Aduhelm

About Aducanumab-avwa

• In 2021, the FDA granted accelerated approval to Aducanumab, marketed as Aduhelm, for the treatment of Alzheimer’s disease. This decision was based on its ability to reduce amyloid-beta plaques, as observed in clinical trials. 
• Aduhelm is an amyloid beta-directed antibody that binds to both soluble and aggregated forms of amyloid-beta peptide, facilitating their removal from the brain. 
• However, continued approval for this indication may depend on the verification of clinical benefits in confirmatory trials. The aim of reducing amyloid-beta plaques is to potentially slow down the progression of Alzheimer’s disease.  
• Aducanumab-avwa is a monoclonal antibody of the immunoglobulin gamma 1 (IgG1) class, targeting both aggregated soluble and insoluble forms of amyloid beta. 
• Alzheimer’s disease is characterized by the accumulation of amyloid beta plaques in the brain. Aduhelm works by decreasing these plaques.

Strength: 

Aduhelm injection is available in two formulations: a 170 mg/1.7 mL injection in a single-dose vial and a 300 mg/3 mL injection in a single-dose vial.

Recommended Dosage:

Before administering Aduhelm diluted solution intravenously, visually inspect it for any particles or discoloration. Do not use the solution if it appears discolored, opaque, or if any foreign particles are present. Infuse the diluted solution intravenously over approximately one hour using an intravenous line equipped with a sterile, low-protein binding, 0.2 or 0.22 micron in-line filter. Promptly stop the infusion at the first sign or symptom consistent with a hypersensitivity-type reaction.

Initial titration phase:

• First infusion: 1 mg/kg
• Second infusion: 1 mg/kg
• Third infusion: 3 mg/kg
• Fourth infusion: 3 mg/kg
• Fifth infusion: 6 mg/kg
• Sixth infusion: 6 mg/kg
• After completing the initial titration phase, the maintenance dose is 10 mg/kg given via intravenous infusion every 4 weeks. 
• Missed doses should be administered as soon as possible, with a minimum interval of 21 days from the preceding infusion.

Monitoring and management for Amyloid Related Imaging Abnormalities (ARIA) include obtaining a recent brain MRI before starting treatment, temporary suspension of treatment for symptomatic or moderate-to-severe ARIA, and cautious resumption of treatment after clinical evaluation and resolution of symptoms along with radiographic stability on follow-up MRI.

Important:

Prepare the Aduhelm diluted solution using an aseptic technique. Each vial is for single use; discard any unused portion. Calculate the dose based on body weight. Ensure the solution is clear; discard if particles or discoloration are present. Withdraw the required volume and add to an infusion bag with 100 mL of 0.9% Sodium Chloride Injection, USP. Gently mix without shaking. Store unused solution in the refrigerator for up to 3 days or at room temperature for up to 12 hours. Allow the solution to warm before infusion.

It’s important to inform your doctor about all the medications you are taking, including prescription and over-the-counter drugs, vitamins, and herbal supplements. Your doctor can assess the potential for interactions and adjust your treatment plan accordingly. 

Warnings & Precautions

• Amyloid Imaging Abnormalities (ARIA) require heightened clinical monitoring, particularly during the initial 8 doses of Aduhelm treatment, especially during titration. 
• Patients experiencing symptoms suggestive of ARIA should undergo a clinical evaluation, including MRI testing if necessary. Aduhelm can lead to amyloid-related imaging abnormalities-edema (ARIA-E) or amyloid-related imaging abnormalities-hemosiderin deposition (ARIA-H), as observed on MRI scans. 
• Prior to initiating treatment, it’s essential to obtain recent brain MRI results. The safety of Aduhelm in patients with specific pre-treatment conditions such as localized superficial siderosis or a high number of brain microhemorrhages requires consideration. 
• Hypersensitivity reactions, such as angioedema and urticaria, have been reported during Aduhelm infusion, necessitating prompt discontinuation and initiation of appropriate therapy at the first sign or symptom consistent with a hypersensitivity reaction.

Common Aduhelm Side Effects:

• ARIA-Edema
• Headache
• ARIA-H Microhemorrhage
• ARIA-H Superficial Siderosis
• Fall
• Dizziness
• Confusion
• Nausea
• Fatigue
• Insomnia
• Injection site reactions (redness, pain, swelling)

Use in Specific Population

• The safety of Aduhelm drug has not been established in pregnant women, and there is insufficient data to evaluate the risk of major birth defects or other adverse outcomes. 
• Animal studies in pregnant rats did not show adverse effects on fetal development, but human data are lacking. The FDA has not assigned a pregnancy category for aducanumab. 
• Regarding breastfeeding, there are no studies on the excretion of aducanumab into human milk or its effects on infants or milk production. 
• The benefits of breastfeeding should be considered against potential risks. Aduhelm’s safety and effectiveness in pediatric patients have not been established. In geriatric patients aged 50–85, including those aged 65 and older, no significant differences in adverse reactions were noted compared to younger patients.

Storage and Handling

• Store vials of Aduhelm in the refrigerator at temperatures between 36°F and 46°F (2°C and 8°C). 
• Do not freeze the medicine. 
• Keep the medicine away from pets and children.