Introduction
Reyvow (lasmiditan) is a novel prescription medication approved by the FDA in October 2019 for the acute treatment of migraine with or without aura in adults. It represents the first medication in a new class of migraine treatments called serotonin (5-HT) 1F receptor agonists, offering an alternative mechanism for patients who cannot tolerate or have contraindications to triptans.
Mechanism of Action
Lasmiditan is a highly selective serotonin 5-HT1F receptor agonist. Unlike triptans which act primarily on 5-HT1B/1D receptors and cause vasoconstriction, lasmiditan's mechanism is believed to be primarily neuronal without significant vasoconstrictive effects. It is thought to inhibit trigeminal pathways by acting on 5-HT1F receptors expressed in the trigeminal ganglion and nerve terminals, thereby reducing the release of calcitonin gene-related peptide (CGRP) and other neuropeptides involved in migraine pathophysiology.
Indications
- Acute treatment of migraine with aura in adults
- Acute treatment of migraine without aura in adults
Reyvow is not indicated for the preventive treatment of migraine.
Dosage and Administration
Available strengths: 50 mg and 100 mg tablets Recommended dosing:- Starting dose: 50 mg, 100 mg, or 200 mg taken orally as needed
- Maximum dose: One dose per 24 hours
- Maximum monthly usage: No more than 4 doses per month
- Take at the onset of migraine symptoms
- May be taken with or without food
- Avoid driving or operating machinery for at least 8 hours after taking
- Hepatic impairment: Use with caution in patients with severe hepatic impairment
- Renal impairment: No dosage adjustment necessary
- Geriatric patients: Use with caution due to increased risk of dizziness and sedation
- Pregnancy: No human data; use only if potential benefit justifies potential risk
- Lactation: Not recommended
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of 1.8 hours. High-fat meal delays absorption (Tmax ~2.8 hours) but does not significantly affect overall exposure. Distribution: Mean apparent volume of distribution is ~54 L. Protein binding is approximately 57-59%. Metabolism: Primarily metabolized via multiple pathways including monoamine oxidase A (MAO-A), CYP450 enzymes (mainly CYP3A4), and glucuronidation. Elimination: Terminal half-life is approximately 5.7 hours. Excretion is primarily renal (66%) with 32% recovered in feces.Contraindications
- Hypersensitivity to lasmiditan or any component of the formulation
Warnings and Precautions
CNS Depression: Reyvow may cause significant sedation and dizziness. Patients should be cautioned about performing activities requiring mental alertness, including driving or operating machinery. Driving Impairment: Reyvow causes driving impairment that may last at least 8 hours. Patients should not drive or engage in potentially hazardous activities until at least 8 hours after each dose. Serotonin Syndrome: Cases have been reported with 5-HT1 agonists. Use with caution, particularly when used concomitantly with other serotonergic drugs. Abuse and Dependence: While not classified as a controlled substance, patients with a history of substance abuse should be monitored closely.Drug Interactions
CNS Depressants: Enhanced sedative effects when used with alcohol, benzodiazepines, opioids, other sedatives, or antipsychotics. MAO Inhibitors: Potential increased exposure to lasmiditan. Avoid concomitant use. Strong CYP3A4 Inhibitors: May increase lasmiditan exposure. Consider dose reduction. Other Serotonergic Drugs: Increased risk of serotonin syndrome when used with SSRIs, SNRIs, TCAs, triptans, opioids, or other serotonergic agents.Adverse Effects
Most common adverse reactions (≥2% and greater than placebo):- Dizziness (16-20%)
- Fatigue (7-9%)
- Paresthesia (5-7%)
- Sedation (5-7%)
- Nausea (3-4%)
- Serotonin syndrome
- Driving impairment
- Severe dizziness or sedation
Monitoring Parameters
- Efficacy: Reduction in migraine pain and associated symptoms at 2 hours
- Safety: Signs of CNS depression, dizziness, sedation
- Functional impairment: Ability to perform tasks requiring alertness
- Signs of serotonin syndrome: agitation, hallucinations, tachycardia, hyperthermia
- Medication overuse: Monitor frequency of use to prevent medication-overuse headache
Patient Education
- Take Reyvow at the first sign of migraine symptoms
- Do not take more than one dose in 24 hours
- Do not take more than 4 doses per month
- Avoid driving, operating machinery, or engaging in hazardous activities for at least 8 hours after taking Reyvow
- Do not consume alcohol while taking Reyvow
- Be aware of potential dizziness, sedation, and fatigue
- Report symptoms of serotonin syndrome immediately (agitation, hallucinations, fast heart rate, fever)
- Inform healthcare providers of all medications being taken
- Store at room temperature away from moisture and heat
References
1. FDA prescribing information: Reyvow (lasmiditan) tablets. October 2019. 2. Kuca B, Silberstein SD, Wietecha L, et al. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology. 2018;91(24):e2222-e2232. 3. Reuter U, Israel H, Neeb L. The pharmacological profile and clinical prospects of lasmiditan in the acute treatment of migraine. Ther Adv Neurol Disord. 2015;8(1):46-54. 4. Shapiro RE, Hochstetler HM, Dennehy EB, et al. Lasmiditan for the acute treatment of migraine: Subgroup analyses by prior response to triptans. Cephalalgia. 2020;40(1):19-27. 5. ClinicalTrials.gov: Phase 3 studies of lasmiditan (SAMURAI, SPARTAN).