Drug Detail:Aduhelm (Aducanumab [ a-due-kan-ue-mab ])
Generic Name: aducanumab 100mg in 1mL
Dosage Form: injection, solution
Drug Class: Miscellaneous central nervous system agents
2.1 Patient Selection
Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology (12.1)].
Dosing Instructions
After an initial titration, the recommended dosage of ADUHELM is 10 mg/kg (see Table 1). ADUHELM must be diluted and is administered as an intravenous infusion over approximately one hour every four weeks.
| Intravenous Infusion (every 4 weeks) |
ADUHELM Dosage (administered over approximately one hour) |
| Infusion 1 and 2 | 1 mg/kg |
| Infusion 3 and 4 | 3 mg/kg |
| Infusion 5 and 6 | 6 mg/kg |
| Infusion 7 and beyond | 10 mg/kg |
If an infusion is missed, resume administration at the same dose as soon as possible and at least 21 days apart.
Monitoring and Dosing Interruptions for Amyloid Related Imaging Abnormalities
ADUHELM can cause amyloid related imaging abnormalities -edema (ARIA-E) and hemosiderin deposition (ARIA-H) [see Warnings and Precautions (5.1)].
Monitoring for ARIA
Obtain recent (within one year) brain magnetic resonance imaging (MRI) prior to initiating treatment with ADUHELM. Obtain MRIs prior to the 5th infusion (first dose of 6 mg/kg), 7th infusion (first dose of 10 mg/kg), 9th infusion (third dose of 10 mg/kg), and 12th infusion (sixth dose of 10 mg/kg).
Recommendations for Dosing Interruptions in Patients with ARIA
If dosing is resumed following a temporary suspension, dosing may resume at that same dose and titration schedule prior to the dosing suspension. The benefits of reaching and maintaining the 10 mg/kg dosage should be considered when evaluating a potential dose suspension.
ARIA-E
The recommendations for dosing interruptions for patients with ARIA-E are provided in Table 2.
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1 Mild: discomfort noticed, but no disruption of normal daily activity. |
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2 Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification. Resumption of dosing should be guided by clinical judgment. |
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3 See table 4. |
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| Clinical Symptom Severity1 | ARIA-E Severity on MRI3 | ||
| Mild | Moderate | Severe | |
| Asymptomatic | May continue dosing at current dose and schedule | Suspend dosing2 | Suspend dosing2 |
| Mild |
May continue dosing based on clinical judgment | Suspend dosing2 | |
| Moderate or Severe |
Suspend dosing1 | ||
ARIA-H
The recommendations for dosing interruptions for patients with ARIA-H are provided in Table 3.
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1 Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; resumption of dosing should be guided by clinical judgment; consider a follow-up MRI to assess for stabilization 2 to 4 months after initial identification. |
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2 Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; use clinical judgment in considering whether to continue treatment or permanently discontinue ADUHELM. |
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3 See table 4. |
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| Clinical Symptom Severity | ARIA-H Severity on MRI3 | ||
| Mild | Moderate | Severe | |
| Asymptomatic | May continue dosing at current dose and schedule | Suspend dosing1 | Suspend dosing2 |
| Symptomatic |
Suspend dosing1 | Suspend dosing1 | |
In patients who develop intracerebral hemorrhage greater than 1 cm in diameter during treatment with ADUHELM, suspend dosing until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. In Studies 1 and 2, dosing was permanently discontinued in patients who developed intracerebral hemorrhage greater than 1 cm in diameter. Use clinical judgment in considering whether to continue treatment after radiographic stabilization and resolution of symptoms or permanently discontinue ADUHELM.
Dilution Instructions
- Prior to administration, ADUHELM must be diluted in 100 mL of 0.9% Sodium Chloride Injection, USP.
- Use aseptic technique when preparing the ADUHELM diluted solution for intravenous infusion.
- Calculate the dose, total volume of ADUHELM solution required, and the number of vials needed based on the patient's actual body weight. Each vial contains an ADUHELM concentration of 100 mg per mL.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Check that the ADUHELM solution is clear to opalescent and colorless to yellow solution. Do not use if opaque particles, discoloration, or other foreign particles are present.
- Remove the flip-off cap from the vial. Insert the syringe needle into the vial through the center of the rubber stopper.
- Withdraw the required volume of ADUHELM from the vial(s) and add to an infusion bag of 100 mL of 0.9% Sodium Chloride Injection, USP. Do not use other intravenous diluents to prepare the ADUHELM diluted solution.
- Each vial is for single-dose only. Discard any unused portion.
- Gently invert the infusion bag containing the ADUHELM diluted solution to mix completely. Do not shake.
- After dilution, immediate use is recommended. If not administered immediately, store the diluted solution of ADUHELM in 0.9% Sodium Chloride Injection, USP refrigerated at 2°C to 8°C (36°F to 46°F) for up to 3 days, or at room temperature up to 30°C (86°F) for up to 12 hours. Do not freeze.
Administration Instructions
- Visually inspect the ADUHELM diluted solution for particles or discoloration prior to administration. Do not use if it is discolored, or opaque or foreign particles are seen.
- Prior to infusion, allow the ADUHELM diluted solution to warm to room temperature.
- Infuse ADUHELM diluted solution intravenously over approximately one hour through an intravenous line containing a sterile, low-protein binding, 0.2 or 0.22 micron in-line filter.
- Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction [see Warnings and Precautions (5.2)].
