AHFS Class:

• Selective Serotonin Agonists 28:32.28

Generic Name(s):

• Lasmiditan Hemisuccinate

Chemical Name:

• 2,4,6-Trifluoro- N -[6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl]benzamide hemisuccinate

Molecular Formula:

• C₁₉H₁₈F₃N₃O₂•½[C₄H₆O₄]

Lasmiditan hemisuccinate is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1F receptors (“ditan”).1,7,8,9,10,11,12,13,17,18

Acute Treatment of Migraine

Lasmiditan hemisuccinate is used for the acute treatment of migraine with or without aura in adults.1,2,3,11,14 The drug is not indicated for prophylaxis of migraine.1

Clinical Experience

Efficacy of lasmiditan for the acute treatment of migraine attacks was established in 2 randomized, double-blind, placebo-controlled studies, SAMURAI (NCT02439320) and SPARTAN (NCT02605174), in adults with a history of migraine with or without aura, according to the International Classification of Headache Disorders (ICHD-II) criteria.1,2,3,19 The mean age of patients in these studies was 42 years (range: 18-81 years); the majority of patients were female (84%) and white (78%).1 Patients with known coronary artery disease, clinically important arrhythmias, or uncontrolled hypertension were excluded from the SAMURAI study but were included in the SPARTAN study.2,3 Concomitant preventive antimigraine medication was used in 22% of the patients at baseline.1 Patients were allowed to take a rescue drug 2 hours after administration of the study drug if needed; however, opioids, barbiturates, serotonin type 1 (5-HT₁) selective receptor agonists (triptans), and ergotamine derivatives were not allowed within 24 hours of study drug administration.1,2,3

In these studies, substantially more patients receiving lasmiditan at all doses evaluated (50 mg, 100 mg, or 200 mg) achieved headache pain freedom at 2 hours compared with patients receiving placebo.1,2,3 In addition, substantially more patients who received lasmiditan compared with placebo achieved freedom from their self-identified most bothersome symptom (photophobia, phonophobia, or nausea) at 2 hours.1,2,3 The most bothersome symptom was photophobia, nausea, and phonophobia in 54, 24, and 22% of patients, respectively.1

In the SAMURAI study, 2231 patients were randomized to receive a single dose of lasmiditan 100 mg, lasmiditan 200 mg, or placebo within 4 hours of onset of a moderate or severe acute migraine attack.1,2 Results showed that 31.8, 28.3, or 15.3% of patients were headache pain free at 2 hours after receiving lasmiditan 200 mg, 100 mg, or placebo, respectively.1 Freedom from the most bothersome symptom at 2 hours was reported in 40.7, 41.2, or 29.6% of patients receiving lasmiditan 200 mg, 100 mg, or placebo, respectively.1 The treatment effect of lasmiditan was observed as early as 1-1.5 hours postdose.2,18

In the SPARTAN study, 3005 patients were randomized to receive a single dose of lasmiditan (50 mg, 100 mg, or 200 mg) or placebo within 4 hours of onset of a moderate or severe acute migraine attack.1,3 In this study, 38.8, 31.4, 28.3, or 21% of patients were headache pain free at 2 hours after receiving lasmiditan 200 mg, lasmiditan 100 mg, lasmiditan 50 mg, or placebo, respectively.1,3 Freedom from the most bothersome symptom was reported in 48.7, 44, 40.8, or 33.2% of patients receiving lasmiditan 200 mg, lasmiditan 100 mg, lasmiditan 50 mg, or placebo, respectively.1,3 The treatment effect of lasmiditan was observed as early as 1-2 hours postdose.3,18

Interim results of a long-term, randomized, open-label extension of the 2 pivotal single-attack trials suggest consistent safety and efficacy over time with long-term intermittent use of lasmiditan (100 mg or 200 mg administered within 4 hours of pain onset); median duration of treatment at the time of interim analysis was 288 days.11,14 A high rate of discontinuation (51.7% at the time of analysis) was observed; reasons for discontinuance included patient request and adverse events in 21.8 and 12.8% of patients, respectively.11,14

