Generic Name

Galcanezumab

Mechanism

• Galcanezumab is a humanized monoclonal antibody that selectively binds to the calcitonin gene‑related peptide (CGRP) ligand, preventing its interaction with the CGRP receptor.
• By neutralizing circulating CGRP, it blocks the vasodilatory and nociceptive signaling responsible for migraine pathophysiology.
• The antibody does not interfere with other CGRP‑dependent physiological functions (e.g., vasculature, cardiac reflexes) because it only targets the ligand, not the receptor.

Pharmacokinetics

• Administration: Subcutaneous injection.
• Absorption: Rapid absorption with peak serum concentrations at ~ 7 days post‑dose.
• Distribution: Primarily intra‑vascular; limited tissue penetration (Vd ≈ 4–5 L).
• Metabolism: Protein catabolism via the reticulo‑endothelial system (not involving CYP enzymes).
• Elimination: Linear clearance; terminal half‑life ≈ 27–32 days, allowing maintenance with quarterly dosing.
• Special Populations: No dose adjustment required for mild/moderate hepatic impairment; renal impairment has negligible effect. Pregnancy data are limited; use only if benefits outweigh risks.

Indications

• Preventive treatment of episodic migraine (≥4–14 headache days/month).
• Preventive treatment of chronic migraine (≥15 headache days/month, with ≥8 migraine days/month).
• Adjunct to other preventive agents when monotherapy inadequate.

Contraindications

• Contraindications:
• Known hypersensitivity to galcanezumab or any excipient.
• Concomitant use of other CGRP‑targeted therapies due to overlapping mechanisms.
• Warnings:
• Injection‑site reactions—pruritus, erythema, or induration.
• Potential for allergic reactions—monitor for anaphylaxis, especially after the first dose.
• Pregnancy—limited data; consider risk–benefit.
• Concomitant anticoagulants—monitor for bleeding at injection sites.

Dosing

• Monthly Schedule:
• *4 mg* every 4 weeks (monthly).
• Quarterly Schedule:
• *300 mg* on day 1, day 15, followed by 75 mg on day 85 (equivalent to 4 mg monthly).
• How to Inject:
• Clean the skin with alcohol; use the pre‑filled syringe or autoinjector.
• Inject subcutaneously into the abdomen, thigh, or upper arm.
• Rotate injection sites to minimize tissue damage.
• Missed Dose: If a dose is missed >2 days, skip and resume next scheduled dose; do not double dose.

Adverse Effects

• Common (≥1 % incidence)
• Injection‑site reactions: erythema, pruritus, induration.
• Upper respiratory tract infections.
• Headache (may persist during initiation).
• Serious (rare)
• Anaphylaxis or severe allergic reaction.
• Cardiovascular events (myocardial infarction, stroke; data remain limited).
• Severe hepatic enzyme elevations (monitor LFTs, though rare).

Monitoring

• Baseline:
• Migraine diary (frequency, severity, medication use).
• Cardiovascular risk assessment (BP, ECG if indicated).
• Ongoing:
• Injection‑site inspection for rash or swelling.
• Periodic liver function tests if clinically indicated.
• Patient-reported adverse effects during routine visits.

Clinical Pearls

• Efficacy Rapidly Shifts Into Place: While the half‑life is ~30 days, patients often report a *drop in migraine days starting within the first month*, making it ideal for early relief.
• Switching from Oral Preventives: For patients intolerant to β‑blockers or antiepileptics, galcanezumab provides a *non‑oral alternative* that can be added or switched without significant drug interactions.
• Cardio‑Safety Profile: Unlike some vasodilator‑based migraine prophylactics, galcanezumab’s “ligand‑only” action spares peripheral vascular tone, potentially reducing cardiovascular adverse events.
• Injection‑Site Education: Acknowledge that pruritus may lead to repeated injections at the same spot; educating patients on proper rotation helps diminish skin reactions.
• Pregnancy Consideration: Use under a *Risk Evaluation and Mitigation Strategy (REMS)*; counsel that data are limited and off‑label risk exists.

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• *Prepared for medical students and healthcare professionals seeking a concise yet comprehensive reference on Galcanezumab.*