RAYVOW: Uses, Dosage & Side Effects

What Is RAYVOW and What Is It Used For?

RAYVOW contains the active substance lasmiditan (as lasmiditan succinate), which belongs to a new class of acute migraine medications called ditans. Lasmiditan is a selective serotonin 5-HT1F receptor agonist, meaning it specifically activates the 5-HT1F subtype of the serotonin receptor family. This targeted action distinguishes it fundamentally from triptans, which act on the 5-HT1B and 5-HT1D receptor subtypes and produce their therapeutic effect partly through constriction of intracranial blood vessels. By selectively engaging the 5-HT1F receptor, lasmiditan achieves migraine pain relief through a purely neuronal mechanism without any direct vasoconstrictive activity.

The 5-HT1F receptor is expressed on neurons within the trigeminal ganglion, the trigeminal nucleus caudalis in the brainstem, and the thalamus – all key structures within the trigeminovascular pain pathway that underlies migraine headache. During a migraine attack, activation of the trigeminovascular system leads to the release of pro-inflammatory neuropeptides (including calcitonin gene-related peptide, substance P, and neurokinin A) from trigeminal sensory nerve endings. This release promotes neurogenic inflammation around meningeal blood vessels, peripheral sensitization of trigeminal afferents, and ultimately the transmission of pain signals to higher cortical centers. Lasmiditan is thought to interrupt this cascade by activating 5-HT1F receptors on trigeminal neurons, which inhibits the release of these neuropeptides and reduces the transmission of pain signals through the trigeminovascular pathway.

In addition to its peripheral effects on trigeminal nerve endings, lasmiditan crosses the blood-brain barrier and may exert central effects within the brainstem and thalamus. Activation of 5-HT1F receptors in the trigeminal nucleus caudalis and thalamic relay nuclei may help to suppress the central processing of migraine pain signals. This dual peripheral and central mechanism of action may contribute to the ability of lasmiditan to relieve not only headache pain but also the associated symptoms of migraine, including nausea, photophobia (sensitivity to light), and phonophobia (sensitivity to sound).

RAYVOW is indicated for the acute treatment of the headache phase of migraine attacks, with or without aura, in adults. It is specifically designed for on-demand use during an established migraine attack and is not intended for the prevention of migraine or the treatment of other types of headache such as tension-type headache or cluster headache. Clinical trials have demonstrated that RAYVOW can provide meaningful pain relief within 30 minutes of administration in some patients, with statistically significant rates of pain freedom and freedom from most bothersome symptoms at 2 hours post-dose.

The efficacy of RAYVOW was established in two pivotal phase III randomized, double-blind, placebo-controlled clinical trials:

• SAMURAI (Study 3): This trial enrolled 2,231 adults with episodic migraine who treated a single migraine attack. Patients were randomized to receive lasmiditan 100 mg, lasmiditan 200 mg, or placebo. At 2 hours post-dose, significantly more patients in both the lasmiditan 100 mg group (28.2%) and the 200 mg group (32.2%) achieved headache pain freedom compared with placebo (15.3%). Similarly, freedom from the most bothersome symptom (nausea, photophobia, or phonophobia) was significantly higher in both lasmiditan groups.
• SPARTAN (Study 4): This trial enrolled 3,005 adults with episodic migraine and included a 50 mg dose arm. Patients received lasmiditan 50 mg, 100 mg, 200 mg, or placebo. All three lasmiditan doses demonstrated statistically significant superiority over placebo for pain freedom and most bothersome symptom freedom at 2 hours. The 200 mg dose showed the highest response rates, with 38.8% achieving pain freedom versus 21.3% for placebo.

Long-term safety and tolerability were evaluated in the GLADIATOR open-label extension study, in which patients treated up to 12 migraine attacks over approximately 12 months. RAYVOW demonstrated consistent efficacy across multiple attacks, with no evidence of tolerance or diminishing response over time. The safety profile in the long-term study was consistent with that observed in the pivotal trials.

RAYVOW was first approved by the U.S. Food and Drug Administration (FDA) in October 2019, making it the first ditan-class medication to receive regulatory approval anywhere in the world. It was subsequently authorized by the European Medicines Agency (EMA) in April 2022. RAYVOW is classified as a Schedule V controlled substance in the United States due to its potential for abuse, primarily related to its central nervous system depressant effects including feelings of euphoria and relaxation that some users may experience. In the EU, it is available by prescription only but is not classified as a controlled substance.