Clinical Perspective

The American Headache Society (AHS) recommends lasmiditan as an option for the acute treatment of migraine attacks in patients who have contraindications to the use of 5-HT₁ selective receptor agonists (triptans) or who have failed to respond to or tolerate at least 2 oral triptans.15 AHS suggests that if lasmiditan is used, at least 2 migraine attacks should be treated before assessing the drug's efficacy and tolerability for the patient.15 Similar to calcitonin gene-related peptide (CGRP) antagonists (gepants), another group of antimigraine agents with a novel mechanism of action, lasmiditan lacks the vasoconstrictive activity of triptans and ergotamine derivatives and may provide a particular benefit in patients with cardiovascular contraindications to triptans.15 Additional long-term studies are needed to confirm the safety of repeated use of lasmiditan in patients with cardiovascular risk factors, particularly in those with a history of coronary artery disease or stroke.3,13

Some clinicians suggest that lasmiditan appears to have similar efficacy to oral triptans,9,12,13,16 and possibly greater efficacy compared with gepants,16 for the acute treatment of migraine; however, controlled trials are needed to determine relative efficacy compared with other therapies for acute treatment of migraine.8,17

General

Patient Monitoring

• Consider monitoring heart rate following administration of lasmiditan in patients in whom a decrease in heart rate may not be tolerated, including patients taking other drugs that can decrease heart rate.1
• Consider monitoring blood pressure following administration of lasmiditan in patients in whom an increase in blood pressure may not be tolerated.1

Administration

Lasmiditan is administered orally without regard to food.1 Tablets should be swallowed whole and should not be split, crushed, or chewed.1

Because of the risk of CNS sedation, including driving impairment, patients should not drive or operate machinery for at least 8 hours after taking lasmiditan; the drug should not be taken if the patient cannot wait at least 8 hours between dosing and performing hazardous activities that require mental alertness (e.g., driving, operating machinery).1

Dosage

Dosage of lasmiditan hemisuccinate is expressed in terms of lasmiditan.1

Acute Treatment of Migraine Attacks

For the acute treatment of migraine attacks with or without aura in adults, a single oral lasmiditan dose of 50, 100, or 200 mg is given as needed.1 No more than one dose should be taken in a 24-hour period; a second dose of lasmiditan for the same migraine attack has not been shown to be effective.1,6 The safety of treating an average of >4 migraine attacks in a 30-day period has not been established.1

Special Populations

Hepatic Impairment

Dosage adjustments are not necessary in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.1 Lasmiditan has not been studied in patients with severe (Child-Pugh class C) hepatic impairment; use in such patients is not recommended.1

Renal Impairment

The manufacturer makes no specific dosage recommendations for patients with renal impairment.1

Geriatric Patients

Dosage selection for geriatric patients should be cautious, usually starting at the low end of the dosage range, and reflect the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy in such patients.1

Contraindications

• Manufacturer states none known.1

Warnings/Precautions

Driving Impairment

Lasmiditan may cause marked driving impairment.1 In a driving study, a significant, dose-dependent impairment in driving ability was observed 90 minutes after administration of lasmiditan in patients receiving a single 50-, 100-, or 200-mg dose of the drug.1

Lasmiditan should not be taken unless the patient can wait at least 8 hours before performing hazardous activities that require mental alertness (e.g., driving, operating machinery).1 Patients may not be able to assess their driving competence or degree of impairment after taking the drug.1

CNS Depression

Lasmiditan may cause CNS depression (e.g., dizziness, sedation).1

Because of the potential for lasmiditan to cause sedation, other adverse cognitive and/or neuropsychiatric reactions, and driving impairment, caution is advised when other CNS depressants, including alcohol, are used concomitantly with lasmiditan.1

