Tanacetum – Feverfew (Tanaceti parthenii herba)
|Latin name of the genus:||Tanacetum|
|Latin name of herbal substance:||Tanaceti parthenii herba|
|Botanical name of plant:||Tanacetum parthenium (l.) schultz bip.|
|English common name of herbal substance:||Feverfew|
Latin name of the genus: Tanacetum
Latin name of herbal substance: Tanaceti parthenii herba
Botanical name of plant: Tanacetum parthenium (L.) Schultz Bip.
English common name of herbal substance: Feverfew
2.2.Information on traditional/current indications and specified substances/preparations . 13
2.3.Specified strength/posology/route of administration/duration of use for relevant
- 1. Introduction
- 2. Historical data on medicinal use
- 3. Non-Clinical Data
- 3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.1.1. Studies on parthenolide
- 3.1.2. Studies on extracts
- 3.1.3. Studies on the essential oil
- 3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
- 3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
- 3.4. Overall conclusions on non-clinical data
- 4. Clinical Data
- 4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
- 4.2. Clinical Efficacy
- 4.2.1. Dose response studies
- 4.2.2. Clinical studies (case studies and clinical trials)
- 4.2.3. Clinical studies in special populations (e.g. elderly and children)
- 4.3. Overall conclusions on clinical pharmacology and efficacy
- 5. Clinical Safety/Pharmacovigilance
- 6. Overall conclusions
1.1. Description of the herbal substance(s), herbal preparation(s) or combinations thereof
Tanacetum parthenium herba consists of the dried, whole or fragmented aerial parts of Tanacetum parthenium (L.) Schultz Bip. It contains no less than 0.20% of parthenolide (C15H20O3; Mr 248.3), calculated with reference to the dried drug. It has a camphoraceous odour (Ph. Eur. 6th edition 2008).
The genus Tanacetum includes about 50 species, of those only T. santolinoides (D.C.) grows in Egypt (El- Shazly et al. 2002).
T. parthenium (L.) Schulz Bip., also known as feverfew, is a member of the Compositae family (Asteraceae). It is an aromatic, hardy annual herb with
The leafy, more or less branched stem has a diameter of up to 5 mm. It is almost quadrangular, longitudinally channelled, and slightly pubescent. The leaves are ovate, 2 to 5 cm long, sometimes up to 10 cm,
Overview on main active compounds and common qualitative/quantitative characterisation
The most significant components present in feverfew leaves are a complex series of sesquiterpene α- methylenebutyrolactones which are stored in the glandular trichomes on leaves, flowers and seeds. Some of the detected sesquiterpene lactones are known to have biological actions such as cytotoxicity, growth regulation and antimicrobial effects and they cause allergic contact dermatitis. An exocyclic α- methylene function of the sesquiterpene lactones, which may react with sulphydryl groups of proteins, seems to be responsible for these activities (Milbrodt et al. 1997). The predominant sesquiterpene lactone present in feverfew is a germacranolide, parthenolide (PN), which has been indirectly linked to the
Feverfew leaf from
increases until the plant is in full bloom. However, PN is present in the leaves and flower heads, but not in the stems.
Drying at ambient temperature and lyophilisation seems to have no negative influence on the yield of PN.
Figure 1. Chemical structure of parthenolide (from WHO monograph).
Since the PN content greatly varies depending on the part used and the season, it has been proposed to distinguish two qualities of feverfew: A) Tanaceti parthenii folium (feverfew leaf), harvested at an early stage before the formation of the stems and B) Tanaceti parthenii herba (feverfew herb), harvested at full bloom, with a minimum PN content of 0.50% and 0.20% respectively, calculated on a dry weight basis (Hendriks et al. 1997).
The aerial parts of feverfew contain a rich mixture of mono- and sesquiterpenes compounds. Sesquiterpenes contained in the aerial parts are germacrene D,
The presence of different sesquiterpene lactones depends on the habitat of the plant (Milbrodt et al. 1997).
Other reported germacranolides are PN metabolites:
The roots of T. parthenium contain the coumarinic compound isofraxidin (Kisiel & Stojakowska 1997).
Melatonin was identified in four samples from feverfew leaves and a commercial preparation was tested by Murch. The authors of the study suggested that melatonin in plant tissues may explain the antimigraine effects of feverfew (Murch et al. 1997).
Lipophilic flavonoids in the leaf and flower of T. parthenium were identified as methyl ethers of the flavonols
Moreover, antioxidant polyphenolic acids were isolated and characterised as
The analysis of feverfew oil showed the presence of many monoterpenes as
The powdered herbal substance is
Herbalists and naturopathic doctors in the UK favoured the use of the tincture and extracts of feverfew. Feverfew extract with a standardized PN content of at least 250 micrograms per daily dose has been recommended for the treatment and prevention of migraine.
Researchers also paid attention to the other chemical components of feverfew leaf as possible responsible agents for feverfew’s
PN was found to be the main constituent of the biologically active sesquiterpene lactones in ethanol and aqueous extracts of feverfew. The sesquiterpene lactone content of ethanol extracts (ca. 0.5%) were higher than those of the aqueous ones (ca. 0.3%) (Gromek et al. 1991).
