Reyvow

REYVOW^® is indicated for the acute treatment of migraine with or without aura in adults.

The recommended dose of REYVOW is 50 mg, 100 mg, or 200 mg taken orally, as needed. No more than one dose should be taken in 24 hours, and REYVOW should not be taken unless the patient can wait at least 8 hours between dosing and driving or operating machinery

A second dose of REYVOW has not been shown to be effective for the same migraine attack.

The safety of treating an average of more than 4 migraine attacks in a 30-day period has not been established.

REYVOW may be taken with or without food.

Administer tablets whole; do not split, crush, or chew.

REYVOW (lasmiditan) tablets are available in two strengths:

• 50 mg tablet: light gray, oval, film coated, tablets with “L-50” debossed on one side and “4312” on the other
• 100 mg tablet: light purple, oval, film coated, tablets with “L-100” debossed on one side and “4491” on the other

• Based on animal data, may cause fetal harm. (
  8.1 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.
  )
• REYVOW has not been studied in patients with severe hepatic impairment (Child-Pugh C) and its use in these patients is not recommended. (
  8.6 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: Advise patients not to drive or operate machinery until at least 8 hours after taking each dose of REYVOW. Patients who cannot follow this advice should not take REYVOW. Patients may not be able to assess their own driving competence and the degree of impairment caused by REYVOW. (
  5.1 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 (CNS) Depression: REYVOW may cause CNS depression and should be used with caution if used in combination with alcohol or other CNS depressants. (
  5.2 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 ]

  .
  ,
  7.1 CNS Depressants

  Concomitant administration of REYVOW and alcohol or other CNS depressant drugs has not been evaluated in clinical studies. Because of the potential of REYVOW to cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions, REYVOW should be used with caution if used in combination with alcohol or other CNS depressants

  [see Warnings and Precautions ]

  .
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• Serotonin Syndrome: Reactions consistent with serotonin syndrome were reported in patients treated with REYVOW. Discontinue REYVOW if symptoms of serotonin syndrome occur. (
  5.3 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.
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• Medication Overuse Headache: Detoxification may be necessary. (
  5.4 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.
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