Lasmiditan

Indications

Lasmiditan is used for: Acute Migraine

Adult Dose

Acute Migraine Indicated for treatment of acute migraine with or without aura 50 mg, 100 mg, or 200 mg PO PRN Not to exceed more than 1 dose/24 hr Do not take unless patient can wait at least 8 hr between dosing and driving or operating machinery Second dose has not been shown to be effective for the same migraine attack The safety of treating an average of >4 migraine attacks/30 days has not been established Hepatic impairment Mild or moderate (Child-Pugh A or B): No dosage adjustment needed Severe (Child-Pugh C): Not recommended

Child Dose

Renal Dose

Renal impairment No dosage adjustment needed for any degree of renal impairment

Administration

May take with or without food

Contra Indications

Precautions

CNS depression (eg, dizziness, sedation) reported Significant driving impairment may occur; advise patients not to engage in potentially hazardous activities requiring complete mental alertness eg, driving a motor vehicle, operating machinery) for at least 8 hr after each dose; avoid use in patients who are unable to follow this advice Reactions consistent with serotonin syndrome reported; discontinue if symptoms of serotonin syndrome occur Overuse of acute migraine drugs (eg, ergotamines, triptans, opioids, or a combination of these drugs for ≥10 per month) may lead to exacerbation of headache (ie, medication overuse headache); may present as migrainelike daily headaches or as a marked increase in frequency of migraine attacks; detoxification and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary

Pregnancy-Lactation

Pregnancy No adequate data are available on the developmental risk associated with use in pregnant women Clinical considerations Data suggest women with migraine may be at increased risk for preeclampsia and gestational hypertension during pregnancy Animal data 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 in human milk, effects on breastfed infants, or effects on milk production Excretion of lasmiditan and/or metabolites into milk, at levels ~3 times those in maternal plasma, was observed in lactating rats following oral administration

Interactions

Lasmiditan inhibits P-gp and breast cancer-resistant protein (BCRP); avoid coadministration Owing to the potential for sedation, other cognitive and/or neuropsychiatric adverse reactions, and driving impairment, use with caution if used in combination with alcohol or other CNS depressants Coadministration of lasmiditan and drugs (eg, SSRIs, SNRIs, TCAs, MAO inhibitors, trazodone), over-the-counter medications (eg, dextromethorphan), or herbal supplements (eg, St. John’s wort) that increase serotonin may increase the risk of serotonin syndrome; use with caution in patients taking medications that increase serotonin. In a drug interaction study, addition of a single lasmiditan 200-mg dose to propranolol decreased heart rate by an additional 5 bpm compared with propranolol alone, for a mean maximum of 19 bpm; use with caution in patients taking concomitant medications that lower heart rate

Adverse Effects

Side effects of Lasmiditan : >10% Dizziness (9-17%) 1-10% Paresthesia (3-9%) Sedation (6-7%) Fatigue (4-6%) Nausea and/or vomiting (3-4%) Muscle weakness (1-2%) <2% Vertigo Incoordination Lethargy Visual impairment Feeling abnormal Palpitations Anxiety Tremor Restlessness Sleep abnormalities (eg, sleep disturbance, abnormal dreams) Muscle spasm Limb discomfort Cognitive changes Confusion Euphoric mood Chest discomfort Speech abnormalities Dyspnea Hallucinations <1% Hypersensitivity (eg, angioedema, rash, photosensitivity reaction)

Mechanism of Action

Lasmiditan binds with high affinity to the 5-HT1F receptor; it presumably exerts its therapeutic effects for acute migraine through agonist effects at the 5-HT1F receptor; however, the precise mechanism is unknown Serotonin 5-HT1F agonists do not elicit a vasoconstrictive effect