Commercial preparations of feverfew leaves are known to vary widely in the PN content, as shown by various authors. Feverfew products from the European markets have been simultaneously analysed by HPLC, NMR and biological methods and all were consistent in showing a high variability of the PN content (Heptinstall et al. 1992). Mean PN levels of commercial preparations of feverfew leaves exhibited a range from
Nelson et al. (2002) studied the PN content in capsules containing 25 to 500 mg of feverfew leaf, available to consumers, by means of HPLC. The quantity of feverfew leaf in each capsule was similar to that declared on the label. However, the PN content per dosage form varied
Taking into consideration the large variations observed in the PN contents and daily intake as recommended by labelling in commercial feverfew products, as well as that therapeutic efficacy has only been shown for preparations of feverfew that contain PN, it is suggested that manufacturers of feverfew products should use measurements of PN for standardization and quality control (Heptinstall et al. 1992). Among the proposed references for establishing quality control of feverfew preparations, a minimum level of 0.2% PN in dried leaves was adopted by the Ph. Eur. and the French Ministry of Health.
Possible differences in
Another investigation was conducted by the same group of researchers with the aim to evaluate the stability of PN in feverfew solutions versus powdered feverfew (solid state). They further explored the compatibility between commonly used excipients and PN in feverfew. Feverfew extract solution was diluted with different pH buffers to study the solution stability of PN.
Powdered feverfew extract was stored at 40°C/0% to 75% relative humidities (RH) or 31% RH/5 to 50°C to study the influence of temperature and relative humidity on the stability of PN in feverfew solid state. In addition, binary mixtures of feverfew powered extract and different excipients were stored at 50°C/75% RH for excipient compatibility evaluation.
The degradation of PN in feverfew solution appeared to fit a typical
PN degradation in feverfew in the solid state does not fit any obvious reaction model. Both moisture content and temperature play important roles affecting the degradation rate. After 6 months of storage, PN in feverfew remains constant at 5°C/31% RH. However, ~40% PN in feverfew can be degraded if stored at 50°C/31% RH. When the moisture changed from 0% to 75% RH, the degradation of PN in feverfew increased from 18% to 32% after
that PN in feverfew exhibits good compatibility with commonly used excipients under stressed conditions in a
Combinations of herbal substance(s) and/or herbal preparation(s) including a description of vitamin(s) and/or mineral(s) as ingredients of traditional combination herbal medicinal products assessed, where applicable.
Combination products have been designed and their effects on migraine prophylaxis studied.
A study with a daily dose of riboflavin 400 mg, magnesium 300 mg and feverfew 100 mg was conducted. Authors concluded that no significant positive effects were observed (Maizels et al. 2004).
1.2. Information about products on the market in the Member States
Regulatory status overview
MA: Marketing Authorisation TRAD: Traditional Use Registration
Other TRAD: Other national Traditional systems of registration Other: If known, it should be specified or otherwise add ’Not Known’
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in the MSs concerned.
1.3. Search and assessment methodology
This assessment report reviews the scientific literature data available for T. parthenium and from the WHO monograph, European Pharmacopoeia monograph, PubMed, EMA library, internet as well as available information on products marketed in the European Community, including pharmaceutical forms, indications, posology and methods of administration.
The keywords “Tanacetum parthenium”, “Tanaceti herba”, “Chrysanthemum parthenium”, “feverfew”, “parthenolide” in all text fields were used.
Clinical studies conducted on the effects of parthenolide or other single active principles were excluded.
2. Historical data on medicinal use
Feverfew has been described since ancient times as having beneficial medicinal effects and has been recommended for centuries for its medicinal properties.
The herb has also been known under other names such as Matricaria parthenium (L.), Leucanthenum parthenium (L.) Gren. and Gordon, Pyrethrum parthenium (L.), Chrysanthemum parthenium (L.).
The origin of the term parthenium is not certain. According to the ancient Greek author Plutarch, following an incident occurred in the 5th century, feverfew was used to save the life of a person fallen from the Parthenon during its construction. Another explanation is based on the Greek word parthenios meaning ‘virgin’, probably because of the reputation of the herb as an antidote for women’s ailments (Groenewegen et al. 1992).
Feverfew is derived from the Old English name ‘febrifuge’ from the Latin ‘febrifugia’, pointing to one of its benefits in reducing fever. In some other European countries this herb is referred to as ‘motherherb” for example, ‘Mutterkraut’ in Germany, indicating its acclaimed beneficial properties in various women’s conditions. Other names for feverfew include featherfoil, flirtwort and bachelor’s buttons.
The use of feverfew as a medicinal plant can be traced back to the Greek herbal ‘Materia Medica’ by Dioscorides and was successively described by Dodoens in 1619, by Gerard in 1636 and Culpeper in 1650.
It has been used for ‘intermittent fevers’ and for a variety of other conditions and disorders including toothache, rheumatism, psoriasis, insect bites, asthma, stomach ache, menstrual problems and treatment of miscarriage. During the 17th century, it was also used for aiding the ejection of after births and still births, cleansing the kidneys and bladder, strengthening the womb as well as for the treatment of vertigo, spots, wind, colic, and for the treatment of disturbances due to the excessive use of opium. Other uses recommended in the ancient times were the alleviation of St. Antoine’s fire, inflammatory processes and hot swellings (Knight 1995).
