Lasmiditan

 

 

*Shiv Shankar

*Post-graduate Resident, Lady Hardinge Medical College, New Delhi

 

INTRODUCTION:

Migraine is a common neurological disorder characterized by recurrent attacks of moderate to severe headaches, often accompanied by nausea, vomiting, and sensitivity to light and sound. It is a debilitating condition that significantly impacts quality of life and productivity. Traditional treatments for acute migraine attacks often target the trigemino-vascular system, primarily through serotonin (5-HT) 1B/1D receptor agonists such as triptans. However, these drugs are contraindicated in patients with cardiovascular diseases due to their vasoconstrictive effects, creating a need for alternative therapies. Lasmiditan, a selective 5-HT1F receptor agonist, is a novel therapeutic agent developed to address this gap by providing effective migraine relief without vasoconstrictive action. This novel mechanism aligns with the emerging need for safer alternatives for patients with cardiovascular risks. (1, 4)

MECHANISM OF ACTION:

Lasmiditan selectively targets the 5-HT1F receptor, which is primarily expressed in the central and peripheral nervous systems. Activation of 5-HT1F receptors reduces the release of neuropeptides such as calcitonin gene-related peptide (CGRP), a key mediator of migraine pathophysiology, from trigeminal neurons. This action modulates pain pathways and inhibits neuronal sensitization without causing vasoconstriction, making Lasmiditan a safer option for patients with cardiovascular risk factors. (2, 4)

PHARMACOKINETICS:

Absorption: Lasmiditan has a median time to peak plasma concentration (Tmax) of 1.8 hours.

Distribution: The volume of distribution (Vd) is approximately 111 L, with plasma protein binding of around 55%.

Metabolism: Metabolized primarily through non-CYP-mediated pathways, including ketone reduction, oxidative deamination, and glucuronidation.

Excretion: Lasmiditan’s elimination half-life (T1/2) is approximately 5.7 hours, and it is primarily excreted via the urine, with metabolites accounting for most of the elimination. (3, 4)

INDICATION:

Lasmiditan is indicated for the acute treatment of migraine with or without aura in adults. It is not intended for the preventive treatment of migraine.

DOSING:

– Recommended dose: 50 mg, 100 mg, or 200 mg orally as needed.
– Maximum dose: Do not exceed 200 mg in 24 hours.
– Patients should wait at least 24 hours before taking another dose of Lasmiditan.

DOSAGE MODIFICATIONS:

Renal Impairment

No dosage adjustments are necessary for mild to moderate renal impairment. However, it should be used cautiously in patients with severe renal impairment due to limited data. (3)

Hepatic Impairment

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied). (3)

ADVERSE DRUG REACTIONS:

Common: Dizziness, fatigue, paresthesia, somnolence, and nausea.
Rare but serious: Central nervous system depression, driving impairment, Serotonin syndrome and hypersensitivity reactions. (3,4)

CONTRAINDICATIONS:

Hypersensitivity to Lasmiditan or any of its components.
Use with caution in patients with a history of significant central nervous system depression.

CAUTIONS:

 

Driving Impairment: Patients are advised not to drive or operate machinery for at least 8 hours after taking lasmiditan due to the risk of significant central nervous system effects. (3)

Serotonin Syndrome: Monitor for symptoms of serotonin syndrome, especially if used in conjunction with other serotonergic drugs. (3,4)

 

REFERENCES:

 

  1. Goadsby, P. J., Lipton, R. B., & Ferrari, M. D. (2002). Migraine–current understanding and treatment. The New England Journal of Medicine, 346(4), 257–270.
  2. Kuca B, Silberstein SD, Wietecha L, Berg PH, Dozier G, Lipton RB, et al. Lasmiditan is an effective acute treatment for migraine: A phase 3 randomized study. Neurology [Internet]. 2018;91(24).
  3. Lasmiditan: Drug Information. Available at: https://www.uptodate.com/contents/lasmiditan-drug-information.
  4. Harrison’s Principles of Internal Medicine, 21st Edition. Chapter 430: