Tthe FDA ( U.S. Food and Drug Administration ) has approved Reyvow ( Lasmiditan ) an oral medication for the acute treatment of migraine, with or without aura, in adults.
Reyvow has a unique mechanism of action and is the first and only FDA-approved medicine in a new class of acute treatment for migraine ( serotonin (5-HT)1F receptor agonists ).
As with other medicines with central nervous system ( CNS ) activity, the FDA required abuse potential studies for Reyvow. Abuse potential refers to the likelihood that abuse will occur with a particular drug product or substance with CNS activity.
Consistent with the FDA's guidance, Lilly conducted a human abuse potential assessment; as part of that assessment, therapeutic doses of Lasmiditan were associated with less drug liking when compared to Alprazolam, but more than placebo.
The New Drug Application ( NDA ) for Reyvow included data from two phase 3 single-attack studies ( SAMURAI and SPARTAN ), which evaluated the safety and efficacy of Lasmiditan for the acute treatment of migraine in adults.
Both studies met the efficacy endpoints of pain freedom and freedom from most bothersome symptom ( patient selected from nausea, sensitivity to light, or sensitivity to sound ) at two hours following administration of Lasmiditan in comparison to placebo.
Treatment emergent adverse events were generally mild to moderate and the most frequent included dizziness, fatigue, paresthesia ( tingling or numbing sensation on the skin ), sedation ( sleepiness or drowsiness ), nausea and/or vomiting and muscle weakness.
The Reyvow phase 3 development program, including the open-label GLADIATOR study, involved more than 4,000 patients and the treatment of more than 20,000 migraine attacks.
Reyvow is a new oral treatment that binds to 5-HT1F receptors with high affinity and is approved by the FDA for the acute treatment of migraine, with or without aura, in adults. Its therapeutic effects are presumably mediated by agonist effects at this receptor; however, the precise mechanism is unknown.
Reyvow is not indicated for preventive treatment of migraine. Once available, Reyvow can be prescribed to patients in oral doses of 50 mg, 100 mg, and 200 mg as needed.
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.
Additionally, more sleepiness was reported at 8 hours 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.
Reyvow may cause central nervous system ( CNS ) depression, including dizziness and sedation. 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.
Patients should be warned against driving and other activities requiring complete mental alertness for at least 8 hours after Reyvow is taken.
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.
Overuse of acute migraine drugs ( e.g., ergotamines, triptans, opioids, or a combination of 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.
The most common adverse reactions associated with Reyvow ( more than 2% and greater than placebo in clinical studies ) were dizziness, fatigue, paresthesia, sedation, nausea and/or vomiting, and muscle weakness.
In a human abuse potential study in recreational poly-drug users ( n=58 ), single oral therapeutic doses ( 100 mg and 200 mg ) and a supratherapeutic dose ( 400 mg ) of Reyvow were compared to Alprazolam ( 2 mg ) ( C-IV ) and placebo.
With all doses of Reyvow, subjects reported statistically significantly higher drug liking scores than placebo, indicating that Reyvow has abuse potential.
Subjects who received Reyvow reported statistically significantly lower drug liking scores than Alprazolam.
Euphoric mood occurred to a similar extent with Reyvow 200 mg, Reyvow 400 mg, and Alprazolam 2 mg ( 43-49% ).
A feeling of relaxation was noted in more subjects on Alprazolam ( 22.6% ) than with any dose of Reyvow ( 7-11% ).
Phase 2 and 3 studies have indicated that, at therapeutic doses, Reyvow produces adverse events of euphoria and hallucinations to a greater extent than placebo. However, these events occur at a low frequency ( about 1% of patients ).
Physical withdrawal was not observed in healthy subjects following abrupt cessation after 7 daily doses of Lasmiditan 200 mg or 400 mg. ( Xagena )
Source: Eli Lilly, 2019