What Should You Know Before Taking RAYVOW?

Contraindications

The only absolute contraindication to RAYVOW is known hypersensitivity (allergy) to lasmiditan or to any of the excipients in the formulation. If you have ever experienced an allergic reaction to lasmiditan, including rash, swelling of the eyelids, face, or lips, you must not take RAYVOW again. Although severe allergic reactions to lasmiditan are uncommon, they have been reported in post-marketing surveillance and can include symptoms requiring urgent medical attention.

Unlike triptans, RAYVOW does not have specific cardiovascular contraindications. It is not contraindicated in patients with coronary artery disease, cerebrovascular disease, peripheral vascular disease, uncontrolled hypertension, or hemiplegic or basilar migraine. This absence of cardiovascular contraindications reflects the non-vasoconstrictive mechanism of action of lasmiditan and represents one of the key clinical advantages of RAYVOW over triptan-class medications.

Warnings and Precautions

Before starting RAYVOW, discuss the following with your healthcare provider:

• Serotonergic medications: If you are taking any medications that increase serotonin levels – including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAO inhibitors), or triptans – you are at increased risk of serotonin syndrome. This is a rare but potentially life-threatening condition characterized by mental status changes (hallucinations, agitation, coma), rapid heartbeat, blood pressure instability, hyperthermia, muscle rigidity, difficulty walking, and gastrointestinal symptoms (nausea, vomiting, diarrhoea). Symptoms may occur within minutes to hours of taking the combination.
• CNS depressants and alcohol: If you take medications that cause drowsiness (such as sleeping pills, benzodiazepines, opioids, or antipsychotics) or if you consume alcohol, the sedative effects of RAYVOW may be enhanced. This is particularly important in the context of the 8-hour driving restriction, as combined sedative effects may persist longer than expected.
• History of substance abuse: If you have ever been dependent on or abused prescription medications, alcohol, or other substances, inform your doctor. Lasmiditan has been classified as a Schedule V controlled substance in the United States due to its potential for abuse, related to subjective feelings of euphoria and relaxation reported by some users in clinical trials. Your doctor will consider this risk when deciding whether RAYVOW is appropriate for you.
• Medication overuse headache: If you use acute migraine medications, including RAYVOW, too frequently over multiple days or weeks, this can lead to medication overuse headache (MOH), a condition in which headaches become more frequent and more difficult to treat. If you notice your headaches worsening or becoming more frequent despite treatment, inform your doctor, as you may need to stop treatment temporarily.

Children and Adolescents

RAYVOW should not be given to patients under 18 years of age. The safety and efficacy of lasmiditan have not been established in children and adolescents, and there is currently no clinical data to support its use in this age group. Migraine in pediatric patients often differs from adult migraine in its presentation and may respond differently to treatment. Healthcare providers should consider age-appropriate treatment alternatives that have been studied in pediatric populations.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking RAYVOW. The effects of lasmiditan on human pregnancy have not been adequately studied. There is limited clinical data on the use of lasmiditan in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant doses. However, as a precaution, RAYVOW is not recommended during pregnancy, and women of childbearing potential who are not using contraception should discuss family planning with their healthcare provider.

It is not known whether lasmiditan passes into human breast milk. Studies in animals have shown that lasmiditan and its metabolites are excreted in milk. As a precaution, you should avoid breastfeeding for 24 hours after treatment with RAYVOW to minimize the amount of lasmiditan transferred to your nursing infant. Discuss with your doctor whether breastfeeding or RAYVOW treatment should take priority in your particular situation.

The effect of lasmiditan on human fertility is not known. Animal fertility studies have not shown adverse effects at clinically relevant doses.

Driving and Operating Machinery

RAYVOW has a pronounced effect on the ability to drive and use machines. In clinical trials, lasmiditan caused significant central nervous system effects including dizziness, drowsiness, fatigue, and impaired coordination in a substantial proportion of patients. Formal driving performance studies have confirmed that lasmiditan impairs driving ability. You must not drive a vehicle, ride a bicycle, or operate machinery for at least 8 hours after taking each dose, even if you feel well enough to do so. If you cannot comply with this restriction, you should not take RAYVOW. This is particularly important for patients who rely on driving as part of their occupation or daily routine.

Important Information About Ingredients

RAYVOW contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is essentially sodium-free. This is relevant for patients on a controlled sodium diet. The other excipients include croscarmellose sodium, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, and pregelatinized starch. The film coating contains polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, and iron oxide pigments (E172). If you have known intolerances or allergies to any of these substances, inform your healthcare provider.