Serotonin Syndrome

Reactions consistent with serotonin syndrome have been reported in patients receiving lasmiditan, including those not receiving other drugs associated with this adverse effect.1 Serotonin syndrome also may occur in patients receiving lasmiditan concomitantly with serotonergic drugs (e.g., selective serotonin-reuptake inhibitors [SSRIs], selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs), tricyclic antidepressants, MAO inhibitors).1 Symptoms of serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).1 Onset of symptoms typically occurs within minutes to hours of receiving a new or increased dosage of a serotonergic drug.1 If serotonin syndrome is suspected, discontinue lasmiditan.1

Medication Overuse Headache

Excessive use of acute migraine drugs (e.g., 5-HT₁ receptor agonists [triptans], ergotamine derivatives, opioids, or a combination of these drugs on a regular basis for ≥10 days per month) may result in exacerbation of headache.1 Medication overuse headache may present as migraine-like daily headaches or a marked increase in the frequency of migraine attacks.1 Detoxification, including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often include transient worsening of headaches), may be necessary.1

Abuse Potential and Dependence

In controlled clinical studies of lasmiditan, euphoria and hallucination were reported in approximately 1% of patients receiving the drug and more commonly than with placebo.1

In a human abuse potential study in recreational polydrug users, “drug liking” scores in patients receiving single doses of lasmiditan (100, 200, or 400 mg) were higher than in those receiving placebo, and lower (for the 100 and 200 mg doses) than in patients receiving alprazolam (2 mg).1,5 The incidence of euphoric mood (ranging from 43-49%) was similar in patients receiving lasmiditan 200 mg, lasmiditan 400 mg, or alprazolam 2 mg.1,5 A feeling of relaxation was reported more frequently with alprazolam than lasmiditan (23 versus 7-11%, respectively).1,5

Physical withdrawal symptoms were not observed following abrupt cessation after administration of 7 daily doses of lasmiditan 200 or 400 mg in healthy subjects.1

Lasmiditan is subject to control as a schedule V (C-V) drug.1

Clinicians should carefully evaluate patients for a history of drug abuse and monitor patients for signs of lasmiditan misuse or abuse.1

Cardiovascular Effects

A decrease in heart rate of 5-10 beats per minute has been observed in patients receiving lasmiditan.1 Consider heart rate monitoring following administration of lasmiditan in patients in whom a decrease in heart rate may not be tolerated, including patients receiving other drugs that can decrease heart rate.1

Lasmiditan administration may be associated with a transient increase in blood pressure; this effect may be more pronounced in geriatric individuals.1 In healthy volunteers, increases from baseline in ambulatory systolic and diastolic blood pressure of approximately 2-3 mm Hg were observed 1 hour after administration of a single 200-mg dose of lasmiditan compared with a mean increase of up to 1 mm Hg in those receiving placebo.1 In healthy volunteers >65 years of age, a mean increase from baseline in ambulatory systolic blood pressure of 7 mm Hg was observed 1 hour after administration of lasmiditan 200 mg compared with a mean increase of 4 mm Hg in those receiving placebo.1 Consider monitoring blood pressure following administration of lasmiditan in patients in whom an increase in blood pressure may not be tolerated.1

Unlike serotonin type 1 [5-HT₁] selective receptor agonists (triptans), lasmiditan has not been shown to have vasoconstrictive effects;4,8,10,12,13,17,18 however, lasmiditan has not been well studied to date in patients with ischemic cardiac disease.1

Hypersensitivity

Hypersensitivity reactions (e.g., angioedema, rash, photosensitivity) have been reported in patients receiving lasmiditan.1 If a serious or severe hypersensitivity reaction occurs, discontinue lasmiditan and initiate appropriate therapy.1

Specific Populations

Pregnancy

There are no adequate data to date on the developmental risk associated with the use of lasmiditan in pregnant females.1 Animal studies in pregnant rats and rabbits administered lasmiditan orally at dosages resulting in systemic exposures greater (rats) or less (rabbits) than the exposure from the maximum recommended human dosage throughout gestation demonstrated adverse effects on development (increased incidences of fetal abnormalities, increased embryofetal and offspring mortality, decreased fetal body weight).1

