lasmiditan (Rx)

>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)

Contraindications

None

Cautions

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

CNS depression (eg, dizziness, sedation) reported

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

Drug interaction overview

• 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

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

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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 (ie, ditans) do not elicit a vasoconstrictive effect

Absorption

Peak plasma time: 1.8 hr

Distribution

Protein bound: 55-60%

Metabolism

Undergoes hepatic and extrahepatic metabolism primarily by non-CYP enzymes

Also metabolized to M7 (oxidation on piperidine ring) and M18 (combination of M7 and M8 pathways); these metabolites are considered pharmacologically inactive

Elimination

Half-life: 5.7 hr

Primarily eliminated via metabolism, with ketone reduction representing the major pathway

Excretion: Urine (3% [unchanged], ~66% [metabolite S-M8])

Oral Administration

May take with or without food

Storage

Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)