How Does RAYVOW Interact with Other Drugs?

Unlike CGRP monoclonal antibodies, which have minimal drug interaction potential, lasmiditan is a small molecule that is extensively metabolized and can interact with several other medication classes. While lasmiditan is not primarily metabolized by cytochrome P450 (CYP) enzymes – its major metabolic pathway involves non-CYP enzymes including ketone reductase – it does interact with certain drugs through pharmacodynamic mechanisms and has been shown to affect the plasma levels of some concomitant medications. Understanding these interactions is essential for the safe use of RAYVOW, particularly in migraine patients who commonly take multiple medications.

The following table summarizes the key drug interactions to be aware of when using RAYVOW:

Serotonin Syndrome Risk

The most clinically important drug interaction with RAYVOW involves serotonergic medications. Serotonin syndrome is a rare but potentially life-threatening condition that results from excessive serotonergic activity in the central nervous system. It can present as a spectrum ranging from mild symptoms (tremor, diarrhoea, restlessness) to severe, life-threatening manifestations (hyperthermia exceeding 40°C, seizures, coma, cardiovascular collapse). The onset is typically rapid, occurring within minutes to hours of the precipitating event (i.e., taking the drug combination).

Many migraine patients also have comorbid depression or anxiety and take antidepressant medications. In the SAMURAI and SPARTAN clinical trials, approximately 20% of enrolled patients were taking concomitant SSRIs or SNRIs. While the incidence of serotonin syndrome in these trials was very low, the potential risk exists, and patients and physicians should remain vigilant for early signs. If you experience any combination of mental status changes, rapid heartbeat, high body temperature, muscle rigidity, or gastrointestinal distress after taking RAYVOW, seek immediate medical attention.

Heart Rate Effects

Lasmiditan has been associated with a mild decrease in heart rate (averaging 5 to 10 beats per minute) and a slight increase in blood pressure in the hours following dosing. While these changes are generally not clinically significant in most patients, they become relevant when RAYVOW is combined with other drugs that lower heart rate, such as beta-blockers (propranolol, metoprolol, atenolol), non-dihydropyridine calcium channel blockers (verapamil, diltiazem), ivabradine, or digoxin. Propranolol is of particular concern because it is commonly used as a preventive migraine treatment and may be prescribed alongside RAYVOW for acute attacks. Patients taking heart rate–lowering agents should have their pulse monitored and should report any symptoms of excessive bradycardia such as dizziness, lightheadedness, or syncope.

Alcohol

Exercise caution if you consume alcohol when being treated with RAYVOW. Alcohol is itself a central nervous system depressant and may enhance the sedative effects of lasmiditan, including dizziness, drowsiness, and impaired coordination. This is particularly relevant given the mandatory 8-hour driving restriction: combining RAYVOW with alcohol may prolong the period during which you should avoid driving and operating machinery. It is advisable to avoid alcohol consumption entirely on days when you take RAYVOW.

What Is the Correct Dosage of RAYVOW?

Always take RAYVOW exactly as your doctor or pharmacist has instructed. Do not alter your dose without consulting your healthcare provider. RAYVOW should be taken at the onset of the headache phase of a migraine attack. Swallow the tablet whole with a glass of water. RAYVOW can be taken with or without food, though taking it with food may slightly delay the onset of action.

Adults

If the first tablet does not relieve your migraine pain, do not take a second tablet for the same migraine attack, as it is unlikely to provide additional benefit. However, if your migraine completely resolves after the first tablet (50 mg or 100 mg) and then returns later, you may take a second tablet of the same strength, provided that at least 2 hours have elapsed since the first dose. The maximum dose in any 24-hour period is 200 mg.

In clinical trials, the 200 mg dose produced the highest rates of pain freedom at 2 hours (38.8% versus 21.3% for placebo in the SPARTAN trial), but it was also associated with a higher incidence of side effects, particularly dizziness and somnolence. The 100 mg dose offered a favourable balance between efficacy and tolerability and is therefore recommended as the starting dose for most patients.

Missed Dose

RAYVOW is intended for acute on-demand treatment of migraine headache and is only taken when needed during a migraine attack. There is no regular dosing schedule, so the concept of a “missed dose” does not apply. If you forget to take RAYVOW during a migraine attack and the headache has already resolved on its own, there is no need to take a dose retroactively.