The estimated rates of major birth defects and miscarriage among deliveries to females with migraine (2.2-2.9 and 17%, respectively) are similar to rates reported in females without migraine.1 Clinicians should be aware that published data suggest that females with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy.1

To monitor pregnancy outcomes in women who have been exposed to lasmiditan during pregnancy, a pregnancy registry has been established.1 Information about the registry can be obtained by calling 833-464-4724 or visiting [Web].1

Lactation

Lasmiditan (and/or its metabolites) is distributed into milk in rats at concentrations about 3 times greater than in maternal plasma.1 It is not known whether lasmiditan is distributed into human milk.1 The effects of the drug on the breast-fed infant or on milk production also are unknown.1 The manufacturer states that the developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for lasmiditan and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1

Pediatric Use

The manufacturer states that the safety and efficacy of lasmiditan have not been established in pediatric patients.1

Geriatric Use

In controlled clinical trials of lasmiditan, dizziness was reported more frequently in patients ≥65 years of age compared with younger adults (19 versus 14%, respectively).1 In addition, greater increases in systolic blood pressure were observed in patients ≥65 years of age compared with younger adults following administration of the drug.1

The pharmacokinetic profile of lasmiditan in geriatric patients is similar to that in younger adults.1 Clinical trials of lasmiditan did not include sufficient numbers of patients ≥65 years of age to determine whether there are any efficacy differences compared with younger adults.1

Hepatic Impairment

Lasmiditan has not been studied in patients with severe hepatic impairment (Child-Pugh class C); use in such patients is not recommended.1

Renal Impairment

Renal impairment is not expected to affect the pharmacokinetics of lasmiditan.1

Common Adverse Effects

Adverse effects occurring in ≥5% of adults receiving lasmiditan and occurring more frequently than with placebo include dizziness, fatigue, paresthesia, and sedation.1

Lasmiditan is metabolized primarily by non-cytochrome P-450 (CYP) enzymes.1 The drug is a substrate for the efflux transporter P-glycoprotein (P-gp).1

In vitro studies indicate that lasmiditan is an inhibitor of CYP2D6, but not of other CYP isoenzymes.1

In vitro studies indicate that lasmiditan inhibits P-gp, breast cancer resistance protein (BCRP), organic cation transporter 1 (OCT1), multidrug and toxic compound extrusion protein (MATE) 1, and MATE2K.1

Drugs Affecting Hepatic Microsomal Enzymes

Clinically important pharmacokinetic interactions with drugs that inhibit or induce CYP enzymes not expected.1

Drugs Metabolized by Hepatic Microsomal Enzymes

Clinically important pharmacokinetic interactions with drugs metabolized by CYP enzymes not expected.1

Caffeine

Concomitant administration of lasmiditan with the CYP1A2 substrate caffeine did not substantially alter the pharmacokinetics of caffeine.1

Dextromethorphan

Pharmacokinetic modeling suggests that lasmiditan is unlikely to substantially affect exposure to dextromethorphan (CYP2D6 substrate).1

Midazolam

Concomitant administration of lasmiditan with the CYP3A substrate midazolam did not substantially alter the pharmacokinetics of midazolam.1

Tolbutamide

Concomitant administration of lasmiditan with the CYP2C9 substrate tolbutamide did not substantially alter the pharmacokinetics of tolbutamide.1

Drugs Transported by Breast Cancer Resistance Protein

Increased exposure to drugs that are substrates of BCRP is expected when used concomitantly with lasmiditan.1 Lasmiditan should not be used concomitantly with BCRP substrates.1

Drugs Transported by P-glycoprotein

Increased exposure to drugs that are substrates of the P-gp transport system is expected when used concomitantly with lasmiditan.1 Lasmiditan should not be used concomitantly with P-gp substrates.1

