InteractionsGuide Index Page

Case Analysis Toolclose
Enter Each Substance:

Analysis Search Terms:


Botanical Name: Tanacetum parthenium (L.) Schultz Bip.
Pharmacopoeial Name: Tanaceti partheni herba.
Synonyms: Matricaria parthenium L.; Chrysanthemum parthenium (L.) Bernh.; Leucanthemum parthenium (L.) Gren. and Godron; Pyrethrum parthenium L. Sm.
Common Name: Feverfew.

herb description



Parts Used

Aerial herb.

Common Forms

Fresh leaf.

Dried leaf, freeze-dried leaf.

  • Tincture:   1:5 25% ethanol.1

  • Standardized Extract:   Not less than 0.2% parthenolide content.

interactions review

Strategic Considerations

The modern use of feverfew as a specific for migraines followed its adoption by physicians at the London Migraine Clinic in the early 1980s, who investigated anecdotal reports of the effectiveness of the fresh leaf as a migraine prophylactic and treatment. 2,3Following initial studies, its use spread rapidly to North America, and today the herb hovers in the lower ranks of the top-20 best-selling botanicals in the United States, partly because of the large number (29 million) of migraine sufferers seeking effective treatment for the often-refractory condition. This indication was never prevalent in Germany, and the herb is not mentioned by Weiss, 4 Wichtl, 5 or the German Commission E. 6 The first modern-use therapeutic monograph was in the British Herbal Compendium 1 ; this has been superseded by a comprehensive monograph from the European Scientific Cooperative on Phytotherapy (ESCOP) 7 and recent reviews from Mills and Bone 8 and McKenna et al. 9

Despite its current public popularity, recent systematic reviews of the available controlled trial data suggest that the effectiveness of feverfew for migraine prophylaxis is not conclusively established beyond reasonable doubt, although most trials favor the herb against placebo and suggest it has a good safety profile. 10,11

Interpretations of the pharmacodynamics of feverfew extracts that stress only the sesquiterpene lactone parthenolide as the active constituent responsible for the anti-inflammatory and antimigraine actions of the herb have been described as controversial, particularly the so-called serotonin-parthenolide hypothesis of migraine prophylaxis. 12 The recent ESCOP monograph asserts that connections between the constituents of the herb and its migraine prophylactic action should be considered as complex and not definitively established. 7 However, a clearer picture may be emerging from recent studies.

Currently, the pharmacology of feverfew is being intensively reexamined after the discovery of the anti–nuclear factor kappa B (NF-κB) properties of parthenolide. 13-15From an interactions perspective, given the pluripotent activities governed by this transcription factor, inhibition of NF-κB suggests several potentially valuable strategic interactions; these include modulation of adhesion molecule expression, 16 inhibition of inducible nitric oxide synthase (iNOS), 17,18and possible targeting of antireperfusion injury, 19 as well as induction of apoptosis and modulation of drug resistance. 20,21Parthenolide also appears to be a thiol depleter, which may be part of the mechanism underlying its antiaggregatory effect. 22,23The induction of apoptosis by parthenolide also involves thiol antioxidant modulation. 21,24The presence of NF-κB in platelets also suggest that this factor may have a role in aggregation, independently of gene regulation. 25

Parthenolide has recently been shown to be a selective inducer of apoptosis in cells from chronic lymphocytic leukemia (CLL) patients at the relatively low median inhibitory concentration (IC50) of 6.2 µmol. 26 Increasing research interest in the anticancer properties of feverfew and parthenolide are expanding the “herb for migraine” conception of the botanical that characterized feverfew in the late twentieth century.

The official ESCOP monograph lists no known interactions between feverfew and pharmaceuticals, and interactions reports are absent from the literature, although some secondary sources persistently assert an interaction between feverfew and warfarin 7,27(see Theoretical, Speculative, and Preliminary Interactions Research). An interaction with drugs targeting hemostasis is theoretically more likely with antiplatelet thrombolytics, but depending on context and intent, such interactions are as likely to be beneficial as adverse. Protection against gastropathies induced by nonsteroidal anti-inflammatory drugs (NSAIDs) is a more than theoretically possible interaction, and although evidence for adjunctive interactions in oncological therapies (involving NF-κB–mediated activities) is preliminary, this may be an area of future interest as research evidence continues to emerge.

