A focus on new drugs for the acute treatment of migraine

Sara Crystal, MD, is a neurologist and headache specialist and currently serves as the Medical Director of Cove, a digital health program that connects patients to specialized migraine care.

When discussing the general principles of acute treatment, Crystal keeps this in mind: “While not all patients need prescription migraine preventive therapy, all patients should be offered a acute treatment specific to migraine. By the time someone seeks care, they have undoubtedly tried over-the-counter medications and found them to be ineffective.

In terms of treatment goals for acute migraine, Crystal aims to:

  • Pain free in 2 hours
  • No recurrence of pain within 24 hours
  • Minimal need for rescue or repeat dosing
  • Tolerable side effects
  • Ability to resume normal function
  • Decrease in emergency room visits for migraine

Crystal noted that triptans are generally considered first-line therapy in patients without contraindications, with the caveat that patients with the following conditions should not take triptans due to their muscle-constricting effects: vessels:

  • Uncontrolled hypertension (blood pressure >140/90)
  • Cardiovascular disease or risk factors
  • Cerebrovascular disease or stroke
  • History of ischemic colitis
  • Use with caution in patients over 50 years of age due to cardiovascular risk factors
  • Use with caution in patients with Raynaud’s phenomenon

There are 7 different oral triptans available:

  • Naratriptan (Amerge)
  • Almotriptan (Axert)
  • Frovatriptan (Frova)
  • Sumatriptan (Imitrex)
  • Rizatriptan (Maxalt)
  • Eletriptan (Relpax)
  • Zolmitriptan (Zomig)

Patients who experience significant nausea or vomiting, or those who do not respond to oral triptans, may benefit from non-oral triptans, including nasal sprays and injectables. To make this decision, Crystal assesses the patient’s response to the acute medication after 2 different attacks. If the drug is ineffective, she considers another class of drugs; another delivery route can also be considered.

The risk of serotonin syndrome is minimal, Crystal said, referring to this 2018 study published in JAMA Neurology1. Although serotonin syndrome is an important point of counseling, the study concluded that “patients with coexisting affective disorders and migraine do not need to forego managing one condition to treat the other.”1

Other medications that Crystal considers part of a patient’s treatment include:

  • Nonsteroidal anti-inflammatory drugs (NSAIDs), as add-on treatment to triptans
  • Anti-nausea drugs such as ondansetron or metoclopramide for patients with nausea during migraine attacks

According to Crystal, the gepant class of drugs has several advantages over triptans. These small-molecule CGRP receptor antagonists have “better tolerability/side-effect profiles, and they don’t cause vasoconstriction, so they should be safer in patients with stable cardiovascular disease,” she said. stated, but cautioned that there are drug interactions to consider.

For the following medications, always check drug interactions before filling a prescription:

Gepant: Rimegepant orally disintegrating tablet (Nurtec ODT)2.3

  • Rimegepant is a calcitonin gene-linked peptide receptor antagonist indicated for the acute treatment of migraine with or without aura in adults. It is also approved for the prevention of episodic migraine.
  • The dosage of rimegepant in acute treatment is 1 tablet of 75 mg, placed on or under the tongue, for 1 dose as needed. The maximum dose is 75 mg in 24 hours. The safety of using more than 18 doses in 30 days has not been studied.
  • The most common side effects of rimegepant are nausea, abdominal pain, and indigestion.

Drugs interactions :

  • Avoid co-administration of strong CYP3A4 inhibitors, strong and moderate CYP3A inducers and P-gp or BCRP inhibitors.
  • Avoid a second dose of rimegepant within 48 hours when taking a moderate CYP3A4 inhibitor (including grapefruit juice).

Information Note: Allergic reactions can be serious and may occur several days after taking a dose of rimegepant.

Gepant: Ubrogepant (Ubrelvy)4.5

Ubrogepant is a CGRP receptor antagonist indicated for the acute treatment of migraine with or without aura in adults.

The dosage is 50 mg or 100 mg orally as needed. A second dose can be taken at least 2 hours after the first dose if needed, and the maximum dose is 200 mg in 24 hours.

The most common side effects are nausea, drowsiness and dry mouth.

Drugs interactions :

  • Avoid co-administration of strong CYP3A4 inducers.
  • See prescribing information for dosage adjustments for other interacting drugs.

Tip: The patient should not take a second dose of Ubrelvy within 24 hours of consuming grapefruit or grapefruit juice.

Serotonin (5-HT) receptor agonist 1F: Lasmiditan (Reyvow)6.7

  • Lasmiditan is a serotonin (5-HT) 1F receptor agonist. It is indicated for the acute treatment of migraine with or without aura in adults.
  • Lasmiditan is a Schedule V controlled substance. Patients should be advised to avoid alcohol when taking lasmiditan, as alcohol increases the risk of CNS and respiratory depression as well as psychomotor disturbances.
  • The dosage of Lasmiditan is 50 mg, 100 mg or 200 mg orally 1 time as needed. No more than one dose should be taken in 24 hours. The lasmiditan tablet should be swallowed whole and not split, crushed or chewed.
  • The most common side effects are dizziness, sedation, fatigue, paresthesia, nausea and vomiting, muscle weakness, hypersensitivity, increased blood pressure and decreased heart rate.

Drugs interactions :

Lasmiditan can decrease heart rate and should be used with caution in patients taking medications that lower heart rate, such as propranolol.

Avoid concurrent use of drugs that are P-gp or BCRP substrates, as lasmiditan can inhibit both.

Note: Lasmiditan should only be taken if the patient has at least 8 hours before driving or using machines. A second dose of lasmiditan is not effective for the same migraine attack.

There are several non-invasive neuromodulation devices on the market, Crystal added. “These provide a drug-free option and can be used in conjunction with medication,” she said, noting that Nerivio – a smartphone-controlled wearable device – is approved for the acute treatment of migraine.

Be sure to check out the other three parts of this series: Part 1: Non-prescription measures to manage migraine; Part 2: Prescription preventive therapies; and Part 3: An Introduction to CGRP Antagonists

The references

  1. Orlova Y, Rizzoli P, Loder E. Coprescribing combination of triptan antimigraine drugs and selective serotonin reuptake inhibitors or selective norepinephrine reuptake inhibitor antidepressants with serotonin syndrome. JAMA Neurol. 2018;75(5):566–572. doi:10.1001/jamaneurol.2017.5144
  2. Nurtec ODT. DailyMed. Available at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9ef08e09-1098-35cc-e053-2a95a90a3e1d. Accessed on 19/12/2021.
  3. Nurtec ODT. Epocrates. Available at https://online.epocrates.com/drugs/916710/Nurtec-ODT/Monograph. Accessed on 19/12/2021.
  4. Ubrelvy. DailyMed. Available at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fd9f9458-fd96-4688-be3f-f77b3d1af6ab. Accessed on 19/12/2021.
  5. Ubrelvy. Epocrates. Available at https://online.epocrates.com/drugs/907010/Ubrelvy/Monograph. Accessed on 19/12/2021.
  6. Revise. DailyMed. Available at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aea3358c-ff41-4490-9e6d-c7bf7b3de13f&audience=professional. Accessed on 19/12/2021.
  7. Review. Epocrates. Available at https://online.epocrates.com/drugs/910910/Reyvow/Monograph. Accessed on 19/12/2021.

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