Lasmiditan Hemisuccinate

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

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-HT_1F receptor. 5-HT_1F 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).

The recommended dose of Lasmiditan is 50 mg, 100 mg, or 200 mg taken orally, as needed. No more than one dose should be taken in 24 hours, and Lasmiditan should not be taken unless the patient can wait at least 8 hours between dosing and driving or operating machinery. A second dose of Lasmiditan has not been shown to be effective for the same migraine attack. The safety of treating an average of more than 4 migraine attacks in a 30-day period has not been established. Lasmiditan may be taken with or without food.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Hepatic Impairment: No dosage adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B). In patients with severe hepatic impairment (Child-Pugh C) and its use in these patients is not recommended.

CNS Depressants: Concomitant administration of Lasmiditan and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of Lasmiditan to cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions, Lasmiditan should be used with caution if used in combination with alcohol or other CNS depressants

Serotonergic Drugs: Concomitant administration of Lasmiditan and drugs (e.g., SSRIs, SNRIs, TCAs, MAO inhibitors, trazodone, etc.), over-the-counter medications (e.g., dextromethorphan), or herbal supplements (e.g., St. John’s Wort) that increase serotonin may increase the risk of serotonin syndrome. Use Lasmiditan with caution in patients taking medications that increase serotonin.

Heart Rate Lowering Drugs: Lasmiditan has been associated with a lowering of heart rate. In a drug interaction study, addition of a single 200 mg dose of Lasmiditan to propranolol decreased heart rate by an additional 5 beats per minute compared to propranolol alone, for a mean maximum of 19 beats per minute. Use Lasmiditan with caution in patients taking concomitant medications that lower heart rate if this magnitude of heart rate decrease may pose a concern.

P-gp and Breast Cancer Resistant Protein (BCRP): Lasmiditan inhibits P-gp and BCRP in vitro. Concomitant use of Lasmiditan and drugs that are P-gp or BCRP substrates should be avoided.

The most common side effects of Lasmiditan include: Dizziness, Fatigue, Paresthesia, Sedation.

Pregnancy: There are no adequate data on the developmental risk associated with the use of Lasmiditan in pregnant women. In animal studies, adverse effects on development (increased incidences of fetal abnormalities, increased embryofetal and offspring mortality, decreased fetal body weight) occurred at maternal exposures less than (rabbit) or greater than (rat) those observed clinically.

Lactation: There are no data on the presence of Lasmiditan in human milk, the effects of Lasmiditan on the breastfed infant, or the effects of Lasmiditan on milk production. Excretion of Lasmiditan and/or metabolites into milk, at levels approximately 3 times those in maternal plasma, was observed in lactating rats following oral administration of Lasmiditan.

Driving Impairment: Advise patients not to drive or operate machinery until at least 8 hours after taking each dose of Lasmiditan. Patients who cannot follow this advice should not take Lasmiditan. Patients may not be able to assess their own driving competence and the degree of impairment caused by Lasmiditan.

Central Nervous System (CNS) Depression: Lasmiditan may cause CNS depression and should be used with caution if used in combination with alcohol or other CNS depressants.

Serotonin Syndrome: Reactions consistent with serotonin syndrome were reported in patients treated with Lasmiditan. Discontinue Lasmiditan if symptoms of serotonin syndrome occur.

Medication Overuse Headache: Detoxification may be necessary.

Other drugs for migraine

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.