lasmiditan

Brand: Reyvow

Prototype Drug
Drug Class: serotonin 5-HT1F receptor agonist (ditan)
Drug Family: antimigraine
Subclass: first-in-class ditan
Organ Systems: cns

Mechanism of Action

Highly selective 5-HT1F receptor agonist; unlike triptans, it has no 5-HT1B activity (no vasoconstriction) and no clinically significant 5-HT1D activity. 5-HT1F receptors are expressed on trigeminal neurons; inhibiting trigeminal activation aborts migraine without vascular effects.

5-HT1F receptor

Indications

  • acute migraine with or without aura

Contraindications

  • no absolute contraindications related to cardiovascular disease (unlike triptans)

Adverse Effects

Common

  • dizziness
  • somnolence
  • paresthesia
  • fatigue
  • nausea

Serious

  • CNS depression (driving impairment for 8 hours after dose)
  • serotonin syndrome (theoretical with serotonergic drugs)
  • Schedule V controlled substance (abuse potential)

Pharmacokinetics (ADME)

Absorption oral; bioavailability ~40%; food delays but does not reduce absorption
Distribution protein binding ~55-60%
Metabolism hepatic; multiple CYP and non-CYP pathways
Excretion renal (~74%)
Half-life 5.7 hours
Onset 1-2 hours
Peak 1.8 hours
Duration 24 hours (once per migraine attack)
Protein Binding 55-60%
Vd not well characterized

Drug Interactions

Drug / Agent Mechanism Severity
P-glycoprotein inhibitors increase lasmiditan exposure moderate
serotonergic agents theoretical serotonin syndrome risk moderate
CNS depressants additive CNS depression; driving impairment moderate

Nursing Considerations

  1. Patients must not drive or operate heavy machinery for at least 8 hours after lasmiditan administration due to CNS impairment risk.
  2. Does not cause vasoconstriction; can be used in migraine patients with cardiovascular contraindications to triptans.
  3. Schedule V controlled substance; diversion and abuse screening per PDMP as with other controlled substances.
  4. Maximum 1 dose per 24 hours; do not use more than 1 lasmiditan dose per migraine attack.

Clinical Pearls

  • Lasmiditan represents the first mechanistically distinct acute migraine therapy in decades; its lack of vasoconstriction via 5-HT1F selectivity opens triptan-type acute treatment to patients with cardiovascular contraindications.
  • The drivability restriction (8 hours) significantly affects patient lifestyle compared to triptans; this pharmacodynamic property must be incorporated into patient counseling and medication selection.

Safety Profile

Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.