Ancient uses of feverfew may be categorized broadly into three main groups:
1.treatment for fever, headache and migraine;
2.women’s conditions such as difficulties in labour, threatened miscarriage, and regulation of menstruation;
3.relief of stomach ache, toothache and insect bites (Groenewegen et al. 1992).
Bibliographic evidence for a traditional use of feverfew for migraines and headaches are partially traceable in monographs and old texts on herbals (Table 1).
Table 1. Monographs on feverfew
ESCOP= European Scientific Cooperative on Phytotherapy
n/s = not stated
The uterine stimulant effect may explain the folk uses of the plant as abortifacient, emmenagogue and in certain labour difficulties but conflicts with the folk use of the drug in threatened miscarriage (Rateb et al. 2007). This contradictory information supports the common warning of the producers avoiding use of feverfew during pregnancy.
2.1. Information on period of medicinal use in the Community
T. parthenium has a long history of usage in Europe to prevent headache and migraine, for relief in arthritis and for treatment of psoriasis. In recent years, it has become popular also in the United States of America.
Because of all its folk fields of application, feverfew has been long referred to as a ‘medieval aspirin’. In 1772 John Hill claimed that ‘in the worst headache this herb exceeds whatever else is known’ (Heptinstall 1988).
Today’s use started in late 1970s when the British press reported that a group of migraine sufferers from Wales had found relief from attacks after taking the leaves of the plant for some time. Studies carried out reported that patients were successfully using the herb in the prophylaxis of both migraine and arthritis (Knight 1995). Thus the interest in feverfew grew quickly, bringing it back into the limelight from obscurity since the Middle Ages. A number of investigations have now been carried out on the plant’s in vitro biological actions and the chemical components responsible for these actions.
Following the success of feverfew in migraine, the herb was also tried in many other conditions and it has now been claimed (but not scientifically proven) to be effective in arthritis, psoriasis and stress, among others (Groenewegen et al. 1992).
Feverfew products have been widely available in the UK as herbal remedies exempt from licensing under section 12 (2) of Medicines Act 1968. Since April 2007 hard capsules containing 100 mg of powdered feverfew herb have been registered according the new traditional herbal medicinal products registration scheme according to art. 16c of the directive 2001/83/EC as amended.
Feverfew products are currently available in the UK as herbal remedies for oral use for the following indication: “A traditional herbal medicinal product for the prevention of migraine headaches based on traditional use only”. They can be bought without prescription from pharmacies and other outlets. The hard capsules contain as active ingredient powdered feverfew.
Between the early 1970’s and 1988, feverfew products held product licenses in the UK. This information was obtained from the MHRA under a Freedom of Information Act enquiry. Information on indication and posology was not available as these details for “product licenses of right” are not held on the MHRA electronic database (Table 2).
Table 2. Licensed feverfew HMPs since the early 1970s in the UK (data from MHRA).
In Spain, the powdered herbal substance is registered as a traditional herbal medicinal product since 1991, in form of capsules both as a single preparation and in fixed combinations containing 200 mg of
T. parthenium and 100 mg of Anthemis nobilis or 150 mg of T. parthenium and 150 mg of Artemisia.
In France, the powdered herbal substance has been authorised as a traditional medicinal product since 1991, the dry extract (solvent: ethanol 30% V/V, DER
In Denmark, medicinal products containing Tanaceti extracts
An extract corresponding to 0.1 mg of partenolide had been authorised as a medicinal product from 1993 to 2002 and an extract containing 0.2 mg of PN had been authorised from 1997 to 2004. As a fixed combination with Achillea millefolium herba and Populus tremula, the extract corresponding to 1 mg of PN had been authorised from 1993 to 2000. No further information on the type of the above mentioned extracts is available. All these products were withdrawn by the Companies and no information about their possible presence on the EU market as food supplements is available.
In Hungary capsules containing 50 mg of feverfew herb (Chrysanthemi parthenii herba) quantified to 0.4% parthenolid content were on the market from 1993 to 2005.
Food supplements are on the market in Italy, Latvia and Lithuania. In Belgium, an herbal tea containing 11 herbal components is on the market as a food supplement; however that will have to undergo a revision phase according to the new directive 2004/24/EC on THMPs.
In the light of the above evidences, it can be concluded that feverfew herbal medicinal products for migraines have been available for more than 30 years in the European Union and the medicinal use of feverfew for migraine and headaches in Europe is documented since centuries.
2.2. Information on traditional/current indications and specified substances/preparations
The powdered herbal substance is registered in the UK as “a traditional herbal medicinal product used for the prevention of migraine headaches based on traditional use only” (ATC code N02CX), in Spain as “a traditional herbal medicinal products used in case of headache”. In France single preparations containing the comminuted or powdered herbal substance or the dry extract (ethanol 30% V/V, DER
In Hungary, capsules containing feverfew herb are used to reduce the frequency of migraine headaches, to relieve the associated symptoms (pain, nausea, vomiting and vision disturbances) and to relief of headaches occurring prior or during menstruation.
