Reyvow

Limitations of Use

REYVOW is not indicated for the preventive treatment of migraine.

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to REYVOW during pregnancy. Healthcare providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-833-464-4724. To learn more please call or visit www.migrainepregnancyregistry.com.

Risk Summary

There are no adequate data on the developmental risk associated with the use of REYVOW 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 (see Data).

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

Disease-Associated Maternal and/or Embryo/Fetal Risk

Published data have suggested that women with migraine may be at increased risk for preeclampsia and gestational hypertension during pregnancy.

Data

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.

Lactation

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

In controlled clinical trials, dizziness occurred more frequently in patients who were at least 65 years of age (19% for REYVOW, 2% for placebo) compared to patients who were less than 65 years of age (14% for REYVOW, 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 [see Adverse Reactions ]. Clinical studies of REYVOW 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 REYVOW was observed in elderly subjects [see Clinical Pharmacology ]. 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.

Hepatic Impairment

No dosage adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B). REYVOW has not been studied in patients with severe hepatic impairment (Child-Pugh C) and its use in these patients is not recommended.

Driving Impairment

REYVOW may cause significant driving impairment. In a driving study, administration of single 50 mg, 100 mg, or 200 mg doses of REYVOW significantly impaired subjects' ability to drive [see Clinical Studies ]. Additionally, more sleepiness was reported at 8 hours following a single dose of REYVOW 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 REYVOW. Patients who cannot follow this advice should not take REYVOW. 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 REYVOW.

Central Nervous System Depression

REYVOW may cause central nervous system (CNS) depression, including dizziness and sedation [see Adverse Reactions ].

Because of the potential for REYVOW to cause sedation, other cognitive and/or neuropsychiatric adverse reactions, and driving impairment, REYVOW should be used with caution if used in combination with alcohol or other CNS depressants [see Drug Interactions ]. Patients should be warned against driving and other activities requiring complete mental alertness for at least 8 hours after REYVOW is taken [see Warnings and Precautions ].

Serotonin Syndrome

In clinical trials, reactions consistent with serotonin syndrome were reported in patients treated with REYVOW who were not taking any other drugs associated with serotonin syndrome. Serotonin syndrome may also occur with REYVOW 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 REYVOW 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.