Feverfew: Side Effects and Post-Feverfew Syndrome

Feverfew is, by the standards of things people take daily for months, a gentle herb. In the largest trial, side effects possibly related to treatment occurred in 8.4 percent of people on feverfew and 10.2 percent on placebo — that is, slightly less often on the active drug (Diener 2005). The Cochrane review of all six trials found only “mild and transient adverse events, most commonly gastrointestinal complaints and mouth ulcers,” and concluded that feverfew “is not associated with any major safety concerns” (Wider 2015).

That is the honest headline, and it should be said plainly rather than buried under warnings. But short trials in selected patients do not capture everything, and feverfew has four specific issues that a generic “consult your doctor” paragraph would fail you on: the withdrawal reaction, daisy-family allergy, mouth ulcers from chewing the leaf, and its antiplatelet effect. This page covers all four properly, and tells you what to do about each.

Table of Contents

1. The Overall Safety Picture
2. Post-Feverfew Syndrome
3. How to Taper Off
4. Mouth Ulcers and Oral Irritation
5. Asteraceae Allergy and Cross-Reactivity
6. Antiplatelet Effects, Anticoagulants and Surgery
7. Digestive Side Effects
8. Pregnancy, Breastfeeding and Fertility
9. Who Should Not Take Feverfew
10. Drug Interactions
11. When to Stop and Seek Help
12. Key Research Papers
13. Connections

The Overall Safety Picture

What the trial evidence actually supports:

• Diener 2005 — 16 weeks of MIG-99 CO₂ extract at 6.25 mg three times daily in 215 patients in the safety analysis. Treatment-related adverse events: 8.4% on feverfew versus 10.2% on placebo, P = 0.654. No signal at all.
• Pfaffenrath 2002 — 147 patients across three doses, 12 weeks. 35% reported at least one adverse event, but the incidence in the active groups was similar to placebo and no dose-related effect was seen in any safety parameter, including at 18.75 mg three times daily — three times the dose later used in the confirmatory trial.
• Curry 2004 — a phase I dose-escalation trial in cancer patients taking feverfew tablets daily on a 28-day cycle. No significant toxicity, and a maximum tolerated dose was never reached up to 4 mg parthenolide per day.
• Murphy 1988 — eight months of dried leaf in a crossover trial; “no serious side-effects.”
• Cochrane 2015 — across six trials and 561 patients, only mild and transient events, most commonly gastrointestinal complaints and mouth ulcers.

The limits of that evidence matter too. The longest trial ran nine months, so we have essentially no data on multi-year use. Trials exclude pregnant women, children, and people with significant comorbidity. And trial populations use a defined product, whereas real-world users take whatever they bought — a category with documented 160-fold variation in parthenolide delivered (Nelson 2002). Absence of a signal in a 16-week trial of a controlled extract is genuinely reassuring; it is not the same as proof of long-term safety for every product.

Post-Feverfew Syndrome

This is the caution most likely to catch you out, because it happens when you stop, and nothing on a supplement label warns you about it.

What it is: a withdrawal-type cluster reported in people who have taken feverfew regularly for a long period and then stop abruptly. The described features are:

• Rebound headache — migraines returning, often more frequent or more severe than before feverfew was started. This is the dominant feature.
• Anxiety and nervousness
• Insomnia and poor sleep quality
• Fatigue and low energy
• Muscle and joint stiffness or aching, sometimes described as a general achiness
• Nausea in some accounts

Where it comes from. The evidence base is thinner than the confident name suggests, and honesty requires saying so. The primary observation is in the 1985 BMJ trial (Johnson 1985), where 17 people who had been eating fresh feverfew daily were randomised to capsules of freeze-dried feverfew or placebo. Those switched to placebo — i.e. abruptly withdrawn from feverfew without knowing it — had a significant increase in the frequency and severity of headache, nausea and vomiting, “with the emergence of untoward effects during the early months of treatment.” Those untoward effects are the origin of the syndrome. The term “post-feverfew syndrome” itself entered the herbal and review literature from that observation and from subsequent user reports, and it is repeated in review articles (Pareek 2011) rather than resting on a dedicated study.

