Usage
- Brolucizumab is prescribed for the treatment of neovascular (wet) age-related macular degeneration (AMD) and diabetic macular edema (DME).
- Pharmacological classification: Vascular endothelial growth factor (VEGF) inhibitor.
- Mechanism of Action: Brolucizumab binds with high affinity to all isoforms of VEGF-A, thereby preventing these isoforms from interacting with their receptors, VEGFR-1 and VEGFR-2. This inhibition of VEGF signaling reduces vascular permeability and neovascularization, key factors in the pathogenesis of wet AMD and DME.
Alternate Names
- INN: brolucizumab
- Brand Name: Beovu
How It Works
- Pharmacodynamics: Brolucizumab exerts its therapeutic effect by inhibiting VEGF, leading to decreased vascular permeability and suppression of neovascularization in the retina.
- Pharmacokinetics: Brolucizumab is administered via intravitreal injection. Systemic exposure is low. The elimination pathway is not fully characterized but likely involves degradation into small peptides.
- Mode of Action: Brolucizumab is a humanized monoclonal single-chain Fv (scFv) antibody fragment. It binds to and inhibits all isoforms of vascular endothelial growth factor A (VEGF-A).
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Brolucizumab’s primary action is the inhibition of VEGF-A binding to its receptors, VEGFR-1 and VEGFR-2. It does not directly inhibit enzymes or modulate neurotransmitters.
- Elimination Pathways: The elimination pathways for brolucizumab are not fully elucidated. As a protein, it is likely metabolized to small peptides.
Dosage
Standard Dosage
Adults (for both wet AMD and DME):
- Initial Dose (Loading Dose): 6 mg (0.05 mL of a 120 mg/mL solution) administered by intravitreal injection.
- Wet AMD: Monthly for the first three doses.
- DME: Every six weeks for the first five doses.
- Maintenance Dose: 6 mg (0.05 mL) by intravitreal injection every 8–12 weeks for both conditions. The interval can be adjusted based on disease activity assessment by visual acuity and/or anatomical parameters.
Children:
The safety and efficacy of brolucizumab have not been established in pediatric patients.
Special Cases:
- Elderly Patients: No dosage adjustment is required.
- Patients with Renal Impairment: No dosage adjustment is required.
- Patients with Hepatic Dysfunction: No dosage adjustment is required. Note: while no specific adjustment is mentioned, hepatic function should be monitored in these patients.
- Patients with Comorbid Conditions: Monitor patients with cardiovascular disease, diabetes, or a history of intraocular inflammation closely.
Clinical Use Cases
Brolucizumab is specifically indicated for wet AMD and DME. The listed use cases like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations are not relevant to brolucizumab’s application. These are typically relevant to other drug classes, such as anesthetics or sedatives.
Dosage Adjustments
Dosage adjustments during maintenance therapy are based on disease activity as determined by visual acuity and anatomical assessments. The interval should not be less than 8 weeks.
Side Effects
Common Side Effects:
- Blurred vision
- Cataract
- Conjunctival hemorrhage
- Eye pain
- Vitreous floaters
Rare but Serious Side Effects:
- Endophthalmitis
- Retinal detachment
- Retinal vasculitis
- Retinal vascular occlusion
- Intraocular inflammation
- Increased intraocular pressure
Long-Term Effects:
Potential long-term effects are still being investigated but may include changes in vision. Regular monitoring is required.
Adverse Drug Reactions (ADR):
- Intraocular inflammation (including retinal vasculitis)
- Retinal vascular occlusion
Contraindications
- Ocular or periocular infections
- Active intraocular inflammation
- Hypersensitivity to brolucizumab or any of its excipients
Drug Interactions
Currently, no significant drug interactions have been documented.
Pregnancy and Breastfeeding
-
Pregnancy Safety Category: While there are no adequate and well-controlled studies in pregnant women, based on the anti-VEGF mechanism of action, brolucizumab may pose a risk to the fetus. It should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception during treatment and for at least one month after the last dose.
-
Breastfeeding: It is unknown whether brolucizumab is present in human milk. Because of the potential for adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for at least one month after the last dose.
Drug Profile Summary
- Mechanism of Action: Inhibits VEGF-A, leading to decreased vascular permeability and reduced neovascularization.
- Side Effects: Common: blurred vision, cataract, conjunctival hemorrhage, eye pain, vitreous floaters. Serious: endophthalmitis, retinal detachment, retinal vasculitis/occlusion, intraocular inflammation.
- Contraindications: Ocular/periocular infections, active intraocular inflammation, hypersensitivity.
- Drug Interactions: None documented.
- Pregnancy & Breastfeeding: Not recommended during pregnancy and breastfeeding.
- Dosage: 6 mg intravitreally, loading doses monthly (wet AMD) or every 6 weeks (DME) initially; maintenance dose every 8-12 weeks, adjustable based on disease activity.
- Monitoring Parameters: Visual acuity, intraocular pressure, signs of inflammation or infection, anatomical changes of retina (e.g., optical coherence tomography).
Popular Combinations
While brolucizumab is not typically used in combination with other intravitreal agents concurrently, switching between different anti-VEGF agents is common practice depending on patient response and disease activity.
Precautions
- General Precautions: Evaluate patients for infections, inflammation, and other ocular conditions before administration. Monitor intraocular pressure after injection.
- Specific Populations:
- Pregnant Women: Avoid use unless potential benefit outweighs risk.
- Breastfeeding Mothers: Breastfeeding is not recommended.
- Children & Elderly: Safety and efficacy not established in children. No dose adjustment needed for elderly.
- Lifestyle Considerations: Patients may experience temporary blurred vision. Advise caution with driving or operating machinery until vision recovers.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Brolucizumab?
A: For both wet AMD and DME, the initial dose is 6 mg via intravitreal injection. For wet AMD, this is given monthly for the first three doses. For DME, it’s given every six weeks for the first five doses. Maintenance dosing is 6 mg every 8-12 weeks, adjusted based on disease activity.
Q2: What are the most common side effects of Brolucizumab?
A: The most common side effects include blurred vision, cataract, conjunctival hemorrhage, eye pain, and vitreous floaters.
Q3: How does Brolucizumab work?
A: It’s a VEGF inhibitor that binds to and blocks all isoforms of VEGF-A, reducing vascular permeability and neovascularization.
Q4: Is Brolucizumab safe for pregnant or breastfeeding women?
A: It is not recommended for use during pregnancy or breastfeeding due to potential risks to the fetus or infant.
Q5: Are there any contraindications for using Brolucizumab?
A: Yes. It is contraindicated in patients with active or suspected ocular/periocular infections, active intraocular inflammation, and hypersensitivity to brolucizumab or any of its components.
Q6: How is Brolucizumab administered?
A: It is administered via intravitreal injection by a qualified ophthalmologist.
Q7: What should I monitor in patients receiving Brolucizumab?
A: Monitor for visual acuity, intraocular pressure, signs of ocular inflammation or infection, and retinal changes using appropriate imaging techniques.
Q8: What is the treatment interval for Brolucizumab after the loading doses?
A: After the loading doses, the treatment interval is typically every 8-12 weeks but may be adjusted based on individual patient response and disease activity. It should not be less than 8 weeks.
Q9: What is the difference in the initial dosage regimen for wet AMD and DME?
A: For wet AMD, the initial doses are given monthly for three months. For DME, the initial doses are given every six weeks for five doses.
Q10: Can Brolucizumab be used in children?
A: The safety and efficacy of brolucizumab have not been established in pediatric patients, therefore its use is not recommended in this population.
