Class: Selective Serotonin Agonists
Chemical Name: 2,4,6-trifluoro-N-[6-(1-methylpiperidine-4-carbonyl)pyridin-2-yl]benzamide
Molecular Formula: C19H18F3N3O2
CAS Number: 439239-90-4
Lasmiditan succinate is a selective serotonin agonist.
Uses for Lasmiditan
Lasmiditan succinate has the following uses:
Lasmiditan succinate is a serotonin (5-HT) 1F receptor agonist indicated for the acute treatment of migraine with or without aura in adults.
Lasmiditan succinate has the following limitations of use:
Lasmiditan succinate is not indicated for the preventive treatment of migraine.
Lasmiditan Dosage and Administration
Lasmiditan succinate is available in the following dosage form(s) and strength(s):
Tablets: 50 mg, 100 mg.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
The recommended dose is 50 mg, 100 mg, or 200 mg taken orally, as needed.
No more than one dose should be taken in 24 hours.
Cautions for Lasmiditan
Lasmiditan succinate may cause significant driving impairment. In a driving study, administration of single 50 mg, 100 mg, or 200 mg doses of lasmiditan succinate significantly impaired subjects' ability to drive. Additionally, more sleepiness was reported at 8 hours following a single dose of lasmiditan succinate compared to placebo. Advise patients not to engage in potentially hazardous activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery, for at least 8 hours after each dose of lasmiditan succinate. Patients who cannot follow this advice should not take lasmiditan succinate. Prescribers and patients should be aware that patients may not be able to assess their own driving competence and the degree of impairment caused by lasmiditan succinate.
Central Nervous System Depression
Lasmiditan succinate may cause central nervous system (CNS) depression, including dizziness and sedation.
Because of the potential for lasmiditan succinate to cause sedation, other cognitive and/or neuropsychiatric adverse reactions, and driving impairment, lasmiditan succinate should be used with caution if used in combination with alcohol or other CNS depressants. Patients should be warned against driving and other activities requiring complete mental alertness for at least 8 hours after lasmiditan succinate is taken.
In clinical trials, reactions consistent with serotonin syndrome were reported in patients treated with lasmiditan succinate who were not taking any other drugs associated with serotonin syndrome. Serotonin syndrome may also occur with lasmiditan succinate during coadministration with serotonergic drugs [e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors]. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular signs (e.g., hyperreflexia, incoordination), and/or gastrointestinal signs and symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue lasmiditan succinate if serotonin syndrome is suspected.
Medication Overuse Headache
Overuse of acute migraine drugs (e.g., ergotamines, triptans, opioids, or a combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (i.e., medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients including withdrawal of the overused drugs and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
Risk Summary: There are no adequate data on the developmental risk associated with the use of lasmiditan succinate in pregnant women. 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.
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated rates of major birth defects (2.2% to 2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine.
Clinical Considerations: Published data have suggested that women with migraine may be at increased risk for preeclampsia and gestational hypertension during pregnancy.
Animal Data: Oral administration of lasmiditan (0, 100, 175, or 250 mg/kg/day) to pregnant rats throughout organogenesis resulted in increases in skeletal variations at the mid and high doses and reduced fetal body weight at the high dose. The high dose was associated with maternal toxicity. At the no-effect dose (100 mg/kg/day) for adverse effects on embryofetal development in rats, plasma exposure (AUC) was approximately 10 times that in humans at the MRHD.
Oral administration of lasmiditan (0, 50, 75, or 115 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in malformations (skeletal and visceral), increases in skeletal variations and embryofetal mortality, and decreased fetal body weight at the highest dose tested, which was associated with maternal toxicity. Plasma exposure (AUC) at the no-effect dose (75 mg/kg/day) for adverse effects on embryofetal development in rabbits was less than that in humans at the MRHD.
Oral administration of lasmiditan (0, 100, 150, or 225 mg/kg/day) to rats throughout pregnancy and lactation resulted in increases in stillbirth and neonatal mortality at the highest dose tested, which was associated with maternal toxicity and delayed parturition. Plasma exposure (AUC) at the no-effect dose (150 mg/kg/day) for adverse effects on pre- and postnatal development was approximately 16 times that in humans at the MRHD.
Risk Summary: There are no data on the presence of lasmiditan in human milk, the effects of lasmiditan on the breastfed infant, or the effects of lasmiditan on milk production. Excretion of lasmiditan and/or metabolites into milk, at levels approximately 3 times those in maternal plasma, was observed in lactating rats following oral administration of lasmiditan.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for lasmiditan succinate and any potential adverse effects on the breastfed infant from lasmiditan succinate or from the underlying maternal condition.
Safety and effectiveness in pediatric patients have not been established.
In controlled clinical trials, dizziness occurred more frequently in patients who were at least 65 years of age (19% for lasmiditan succinate, 2% for placebo) compared to patients who were less than 65 years of age (14% for lasmiditan succinate, 3% for placebo). A larger increase in systolic blood pressure also occurred in patients 65 years of age and older compared to patients who were less than 65 years of age. Clinical studies of lasmiditan succinate did not include sufficient numbers of subjects aged 65 and over to determine whether there is a difference in efficacy in these patients compared to younger subjects. However, in clinical pharmacology studies, no clinically relevant effect on exposure to lasmiditan succinate was observed in elderly subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
No dosage adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B). Lasmiditan succinate has not been studied in patients with severe hepatic impairment (Child-Pugh C) and its use in these patients is not recommended.
Common Adverse Effects
Most common adverse reactions (≥5% and > placebo) were dizziness, fatigue, paresthesia, and sedation.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Lasmiditan succinate may further lower heart rate when administered with heart rate lowering drugs.
Avoid concomitant use with P-gp and Breast Cancer Resistance Protein (BCRP) substrates.
Mechanism of Action
Lasmiditan binds with high affinity to the 5-HT1F receptor. Lasmiditan presumably exerts its therapeutic effects in the treatment of migraine through agonist effects at the 5-HT1F receptor; however, the precise mechanism is unknown.
Advice to Patients
Advise the patient to read the FDA-approved patient labeling.
Advise patients not to engage in potentially hazardous activities requiring complete mental alertness, such as driving a motor vehicle or operating machinery for at least 8 hours after taking each dose of lasmiditan succinate. Patients who cannot follow this advice should not take lasmiditan succinate. Patients may not be able to assess their own driving competence and the degree of impairment caused by lasmiditan succinate.
Inform patients that lasmiditan succinate may cause dizziness and sedation. Advise patients to use caution if taking lasmiditan succinate in combination with alcohol or other CNS depressants.
Caution patients about the risk of serotonin syndrome with the use of lasmiditan succinate, particularly during combined use with serotonergic medications such as SSRIs, SNRIs, TCAs, or MAO inhibitors.
Medication Overuse Headache
Inform patients that use of drugs to treat migraine attacks for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary).
Advise patients to seek immediate medical attention if they experience any symptoms of serious or severe hypersensitivity reaction.
Abuse and Dependence
Advise patients that lasmiditan succinate is a federally controlled substance because it has the potential to be abused. Advise patients to keep their medication secure.
Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant.
Inform patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed.
AHFSfirstRelease™. For additional information 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 uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Lasmiditan succinate preparations are subject to control under the Federal Controlled Substances Act of 1970 as a schedule V (C-V) drug.
Eli Lilly and Company
Eli Lilly and Company
AHFS Drug Information. © Copyright 2022, Selected Revisions February 24, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.