Introduction
Galcanezumab is a humanized monoclonal antibody specifically designed for the preventive treatment of migraine. Marketed under the brand name Emgality®, it belongs to the class of calcitonin gene-related peptide (CGRP) antagonists, representing a significant advancement in migraine management. Approved by the FDA in 2018, galcanezumab offers a targeted approach for patients with frequent migraine attacks.
Mechanism of Action
Galcanezumab selectively binds to calcitonin gene-related peptide (CGRP) ligand, preventing its binding to the CGRP receptor. CGRP is a neuropeptide widely distributed in the central and peripheral nervous systems that plays a crucial role in migraine pathophysiology by mediating vasodilation, neurogenic inflammation, and pain transmission. By neutralizing CGRP, galcanezumab interrupts the migraine cascade without causing vasoconstriction, making it particularly suitable for patients with cardiovascular contraindications to triptans.
Indications
- Preventive treatment of migraine in adults
- Treatment of episodic cluster headache in adults (FDA-approved with specific dosing regimen)
Dosage and Administration
Initial dosing: 240 mg (administered as two consecutive 120 mg subcutaneous injections) Maintenance dosing: 120 mg subcutaneously once monthly Special populations:- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly: No dosage adjustment recommended
- Pregnancy: Limited data available - use only if potential benefit justifies potential risk
- Pediatrics: Safety and effectiveness not established
- Administer subcutaneously in abdomen, thigh, back of upper arm, or buttock
- Rotate injection sites
- Allow solution to reach room temperature for 30 minutes before injection
Pharmacokinetics
Absorption: Bioavailability approximately 85% following subcutaneous administration Distribution: Volume of distribution ~6.3 L; limited extravascular distribution Metabolism: Degraded via proteolytic enzymes throughout the body (similar to endogenous IgG) Elimination: Half-life ~27 days; clearance ~0.008 L/hour Time to peak concentration: ~5 days post-doseContraindications
- Hypersensitivity to galcanezumab or any component of the formulation
- Serious hypersensitivity reactions, including anaphylaxis, have been reported
Warnings and Precautions
- Hypersensitivity reactions: Monitor patients for signs of hypersensitivity
- Constipation: Has been reported with CGRP monoclonal antibodies
- Pregnancy: Limited human data - consider benefits versus risks
- Immunogenicity: Patients may develop anti-drug antibodies
Drug Interactions
- No formal drug interaction studies conducted
- Theoretical potential for interactions with other monoclonal antibodies
- No expected interactions with cytochrome P450 substrates
- No clinically significant interactions with commonly co-administered migraine medications
Adverse Effects
Most common adverse reactions (≥2% and more frequent than placebo):- Injection site reactions (pain, erythema, pruritus)
- Constipation
- Hypersensitivity reactions (angioedema, urticaria, dyspnea)
- Severe constipation requiring hospitalization
Monitoring Parameters
- Monthly migraine day frequency and severity
- Injection site reactions
- Signs of hypersensitivity
- Bowel function (constipation)
- Headache diary maintenance
- Patient-reported outcomes and quality of life measures
Patient Education
- Proper injection technique and site rotation
- Storage requirements (refrigerate at 2-8°C; do not freeze)
- Recognition of hypersensitivity reactions
- Importance of consistent monthly dosing
- Maintenance of headache diary
- Reporting of constipation or severe abdominal pain
- Not for acute migraine treatment
- Discuss pregnancy plans with healthcare provider
References
1. FDA Prescribing Information: Emgality (galcanezumab-gnlm). 2022 2. Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018;75(9):1080-1088 3. Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442-1454 4. Dodick DW, Goadsby PJ, Lucas C, et al. Phase 3 randomized, placebo-controlled study of galcanezumab in patients with chronic cluster headache: Results from 3-month double-blind treatment. Cephalalgia. 2020;40(9):935-948 5. Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurol. 2018;18(1):188