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Gepants: Highly-tolerable migraine-specific medications for migraine attacks
Gepants: Highly-tolerable migraine-specific medications for migraine attacks
Migraine attacks often require treatments designed specifically for migraine biology—not just general pain medications.
Gepants are a newer class of migraine-specific medications that can stop migraine attacks by blocking CGRP (calcitonin gene-related peptide), one of the key chemicals involved in migraine pain signaling.
Unlike older migraine medications, gepants:
Do not constrict blood vessels
Are generally very well tolerated
May be used in people who cannot take triptans
Have a low risk of medication-overuse headache
The two gepants currently available in Canada for acute migraine treatment are:
At the Ottawa Headache Centre, we use gepant as part of a structured acute treatment plan. They are not used indiscriminantly, but rather precisely based on each person's migraine pattern.
The specialists at the Ottawa Headache Centre have developed medication handouts on gepants: feel free to use them and share with your doctor.
If you are a doctor looking for a gepant prescribing guide take a look at our guide under Clinical Guidance.
What are gepants and how do they work?
What are gepants and how do they work?
Gepants are migraine medications designed specifically to block CGRP - a neuropeptide involved in migraine.
Gepants are small molecule CGRP antagonists that are taken orally.
CGRP is a key molecule involved in migraine that contributes to:
Pain transmission
Sensitization of the trigeminal nerve
Neurogenic inflammation
Worsening of migraine attacks
During migraine attacks, CGRP levels rise. Gepants work by blocking CGRP activity and calming the migraine pathway.
Reducing activation of migraine pain pathways
Reducing activation of migraine pain pathways
Gepants reduce the pain that is associated from activation of the trigeminal nerve.
Decrease frequency of attacks and their duration
Decrease frequency of attacks and their duration
Gepants reduce migraine attack duration and frequency, and do not seem to be associated with medication-overuse headache.
Reducing associated migraine symptoms
Reducing associated migraine symptoms
Not only do they aim to stop migraine pain, gepants also reduce sensitivity to light, sensitivity to sound, and nausea.
Using gepants for migraine attacks
Using gepants for migraine attacks
At the Ottawa Headache Centre gepants are generally used for migraine attacks when:
they are used as part of a comprehensive migraine treatment strategy
triptans have been ineffective
triptans are poorly tolerated
triptans are contraindicated or unsafe
there is a high frequency of migraine attacks needing frequent medications
alongside the treatment of medication-overuse headache.
How to use gepants effectively and safely
How to use gepants effectively and safely
Like all acute migraine treatments, gepants work best when taken early.
A few practical principles matter:
1. Treat
early
1. Treat
early
Migraine is like a fire—it is much easier to put out a spark than a forest fire.
The window: Take your medication within 30 to 60 minutes of the onset of pain.
2. Choose
correctly
2. Choose
correctly
Choose based on the speed and severity of the attack:
Mild: Start with your simple analgesic.
Moderate to severe: Use your migraine specific agent (triptan or gepant).
A fast, explosive attack may call for a faster route such as nasal or subcutaneous (i.e., injectable) treatment. A slower attack with frequent recurrence may be better served by a longer-acting triptan.
3. Combine
or repeat
3. Combine
or repeat
Most acute treatments require a "wait and see" period before a second dose is safe or effective.
The 2-hour rule: For most triptans and (some) gepants, if the pain has not improved you may take a second dose 2 hours after the first.
4. Treat
safely
4. Treat
safely
To prevent medication-overuse headache (MOH), use your medications safely.
Simple analgesics: 14 days per month
Triptans: 9 days per month
Choosing the right gepant to treat migraine attacks
Choosing the right gepant to treat migraine attacks
In Canada there are two available gepants to treat acute migraine attacks: rimegepant (Nurtec®) and ubrogepant (Ubrelvy®). They block CGRP and have the same effect on calming the migraine pathways.
Nurtec®: An orally dissolvable gepant
Nurtec®: An orally dissolvable gepant
Nurtec® is available as a once daily 75 mg oral dissolvable tablet. It dissolves on the tongue and o water required.
It is also approved as a preventive treatment outside Canada.
Ubrelvy®: An oral tablet gepant
Ubrelvy®: An oral tablet gepant
Ubrelvy® was the first acute gepant available in Canada. It is available as 50 mg or 100 mg oral tablets taken at the onset of a migraine.
The dose can be repeated 2 hours later if needed.
Side effects and safety of gepants
Side effects and safety of gepants
Gepants are generally well tolerated.
Possible side effects of gepants include:
Fatigue
Nausea
Dry mouth
Drowsiness
Constipation (more common with high frequency use)
Who should avoid taking gepants for migraine attacks?