Pharmacokinetic data on the herb are meager; a recent report suggests that parthenolide and other sesquiterpene lactones exhibit a high degree of protein binding in human plasma. 28 The metabolic fate of parthenolide and its possible modulation of the cytochrome P450 (CYP450) system is unknown, but to date the herb does not appear to be associated with any obvious pharmacokinetic interactions.

herb-drug interactions
Indomethacin and Related Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Taxanes: Paclitaxel, Docetaxel
Acetylsalicylic Acid, Clopidogrel, Ticlopidine, and Other Antiplatelet Thromboprophylactics
  • Evidence: Acetylsalicylic acid (acetosal, acetyl salicylic acid, ASA, salicylsalicylic acid; Arthritis Foundation Pain Reliever, Ascriptin, Aspergum, Asprimox, Bayer Aspirin, Bayer Buffered Aspirin, Bayer Low Adult Strength, Bufferin, Buffex, Cama Arthritis Pain Reliever, Easprin, Ecotrin, Ecotrin Low Adult Strength, Empirin, Extra Strength Adprin-B, Extra Strength Bayer Enteric 500 Aspirin, Extra Strength Bayer Plus, Halfprin 81, Heartline, Regular Strength Bayer Enteric 500 Aspirin, St. Joseph Adult Chewable Aspirin, ZORprin); combination drugs: ASA and caffeine (Anacin); ASA, caffeine, and propoxyphene (Darvon Compound); ASA and carisoprodol (Soma Compound); ASA, codeine, and carisoprodol (Soma Compound with Codeine); ASA and codeine (Empirin with Codeine); ASA, codeine, butalbital, and caffeine (Fiorinal).
  • Extrapolated, based on similar properties: Cilostazol (Pletal), clopidogrel (Plavix), dipyridamole (Permole, Persantine), ticlopidine (Ticlid), combination drug: ASA and extended-release dipyridamole (Aggrenox, Asasantin).
Potential or Theoretical Adverse Interaction of Uncertain Severity

Probability: 5. Improbable
Evidence Base: Inadequate

Effect and Mechanism of Action

Aspirin (acetylsalicylic acid, ASA) is a well-documented antiplatelet agent acting through inhibition of cyclooxygenase production of thromboxane A 2 (TXA 2 ). Ticlopidine interacts with glycoprotein IIb/IIIa to inhibit fibrinogen binding to activated platelets and has been used for prevention of thrombosis when aspirin is poorly tolerated. Because of reports of hematological adverse effects associated with ticlopidine, clopidogrel (Plavix) is currently the preferred antiplatelet agent in such cases. As with ticlopidine, clopidogrel is another irreversible antiplatelet drug operating through adenosine diphosphate (ADP) receptor antagonism. The potential interaction is thus a theoretical additive pharmacodynamic increase in antiplatelet activity. Such an additive effect may theoretically increase the likelihood of bleeding disorders related to disturbances of primary hemostasis.


In vitro investigations have demonstrated antiaggregatory actions of feverfew extracts and isolated parthenolide. Several aggregatory stimuli are inhibited by parthenolide, including ADP, collagen, and arachidonate. 43-46 Platelet secretory activity is also inhibited by parthenolide, reducing 5-hydroxytryptamine (5-HT, serotonin) release. 44,47,48 Thiol depletion plays a significant role in the mechanism. 22,49,50 Interestingly, the antiaggregatory effects of feverfew extracts and isolated parthenolide appear to be equivalent in magnitude. 51

In a comprehensive review of antiplatelet activity of plant compounds, Venton et al. 52 stressed that because the relevant assay technologies are currently quite straightforward, many plant extracts and isolated compounds have been screened in vitro for platelet-inhibiting properties. Although many potentially active compounds that inhibit activation by one or more agonists have been identified, none has yet been transformed into a clinically effective antithrombotic drug. 52 Other than the pharmacokinetic modeling studies by Boik, 33 there has been little attempt to create meaningful algorithms to extrapolate in vitro IC 50 values from the different study methods into meaningful estimates of likely therapeutic levels of the compounds after therapeutic oral doses of herb.