So the correct status is: a well-described clinical observation from a controlled trial, plus consistent user reports, without a dedicated withdrawal study. That is enough to act on — the intervention (taper instead of stopping) costs nothing and risks nothing — but not enough to quote incidence figures, and you should be sceptical of any source that gives you one.

Why it might happen. Two plausible accounts, neither proven:

1. Nerve resensitisation. Parthenolide acts on the TRPA1 channel of trigeminal nerve endings as a partial agonist that then desensitises them, leaving the pain fibres unresponsive — “defunctionalised” (Materazzi 2013). Remove the compound and those terminals recover their sensitivity. A period of heightened reactivity as they come back online is exactly what you would predict, and it mirrors what happens when capsaicin treatment stops.
2. Unmasking. If feverfew was genuinely suppressing attacks, stopping simply returns you to baseline — which feels much worse by contrast, and can be over-interpreted as a rebound. The 1985 trial cannot fully distinguish these, because the placebo group's deterioration is consistent with both.

Practically, it does not much matter which is right. The advice is the same.

How to Taper Off

If you have been taking feverfew daily for more than a few weeks and want to stop — for any reason, including because you think it is not working — come off it gradually.

A reasonable schedule:

1. Week 1: halve the daily dose. If you take two capsules a day, take one.
2. Week 2: halve again, or move to alternate days.
3. Week 3: stop.
4. If rebound headache, anxiety or stiffness appears at any step, go back up one step, hold for a week or two, and then step down more slowly.

Three practical points that make the difference:

• Taper even if you are stopping because it did not help. If you quit abruptly and rebound follows, you will conclude it was working after all — and you will have learned the wrong thing. A taper gives you a clean answer.
• Plan around surgery. The advice to stop feverfew about two weeks before an operation is about bleeding risk, but that stop should still be a taper. Start the taper three to four weeks before the date so it is complete with two weeks to spare.
• Do not confuse rebound with medication-overuse headache. If you have also been taking acute painkillers on more than 10–15 days a month, that is a separate and very common cause of worsening headache, and it needs its own plan with a clinician.

Mouth Ulcers and Oral Irritation

This is feverfew's signature adverse effect, and it is one of the two most commonly reported in the trial literature (Wider 2015).

What happens: painful aphthous-type ulcers inside the mouth, a sore or inflamed tongue and lips, swelling of the oral tissues, and sometimes a temporary loss or alteration of taste. It usually resolves within days to a couple of weeks after stopping.

Who gets it: overwhelmingly people who chew fresh leaves, which is the traditional method. This makes chemical sense — parthenolide is a reactive electrophile that binds covalently to protein thiol groups, and pressing raw leaf against the mucosa delivers it at high local concentration to a delicate tissue.

What to do:

• Switch to capsules. Dried-leaf or extract capsules swallowed whole bypass the oral mucosa almost entirely, and this is the single most effective fix.
• If ulcers appear on capsules, stop and reassess — it is less expected and may indicate sensitivity.
• Persistent or recurrent mouth ulcers deserve a proper look regardless: they can also reflect iron, B₁₂ or folate deficiency, coeliac disease, or other conditions, and blaming a supplement can delay a real diagnosis. An ulcer that has not healed in three weeks needs medical or dental review.

Asteraceae Allergy and Cross-Reactivity

Feverfew belongs to the Asteraceae (Compositae) family — the daisy family, one of the largest plant families on earth. Family membership matters here because the sesquiterpene lactones that make these plants pharmacologically interesting also make them a leading cause of plant contact allergy in Europe.

Plants that commonly cross-react:

• Ragweed (Ambrosia) — the classic hay-fever cross-reactor
• Chrysanthemum and tansy
• Marigold (Calendula, Tagetes)
• Chamomile — both German and Roman; see Chamomile
• Daisies, yarrow, arnica, echinacea, artichoke, dandelion, lettuce, sunflower and many others

Feverfew is specifically recognised as “an important sensitizer in European Compositae-allergic patients, mainly because of its content of the sesquiterpene lactone parthenolide” (Paulsen 2010). That Danish study makes a further point worth knowing: when feverfew-allergic patients were patch tested with creams containing a parthenolide-depleted feverfew extract, four of seven still reacted — so removing the main sensitiser did not reliably make the extract safe for already-sensitised people. Occupational contact dermatitis to Tanacetum parthenium is also documented (Hashimoto 2019).

