Key points
- Triptans (such as sumatriptan, rizatriptan and zolmitriptan) treat a migraine attack. They must not be used by people with coronary heart disease, previous stroke or TIA, uncontrolled high blood pressure, peripheral vascular disease, or hemiplegic or basilar migraine.
- Gepants block the CGRP receptor. Ubrogepant and nasal zavegepant treat attacks, atogepant prevents migraine, and rimegepant does both. They are an option for some people who cannot take triptans.
- CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) are monthly or 3-monthly injections or infusions for prevention.
- All CGRP medicines in the US now carry warnings that they can cause new or worsening high blood pressure and Raynaud's phenomenon. The antibodies also carry a warning for constipation with serious complications.
- Taking triptans or other acute migraine medicines on 10 or more days a month can lead to medication-overuse headache. For paracetamol, aspirin or NSAIDs alone, NICE uses 15 or more days a month.
How these medicines work
Triptans are serotonin 5-HT1B/1D receptor agonists. NINDS describes them as acting like serotonin in the brain to relieve symptoms. They treat an attack and are not indicated for prevention. The sumatriptan label advises reconsidering the diagnosis if the first treated attack does not respond.
CGRP medicines act on the calcitonin gene-related peptide pathway. Gepants are tablets or a nasal spray labelled as CGRP receptor antagonists. Among the antibodies, erenumab is labelled as a CGRP receptor antagonist and fremanezumab, galcanezumab and eptinezumab as CGRP antagonists.
Which medicine for which use (US labels)
| Medicine | Use | Usual adult dose | First FDA approval |
|---|---|---|---|
| Sumatriptan tablets | Acute | 25–100 mg; a second dose only if the first helped, at least 2 hours later; maximum 200 mg in 24 hours | Long established |
| Ubrogepant | Acute | 50 or 100 mg; second dose after at least 2 hours; maximum 200 mg in 24 hours | 2019 |
| Rimegepant (dissolving tablet) | Acute and preventive (episodic) | 75 mg as needed (maximum 75 mg a day), or 75 mg every other day for prevention | 2020; prevention added 2021 |
| Zavegepant nasal spray | Acute | 10 mg (one spray) once in 24 hours | 2023 |
| Atogepant | Preventive (episodic and chronic) | 10, 30 or 60 mg daily (60 mg for chronic migraine) | 2021; chronic migraine added 2023 |
| Erenumab | Preventive | 70 or 140 mg injection monthly | 2018 |
| Fremanezumab | Preventive | 225 mg monthly or 675 mg every 3 months | 2018; children 6–17 years (45 kg or more, episodic) added 2025 |
| Galcanezumab | Preventive; also episodic cluster headache | 240 mg loading dose, then 120 mg monthly | 2018 |
| Eptinezumab | Preventive | 100 mg (or 300 mg) by IV infusion every 3 months | 2020 |
A fixed combination of meloxicam and rizatriptan was FDA-approved for acute migraine in adults in January 2025. It carries the NSAID boxed warning for serious heart, stroke and stomach bleeding risks.
Approvals and reimbursement differ by country. In England, NICE CG150 recommends a triptan plus an NSAID or paracetamol first. It reserves oral gepants for acute treatment in adults in whom at least 2 triptans did not work well enough or are unsuitable, and NSAIDs and paracetamol also did not work well enough. CGRP antibodies and atogepant are recommended for prevention only after at least 3 preventive medicines have not worked or are unsuitable, in adults with at least 4 migraine days a month (erenumab at the 140 mg dose only). Rimegepant is recommended for prevention of episodic migraine only (4 to 14 attacks a month), after the same 3 preventive medicines.
Safety: what to check
Triptans
- Do not use with coronary artery disease or coronary vasospasm, Wolff-Parkinson-White syndrome or similar rhythm pathways, previous stroke or TIA, hemiplegic or basilar migraine, peripheral vascular disease, ischaemic bowel disease, uncontrolled hypertension, or severe liver impairment (sumatriptan). The same cardiovascular and hemiplegic or basilar migraine contraindications appear on the labels of the other US triptans.
- Heart checks: people with several cardiovascular risk factors (older age, diabetes, hypertension, smoking, obesity, strong family history) should have a cardiovascular evaluation before the first dose. If the result is negative, the label suggests considering the first dose under medical supervision with an ECG.
- Chest, throat or jaw tightness after a dose is usually not cardiac, but heart attacks and serious arrhythmias have been reported within hours of a dose, sometimes in people without known heart disease. Seek urgent care for chest pain that is severe or does not settle.
- Timing with other medicines: do not take within 24 hours of another triptan or an ergot (ergotamine, dihydroergotamine). Do not take sumatriptan with, or within 2 weeks of, an MAO-A inhibitor.
