aducanumab

Action and Spectrum

Actions and Spectrum: 

aducanumab is a monoclonal antibody that has been developed for the treatment of Alzheimer’s disease. It targets and binds to beta-amyloid plaques, considered a hallmark of Alzheimer’s disease. 

Action: 

• Targeting Beta-Amyloid: aducanumab specifically binds to aggregated forms of beta-amyloid, which are believed to contribute to the development and progression of Alzheimer’s disease. It recognizes the beta-amyloid plaques and helps facilitate their clearance from the brain. 
• Amyloid Plaque Removal: aducanumab triggers the immune system to remove the plaques once bound to beta-amyloid. It recruits immune cells called microglia, which can engulf and eliminate the beta-amyloid aggregates. 
• Reduction of Plaque Burden: By promoting the clearance of beta-amyloid plaques, aducanumab aims to reduce the overall burden of these plaques in the brain. The clearance of plaques is hypothesized to slow the progression of Alzheimer’s disease potentially. 

Spectrum: aducanumab is primarily developed for the treatment of Alzheimer’s disease. It explicitly targets beta-amyloid plaques, a characteristic feature of Alzheimer’s pathology. However, it’s important to note that aducanumab’s clinical use and efficacy have been debated and controversial in the medical and scientific communities. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Headache (21%) 

Falls (15%) 

ARIA-H superficial siderosis (15%) 

Amyloid-related imaging abnormalities-edema (35%) 

ARIA-H microhemorrhage (19%) 

1-10% 

Altered mental status 

Diarrhea 

Delirium 

Confusion 

Disorientation 

<1%  

Frequency not defined 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Known Hypersensitivity: Individuals with known hypersensitivity or allergic reaction to aducanumab or any of its components should not receive the medication. 
• Severe Allergic Reactions: Caution may be warranted if a patient has a history of severe allergic reactions (e.g., anaphylaxis) to monoclonal antibodies or other biologic agents. 
• Active Infection: aducanumab’s safety profile in active infections may need to be evaluated, as immunomodulatory therapies can potentially affect the immune response. 
• Pregnancy and Lactation: The safety of aducanumab during pregnancy and lactation has not been established. Therefore, it is typically not recommended for use in pregnant or breastfeeding individuals unless the potential benefits outweigh the potential risks. 

Caution 

• Monitoring for Adverse Effects: Close monitoring may be necessary during treatment with aducanumab to assess for any potential adverse effects or allergic reactions. This may include regular clinical evaluations, laboratory tests, or imaging studies deemed appropriate by the healthcare provider. 
• Infusion Reactions: aducanumab is typically administered through intravenous infusion, which carries a risk of infusion-related reactions. Caution may be warranted to monitor patients during and after the infusion for signs of infusion reactions, such as fever, chills, rash, difficulty breathing, or changes in blood pressure. Appropriate measures should be in place to manage and treat any potential reactions. 
• Bleeding Risk: aducanumab’s effects on bleeding risk are not yet fully characterized. Therefore, caution may be needed when considering its use in individuals with a history of bleeding disorders or those taking medications that increase the risk of bleeding, like anticoagulants (blood thinners). 
• Immunomodulatory Effects: aducanumab’s impact on the immune system is not yet fully understood. As with any immunomodulatory therapy, caution may be warranted in individuals with compromised immune function or those at higher risk of infections. 
• Drug Interactions: aducanumab’s potential interactions with other medications have not been extensively studied. It is essential to consider potential drug-drug interactions when prescribing aducanumab, especially in individuals taking other medications that may affect the immune system or increase the risk of adverse effects. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk: Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

aducanumab is a monoclonal antibody with a specific pharmacological action targeting beta-amyloid plaques, characteristic of Alzheimer’s disease pathology. It selectively binds to aggregated forms of beta-amyloid, promoting the recruitment and activation of microglia, the brain’s immune cells. This immune response aids in clearing beta-amyloid plaques, potentially reducing their burden on the brain. By facilitating the removal of these plaques, aducanumab aims to slow down the progression of Alzheimer’s disease. 