In Denmark, the extract corresponding to 0.1 mg or 0.2 mg PN were authorised as an herbal medicinal product for the prevention of milder forms of migraine, when a doctor has excluded other reasons for the condition (ATC code N02CX). The fixed combination of the Tanaceti extract containing 0.1 mg PN plus Achilleae millefolii herba and Populus tremula (Gitadyl) was authorised as a non- steroidal
Feverfew is used mainly for migraine, arthritis, rheumatic diseases and allergies. It has also been used in the treatment of tinnitus, vertigo, fever, difficult labour, toothache, insect bites and asthma.
In folk medicine, feverfew has been used for cramps, as a tonic, a stimulant, a digestive substance, blood detoxicant, migraine prophylaxis, intestinal parasites and gynecological disorder. The herb is also used as a wash for inflammation and wounds, as a tranquilizer, an antiseptic and as a mouthwash following tooth extraction. It is used externally as an antiseptic and insecticide.
The herbal infusion has been used for dysmenorrhea. In postpartum care, it has been used to reduce bleeding (lochia) (PDR monographs 2007).
2.3. Specified strength/posology/route of administration/duration of use for relevant preparations and indications
Feverfew has been administered in a variety of ways, both for internal and external use.
It has been used as a dried powder taken with honey (presumably because of its bitter taste), or as a bath using decoction made with wine (for the women’s conditions) or as syrup. In most cases, it was advised to use the leaves, but for some conditions it was suggested to use the flowers (Groenewegen et al. 1992).
Feverfew is supplied as whole or fragmented herbal substance for decoction or infusion or powdered or as extracts in capsules, tablets, tinctures and drops.
Herbal tea as an infusion: 2 teaspoons of the herbal substance per cup, brew for 15 minutes. Three cups to be taken daily for dysmenorrhea (PDR monograph 2007).
A stronger infusion, made with doubled amount and allowed to steep for 25 minutes, is used for washes (PDR monograph 2007).
It is commonly taken orally in tablets or capsules, often with food to disguise its bitter taste. The stated amounts of feverfew per tablet or capsule for different products generally vary from 25 to 250 mg (Heptinstall 1988).
The daily dose of feverfew has not been clearly defined yet. Jin et al. (2007) suggests a daily dose of
For the treatment of migraine, 200 to 250 mg daily (standardized on 0.2% PN content) is used or 25 mg of freshly dried powdered feverfew extract that corresponds to 0.1 mg of sesquiterpene lactones (PDR monograph 2007). Positive effects were recorded in a few clinical studies with the posology of about 100 mg daily of feverfew extract.
The powdered herbal substance for oral use is administered in form of capsules. The recommended dosage in the UK is 1 capsule containing 100 mg to be taken once daily for three months, in Hungary two capsules containing 50 mg 2 times daily for two months, in France 1 capsule containing 260 mg 3 times daily and in Spain 1 or 2 capsules containing 200 mg/capsule up to 3 times daily.
The comminuted herbal substance had been used in form of herbal tea; in France the posology was 1 to 2 sachets daily (1 sachet containing 1.35 g).
The dry extract (ethanol 30% V/V, DER
An extract corresponding to 0.1 mg PN was orally used in Denmark in tablets,
The recommended dosage for the fresh material varies from 1 to 3 leaves (25 to 75 mg) once or twice daily (Heptinstall 1988).
Feverfew leaves are used mainly in the prophylaxis both of migraine and arthritis but sometimes in single high doses to control the migraine attacks. The estimated period of use as a prophylactic agent varies from instant relief to over a period of months in case of migraine. An average of 7 days is claimed for the relief of arthritis pain and an average of 14 to 28 days to reduce the inflammation and improve the mobility (Groenewegen et al. 1992).
3.1. Overview of available pharmacological data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
Feverfew has been largely investigated for its traditional uses in medicine such as treatment of fever, headache, migraine, stomach ache, insect bites, bronchitis, arthritis, cold, as an abortifacient, and for alleviating menstrual cramps (Rateb et al. 2007).
The main active constituent in feverfew is the sesquiterpene lactone PN that contains a highly electrophilic
PN inhibits platelet aggregation and serotonin release from platelets granules and it is a well documented inhibitor of the transcription factor
become one of the major strategies in anticancer therapy. According to numerous data, PN is also the inhibitor of IκB kinases complex (IKC), with the sustained cytoplasmic retention of
This section is constituted of three separate paragraphs on studies describing effects of PN, extracts and essential oil activity.