There are no preclinical studies or clinical reports confirming this interaction. On the contrary, the original clinical investigators of feverfew at the London Migraine Clinic reported to the Lancetin 1982 that they had tested 10 patients who had taken feverfew for 3½ to 8 years and assayed dose–aggregatory response curves to several platelet agonists, including ADP, thrombin, serotonin, and a prostaglandin analog (U46619). Aggregation responses to ADP and thrombin were identical to controls who had not taken feverfew for 6 months. 53 This was in direct conflict with in vitro findings of Makheja and Bailey 43 published earlier in 1982, confirming that extrapolation from in vitro activity to in vivo effects is problematic.

Clinical Implications and Adaptations

At present, this potential interaction can be considered clinically insignificant, if in fact it exists. Monitoring migraine or arthritis patients who may be combining substantial doses of feverfew chronically with antiplatelet drugs for signs relating to disturbances of primary hemostasis may be prudent (e.g., petechiae, ecchymoses, superficial bleeds at mucous membranes).

theoretical, speculative, and preliminary interactions research, including overstated interactions claims
5-Hydroxytryptamine Receptor Agonists (Triptans)
Warfarin and Related Oral Vitamin K Antagonist Anticoagulants
  • 1.Bradley P. British Herbal Compendium. 1 vol. Bournemouth, UK: British Herbal Medical Association; 1992.
  • 2.Johnson S. Feverfew—a Traditional Herbal Remedy for Migraine and Arthritis. London: Sheldon Press; 1984.
  • 3.Johnson ES, Kadam NP, Hylands DM, Hylands PJ. Efficacy of feverfew as prophylactic treatment of migraine. Br Med J (Clin Res Ed) 1985;291:569-573.View Abstract
  • 4.Weiss R. Herbal Medicine. Meuss A, Translator. 6th ed. Beaconsfield, UK: Beaconsfield Publishers Ltd; 1988.
  • 5.Bisset N. Wichtl’s Herbal Drugs and Phytopharmaceuticals. 2nd ed. Stuttgart: Medpharm GmbH; 1994.
  • 6.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council: Integrative Medicine Communications; 1998.
  • 7.ESCOP. Tanceti Partheni Herba. ESCOP Monographs: the Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003:492-498.
  • 8.Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh: Churchill Livingstone; 2000.
  • 9.McKenna D, Jones K, Hughes K, Humphrey S. Feverfew. Botanical Medicines. 2nd ed. Binghamton, NY: Haworth Press; 2002:349-373.
  • 10.Ernst E, Pittler MH. The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a systematic review. Public Health Nutr 2000;3:509-514.View Abstract
  • 11.Pittler M, Ernst E. Feverfew for preventing migraine. Cochrane Database Syst Rev 2004;1:CD002286.View Abstract
  • 12.Awang DVC. Prescribing therapeutic feverfew (Tanacetum parthenium (L.) Schultz Bip., syn. Chrysanthemum parthenium (L.) Bernh.). Integr Med 1998;1:11-13.
  • 13.Rungeler P, Castro V, Mora G et al. Inhibition of transcription factor NF-κB by sesquiterpene lactones: a proposed molecular mechanism of action*1. Bioorg Med Chem 1999;7:2343-2352.View Abstract
  • 14.Koch E, Klaas CA, Rungeler P et al. Inhibition of inflammatory cytokine production and lymphocyte proliferation by structurally different sesquiterpene lactones correlates with their effect on activation of NF-κB1. Biochem Pharmacol 2001;62:795-801.View Abstract
  • 15.Kwok BH, Koh B, Ndubuisi MI et al. The anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IκB kinase. Chem Biol 2001;8:759-766.View Abstract
