Lasmi

Approved Indication:

• Acute Treatment of Migraine with or without Aura in Adults:
  Lasmiditan Hemisuccinate is indicated for the acute treatment of migraine attacks, with or without aura, in adult patients.

Limitations of Use:

• Not indicated for the preventive treatment of migraine.
• Not indicated for the treatment of cluster headaches.

Off-label/Clinically Accepted Uses:

• Currently, there are no widely recognized off-label indications due to its recent approval and specific targeting mechanism. Clinical research is ongoing.

Route of Administration: Oral

Adults:

• Recommended Dose: 50 mg, 100 mg, or 200 mg orally once, as needed for migraine attacks.
• Maximum Dose: Do not exceed one dose in 24 hours.
• Second Dose: Do not administer a second dose within the same migraine attack due to potential CNS effects and increased side effect risk.

Pediatrics:

• Not approved for use in patients under 18 years of age; safety and efficacy have not been established.

Elderly:

• No dose adjustment needed. However, increased CNS sensitivity (e.g., dizziness, sedation) may occur; monitor accordingly.

Renal Impairment:

• No dose adjustment required for mild to moderate impairment.
• Use with caution in severe renal impairment; clinical data are limited.

Hepatic Impairment:

• No dose adjustment for mild or moderate impairment.
• Use with caution in severe hepatic impairment (Child-Pugh C); data are limited.

Administration Advice:

• Can be taken with or without food.
• Advise patients not to drive or operate machinery for at least 8 hours after taking lasmiditan, even if they feel well.

Lasmiditan is a selective 5-HT1F receptor agonist (a ditan), which targets serotonin 5-HT1F receptors in the trigeminal pathway involved in migraine pathophysiology. Unlike triptans, it does not cause vasoconstriction. It acts centrally to inhibit the release of pro-inflammatory neuropeptides and modulates neuronal excitability in the trigeminal system, thereby relieving migraine symptoms such as headache, photophobia, and nausea.

• Absorption: Rapid absorption; peak plasma concentration (Tmax) achieved in ~1.8 hours.
• Bioavailability: ~40%
• Distribution: Moderate volume of distribution (~180 L)
• Protein Binding: ~55%
• Metabolism: Primarily via non-CYP-mediated pathways, mainly by ketone reduction, followed by conjugation (e.g., glucuronidation).
• Half-life: ~5.7 hours
• Elimination: Mostly excreted in the urine as metabolites.
• Onset of Action: Clinical relief may begin within 1–2 hours.

Pregnancy:

• FDA Pregnancy Category: Not assigned (new labeling format used).
• Current data: Animal studies show no direct teratogenicity at clinical exposure levels, but human data are limited. Use only if clearly needed, especially during the first trimester.

Lactation:

• Unknown if excreted in human milk.
• Animal studies show drug presence in milk; caution is advised.
• Consider risk vs benefit when prescribing to breastfeeding mothers. Monitor the infant for sedation or feeding issues.

• Primary Class: Antimigraine Agent
• Subclass: Selective 5-HT1F Receptor Agonist (Ditan)

• Known hypersensitivity to lasmiditan or any of its components
• Severe hepatic impairment (use caution; not contraindicated but unstudied)
• Use of other serotonergic drugs without monitoring (see interactions)
• Recent driving or hazardous machinery use within 8 hours of dose

• CNS Depression: May cause significant dizziness, sedation, fatigue, and impaired psychomotor performance. Advise no driving for at least 8 hours post-dose.
• Serotonin Syndrome: Risk increases when used with SSRIs, SNRIs, triptans, MAOIs, or other serotonergic agents.
• Drug Abuse Potential: Lasmiditan is classified as a Schedule V controlled substance due to observed euphoria in trials.
• Heart Rate Reduction: Lasmiditan may cause mild decreases in heart rate.
• Elderly Patients: Increased sensitivity to CNS effects may occur.

Common (≥2%):

• Central Nervous System: Dizziness, fatigue, paresthesia, somnolence, sedation, vertigo
• Gastrointestinal: Nausea
• Psychiatric: Euphoria

Less Common:

• Palpitations
• Dry mouth
• Tremor

Serious or Rare:

• Serotonin syndrome (especially with co-administered serotonergic agents)
• Hypersensitivity reactions (rash, pruritus)
• Driving impairment or accidents due to CNS sedation

Timing of Onset: Typically occurs within the first 2 hours of dosing; dose-related.

• CNS Depressants: Additive sedative effects with alcohol, opioids, benzodiazepines, and other CNS depressants.
• Serotonergic Drugs: Increased risk of serotonin syndrome with SSRIs, SNRIs, triptans, MAOIs, and certain TCAs.
• P-gp and BCRP Substrates: Lasmiditan may increase plasma concentrations of these agents; caution advised.
• No significant CYP450 involvement, minimizing CYP-based interactions.

• FDA Approval: Lasmiditan was approved in 2019 for acute migraine treatment based on the SAMURAI and SPARTAN Phase III trials.
• Driving Warning Added: Based on CNS effects, FDA-mandated warning prohibits driving or operating heavy machinery for at least 8 hours post-dose, even if the patient feels well.
• Controlled Substance Classification: As of 2020, lasmiditan is designated as a Schedule V drug by the DEA

• Storage Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C (59°F–86°F).
• Humidity & Light: Store in a dry place, protected from excessive moisture and light.
• Handling: No refrigeration required. Do not crush or split tablets.
• Packaging: Keep in original container until time of use.