LASMIDITAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LASMIDITAN (LASMIDITAN).
Lasmiditan is a selective serotonin 5-HT1F receptor agonist. It acts centrally to inhibit trigeminal nerve activation and release of neuropeptides such as calcitonin gene-related peptide (CGRP), thereby aborting migraine pain without vasoconstriction.
| Metabolism | Primarily metabolized by non-CYP cytosolic enzymes (aldehyde oxidase) and to a lesser extent by CYP2C9, CYP2J2, and CYP3A4; also undergoes glucuronidation by UGT1A1, UGT2B7, and UGT2B17. |
| Excretion | Primarily hepatic metabolism (CYP3A4); <1% excreted unchanged in urine; ~50% fecal elimination mainly as metabolites. |
| Half-life | Terminal elimination half-life: 5.7 hours (range 4-7 hours); supports BID dosing for acute treatment. |
| Protein binding | Approximately 60-70% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | ~50 L (0.7 L/kg in 70 kg adult); moderate tissue distribution, not extensively sequestered. |
| Bioavailability | Oral: ~40% (absolute bioavailability); food does not significantly affect absorption. |
| Onset of Action | Oral: 30-60 minutes to meaningful headache relief; median time to pain freedom ~1.5 hours in clinical trials. |
| Duration of Action | Duration of effect: 8-12 hours; sustained relief for 24 hours in many patients; not intended for prophylactic use. |
50 mg or 100 mg orally as a single dose; may repeat after at least 2 hours if needed, not to exceed 200 mg in 24 hours.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate impairment; not recommended if eGFR < 15 mL/min |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Not recommended; Child-Pugh C: Contraindicated |
| Pediatric use | Not established; safety and efficacy in patients < 18 years not studied |
| Geriatric use | No specific dose adjustment; use with caution due to potential for reduced hepatic/renal function and increased sensitivity |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LASMIDITAN (LASMIDITAN).
| Breastfeeding | No human data on lasmiditan excretion in breast milk. In animal studies, lasmiditan is excreted in rat milk. M/P ratio unknown. Due to potential for adverse effects in nursing infants (e.g., CNS depression), caution is advised. Use only if benefit outweighs risk and monitor infant for drowsiness, poor feeding. |
| Teratogenic Risk | Lasmiditan is contraindicated in pregnancy due to teratogenicity observed in animal studies. In rats and rabbits, fetal malformations and decreased fetal weights occurred at clinically relevant exposures. There are no adequate human data, but based on animal findings, there is a risk of congenital anomalies, particularly during the first trimester. Avoid use in pregnant women or those planning pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 2 weeks of discontinuation of MAOI therapy"]
| Precautions | ["Driving impairment: Lasmiditan can cause dizziness, fatigue, and somnolence; patients should not drive within 8 hours of taking lasmiditan or until they feel fully recovered.","Serotonin syndrome: Risk when used concurrently with serotonergic drugs (e.g., SSRIs, SNRIs, MAOIs, triptans).","CNS depression: May cause lethargy, sedation, and coordination difficulties; caution with alcohol or other CNS depressants.","Hypersensitivity reactions: Angioedema, rash, urticaria have been reported.","Palpitations and tachycardia: Some patients experience increased heart rate."] |
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| Fetal Monitoring | Not indicated if drug is contraindicated. However, if inadvertent exposure during pregnancy, monitor fetal growth and development via ultrasound. Assess for CNS effects in neonates if used near term. |
| Fertility Effects | No human fertility studies. In animal studies, no impairment of fertility was observed at exposures up to 7 times the maximum recommended human dose. However, due to potential hormonal or CNS effects, may theoretically affect reproductive function, but not established. |