3.1.1. Studies on parthenolide
Studies on PN have shown that this compound possesses several biological properties such as antitumoral,
22.214.171.124. Antitumoral activity
PN has been shown to withdraw cells from cell cycle or to promote cell differentiation and finally to induce programmed cell death. Recent advances in molecular biology indicate that this sesquiterpene lactone might evoke the
Glioblastomas are difficult to treat and frequently aggressive and fatal. Treatment of glioblastoma cells with PN resulted in rapid apoptosis through caspase 3/7 without a suppression of
PN inhibits cell growth irreversibly at concentrations above 5.0 µM and an exposure time of 24 h. At lower concentrations the effect is reversible; PN acted as a cytostatic over multiple cell generations for mouse fibrosarcoma
Transcription factors such as
The anticancer property of PN was tested in an
signalling led to the sensitization of JB6 cells to
Another research demonstrated that PN is able to induce robust apoptosis in primary human acute myeloid leukemia (AML) cells and blast crisis chronic myeloid leukaemia (CML) cells while sparing normal hematopoietic cells. Furthermore, analysis of progenitor cells using in vitro colony assays as well as stem cells using the nonobese diabetic/severe combined immunodeficient xenograft model showed, that PN also preferentially targets AML progenitor and stem cell populations. Notably, in comparison to the standard chemotherapy drug cytosine arabinoside
To investigate PN anticancer activity in ultraviolet B
The effects of PN induced apoptosis in
The inhibitory activity of PN and golden feverfew extract against two human breast cancer cell lines (Hs60ST and
Studies of intensive immunotherapy revealed several metabolic inhibitors, such as cycloheximide, actinomycin D, anisomycin, harringtonine and other metabolic inhibitors, which are able to modulate the resistance of various cancer cells to cytokine induced cell death. However, the clinical use of several tumor cell death promoting agents is limited, because they act
cytotoxic. In turn, due to its low toxicity PN seems to be the ideal agent in future
The protein tyrosine kinase (PTK) inhibitors radicicol and herbimycin A inhibit the expression of the
Excessive nitric oxide production by inducible nitric oxide synthase (iNOS) in stimulated inflammatory cells is thought to be a causative factor of cellular injury in inflammatory disease states. Compounds inhibiting iNOS transcriptional activity in inflammatory cells are potentially
In order to identify the molecular mechanisms of parthenolide’s
The NO donor glyceryl trinitrate (GTN) provokes delayed migraine attacks when infused into migraineurs and also causes iNOS expression and delayed inflammation within rodent dura mater. Sodium nitroprusside, a NO donor as well, also increases iNOS expression. As inflammation and iNOS are potential therapeutic targets, Reuter et al. (2002) examined transcriptional regulation of iNOS following GTN infusion and the consequences of its inhibition within dura mater. They show that intravenous GTN increases NO production within macrophages, iNOS expression is preceded by significant nuclear factor kappa B
Pharmacological control of
dependent manner. The authors suggested that
The massive hyperplasia of synovial fibroblasts is one of the most striking features of rheumatoid arthritis. The effect of PN on the proliferation of rabbit synoviocytes cell line
126.96.36.199. Antimicrobial activity
PN showed significant activity against the promastigote form of L. amazonensis with 50% inhibition of cell growth at a concentration of 0.37 µg/ml. For the intracellular amastigote form, PN reduced by 50% the survival index of parasites in macrophages when it was used at 0.81 µg/ml. The purified compound showed no cytotoxic effects against J774G8 macrophages in culture and did not cause lysis in sheep blood when it was used at higher concentrations that inhibited promastigote forms. Sodium dodecyl
188.8.131.52. Antioxidant activity
A study was performed to investigate the protective effect of PN against oxidative
184.108.40.206. Effects on smooth muscle contractility
Extracts of feverfew and PN inhibit smooth muscle contractility in a
220.127.116.11. Antimigraine effects
Although migraine is a complex neurovascular disorder, serotonin based mechanisms are central to its pathophysiology. Antimigraine drugs interact predominantly with receptors of
In another report by Bejar et al. (1996) no
3.1.2. Studies on extracts
Extracts of T. parthenium (L.) showed antimicrobial, analgesic,
18.104.22.168. Antimicrobial activity
The activity of crude extracts, fractions and PN (pure compound) obtained from T. parthenium against two forms of the parasite Trypanosoma cruzi was investigated. One thousand grams of dried aerial parts were sequentially extracted by exhaustive maceration in ethanol/water 9:1. The powder resulting from lyophilization, soluble in water, was termed the aqueous crude extract (WCE). The residue was dissolved in ethanol or
Other investigations showed that the ethanolic extracts possess high activity against all Gram positive bacteria, on some Gram negative bacteria and on some fungi (Kalodera et al. 1997).
The alcoholic extracts of flowers and leaves and PN showed significant analgesic,
Feverfew inhibits human blood platelet aggregation and secretion induced by a number of agents
in vitro and this may be related to the beneficial effects in migraine. The inhibitory activity of PN was compared with that of crude feverfew leaves extract by Groenewegen & Heptinstall (1990). The effects of both on
The effect of feverfew as a whole plant on an aqueous extract equivalent to 20 mg dried plant per ml, has been examined on both
A feverfew extract produced a
Crude chloroform extracts of fresh feverfew leaves (rich in sesquiterpene lactones) and of commercially available powdered leaves
The bioactivity of feverfew leaf extracts has been analysed by use of a human polymorphonuclear leukocyte (PMNL) bioassay to assess the relative contributions of solvent extraction and PN content to the biological potency of the extract. Extracts prepared in
leaf weight. The mean ratio of PN concentration to the PN
Oral administration of a water feverfew extract (composition unknown) led to significant anti- nociceptive and
Both crude ethanol feverfew extracts and purified PN were examined for their ability to modulate adhesion molecule expression in human synovial fibroblasts.
