Lasmiditan
Lasmiditan Uses, Dosage, Side Effects, Food Interaction and all others data.
Lasmiditan is an oral medication used in the termination of migraine headaches that was first approved for use in the United States in October 2019.
Traditionally, the triptan class of anti-migraine medications (e.g. sumatriptan) have seen preferential use in the acute treatment of migraines due to their relatively favourable efficacy and safety. Their use is not devoid of concerns, however, and their vasoconstrictive activity can lead to blood pressure lability and other cardiovascular side effects - for this reason, these medications are less suitable for use in patients with pre-existing cardiovascular disorders. Triptans abort migraines via action at several serotonin receptors, including 5-HT1D and 5-HT1B receptors, and activity at the 5-HT1B receptor has been specifically implicated in their vasoconstrictive activity.
Lasmiditan, in contrast, is a highly selective agonist of 5-HT1F receptors, carrying virtually no affinity for other receptors which appear to be largely responsible for the adverse effect profile of its predecessors - in other words, lasmiditan’s selectivity allows for the successful termination of migraines without causing vasoconstriction. Selectivity for 5-HT1F, a lack of vasoconstrictive activity, and the ability to terminate migraines through neuronal inhibition has resulted in the creation of a new class of anti-migraine medications in which lasmiditan is the first and only member: the neurally-acting anti-migraine medications (NAAMAs).
| Trade Name | Lasmiditan |
| Availability | Prescription only |
| Generic | Lasmiditan |
| Lasmiditan Other Names | Lasmiditan |
| Related Drugs | Emgality, Trokendi XR, Reyvow, Ubrelvy, Botox, diclofenac, celecoxib, metoclopramide, sumatriptan, Imitrex |
| Weight | 100mg, 50mg |
| Type | Oral tablet |
| Formula | C19H18F3N3O2 |
| Weight | Average: 377.367 Monoisotopic: 377.135111321 |
| Protein binding | Lasmiditan exhibits a concentration-independent plasma protein binding of approximately 55-60%. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Lasmiditan is an oral 5HT1F agonist used for the acute treatment of migraine headache with or without aura.
Lasmiditan is indicated for the acute treatment of migraine with or without aura in adults.
Lasmiditan is also used to associated treatment for these conditions: Migraine Headache, With or Without Aura
How Lasmiditan works
The acute treatment of migraine headaches has, in the past, been achieved via constriction of cerebral blood vessels, as the acute dilation of these vessels observed during migraines was thought to be the cause of the associated pain. The neurogenic hypothesis of migraine pathophysiology, an alternative to the vascular hypothesis, suggests that cerebral vasodilation is a secondary mechanism in migraine pathogenesis, and that the main contributor to migraine headache pain is the increased pathogenic firing of trigeminal nerve pathways.
While the precise mechanism of action of lasmiditan is unclear, it likely supports this neurogenic hypothesis by exerting its therapeutic effects through potent and selective agonism of the 5-HT1F receptor. 5-HT1F receptors are found in both the central and peripheral nervous system (on the central and peripheral ends of trigeminal neurons) and appear to contribute to hyperpolarization of nerve terminals and inhibition of trigeminal neuronal activity. Lasmiditan's agonism at these receptors may, therefore, inhibit the firing of trigeminal nerves responsible for migraine headache pain.
Lasmiditan has virtually no affinity for other 5-HT receptor subtypes or monoamine receptors (e.g. adrenergic, dopaminergic).
Toxicity
Data regarding overdose of lasmiditan is currently unavailable. Non-clinical murine toxicology studies revealed no evidence of carcinogenesis, mutagenesis, or impairment of fertility at plasma concentrations well above those seen in humans.
Food Interaction
- Avoid alcohol.
- Take with or without food. Co-administration with food slightly alters pharmacokinetics, but not to a clinically significant extent.
Lasmiditan Drug Interaction
Major: almotriptan, citalopramModerate: aripiprazole, zolpidem, diphenhydramine, rimegepant, acetaminophen / oxycodone, topiramate, ubrogepantUnknown: isotretinoin, erenumab, fluticasone / salmeterol, fremanezumab, ethinyl estradiol / levonorgestrel, ipratropium nasal, amoxicillin / clavulanate, onabotulinumtoxinA, cyanocobalamin, cholecalciferol, lisdexamfetamine
Lasmiditan Disease Interaction
Major: hepatic dysfunctionModerate: CNS depression, drug abuse, serotonin syndrome
Volume of Distribution
Lasmiditan has been shown to penetrate the blood-brain barrier.
Elimination Route
Oral absorption of lasmiditan is quick, with a median tmax of 1.8 hours. An open-label study looking at absorption pharmacokinetics found the Cmax and AUC0-t of lasmiditan following oral administration to be 322.8 ± 122.0 ng/mL and 1892 ± 746.0 ng.h/mL, respectively. The oral bioavailability of lasmiditan has been reported as approximately 40%.
Co-administration of lasmiditan with a high-fat meal increased its Cmax and AUC by 22% and 19%, respectively, and delayed Tmax by approximately 1 hour - these differences in absorption are relatively minor and unlikely to be clinically significant. Similarly, severe renal impairment and mild-moderate hepatic impairment were found to increase both AUC and Cmax, but not to a clinically significant extent.
Half Life
The mean elimination half-life of lasmiditan is 5.7 hours.
Elimination Route
Lasmiditan is eliminated primarily via metabolism, with renal excretion accounting for a small fraction of its total elimination. Of the small amount of drug found in the urine post-dose, approximately 66% is comprised of lasmiditan's S-M8 metabolite. Only 3% of an administered dose of lasmiditan was recovered unchanged in the urine, further implying a relatively extensive metabolism of this drug.
Innovators Monograph
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