CNS Depressants

Additive adverse CNS effects can occur when lasmiditan is used concomitantly with alcohol or other CNS depressants.1 Caution is advised if lasmiditan is used concomitantly with alcohol or other CNS depressants.1

Drugs that Lower Heart Rate

Additive heart rate lowering effects can occur when lasmiditan is used concomitantly with other drugs that can lower heart rate.1,4 Administration of a single oral 200-mg dose of lasmiditan with propranolol (80 mg twice daily) resulted in an additional decrease in heart rate of 5 beats per minute compared with administration of propranolol alone, for a mean maximum decrease of 19 beats per minute.1,4 Lasmiditan should be used with caution in patients receiving other drugs that lower heart rate, particularly when bradycardic effects of this magnitude may be a concern.1

Concomitant administration of lasmiditan with propranolol did not result in a substantial pharmacokinetic interaction.1,4

Serotonergic Drugs

Risk of serotonin syndrome may be increased when lasmiditan is used concomitantly with other serotonergic drugs (e.g., dextromethorphan, selective serotonin-reuptake inhibitors [SSRIs], selective serotonin- and norepinephrine-reuptake inhibitors [SNRIs], tricyclic antidepressants, MAO inhibitors, trazodone) or herbal supplements (e.g., St. John's wort [ Hypericum perforatum ]).1 Lasmiditan should be used with caution in patients receiving other serotonergic agents.1

Concomitant administration of lasmiditan with sumatriptan (an OCT1 substrate) did not substantially alter the pharmacokinetics of sumatriptan.1

Topiramate

Concomitant administration of lasmiditan with topiramate did not substantially alter exposure to topiramate.1

Description

Lasmiditan hemisuccinate, a selective serotonin (5-hydroxytryptamine; 5-HT) type 1F receptor agonist (“ditan” or neurally acting antimigraine agent [NAAMA]), is an antimigraine agent.1,7,8,9,10,11,17,18 Lasmiditan differs structurally from 5-HT₁ selective receptor agonists (triptans);7,8,10,12,13,18 the indole structure of triptans, which closely resembles the 5-HT receptor, is replaced in lasmiditan by a pyridinoyl-piperidine scaffold.10,12,13 Unlike triptans, which bind to 5-HT_1B and 5-HT_1D receptors, and with varying affinity to 5-HT_1F receptors,2,8,10,12,13,16 lasmiditan has high affinity and selectivity for the 5-HT_1F receptor;1,2,3,4,7,11,12,13,18 lasmiditan has shown over 440-fold higher selectivity and affinity for the 5-HT_1F receptor compared with the 5-HT_1A, 5-HT_1B, and 5-HT_1D receptors and low cross-reactivity with other members of the 5-HT receptor family.7,11,13,18 5-HT_1F receptors are not involved in vasoconstriction.7,9 Lasmiditan has shown no binding affinity across a range of receptors known to regulate vasoconstriction7,13 (including post-synaptic 5-HT_1B receptors found on vascular smooth muscle, activation of which is thought to result in vasoconstrictive properties of the triptans),2,8,10,11,12 and no evidence of vasoconstriction was observed in preclinical studies of lasmiditan.4,8,10,12,13

The mechanisms involved in the pathogenesis of migraine are not fully understood, and the precise mechanism of action of lasmiditan in the management of migraine has yet to be established.1,3,8,10,18 Lasmiditan penetrates the blood-brain barrier and is postulated to have both central and peripheral effects.4,5,7,8,11,12,14,17 5-HT_1F receptors have been identified in various locations in the trigeminovascular system, which is thought to be involved in the pathogenesis of migraine,7,10,11,12,13,17 most notably peripherally in the trigeminal ganglion or trigeminal afferents and centrally in the trigeminal nucleus caudalis;7,8,9,10,12 5-HT_1F receptors also are present in the cortex and cerebellum.8 5-HT_1F receptors are located on peripheral and central sensory trigeminal neurons and appear to function by hyperpolarizing nerve terminals and thereby inhibiting trigeminal impulses.8,12 Lasmiditan may exert its therapeutic effects in acute migraine by decreasing neuropeptide release (e.g., calcitonin gene-related peptide [CGRP], substance P) and inhibiting pain pathways, including those in the trigeminal nerve and ganglion;4,7,9,10,11,12,13 modulation of dural neurogenic inflammation, possibly through blockade of plasma protein extravasation, also may play a role.9,10,12,13,18 Significant improvement in pain freedom has been observed within 1-1.5 or 2 hours following administration of lasmiditan.2,3,18