What reactions look like: most are contact reactions — itchy rash, redness, swelling where the plant touched skin, sometimes an airborne pattern on the face and neck in gardeners. Systemic allergic reactions to oral feverfew are rare but possible; anything involving lip, tongue or throat swelling, wheeze, or faintness is an emergency.

What to do: if you have known ragweed, chrysanthemum, chamomile or general Compositae allergy, be cautious. If you decide to try feverfew anyway, do so knowingly, start with the smallest dose and stop at the first sign of rash, itching or oral swelling. Avoid handling the fresh plant. Anyone with a history of anaphylaxis to a plant in this family should not take it.

Antiplatelet Effects, Anticoagulants and Surgery

This caution is not theoretical hand-waving imported from a generic herb list — it comes directly from feverfew's own pharmacology, studied in human platelets.

Feverfew extracts inhibit platelet aggregation and the secretion of granules from platelets and white blood cells, blocking serotonin release triggered by ADP, adrenaline, arachidonate, collagen and thromboxane analogues (Heptinstall 1985). The mechanism appears to be neutralisation of sulphydryl groups on platelet proteins (Heptinstall 1987), and purified parthenolide reproduces the effect (Groenewegen 1990). Importantly, this works differently from aspirin — thromboxane synthesis is not inhibited — so the effects are not redundant and could in principle add together. A small 1982 study reported altered platelet aggregation responses in people actually taking feverfew for migraine (Biggs 1982).

Practical guidance:

• On warfarin: discuss with the prescriber or anticoagulation clinic before starting, and monitor the INR more closely for the first few weeks after any change.
• On a DOAC (apixaban, rivaroxaban, edoxaban, dabigatran): there is no INR to watch, so the practical advice is caution and awareness of bleeding signs. Discuss it.
• On aspirin or clopidogrel: the combination is plausibly additive. Mention it to your doctor.
• With other antiplatelet supplements — high-dose fish oil, garlic, ginkgo, vitamin E, high-dose ginger, willow bark — the same logic applies, and stacking several is where problems become likely.
• Before surgery or dental extraction: stop about two weeks beforehand, tapered rather than abrupt, and tell the surgeon and anaesthetist. Platelet effects need time to wash out as new platelets circulate.
• With a bleeding disorder or low platelets: avoid unless a haematologist says otherwise.

To keep this proportionate: no serious bleeding event attributable to feverfew appears in the trial literature, and the trials found no excess of adverse events overall. The concern is mechanistic and precautionary, and it is most relevant to people already on blood thinners or facing a procedure.

Digestive Side Effects

The other commonly reported category in trials. Nausea, indigestion, bloating, abdominal discomfort, wind and occasionally diarrhoea — generally mild and often settling within a couple of weeks.

Practical fixes: take it with food; split the dose across the day rather than taking it all at once (the best trial dosed three times daily anyway); start at a lower dose and build up; and if it persists past a few weeks, it is reasonable to conclude feverfew does not suit you. Bitter herbs commonly cause this, and feverfew is notably bitter.

One longer-term theoretical concern has been raised in the review literature: feverfew has COX-2 inhibiting activity, and one systematic review flagged this as a reason for caution with very long-term dosing, particularly in people with coronary disease (Saranitzky 2009). No clinical harm has been demonstrated. It is worth a mention to your doctor if you have cardiovascular disease and intend to take feverfew indefinitely.

Pregnancy, Breastfeeding and Fertility

Avoid feverfew in pregnancy. This is one of the firmer “no” recommendations for a herb whose overall safety record is otherwise good, and there are two independent reasons.

Traditional use. Feverfew has a long folk reputation as an emmenagogue — a substance used to bring on menstruation — and was historically given to assist labour and expel the placenta. Traditional use is not evidence of efficacy, but a plant traditionally used to affect the uterus is a plant to avoid when you are trying to keep a pregnancy.