- Serotonin syndrome: rare but serious, mainly when combined with SSRIs, SNRIs, tricyclic antidepressants or MAO inhibitors. Signs include agitation, hallucinations, fast heartbeat, fever, muscle stiffness, unsteadiness and seizures. Stop the triptan and get urgent help.
- Liver: in mild to moderate liver impairment, the maximum single dose of sumatriptan is 50 mg.
- Breastfeeding: sumatriptan passes into breast milk. Avoiding breastfeeding for 12 hours after a dose minimises infant exposure.
- Older adults: cardiovascular evaluation is recommended when other risk factors are present.
Gepants
- Allergic reactions, including anaphylaxis and breathing difficulty, can occur up to days after a dose.
- Blood pressure and Raynaud's phenomenon: check blood pressure during treatment and report cold, painful or colour-changing fingers or toes.
- Interactions: ubrogepant must not be used with strong CYP3A4 inhibitors (such as ketoconazole, itraconazole or clarithromycin). Its dose is reduced with moderate inhibitors such as fluconazole, verapamil or grapefruit juice. Rimegepant should be avoided with strong CYP3A4 inhibitors and with strong or moderate CYP3A inducers (such as rifampicin). Atogepant is limited to 10 mg daily with strong CYP3A4 inhibitors. Zavegepant should be avoided with OATP1B3 or NTCP inhibitors and inducers. Nasal decongestant sprays should be avoided with zavegepant; if one is unavoidable, use it at least 1 hour after zavegepant.
- Kidneys and liver: rimegepant should be avoided in severe liver impairment and in end-stage kidney disease (creatinine clearance below 15 mL/min). Ubrogepant is limited to 50 mg doses in severe liver or kidney impairment and should be avoided in end-stage kidney disease. Atogepant is limited to 10 mg in severe kidney impairment, and is not recommended for chronic migraine at that stage.
- Frequency: safety has not been established for more than 8 attacks a month treated with ubrogepant or zavegepant, or more than 18 doses a month of rimegepant.
CGRP monoclonal antibodies
- Constipation: constipation with serious complications, sometimes needing hospital care, is a labelled warning for all four antibodies. With erenumab, constipation is one of the most common side effects together with injection-site reactions.
- Hypertension and Raynaud's phenomenon, new or worsening, are class warnings.
- Allergic reactions, including anaphylaxis and angioedema, can occur hours to weeks after a dose. With eptinezumab most occur during the infusion.
Pregnancy and breastfeeding
The gepant and antibody labels state that there are no adequate data on their use in pregnancy, and pregnancy exposure registries are in place. Anyone planning a pregnancy should discuss timing with the prescriber. NICE advises paracetamol first for an attack in pregnancy and specialist advice if prevention is needed.
Frequently asked questions
Can I take a triptan if I have high blood pressure?
Not if it is uncontrolled. If blood pressure is well controlled, a clinician should assess overall cardiovascular risk first. Gepants are an alternative for some people who cannot take triptans, but they also carry a hypertension warning.
Can I take a triptan with an SSRI or SNRI antidepressant?
The combination is not a contraindication on the sumatriptan label, but the label warns about serotonin syndrome, particularly with SSRIs, SNRIs, tricyclics and MAO inhibitors. Know the warning signs and seek urgent help if they appear.
How often can I use acute migraine medicines?
The sumatriptan label warns that using acute migraine drugs such as triptans, ergotamine, opioids or combinations on 10 or more days a month may worsen headache (medication-overuse headache). NICE uses 15 or more days a month for paracetamol, aspirin or NSAIDs alone. Keep a diary of headache days and doses, and ask about prevention if attacks are frequent.
How soon do preventive treatments work?
NICE advises reviewing any preventive treatment 3 to 6 months after starting it, to decide whether it is helping enough to continue. For CGRP medicines, NICE advises stopping after 12 weeks if migraine frequency has not fallen by at least 50% (episodic migraine) or 30% (chronic migraine).
Sources
- US FDA label, sumatriptan tablets. DailyMed
- US FDA labels: rimegepant (Nurtec ODT), ubrogepant (Ubrelvy), atogepant (Qulipta), zavegepant (Zavzpret). rimegepant, ubrogepant, atogepant, zavegepant
- US FDA labels: erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), eptinezumab (Vyepti). erenumab, fremanezumab, galcanezumab, eptinezumab
- US FDA label, meloxicam and rizatriptan (Symbravo). DailyMed
- US FDA. Drugs@FDA approval history. accessdata.fda.gov
- NICE. Headaches in over 12s: diagnosis and management (CG150). nice.org.uk/guidance/cg150
- US National Institute of Neurological Disorders and Stroke. Migraine. ninds.nih.gov
This article is for education and does not replace advice from a doctor or pharmacist who knows the person's history. Approved uses and doses differ between countries; check your local product information.