Overdose

If you have taken more RAYVOW than prescribed, contact your doctor or nearest emergency department immediately. In the event of an overdose, you may experience intensified versions of the known side effects, including severe dizziness, profound drowsiness, nausea, vomiting, visual disturbances, and impaired coordination. There is no specific antidote for lasmiditan overdose. Treatment is supportive and symptomatic. Given the central nervous system depressant properties of lasmiditan, monitoring of vital signs and observation for signs of respiratory depression are warranted in overdose situations.

What Are the Side Effects of RAYVOW?

Like all medicines, RAYVOW can cause side effects, although not everybody gets them. The frequency and severity of side effects tend to be dose-related, with higher doses (200 mg) generally producing more side effects than lower doses (50 mg). Most side effects are mild to moderate in severity and resolve within a few hours of onset. The central nervous system effects (dizziness, drowsiness, fatigue) are the most commonly reported and are the primary reason for the 8-hour driving restriction.

In clinical trials, most side effects occurred within the first 2 hours of dosing and resolved spontaneously within 4–8 hours. The incidence of dizziness was dose-related: approximately 9% with the 50 mg dose, 15% with the 100 mg dose, and 17% with the 200 mg dose, compared with 3% for placebo. Somnolence was reported by approximately 5–7% of patients across all active doses, compared with 2% for placebo.

Regarding the abuse potential, in clinical studies comparing lasmiditan to alprazolam (a known drug of abuse), lasmiditan produced subjective effects including “drug liking” and “feeling high” that were significantly greater than placebo, though generally less than those produced by alprazolam. This finding led to its classification as a Schedule V controlled substance in the United States. However, in clinical practice and long-term use studies, the rate of misuse, abuse, or dependence has been very low.

The long-term safety data from the GLADIATOR extension study (treating up to 12 attacks over approximately 12 months) showed that the side effect profile remained consistent over time with no new safety signals emerging. There was no evidence of medication overuse headache developing at higher rates compared with other acute migraine treatments, and no evidence of withdrawal symptoms upon discontinuation.

How Should You Store RAYVOW?

Keep RAYVOW out of the sight and reach of children. This is particularly important as RAYVOW is a centrally acting medication that can cause significant drowsiness and other effects if taken accidentally by a child.

Do not use RAYVOW after the expiry date stated on the blister pack and carton after “EXP.” The expiry date refers to the last day of the stated month. There are no special storage conditions required – RAYVOW can be stored at normal room temperature.

Keep the tablets in the original blister pack to protect them from moisture. Do not remove a tablet from the blister pack until you are ready to take it. The unit-dose blister design is specifically intended to facilitate use during a migraine attack, when you may be experiencing symptoms such as nausea, visual disturbances, or cognitive difficulties.

Do not dispose of medicines in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures help to protect the environment.

What Does RAYVOW Contain?

The active substance in RAYVOW is lasmiditan, present in the tablet as lasmiditan succinate. Three tablet strengths are available:

• RAYVOW 50 mg: Each film-coated tablet contains 50 mg of lasmiditan (as succinate). Light grey, oval tablet marked “4312” on one side and “L-50” on the other.
• RAYVOW 100 mg: Each film-coated tablet contains 100 mg of lasmiditan (as succinate). Light purple, oval tablet marked “4491” on one side and “L-100” on the other.
• RAYVOW 200 mg: Each film-coated tablet contains 200 mg of lasmiditan (as succinate). Grey, oval tablet marked “4736” on one side and “L-200” on the other.

The other ingredients (excipients) in the tablet core are: croscarmellose sodium, magnesium stearate, microcrystalline cellulose, sodium lauryl sulfate, and pregelatinized starch.

The film coating of the 50 mg and 200 mg tablets (grey colour blend) contains: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, and black iron oxide (E172). The film coating of the 100 mg tablets (purple colour blend) contains: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, black iron oxide (E172), and red iron oxide (E172).

RAYVOW is available in unit-dose blisters made of polychlorotrifluoroethylene/polyvinyl chloride (PCTFE/PVC) or polyvinyl chloride (PVC) sealed with aluminium foil, in pack sizes of 2, 4, 6, 12, and 16 film-coated tablets. Not all pack sizes may be marketed in all countries.

The marketing authorisation holder is Eli Lilly Nederland B.V., Orteliuslaan 1000, 3528 BD Utrecht, Netherlands. The manufacturer is Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain.