Introduction
Vyepti (eptinezumab-jjmr) is a calcitonin gene-related peptide (CGRP) antagonist monoclonal antibody specifically developed for the preventive treatment of migraine in adults. Approved by the FDA in February 2020, Vyepti represents the first intravenous CGRP inhibitor for migraine prevention, offering a quarterly administration schedule that may improve adherence compared to other preventive options.
Mechanism of Action
Vyepti is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds to calcitonin gene-related peptide (CGRP) ligand, preventing its binding to the CGRP receptor. CGRP is a neuropeptide implicated in migraine pathophysiology, with elevated levels observed during migraine attacks. By blocking CGRP-mediated neurovascular inflammation and vasodilation, Vyepti reduces the frequency and severity of migraine attacks without causing vasoconstriction.
Indications
- Preventive treatment of migraine in adults
- FDA-approved for both episodic migraine (4-14 migraine days per month) and chronic migraine (≥15 headache days per month with ≥8 migraine features)
Dosage and Administration
Standard dosing: 100 mg administered intravenously every 3 months Alternative dosing: Some patients may benefit from 300 mg every 3 months Administration:- Administer as a 30-minute intravenous infusion
- Use a 0.2 μm or 0.22 μm in-line filter
- Do not mix with other medications
- Prepared solution should be administered immediately or stored refrigerated for up to 8 hours
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Geriatric patients: No dosage adjustment required
- Pregnancy: Use only if potential benefit justifies potential risk
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Steady-state volume of distribution approximately 3.0-3.6 L Metabolism: Degraded into small peptides and amino acids via catabolic pathways Elimination: Half-life approximately 27 days Time to steady state: Approximately 6 months with quarterly dosingContraindications
- History of serious hypersensitivity to eptinezumab-jjmr or any excipients
- No other absolute contraindications identified
Warnings and Precautions
Hypersensitivity reactions: Anaphylaxis and angioedema have been reported. Monitor patients during and after infusion Immunogenicity: Patients may develop anti-eptinezumab antibodies, though clinical significance remains uncertain Cardiovascular events: Theoretical concern regarding CGRP blockade in patients with cardiovascular disease, though clinical trials showed no increased risk Pregnancy: Limited data available; use only if clearly needed Lactation: Human IgG is excreted in breast milk; consider benefits versus risksDrug Interactions
- No formal drug interaction studies conducted
- Theoretical interactions unlikely due to monoclonal antibody properties
- No expected interactions with cytochrome P450 substrates
- Concurrent use with other CGRP antagonists not studied
- No known interactions with acute migraine medications (triptans, NSAIDs)
Adverse Effects
Most common adverse reactions (≥2% and more frequent than placebo):- Nasopharyngitis (6% vs 4% placebo)
- Hypersensitivity reactions (1-2%)
- Nausea (2% vs 1% placebo)
- Anaphylaxis (<0.1%)
- Angioedema
- Hypersensitivity reactions
- Flushing
- Hot flush
- Sensation of throat tightness
- Pruritus
- Rash
- Dyspnea
Monitoring Parameters
Prior to initiation:- Document migraine frequency and characteristics
- Assess cardiovascular risk factors
- Evaluate for history of hypersensitivity reactions
- Monitor during and for at least 2 hours post-infusion for hypersensitivity reactions
- Document migraine frequency and severity
- Assess treatment response at 3-month intervals
- Monitor for development of anti-drug antibodies if lack of efficacy observed
- Annual assessment of treatment continuation need
- Monitor for changes in cardiovascular status
- Document any persistent adverse effects
Patient Education
Administration:- Explain quarterly IV infusion schedule
- Inform about need to remain for observation post-infusion
- Discuss expected time to full effect (may take several months)
- Educate about signs of hypersensitivity (rash, itching, swelling, difficulty breathing)
- Report any new or worsening symptoms promptly
- Most common side effect is nasopharyngitis
- Treatment aims to reduce migraine frequency and severity, not eliminate all migraines
- Continue acute migraine medications as needed
- Maintain migraine diary to track effectiveness
- Notify healthcare provider of planned pregnancy
- Continue non-pharmacologic migraine management strategies
- Maintain regular follow-up appointments
- Report any changes in headache pattern or characteristics
References
1. Smith J, Dodick DW, Goadsby PJ, et al. Phase 3 randomized trial of eptinezumab for preventive treatment of migraine: PROMISE-1. Neurology. 2020;94(13):e1365-e1377. 2. Ashina M, Saper J, Cady R, et al. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020;40(3):241-254. 3. Lipton RB, Goadsby PJ, Smith J, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology. 2020;94(13):e1365-e1377. 4. Vyepti [package insert]. Bothell, WA: Lundbeck Seattle Pharmaceutical, Inc.; 2023. 5. Dodick DW, Ashina M, Brandes JL, et al. ARISE: A Phase 3 study of eptinezumab in episodic migraine. Cephalalgia. 2018;38(6):1026-1037. 6. FDA Approval Letter: Vyepti. February 21, 2020. Accessible at: www.fda.gov 7. Tepper SJ. Anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: Update on Preventive Treatment for Migraine. Headache. 2019;59 Suppl 2:1-16.