Chen & Leung (2007) tested three different feverfew extracts to check possible differences in gene response of human cells. The standard reference extract (SRE) was obtained by extraction of 2 g of dried leaf powder with 20 ml of 90% ethanol under mild conditions (sonication for 30 min with no evaporation or exposure to the air). A carbon dioxide supercritical fluid extract was prepared under conditions giving a spectrum of components similar in ratio of concentration to the SRE which contains most of the volatile components of feverfew including camphor, chrysantenylacetate and PN. A negative control extract was prepared with the same extraction solvent and DER but under stress condition (extraction or 19 days, moderate heat up to 50°C and evaporation). Both, a standard reference ethanolic extract and the carbon dioxide supercritical fluid extract of feverfew exhibited blockade on
22.214.171.124. Effects on vessels and smooth muscle cells
Barsby et al. (1992) showed that samples prepared from chloroform extracts of fresh leaves of feverfew strongly inhibited responses of rabbit aortic rings to phenylephrine,
Thakkar et al. (1983) demonstrated that phospholipase A activity, measured in homogenates and acid extracts of smooth muscle cells from rat aorta and mesenteric artery, was inhibited by an extract from the leaves of feverfew plant.
The effects of a chloroform feverfew extract of fresh leaves on potassium currents in smooth muscle were studied by Barsby et al. (1993). The currents were recorded from single cells dissociated from the rat anococcygeus and the rabbit ear artery using the
126.96.36.199. Antithrombotic activity
Chloroform and water extracts of feverfew inhibited secretory activity in blood platelets and polymorphonuclear leucocytes (PMNs). Release of serotonin from platelets induced by various aggregating agents (adenosine diphosphate, adrenaline, sodium arachidonate, collagen, aM U46619) was inhibited. Platelet aggregation was consistently inhibited but thromboxane synthesis was not. Feverfew also inhibited release of vitamin
Loesche et al. (1988) demonstrated that chloroform feverfew leaves extract inhibits aggregatory and secretory responses in human platelets and granulocytes, and such inhibition may be relevant to the beneficial effects. It has been suggested that feverfew extracts inhibit platelet behaviour via effects on platelet sulphydryl groups. In another study, researchers found evidence that feverfew inhibits uptake as well as liberation of arachidonic acid into/from platelet membrane phospholipids.
The same group studied the effect of feverfew on the interaction of platelets with different types of collagen immobilized plastic as well as on the integrity of endothelial cells monolayer in perfused rabbit aorta. Feverfew leaves were dried in air, powdered and extracted with chloroform (20 ml/g leaves). The extract was dried under nitrogen and the residue dissolved in
Chloroform/methanolic and water extracts of the herb were found to inhibit
the inhibitory effects. The authors suggest that pharmacological properties of feverfew may thus be due to cytotoxicity (O’Neill et al. 1987).
188.8.131.52. Antioxidant activity
In another study, the antioxidant activities of an ethanolic feverfew extract and its bioactive components were determined in terms of their free
± 0.10% and 0.68% ± 0.07%, respectively. Total phenolic content of the feverfew extract was measured in 21.21 ± 2.11 μg gallic acid equivalent per mg dry material. The feverfew alcoholic extract possessed a strong DPPH free
184.108.40.206. Antimigraine effects
To study the mechanism of antimigraine activity of T. parthenium, its extracts and PN were tested for their effects on
Tassorelli et al. (2005) studied the biological effects of different T. parthenium extracts and purified PN in an animal model of migraine based on the quantification of neuronal activation induced by nitroglycerin. The methanolic extract enriched in PN significantly reduced
3.1.3. Studies on the essential oil
The essential oil showed bactericidal and fungicidal activity. Gram positive species demonstrated a significantly lower sensitivity than the Gram negative ones, moulds, the dermatophytes and some fungi. Regarding the Gram positive species, the essential oil has a strong bactericidal effect only on the Bacillus species, while this effect is negligible on other species (Sarcina flava, Staphylococcus aureus, Enterobacter sp.). The oil has a strong bactericidal effect on many of the Gram negative species:
Escherichia coli, Klebsiella oxitoca, Salmonella, sp., Shigella sonnei, Serratia marcescens and Citrobacter freundii. On Candida tropicalis, C. pseudotropicalis and C. apicola, the essential oil has a strong fungicidal effect. The microbicidal effect on moulds (Aspergillus flavus, A. ochraceus, A. niger) and dermatophytes (Microsporum gypseum, Trichophyton mentagrophytes and Epidermophyton floccosum) has also been determined (Kalodera et al. 1997).
3.2. Overview of available pharmacokinetic data regarding the herbal substance(s), herbal preparation(s) and relevant constituents thereof
No data available.
3.3. Overview of available toxicological data regarding the herbal substance(s)/herbal preparation(s) and constituents thereof
Single/repeat dose toxicity, genotoxicity, carcinogenicity and local tolerance studies have not been performed.