Following oral administration, lasmiditan is rapidly absorbed, with peak plasma concentrations achieved in approximately 1.8 hours.1 Oral bioavailability of the drug has been reported to be about 40%.12 Pharmacokinetics of the drug are linear following oral administration as a liquid at doses of 25-400 mg.12 The pharmacokinetics of the drug are similar when administered during an acute migraine attack compared with during the interictal period.1 Higher peak concentrations and AUC and delayed absorption have been observed following administration of lasmiditan with a high-fat meal compared with fasting administration.1,7,12,13 These differences are not expected to be clinically important, and the drug was administered without regard to meals in controlled clinical trials.1 Plasma protein binding of lasmiditan is about 55-60% and is not concentration-dependent at plasma concentrations of 15-500 ng/mL.1 Lasmiditan penetrates the blood-brain barrier.4,5,7,8,11,12,14

Lasmiditan is eliminated primarily by hepatic and nonhepatic metabolism via predominantly non-cytochrome P-450 (CYP) enzymes, with ketone reduction as the major pathway.1,4 The drug also is metabolized to M7 via oxidation on the piperidine ring and to M18 via a combination of M7 and M8 pathways; these metabolites are considered pharmacologically inactive.1 Renal excretion plays a minor role in clearance of lasmiditan, with about 3% of a dose excreted unchanged in urine.1 The metabolite S-M8 comprised approximately 66% of the dose in urine, with the majority recovered within 48 hours after oral administration.1 The mean elimination half-life of lasmiditan is approximately 5.7 hours.1 Accumulation of the drug has not been observed with daily dosing.1 Age, sex, race, ethnicity, and body weight do not appear to substantially affect the pharmacokinetics of the drug.1 Increased AUC (26%) and peak plasma concentrations (21%) have been reported in subjects ≥65 years of age compared with adults ≤45 years of a however, these differences are not considered clinically important.1 Increases in AUC (18%) and peak plasma concentrations (13%) have been reported in subjects with severe renal impairment (estimated GFR <30 mL/minute per 1.73 m²) compared with those with normal renal function; these differences are not considered clinically important.1 Increases in AUC and peak plasma concentrations of 11 and 19%, respectively, in patients with mild hepatic impairment (Child-Pugh class A) and of 35 and 33%, respectively, in patients with moderate hepatic impairment (Child-Pugh class B) have been reported; these differences are not considered clinically important.1 The pharmacokinetics of lasmiditan have not been studied in subjects with severe hepatic impairment (Child-Pugh class C).1

Advice to Patients

• Importance of instructing patients to read the manufacturer's information for patients (medication guide).1
• Advise patients to swallow tablets whole; do not split, crush, or chew.1
• Importance of advising patients to avoid potentially dangerous activities requiring complete mental alertness (e.g., driving, operating machinery) for ≥8 hours after taking lasmiditan.1 Importance of not taking drug if unable to comply.1 Importance of informing patients of possible inability to assess own driving competence or degree of impairment after taking the drug.1
• Risk of dizziness or sedation; importance of exercising caution if taking lasmiditan concomitantly with alcohol or other CNS depressants.1
• Importance of informing patients of risk of serotonin syndrome, particularly with concurrent use of lasmiditan and serotonergic drugs (e.g., SSRIs, SNRIs, tricyclic antidepressants, MAO inhibitors).1
• Overuse (i.e., ≥10 days per month) of drugs used to treat acute migraine attacks may exacerbate headaches; importance of recording headache frequency and drug use (e.g., by keeping a headache diary).1
• Risk of hypersensitivity reaction; importance of seeking immediate medical attention if symptoms of serious or severe hypersensitivity reaction occur.1
• Importance of advising patients of lasmiditan's abuse potential and importance of keeping drug secure.1
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
• Importance of females informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to lasmiditan during pregnancy.1
• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Additional Information

