Migraine
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).
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.
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.