Yao et al. (2006) carried out a preliminary screen of a commonly used formulation of feverfew in order to determine its potential for reproductive toxicity. The recommended human dose is 1 g/day. The extract of feverfew used consisted of a commercial preparation of the dried leaf of the feverfew plant extracted in 60% ethanol in a 1:2 dilution, giving a final concentration of 200 mg/ml feverfew standardized to 0.7 mg/ml of PN. The reported teratogenic threshold of ethanol is 2 g/kg in the Long- Evans rat, used in the study. The upper dose of the ethanol content of the feverfew concentrate was therefore limited to 1.98 g/kg. This meant that the maximum dose of feverfew that could be delivered to the rat was 839 mg/kg/day or 58.7 times the recommended human dose. Treated rats were dosed with 12.8 ml/kg/day of a 65.2 mg/ml feverfew solution. Control rats received either 12.8 mg/kg of distilled water or 20% (v/v) ethanol. Five female rats were orally dosed with 839 mg/kg feverfew daily on either gestation days (GD)
3.4. Overall conclusions on
Several non clinical investigations support feverfew traditional medicinal uses.
The sesquiterpene lactone PN containing an
active constituent. PN possesses
The role of PN in the antimigraine effects of feverfew was investigated and antagonism of serotonin receptors and inhibition of neuronally released
Alcoholic extracts of flowers and leaves showed significant analgesic,
Water, ethanolic and
Chloroform extracts of fresh leaves of feverfew strongly inhibit responses of vessels to contracting agents and both chloroform and water extracts of feverfew inhibit secretory activity in blood platelets and polymorphonuclear leucocytes (PMNs) and release of serotonin from platelets induced by various aggregating agents.
Both feverfew and PN inhibit smooth muscle contractility in a
A preliminary study, to determine its potential for reproductive toxicity, was conducted in the rat. The dose of feverfew delivered daily corresponded to about 58.7 times the recommended human dose. Treatment induced both maternal and embryo toxicity, however, the same authors considered the study preliminary and suggested that a comprehensive reproductive study of feverfew is to be warranted.
The essential oil possesses bactericidal and fungicidal properties.
In conclusion, PN and different preparations of T. parthenium show biological activities in vitro and in vivo in experimental models. These findings support the traditional use in migraine prevention and in minor pain syndromes such mild articular pain.
4. Clinical Data
4.1. Clinical pharmacology
Migraine is a recurrent
Migraine is heterogeneous (among sufferers and between attacks) in frequency, duration and disability. Some migraineurs have less than one attack a month while others have one or more attacks a week. Some are quite disabled by their headaches, while others are not. Therefore, it is appropriate to stratify the care of the migraine population by headache frequency, severity and level of disability. Furthermore, prevention needs to be considered for those patients whose migraine has a substantial impact on their lives.
Migraine is considered a genetic disorder of neuronal
There are two ways to treat migraine headache: the acute therapy to terminate the headache when needed and the preventive therapy, in which treatment is given chronically to reduce attack frequency, severity and duration, to improve responsiveness to acute therapy, and to improve function and reduce disability (Bamford et al. 2009).
The aim of a preventive treatment for migraine is to prevent or reduce the frequency and/or to attenuate severity of new migraine attacks, to improve response to acute medications, to improve patient function and to reduce disability.
Prophylactic drug treatment of migraine should be considered and discussed with the patient when one or more of the following problems occur:
–quality of life, business duties, or school attendance are severely impaired;
–frequency of attacks per month is two or higher;
–migraine attacks do not respond to acute drug treatment;
–frequent, very long, or uncomfortable auras occur.
In summary, patients with high frequencies of migraine, high disability or impact from migraine, and frequent users of acute migraine medications merit migraine prophylaxis in the form of daily medication.
Medications with the best evidence for efficacy in the prevention of migraine are amitriptyline, propranolol, timolol, valproate, and topiramate. Options available include alternative and complementary therapies, optimized lifestyles with changes as necessary, dietary and substance changes and drug prevention (Taylor 2009).
Although all migraine preventive medications are
Use of feverfew in the migraine treatment
Feverfew leaf extracts inhibit human blood platelet aggregation and secretion induced by a number of agents in vitro and this may relate to the beneficial effects in migraine. These effects are similar to those shown for drugs preventing migraine attacks (i.e. tryptans). On this basis, use of T. parthenium is not considered useful for acute therapy to terminate the headache but more suitable for the prevention (or prophylaxis) of migraine attacks. In conclusion, it can be given chronically to reduce attack frequency, severity and duration, to improve responsiveness to acute therapy, to improve function and reduce disability. Since feverfew appears to have a relatively benign side effect profile, it is considered as an option for migraine prophylaxis. Feverfew treatment has been assigned to ‘class B recommendation’ within guidelines on management of migraine in clinical practice differentiating between class A, B and C
4.1.1. Overview of pharmacodynamic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
Feverfew has traditionally been used for fever, women’s ailments, inflammatory conditions, psoriasis, toothache, insect bites, rheumatism, asthma and
Feverfew extract enables the release of serotonin
A role of the sesquiterpene lactone PN in migraine prophylaxis was supported by in vitro studies suggesting inhibition of serotonin release from blood platelets but this hypothesis is not commonly shared. PN also markedly interferes with both contractile and relaxant mechanisms of blood vessels. The pharmacological role of feverfew in the migraine pathophysiology is not completely understood.