Overview^® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Lilly USA. Reyvow^® (lasmiditan hemisuccinate) tablets prescribing information. Indianapolis, IN; 2022 Jan. [Web]

2. Kuca B, Silberstein SD, Wietecha L et al. Lasmiditan is an effective acute treatment for migraine. Neurology . 2018; 91:e2222-32. [PubMed 30446595]

3. Goadsby PJ, Wietecha LA, Dennehy EB et al. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain . 2019; 142:1894-904. [PubMed 31132795]

4. Tsai M, Case M, Ardayfio P et al. Effects of lasmiditan on cardiovascular parameters and pharmacokinetics in healthy subjects receiving oral doses of propranolol. Clin Pharmacol Drug Dev . 2020; 0:1-10. [PubMed 31950732]

5. Wilbraham D, Berg PH, Tsai M et al. Abuse potential of lasmiditan: a phase 1, randomized, placebo- and alprazolam-controlled crossover study. J Clin Pharmacol . 2020; 60:495-504 [PubMed 31745991]

6. Loo LS, Plato BM, Turner IM et al. Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: findings from the phase 3 trials (SAMURAI and SPARTAN). BMC Neurol . 2019; 19:191. [PubMed 31409292]

7. Negro A, Koverech A, Martelletti P. Serotonin receptor agonists in the acute treatment of migraine: a review on their therapeutic potential. J Pain Res . 2018; 11:515-26. [PubMed 29563831]

8. Rizzoli PB. Emerging therapeutic options for acute migraine: focus on the potential of lasmiditan. Neuropsychiatr Dis Treat . 2014; 10:547-52. [PubMed 24729708]

9. Do TP, Guo S, Ashina M. Therapeutic novelties in migraine: new drugs, new hope? J Headache Pain . 2019; 20(1):37. [PubMed 30995909]

10. Rubio-Beltrán E, Labastida-Ramírez A, Villalón CM et al. Is selective 5-HT_1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther . 2018; 186:88-97. [PubMed 29352859]

11. Brandes JL, Klise S, Krege JH et al. Interim results of a prospective, randomized, open-label phase 3 study of the long-term safety and efficacy of migraine (the GLADIATOR study). Cephalalgia . 2019; 39:1343-1357 [PubMed 31433669]

12. Vila-Pueyo M. Targeted 5-HT_1F therapies for migraine. Neurotherapeutics . 2018; 15:291-303. [PubMed 29488143]

13. Oswald JC, Schuster NM. Lasmiditan for the treatment of acute migraine: a review and potential role in clinical practice. J Pain Res . 2018; 11:2221-7. [PubMed 30323656]

14. Lipton RB, Lombard L, Ruff DD et al. Trajectory of migraine-related disability following long-term treatment with lasmiditan: results of the GLADIATOR study. J Headache Pain . 2020; 21:20. [PubMed 32093628]

15. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache . 2019; 59:1-18. [PubMed 30536394]

16. Goadsby PJ. Primary headache disorders: five new things. Neurol Clin Pract . 2019; 9:233-240. [PubMed 31341711]

17. Anon. Lasmiditan (Reyvow) and ubrogepant (Ubrelvy) for acute treatment of migraine. Med Lett Drugs Ther . 2020; 62:35-9.

18. Lamb YN. Lasmiditan: first approval. Drugs . 2019; 79:1989-96. [PubMed 31749059]

19. U.S. National Library of Medicine. ClinicalTrials.gov. Accessed 2020 Sep 23. Available at http:clinicaltrials.gov.