride injection; do not use any other diluents.

Mix the final diluted solution for infusion by gentle inversion; do not shake. Allow the diluted solution to warm up to room temperature prior to infusion.

Administer immediately. If immediate administration is not possible, the diluted solution may be stored at 2–8°C for up to 3 days or at room temperature (up to 30°C) for up to 12 hours.

Rate of Administration

Administer by IV infusion over approximately 1 hour.

Dosage

Calculate dose based on actual body weight.

Adults

Alzheimer's Disease

Initial Titration

Titrate dosage according to the following schedule; administer IV infusions every 4 weeks:

• Infusion 1 (at week 0) and infusion 2 (at week 4): 1 mg/kg

• Infusion 3 (at week 8) and infusion 4 (at week 12): 3 mg/kg

• Infusion 5 (at week 16) and infusion 6 (at week 20): 6 mg/kg

Maintenance Dosing

Recommended maintenance dosage starting with infusion 7 (week 24) is 10 mg/kg every 4 weeks.

Therapy Interruption for Toxicity

Discontinue if radiographic severe ARIA-H is observed. May resume with caution after clinical evaluation and a follow-up MRI documents radiographic stabilization. For amyloid related imaging abnormalities-edema (ARIA-E) or mild/moderate ARIA-H, treatment may continue with caution. If dosing is temporarily suspended, dosing may resume at that same dose and titration schedule. There are no systematic data on continued dosing following detection of radiographically moderate or severe ARIA.

Special Populations

Hepatic Impairment

No special population dosage recommendations at this time.

Renal Impairment

No special population dosage recommendations at this time.

Geriatric Patients

No special population dosage recommendations at this time.

There is no information regarding drug interactions with aducanumab in the prescribing information for the drug.