What are the dosing schedule, indications, contraindications, precautions, common side effects, and alternative therapies for Emgality (galcanezumab) for preventive treatment of migraine in adults?

Emgality (Galcanezumab) for Migraine Prevention

Dosing Schedule

Emgality is administered as a 240 mg loading dose (two consecutive 120 mg subcutaneous injections) followed by 120 mg monthly injections for migraine prevention. 1

• Allow the medication to sit at room temperature for 30 minutes before injection; never use heat sources like microwaves or hot water 1
• Inject subcutaneously into the abdomen, thigh, back of upper arm, or buttocks, avoiding areas that are tender, bruised, red, or hard 1
• If a dose is missed, administer as soon as possible and resume monthly dosing from that date 1
• The medication is designed for patient self-administration after proper training 1

Indications

Emgality is FDA-approved for preventive treatment of migraine in adults and for treatment of episodic cluster headache in adults. 1

• For episodic cluster headache, the dosing differs: 300 mg (three consecutive 100 mg injections) at cluster period onset, then monthly until the cluster period ends 1
• Galcanezumab is classified as second-line therapy by the American College of Physicians, reserved for patients who fail or cannot tolerate first-line preventives including beta-blockers (metoprolol, propranolol), valproate, venlafaxine, or amitriptyline 2, 3
• This positioning is driven primarily by cost differences (annual costs $7,071-$22,790 for CGRP-mAbs versus $67-$393 for conventional preventives) rather than efficacy differences 3

Contraindications

The only absolute contraindication is serious hypersensitivity to galcanezumab or any excipients. 1

• Hypersensitivity reactions including dyspnea, urticaria, rash, anaphylaxis, and angioedema have been reported 1
• Unlike erenumab (another CGRP-mAb), galcanezumab has not been associated with development or worsening of hypertension in post-marketing surveillance 3
• Galcanezumab does not carry the contraindications associated with conventional preventives: no restrictions for coronary heart disease, inflammatory bowel disease, COPD, nephrolithiasis, asthma, cardiac failure, or atrioventricular block 3

Precautions

Discontinue Emgality immediately if serious or severe hypersensitivity reactions occur and initiate appropriate therapy. 1

• Inspect the solution before administration; do not use if cloudy or containing visible particles 1
• The solution should be clear to opalescent, colorless to slightly yellow to slightly brown 1
• Protect from direct sunlight and do not shake the product 1
• Discuss adverse effects during pregnancy and lactation with patients of childbearing potential 3

Common Side Effects

The most common adverse events are injection-site pain, nasopharyngitis, and upper respiratory tract infection, though rates are generally similar to placebo. 4

• Meta-analysis of six randomized trials (4,023 patients) found injection-site pain and nasopharyngitis rates did not substantially differ from placebo 4
• Galcanezumab 120 mg was associated with higher rates of upper respiratory tract infection compared to placebo, but the 240 mg dose was not 4
• Adverse events in real-world Italian cohort study (163 patients) were reported in up to 10.3% of patients, with none classified as serious 5
• Discontinuation rates due to adverse events are generally low with CGRP antagonists 3

Efficacy Assessment Timeline

Evaluate therapeutic benefit only after 3-6 months of treatment, as earlier assessment may miss the full effect. 3

• Galcanezumab reduces migraine headache days by approximately 0.76-0.80 fewer days per month compared to valproate or topiramate 2, 3
• Real-world data from Italy showed reduction of 8 monthly migraine days in high-frequency episodic migraine and 13 monthly headache days in chronic migraine at 6 months 5
• Responder rates (≥50% reduction) were 76.5% in episodic migraine and 63.5% in chronic migraine patients in real-world settings 5
• Galcanezumab provides early onset of action, with lower percentage of patients experiencing migraine on the first day after injection 6

Treatment Duration and Discontinuation

After 6-12 months of successful therapy, consider pausing galcanezumab to determine whether preventive treatment can be stopped. 3

• No tapering is required when discontinuing galcanezumab 3
• The medication shows gradual reduction of effect upon cessation without signs of rebound headache 6
• Success should be quantified by calculating percentage reduction in monthly migraine days or monthly moderate-to-severe headache days 3

Alternative Therapies

First-Line Options (Use Before Galcanezumab)

Beta-blockers (propranolol 80-240 mg daily or metoprolol) and antidepressants (amitriptyline or venlafaxine) are recommended as first-line therapy. 3

• Valproate is effective first-line but absolutely contraindicated in women of childbearing potential 3
• Candesartan (angiotensin II-receptor blocker) is another first-line option 3
• These conventional preventives cost $67-$393 annually, representing a 100-fold cost difference compared to CGRP-mAbs 3

Other CGRP-Targeting Therapies

If route of administration is a concern, consider oral gepants (atogepant for prevention, rimegepant for acute treatment) as alternatives to injectable CGRP-mAbs. 3, 7

• Patients generally prefer oral treatments over injectables (moderate-certainty evidence) 3
• Atogepant 60 mg daily shows greatest reduction in monthly migraine days (mean difference -1.48 days) 3
• No direct comparative evidence shows superiority of one CGRP-mAb over another in terms of efficacy 3
• Fremanezumab offers flexibility with both monthly and quarterly dosing intervals 3

Non-Pharmacological Options

Non-invasive neuromodulatory devices, biobehavioral therapy, and acupuncture have evidence of benefit for migraine prevention. 3

Clinical Pitfalls to Avoid

Do not discontinue galcanezumab prematurely; patients must complete a minimum of 3-6 months before efficacy can be properly assessed. 3

• Do not use galcanezumab as first-line therapy unless all conventional preventives are contraindicated, as this conflicts with guideline recommendations and cost-effectiveness principles 3
• Insurance often requires failure of 2-3 traditional preventives before approving CGRP therapies 3
• In chronic migraine patients, normal body weight and lower number of failed preventive treatments are positively associated with galcanezumab effectiveness 5
• Real-world effectiveness appears superior to randomized clinical trial results, with only 6.1% dropout rate for inefficacy 5

Mechanism of Action

Galcanezumab is a humanized monoclonal antibody that directly binds to the CGRP peptide itself, preventing it from activating its receptor and reducing free, bioavailable CGRP. 7, 8

• This differs from erenumab, which binds to the CGRP receptor rather than the peptide 7
• CGRP is a potent vasodilator implicated in nociceptive transmission and migraine pathogenesis 8
• CGRP levels are elevated during migraine attacks and normalize with effective treatment 7