  • 16.Piela-Smith TH, Liu X. Feverfew extracts and the sesquiterpene lactone parthenolide inhibit intercellular adhesion molecule-1 expression in human synovial fibroblasts. Cell Immunol 2001;209:89-96.View Abstract
  • 17.Fiebich BL, Lieb K, Engels S, Heinrich M. Inhibition of LPS-induced p42/44 MAP kinase activation and iNOS/NO synthesis by parthenolide in rat primary microglial cells. J Neuroimmunol 2002;132:18-24.View Abstract
  • 18.Fukuda K, Hibiya Y, Mutoh M et al. Inhibition by parthenolide of phorbol ester-induced transcriptional activation of inducible nitric oxide synthase gene in a human monocyte cell line THP-1. Biochem Pharmacol 2000;60:595-600.View Abstract
  • 19.Hausenloy DJ, Yellon DM. New directions for protecting the heart against ischaemia-reperfusion injury: targeting the reperfusion injury salvage kinase (RISK) pathway. Cardiovasc Res 2004;61:448-460.View Abstract
  • 20.Cory AH, Cory JG. Augmentation of apoptosis responses in p53-deficient L1210 cells by compounds directed at blocking NF-κB activation. Anticancer Res 2001;21:3807-3811.View Abstract
  • 21.Wen J, You KR, Lee SY et al. Oxidative stress-mediated apoptosis: the anticancer effect of the sesquiterpene lactone parthenolide. J Biol Chem 2002;277:38954-38964.View Abstract
  • 22.Heptinstall S, Groenewegen WA, Spangenberg P, Loesche W. Extracts of feverfew may inhibit platelet behaviour via neutralization of sulphydryl groups. J Pharm Pharmacol 1987;39:459-465.View Abstract
  • 23.Heptinstall S. Feverfew—an ancient remedy for modern times? J R Soc Med 1988;81:373-374.
  • 24.Zhang S, Ong C-N, Shen H-M. Critical roles of intracellular thiols and calcium in parthenolide-induced apoptosis in human colorectal cancer cells. Cancer Lett 2004;208:143-153.View Abstract
  • 25.Liu F, Morris S, Epps J, Carroll R. Demonstration of an activation regulated NF-κB/I-κBα complex in human platelets. Thromb Res 2002;106:199-203.View Abstract
  • 26.Steele AJ, Jones DT, Ganeshaguru K et al. The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro. Leukemia 2006;20:1073-1079.View Abstract
  • 27.Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-1227; quiz 1228-1230.
  • 28.Wagner S, Kratz F, Merfort I. In vitro behaviour of sesquiterpene lactones and sesquiterpene lactone-containing plant preparations in human blood, plasma and human serum albumin solutions. Planta Med 2004;70:227-233.View Abstract
  • 29.Tournier H, Schinella G, de Balsa EM et al. Effect of the chloroform extract of Tanacetum vulgare and one of its active principles, parthenolide, on experimental gastric ulcer in rats. J Pharm Pharmacol 1999;51:215-219.View Abstract
  • 30.Maria AO, Franchi AM, Wendel GH et al. Gastric cytoprotective activity of dehydroleucodine in rats: role of prostaglandins. Biol Pharm Bull 1998;21:335-338.View Abstract
  • 31.Ianaro A, Ialenti A, Maffia P et al. Role of cyclopentenone prostaglandins in rat carrageenin pleurisy. FEBS Lett 2001;508:61-66.View Abstract
  • 32. DeWeerdt C, Bootsma H, Hendricks H. Herbal medicines in migraine prevention. Phytomedicine 1996;3:225-230.
  • 33.Boik J. Natural Compounds in Cancer Therapy. Princeton, Minn: Oregon Medical Press; 2001.
  • 34.Bharti AC, Aggarwal BB. Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol 2002;64:883-888.View Abstract
  • 35.Bharti AC, Aggarwal BB. Chemopreventive agents induce suppression of nuclear factor-κB leading to chemosensitization. Ann N Y Acad Sci 2002;973:392-395.View Abstract
