Supplements and Zolmitriptan.
Zolmitriptan, sold under the brand names Zomig, Zomig Rapimelt, is an analgesic.
Zolmitriptan shares the triptan contraindications in ischaemic heart disease and uncontrolled hypertension. It is metabolised by the liver enzyme CYP1A2 to an active metabolite, which monoamine oxidase A then breaks down further. MAO-A inhibitors raise its levels, and cimetidine, an older ulcer and reflux medicine, raised zolmitriptan levels by about half and doubled those of the active metabolite. With an MAO-A inhibitor, cimetidine, or a CYP1A2 inhibitor such as fluvoxamine or a quinolone antibiotic like ciprofloxacin, the UK prescribing information recommends a maximum of 5 mg in 24 hours, half the usual 10 mg limit, rather than a contraindication. Among supplements, the ones to flag are serotonergic products (St John's Wort, 5-HTP, rhodiola, tryptophan, saffron, SAMe), for the risk of serotonin syndrome. A case with eletriptan (another triptan), fluoxetine and St John's Wort (Bonetto 2007) met neither of the two standard sets of diagnostic criteria in the American Headache Society's review, which advised vigilance rather than restricting co-prescribing (Evans 2010). 5-HTP is the exception, marked red here with advice not to take it with zolmitriptan, because the body turns it straight into serotonin. Rhodiola also inhibits MAO-A in laboratory studies (van Diermen 2009), which in theory could raise that metabolite.
Below are the 6 documented pairs we have explicitly assessed against Zolmitriptan in the Distil database: 1 red and 5 amber. The pairs cluster around 1 mechanism: Additive serotonergic activity. Every call is cited to either a clinical reference (PMID) or the British National Formulary. Anything not on this list is either still to be assessed or beyond our database scope. The checker beneath surfaces assessments by supplement, and the missing-item form at the bottom of the page routes any uncatalogued supplement into our next curation pass.
Documented interactions
Last reviewed 13 September 2026. Each interaction below lists the evidence its assessment drew on: some rest on studies of the exact pair, others on mechanism evidence, where a citation may support one part of the reasoning rather than the exact combination. The evidence line on each entry says which.
Additive serotonergic activity
Red Does 5-HTP interact with Zolmitriptan?
5-HTP is turned into serotonin in the body, and zolmitriptan is a migraine medicine that acts on serotonin receptors, so taking the two together can cause serotonin syndrome (agitation, sweating, tremor, a racing heart, confusion). Do not take 5-HTP with zolmitriptan; if you already take both, tell the prescriber who manages your zolmitriptan, and do not stop zolmitriptan on your own.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does L-Tryptophan interact with Zolmitriptan?
Tryptophan is the building block your body uses to make serotonin, and zolmitriptan is a serotonin-receptor drug used for migraine. In theory the two together could raise serotonin activity. The American Headache Society reviewed the published cases of serotonin syndrome with triptans and found the evidence too weak to show a link, while still advising vigilance, so be alert to symptoms like agitation, sweating, shivering, tremor, muscle twitching, or a racing heart, and mention the tryptophan to your GP, especially if you also take an antidepressant.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Rhodiola Rosea interact with Zolmitriptan?
Rhodiola has mild effects on serotonin pathways, and zolmitriptan is a serotonin-receptor drug used for migraine, so in theory taking them together could add to that serotonin effect. The American Headache Society reviewed the published cases of serotonin syndrome with triptans and found the evidence too weak to show a link, while still advising vigilance, so it is worth mentioning the rhodiola to your GP, especially if you also take an antidepressant. If you notice restlessness, sweating, tremor, or a racing heart, stop and seek advice.
Evidence: No direct study of this exact combination yet; the caution rests on a plausible mechanism or on reports involving a related medicine.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does SAMe interact with Zolmitriptan?
SAMe has its own antidepressant, serotonin-related activity, and zolmitriptan is a serotonin-receptor drug used for migraine. In theory they could add to each other's serotonin effect. The American Headache Society reviewed the published cases of serotonin syndrome with triptans and found the evidence too weak to show a link, while still advising vigilance, so it is worth telling your GP, and seek help if you notice agitation, sweating, shivering, tremor, or a racing heart, especially if you also take an antidepressant.
Evidence: No direct study of this exact combination yet; the caution rests on a plausible mechanism or on reports involving a related medicine.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does Saffron Extract interact with Zolmitriptan?
Saffron has its own mild antidepressant effect that appears to act on serotonin, and zolmitriptan is a serotonin-receptor drug used for migraine. Taking them together may add to that serotonin effect. The American Headache Society reviewed the published cases of serotonin syndrome with triptans and found the evidence too weak to show a link, while still advising vigilance, so mention the saffron to your GP, especially if you also take an antidepressant, and seek help if you notice agitation, sweating, tremor or a racing heart.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
Amber Does St John's Wort interact with Zolmitriptan?
St John's Wort raises serotonin in its own right, and zolmitriptan is a serotonin-receptor drug for migraine. In theory the two could add up. The American Headache Society reviewed the published cases of serotonin syndrome with triptans and found the evidence too weak to show a link, while still advising vigilance, and the UK prescribing information for zolmitriptan warns that St John's Wort may increase side effects. Be alert to agitation, sweating, tremor, shivering or a racing heart, and mention the St John's Wort to your GP, especially if you also take an antidepressant.
Evidence: Limited human data, from small studies or case reports.
Reviewer-flagged: awaiting clinical-reviewer sign-off.
What this list does not say. Pairs not flagged here are not implicitly safe. They are either not yet in our database, or fall outside our inclusion scope (food-supplement interactions only; for drug-drug interactions, the BNF is authoritative). Use the checker below to surface any supplement, and submit a missing item if you take something we have not catalogued.
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How we grade severity, choose what's in scope, and what we exclude.
Every call on this page is reasoned. We publish the full rubric for severity tiers, the medication inclusion logic, the evidence grades we accept, and what we deliberately leave out. About three thousand words. Worth reading once if you use this tool more than occasionally.
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- what to keep, change or stop from what you already take, plus the order to introduce anything new
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The interaction check is one section of the full report. You also get the reasoning behind each recommendation and the evidence references used.
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