Pharmacodynamics: 

Mechanism of action: The action of aducanumab is primarily based on its ability to target and bind to beta-amyloid plaques, characteristic features of Alzheimer’s disease.  

• Binding to Beta-Amyloid: aducanumab is a monoclonal antibody that specifically recognizes and binds to aggregated forms of beta-amyloid. Beta-amyloid is a protein fragment that accumulates and forms plaques in the brains of individuals with Alzheimer’s disease. 
• Facilitating Clearance: Once bound to beta-amyloid, aducanumab facilitates the clearance of these plaques. It does this by activating the immune system, specifically by recruiting immune cells called microglia. 
• Microglia-Mediated Clearance: Microglia are responsible for engulfing and removing cellular debris and foreign substances in the brain, including beta-amyloid plaques. aducanumab promotes microglia’s activation and phagocytic activity, enhancing their ability to recognize and eliminate beta-amyloid aggregates. 
• Reduction of Plaque Burden: By promoting the clearance of beta-amyloid plaques, aducanumab aims to reduce the overall burden of these plaques in the brain. The reduction of plaque burden is hypothesized to potentially slows the progression of the Alzheimer’s disease and preserve cognitive function. 

Pharmacokinetics: 

Absorption 

aducanumab is typically administered intravenously, allowing for direct entry into the bloodstream. Intravenous administration ensures the complete bioavailability of the medication. 

Distribution 

Following intravenous administration, aducanumab would be expected to distribute throughout the body, crossing the blood-brain barrier to target beta-amyloid plaques in the brain.  

Metabolism 

Monoclonal antibodies, including aducanumab, are generally metabolized by enzymatic processes in the body, predominantly in the liver. 

Elimination and Excretion 

Eliminating monoclonal antibodies typically occurs through various mechanisms, such as renal excretion, hepatic metabolism, and potentially through proteolytic degradation. 

Adminstartion

Administration: 

Intravenous administration 

aducanumab is typically administered through intravenous (IV) infusion, which involves delivering the medication directly into the bloodstream. The specific administration protocol, including dosage, infusion rate, and frequency, would be determined by the prescribing healthcare provider based on individual patient factors. 

The administration of aducanumab through IV infusion generally involves the following steps: 

• Preparation: aducanumab is supplied as a sterile solution in vials or infusion bags. The healthcare provider will follow appropriate aseptic techniques to prepare the medication for administration, ensuring that the proper dosage is calculated and verified. 
• Intravenous Access: The healthcare provider will establish an appropriate intravenous access point, typically in a vein in the arm. This can be done using an IV catheter or a peripheral intravenous line. 
• Infusion: The prepared aducanumab solution is administered slowly into the vein over a specified duration. The infusion rate and duration may vary depending on the specific dosing regimen the healthcare provider prescribes. It is common for the initial infusion to be administered over a more extended period to monitor for any potential adverse reactions or infusion-related events. 
• Monitoring: During and after the infusion, the patient will be monitored for any signs of adverse reactions or infusion-related events. Vital signs like BP, heart rate, and temperature may be monitored regularly. 
• Follow-up Infusions: aducanumab treatment is typically administered in multiple doses over some time. The specific dosing regimen, including the interval between infusions, would be determined by the prescribing healthcare provider based on individual patient needs. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: aducanumab 

Pronounced: [ A-due-KAN-ue-mab ] 

Why do we use aducanumab? 

aducanumab is a monoclonal antibody that has been developed for the treatment of Alzheimer’s disease. Its primary use is to target and remove beta-amyloid plaques, considered a hallmark of Alzheimer’s pathology.  

• Treatment of Alzheimer’s Disease: aducanumab is intended for use in patients with mild cognitive impairment/mild dementia stage of Alzheimer’s disease. It is specifically designed to target beta-amyloid plaques in the brain and potentially slow down the progression of the disease. 
• Reduction of Beta-Amyloid Plaques: aducanumab aims to reduce the burden of beta-amyloid plaques in the brain. Binding to aggregated forms of beta-amyloid helps facilitate the clearance of these plaques through the recruitment of immune cells called microglia.