Experimental data. The only reproductive screening study is in rats, and its results do not reassure. Female rats were dosed orally with 839 mg/kg feverfew daily on gestation days 1–8 or 8–15. Fetuses exposed on days 8–15 were smaller than controls, apparently because of an increased frequency of runts in treated litters; pre-implantation loss appeared increased in the early-exposure group though not significantly; and feverfew induced toxicity in cultured rat embryos. The authors' conclusion was that a comprehensive reproductive study is warranted (Yao 2006).

Read that carefully: it is an animal screen at a high dose, and it is not evidence that feverfew causes birth defects in humans. What it is, is the only experimental look anyone has taken, and it came back with enough of a signal that the researchers asked for a full study — which has not been done. With a supplement whose benefit is 0.6 attacks per month, there is no version of that risk-benefit calculation that favours taking it while pregnant.

Breastfeeding: avoid. There is no adequate safety data on transfer into milk or effects on the infant.

Trying to conceive: the sensible approach is to stop feverfew (tapered) when you start trying, rather than after a positive test — organogenesis is well underway before most pregnancies are confirmed, and the rat data implicated the gestation day 8–15 window.

Who Should Not Take Feverfew

Drug Interactions

Feverfew has fewer documented interactions than its reputation suggests, and the ones that matter follow from its pharmacology rather than from case reports.

• Anticoagulants and antiplatelet drugs — the principal concern. Covered above.
• NSAIDs — theoretical additive effects on prostaglandin pathways and on gastric tolerance; also the COX-2 point raised by Saranitzky 2009. Mention it if you use NSAIDs regularly.
• Triptans and other serotonergic drugs — often listed as a caution because feverfew affects platelet serotonin release. There is no clinical evidence of a serotonin-syndrome-type interaction, and the mechanism (blocking release from platelets) is not the mechanism of serotonin toxicity. Worth telling your doctor; not a reason for alarm.
• Herbal blends — the practical risk is stacking several antiplatelet botanicals without realising it. Read the full ingredient list of any “migraine formula.”
• Cytochrome P450 — feverfew is not a well-established inducer or inhibitor of the major drug-metabolising enzymes, but it also has not been studied thoroughly. If you take a narrow-therapeutic-index drug — warfarin, digoxin, lithium, an antiepileptic, an immunosuppressant — tell your pharmacist about every supplement you take, feverfew included.

When to Stop and Seek Help

Stop feverfew and get urgent medical attention if you develop:

• Swelling of the lips, tongue or throat, difficulty breathing, wheeze, or faintness — possible anaphylaxis
• Unusual bruising, bleeding gums, nosebleeds that will not stop, blood in urine or stool, or black tarry stools
• A sudden severe “worst ever” headache, headache with fever and neck stiffness, headache with new weakness, numbness, confusion, visual loss or speech difficulty, or headache after a head injury — these need emergency assessment regardless of any supplement

Stop and arrange a routine review if you get a persistent rash, mouth ulcers that do not settle after switching to capsules, jaundice or dark urine, or digestive symptoms lasting beyond a few weeks.

Always tell your clinicians you take feverfew — specifically before surgery, before dental extraction, when starting an anticoagulant, and when pregnant or planning pregnancy. Supplements are omitted from medication lists constantly, and this is one where the omission genuinely matters.

Key Research Papers

Every identifier was verified live against NCBI E-utilities before being written here.