  • 36.Pahl HL. Activators and target genes of Rel/NF-κB transcription factors. Oncogene 1999;18:6853-6866.View Abstract
  • 37.Cory AH, Cory JG. Lactacystin, a proteasome inhibitor, potentiates the apoptotic effect of parthenolide, an inhibitor of NF-κB activation, on drug-resistant mouse leukemia L1210 cells. Anticancer Res 2002;22:3805-3809.View Abstract
  • 38.Sweeney CJ, Mehrotra S, Sadaria MR et al. The sesquiterpene lactone parthenolide in combination with docetaxel reduces metastasis and improves survival in a xenograft model of breast cancer. Mol Cancer Ther 2005;4:1004-1012.View Abstract
  • 39. DeGraffenried LA, Chandrasekar B, Friedrichs WE et al. NF-κB inhibition markedly enhances sensitivity of resistant breast cancer tumor cells to tamoxifen. Ann Oncol 2004;15:885-890.View Abstract
  • 40.Yip-Schneider MT, Nakshatri H, Sweeney CJ et al. Parthenolide and sulindac cooperate to mediate growth suppression and inhibit the nuclear factor-kappa B pathway in pancreatic carcinoma cells. Mol Cancer Ther 2005;4:587-594.View Abstract
  • 41.Taguchi T, Takao T, Iwasaki Y et al. Suppressive effects of dehydroepiandrosterone and the nuclear factor-κB inhibitor parthenolide on corticotroph tumor cell growth and function in vitro and in vivo. J Endocrinol 2006;188:321-331.View Abstract
  • 42.Wu C, Chen F, Rushing JW et al. Antiproliferative activities of parthenolide and golden feverfew extract against three human cancer cell lines. J Med Food 2006;9:55-61.View Abstract
  • 43.Makheja AN, Bailey JM. A platelet phospholipase inhibitor from the medicinal herb feverfew (Tanacetum parthenium). Prostaglandins Leukot Med 1982;8:653-660.View Abstract
  • 44.Heptinstall S, White A, Williamson L, Mitchell JR. Extracts of feverfew inhibit granule secretion in blood platelets and polymorphonuclear leucocytes. Lancet 1985;1:1071-1074.View Abstract
  • 45.Loesche W, Mazurov AV, Voyno-Yasenetskaya TA et al. Feverfew—an antithrombotic drug? Folia Haematol Int Mag Klin Morphol Blutforsch 1988;115:181-184.
  • 46.Loesche W, Groenewegen WA, Krause S et al. Effects of an extract of feverfew (Tanacetum parthenium) on arachidonic acid metabolism in human blood platelets. Biomed Biochim Acta 1988;47:S241-243.View Abstract
  • 47.Groenewegen WA, Knight DW, Heptinstall S. Compounds extracted from feverfew that have anti-secretory activity contain an alpha-methylene butyrolactone unit. J Pharm Pharmacol 1986;38:709-712.View Abstract
  • 48.Marles RJ, Kaminski J, Arnason JT et al. A bioassay for inhibition of serotonin release from bovine platelets. J Nat Prod 1992;55:1044-1056.View Abstract
  • 49.Heptinstall S, Groenewegen WA, Spangenberg P, Losche W. Inhibition of platelet behaviour by feverfew: a mechanism of action involving sulphydryl groups. Folia Haematol Int Mag Klin Morphol Blutforsch 1988;115:447-449.View Abstract
  • 50.Till U, Bergmann I, Breddin K et al. Sulfhydryl/disulfide-status of blood platelets: a target for pharmacological intervention? Prog Clin Biol Res 1989;301:341-345.
  • 51.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. J Pharm Pharmacol 1990;42:553-557.View Abstract
  • 52.Venton DL, Kim SO, LeBreton GC. Antiplatelet activity from plants. In: Wagner H, Farnsworth NR, eds. Economic and Medicinal Plant Research. 5 vol. London: Academic Press; 1991:323-351.
  • 53.Biggs MJ, Johnson ES, Persaud NP, Ratcliffe DM. Platelet aggregation in patients using feverfew for migraine. Lancet 1982;2:776.View Abstract