Who should avoid taking gepants for migraine attacks?
While gepants are generally well tolerated and side effects are uncommon, they should be avoided by some people including:
During pregnancy
Those with severe liver disease
Those with renal failure
When there are major drug interactions
During breastfeeding or lactation they may be used after an informed discussion with a doctor. If you are breastfeeding, we can help discuss the safety data available with you.
How do gepants compare with triptans in treating migraine attacks?
How do gepants compare with triptans in treating migraine attacks?
Both gepants and triptans are migraine-specific treatments, but they work differently.
Gepants
Gepants
As compared with triptans, gepants:
Block CGRP
Prevent vasodilation
May be generally less effective
May be generally better tolerated
Do not appear to cause medication-overuse headache
Have fewer cardiovascular restrictions
Triptans
Triptans
As compared with gepants, triptans:
Activate serotonin receptors
Result in vasoconstriction
May be generally more effective
May generally produce more side effects
Associated with medication-overuse headache if using more than 9 days per month
Have more cardiovascular restrictions
While these features tend to be trends, it is often unpredictable which medication class may work better for each person.
At the Ottawa Headache Centre we regularly use both gepants and triptans - often in combination - to provide an effective, safe, and individualized treatment plan.
What are alternatives to gepants to treat acute migraine attacks
What are alternatives to gepants to treat acute migraine attacks
Simple analgesics
Simple analgesics
Oral simple analgesics are best used for mild to moderate attacks.
Common options: Ibuprofen (Advil®/Motrin®), naproxen (Aleve®), acetaminophen (Tylenol®).
Limit: Do not exceed 14 days per month.
Triptans act on serotonin receptors in the brain. This helps calm overactive migraine pain pathways, reduce migraine-related inflammation, restore normal nerve signaling.
They are migraine-specific medications rather than general painkillers.
Common options: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan.
Limit: Do not exceed 9 days per month.
Ergotamine
Ergotamine
A highly specialized migraine treatment used in select cases. Ergot medications act on multiple brain and vascular pathways to stop severe attacks, particularly when other migraine-specific options have failed.
Nerve blocks
Nerve blocks
Targeted local anesthetic injections used to calm irritated pain pathways in the head and neck. Nerve blocks can provide rapid relief during prolonged attacks or help break cycles of frequent migraine.
Complementary adjuncts
Complementary adjuncts
Additional treatments that support migraine control alongside primary medications. These may include anti-nausea medications (such as metoclopramide), neuromodulation devices, selected supplements, and lifestyle strategies aimed at improving attack response and overall migraine stability.
Treating your migraine attacks: what you need to know
Treating your migraine attacks: what you need to know
Needing more than rescue medication?
Needing more than rescue medication?
If your acute medications are ineffective, or you are consistently using them close to their safe limit, you may benefit from migraine preventives.
Learn more about:
Ask for a referral from your doctor and we would be happy to explore a migraine preventive strategy that works for you.
Common questions about gepants
Common questions about gepants
What are safer acute options for treating migraine in pregnancy?
What are safer acute options for treating migraine in pregnancy?
Gepants should be avoided in pregnancy.
Safer options include:
Non-medication strategies first
Acetaminophen is first-line
NSAIDs only in limited situations (avoid in third trimester)
Sumatriptan is the best-studied triptan in pregnancy and may be used when needed
Craniofacial nerve blocks (e.g. occipital nerve blocks) are a safe option in pregnancy
We can help you decide on the acute strategies that are right for you.
What about migraine during breastfeeding and lactation?
What about migraine during breastfeeding and lactation?
Gepants have yet to be proven safe in breastfeeding and lactation, although some specialists prescribe them with caution. We can help you choose and time doses safely.
Most migraine medications are compatible with breastfeeding and lactation.
Of the triptans, sumatriptan and eletriptan carry the most evidence for use.
Can gepants be combined with other migraine treatments?
Can gepants be combined with other migraine treatments?
Yes.
Depending on the individual plan, gepants may be combined with:
NSAIDs
Neuromodulation devices
Next steps
Next steps
Effective migraine care is not just about stopping individual attacks — it’s about building a strategy that works over time.
If your current acute treatment is inconsistent, poorly tolerated, or needed frequently, speak with your doctor about a referral to the Ottawa Headache Centre.
We would be pleased to help you develop a personalized plan designed for stability, safety, and long-term control.
Disclaimer
Disclaimer
This material is provided for educational purposes and does not replace independent clinical judgment or institutional protocols. Management decisions remain the responsibility of the treating clinician.
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