Withdrawal and overall tolerability

1. Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. British Medical Journal (Clinical Research Ed.). 1985;291(6495):569–573. The source of the post-feverfew withdrawal description: habitual users switched to placebo had significantly worse headache, nausea and vomiting with “untoward effects” in the early months.
2. Wider B, Pittler MH, Ernst E. Feverfew for preventing migraine. Cochrane Database of Systematic Reviews. 2015;4(4):CD002286. Only mild and transient adverse events across six trials; no major safety concerns.
3. Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH. Efficacy and safety of 6.25 mg t.i.d. feverfew CO₂-extract (MIG-99) in migraine prevention. Cephalalgia. 2005;25(11):1031–1041. Adverse events 8.4% versus 10.2% on placebo.
4. Pfaffenrath V, Diener HC, Fischer M, Friede M, Henneicke-von Zepelin HH. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine prophylaxis. Cephalalgia. 2002;22(7):523–532. No dose-related effect on any safety parameter up to 18.75 mg three times daily.
5. Curry EA 3rd, Murry DJ, Yoder C, et al. Phase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer. Investigational New Drugs. 2004;22(3):299–305. No dose-limiting toxicity; maximum tolerated dose not reached.
6. Pareek A, Suthar M, Rathore GS, Bansal V. Feverfew (Tanacetum parthenium L.): a systematic review. Pharmacognosy Reviews. 2011;5(9):103–110. Review-level description of post-feverfew syndrome.
7. Ernst E, Pittler MH. The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a systematic review. Public Health Nutrition. 2000;3(4A):509–514.

Allergy and contact sensitisation

1. Paulsen E, Christensen LP, Fretté XC, Andersen KE. Patch test reactivity to feverfew-containing creams in feverfew-allergic patients. Contact Dermatitis. 2010;63(3):146–150. Four of seven feverfew-allergic patients reacted to a parthenolide-depleted cream.
2. Hashimoto T, Yokozeki H. Occupational contact dermatitis caused by Eucalyptus species and Tanacetum parthenium. Contact Dermatitis. 2019;80(5):333–334.
3. Sur R, Martin K, Liebel F, Lyte P, Shapiro S, Southall M. Anti-inflammatory activity of parthenolide-depleted feverfew (Tanacetum parthenium). Inflammopharmacology. 2009;17(1):42–49. The extract developed specifically to remove parthenolide as a skin sensitiser.

Bleeding and platelet effects

1. Heptinstall S, White A, Williamson L, Mitchell JR. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes. The Lancet. 1985;1(8437):1071–1074.
2. Heptinstall S, Groenewegen WA, Spangenberg P, Lösche W. Extracts of feverfew may inhibit platelet behaviour via neutralization of sulphydryl groups. Journal of Pharmacy and Pharmacology. 1987;39(6):459–465.
3. Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro. Journal of Pharmacy and Pharmacology. 1990;42(8):553–557.
4. Biggs MJ, Johnson ES, Persaud NP, Ratcliffe DM. Platelet aggregation in patients using feverfew for migraine. The Lancet. 1982;2(8301):776.
5. Saranitzky E, White CM, Baker EL, Baker WL, Coleman CI. Feverfew for migraine prophylaxis: a systematic review. Journal of Dietary Supplements. 2009;6(2):91–103. Raises the long-term COX-2 inhibition question.

Pregnancy and mechanism of rebound

1. Yao M, Ritchie HE, Brown-Woodman PD. A reproductive screening test of feverfew: is a full reproductive study warranted? Reproductive Toxicology. 2006;22(4):688–693. The only experimental reproductive data; smaller fetuses and embryotoxicity in culture.
2. Materazzi S, Benemei S, Fusi C, et al. Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel. Pain. 2013;154(12):2750–2758. Nerve defunctionalisation — the most plausible mechanism for a rebound on withdrawal.
3. Nelson MH, Cobb SE, Shelton J. Variations in parthenolide content and daily dose of feverfew products. American Journal of Health-System Pharmacy. 2002;59(16):1527–1531. Why trial safety data may not describe the product you bought.

Live PubMed Searches

1. Feverfew adverse effects and safety
2. Post-feverfew syndrome and withdrawal
3. Compositae contact allergy
4. Parthenolide skin sensitisation
5. Herbal supplements and perioperative bleeding
6. Herbal medicine safety in pregnancy
7. Recurrent aphthous ulcers — other causes
8. Medication-overuse headache

Connections

• All Herbs
• Feverfew Benefits — hub
• Migraine Prevention — what the trials found
• How Parthenolide Works — the chemistry behind the side effects
• Choosing a Product and Dosing
• Feverfew — the main herb page
• Migraine
• Neurology
• Chamomile — the Asteraceae herb most likely to cross-react
• Butterbur — another Asteraceae migraine herb, with a liver-toxicity problem
• Ginger

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