Lasmiditan

• Acute Migraine Treatment
• Migraine with Aura
• Migraine without Aura
• Alternative to Triptans

Lasmiditan is a selective serotonin 5-HT1F receptor agonist used for the acute treatment of migraine with or without aura in adults. This first-in-class "ditan" offers a non-vasoconstricting alternative to triptans for patients who cannot use vasoconstrictive therapies.

Mechanism of Action

Lasmiditan is a highly selective agonist of the serotonin 5-HT1F receptor, with high affinity and selectivity for 5-HT1F over 5-HT1B and 5-HT1D receptors. Unlike triptans, which work primarily through 5-HT1B/1D receptors and cause vasoconstriction, lasmiditan's 5-HT1F agonism does not cause vasoconstriction of blood vessels. The 5-HT1F receptor is located on trigeminal nerve endings and in the trigeminal nucleus caudalis, areas involved in migraine pathophysiology. Activation of these receptors is thought to inhibit neuropeptide release and reduce pain signal transmission in the trigeminal system, providing migraine relief without cardiovascular effects.

Available Formulations

Lasmiditan is available as oral tablets in 50 mg and 100 mg strengths. The tablets can be taken with or without food. Lasmiditan is a Schedule V controlled substance due to potential for euphoria and sedation that could lead to abuse.

Medical Uses

Lasmiditan is FDA-approved for the acute treatment of migraine with or without aura in adults. It is not indicated for the preventive treatment of migraine. Clinical trials demonstrated significant improvement in pain freedom and freedom from most bothersome symptom at 2 hours compared to placebo. It is particularly useful for patients with cardiovascular disease or cardiovascular risk factors who cannot use triptans.

Dosing Guidelines

The recommended dose is 50 mg or 100 mg taken orally as needed for acute migraine. A maximum of one dose should be taken in 24 hours. The safety of treating more than 4 migraines in 30 days has not been established. Patients should not drive or operate machinery for at least 8 hours after taking lasmiditan, even if they feel well enough to do so.

Important Safety Information

Lasmiditan can cause significant CNS depression, including dizziness, fatigue, and sedation. Patients must be advised not to drive or operate machinery for at least 8 hours after taking lasmiditan. This restriction applies regardless of how the patient feels. Serotonin syndrome can occur, especially when combined with other serotonergic drugs. There is potential for abuse due to euphoria and drug-liking effects. The medication should be used with caution in patients with a history of substance abuse.

Drug Interactions

Concurrent use with serotonergic drugs (SSRIs, SNRIs, TCAs, MAOIs, triptans) may increase the risk of serotonin syndrome. P-glycoprotein or BCRP inhibitors may increase lasmiditan exposure; clinical significance is unknown. Heart rate-lowering drugs may have additive effects on heart rate reduction (lasmiditan can cause mild heart rate decrease). No significant CYP450 interactions have been identified.

Special Populations

There are no adequate data on lasmiditan use during pregnancy. Animal studies showed developmental toxicity at high doses. Use during pregnancy only if clearly needed. It is unknown whether lasmiditan is excreted in human breast milk. Safety and efficacy have not been established in pediatric patients. Clinical trials included patients up to 82 years; elderly patients may be more susceptible to CNS effects. No dose adjustment is needed for mild, moderate, or severe renal impairment. No dose adjustment is needed for mild to moderate hepatic impairment; lasmiditan has not been studied in severe hepatic impairment.