4.1.2. Overview of pharmacokinetic data regarding the herbal substance(s)/preparation(s) including data on relevant constituents
No data available.
4.2. Clinical Efficacy
4.2.1. Dose response studies
The efficacy and safety of T. parthenium (feverfew) in migraine
A study was designed with the primary objective to show a
The highest absolute change of migraine attacks was observed under treatment with 6.25 mg t.i.d. (mean ± SD = – 1.8 ± 1.5 per 28 days) compared with placebo (- 0.3 ± 1.9; P=0.02). Overall, 52 of 147 (35%) patients reported at least one adverse event.
The incidence of adverse events in the active treatment groups was similar to that in the placebo group, and no
4.2.2. Clinical studies (case studies and clinical trials)
Clinical studies with feverfew for prevention of migraine
Efficacy of feverfew as prophylactic treatment of migraine.
A double blind placebo controlled trial including seventeen patients who already ate fresh leaves of feverfew daily as prophylaxis against migraine was carried out. Patients who had suffered from classical or common migraine for at least two years, with eight or fewer attacks per month, were allocated randomly to receive either feverfew
The use of feverfew for migraine prophylaxis was assessed in a randomised, double blind, placebo- controlled crossover study. After a
Herbal medicines in migraine prevention: Randomized
De Weerdt et al. (1996) assessed 50 patients diagnosed according to the criteria of the International Headache Society (IHS 1988). Patients suffering from migraine with or without aura received daily either one capsule of an alcoholic feverfew extract (143 mg) or placebo in a randomised crossover trial. The extract was obtained subjecting feverfew powder to 19 days of prolonged exposure to 90% ethanol, moderate heat (up to 90°C) and evaporation. A
Feverfew (T. parthenium) as a prophylactic treatment for migraine: A
The crossover trial conducted by Palevitch et al. (1997) included 57 patients with migraine diagnosed by medical examination (diagnostic criteria not specified). During the preliminary, open phase of the trial, each patient received 100 mg feverfew daily for 2 months. The PN content of the dried leaves was 0.2% as determined by HPLC. 50 mg of fine powdered leaves was packed in small gelatin capsules. Powdered dry leaves of parsley (Petroselinum crispum), were prepared in the same way and
served as the placebo control. Thereafter, in the
Efficacy and safety of 6.25 mg t.i.d. feverfew
The efficacy and tolerability of a
Table 3. Efficacy of feverfew as prophylactic treatment of migraine
Table 6. Feverfew (Tanacetum parthenium) as a prophylactic treatment for migraine: A placebo- controlled
Table 7. The efficacy and safety of Tanacetum parthenium (feverfew) in migraine
Table 8. Efficacy and safety of 6.25 mg three times daily feverfew
Reviews on clinical studies with feverfew for prevention of migraine
The first systematic review on feverfew as a preventive treatment for migraine was published by Vogler et al. in 1998. Only randomized,
Five trials met the inclusion/exclusion criteria. The majority favoured feverfew over placebo. Three studies reported positive results in favour of feverfew. In total, 216 patients were included, both men and women suffering from classical and/or common migraine. The author concluded that the effectiveness of feverfew in the prevention of migraine has still not been established beyond reasonable doubt (Vogler et al. 1998).
Ernst published in the year 2000 a systematic review on the efficacy and safety of feverfew. Only randomized,
A Cochrane review on feverfew for preventing migraine was released in 2004. The aim of the review was to systematically evaluate the evidence from
Publications describing (or which might describe)
Five trials (343 patients) met the inclusion criteria. Results from these trials were mixed and did not convincingly establish that feverfew is efficacious for preventing migraine. Only mild and transient adverse events were reported in the included trials (Pittler & Ernst 2004).
The authors concluded that there is insufficient evidence from randomised,
Another explanation suggests only a secondary role for serotonin in the etiology of migraine. Assuming that
Another hypothesis suggests that an essential oil constituent of feverfew, chrysanthenyl acetate, may be important. This component inhibits prostaglandin synthetase in vitro and seems to possess analgesic properties. Other investigators agree that PN is not the only pharmacologically active constituent in feverfew.
A link between the relatively high concentration of melatonin in different feverfew varieties and a decrease in melatonin excretion during migraine attacks has also been suggested.
An alternative explanation for negative trial results is offered by the fact that some commercial preparations are
Clinical studies with combination products
To determine the efficacy for migraine prophylaxis of a preparation containing a combination of riboflavin, magnesium and feverfew a randomized
Forty nine patients completed the
Author’s conclusion: riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300 mg and feverfew 100 mg. The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis and suggests that riboflavin 25 mg may be an active
comparator. There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis (Maizels et al. 2004).
Feverfew and Salix alba (white willow) either alone or in combination have been shown to inhibit binding to
On this basis, a prospective,
Attack frequency was reduced by 57.2% at 6 weeks (p<0.029) and by 61.7% at 12 weeks (p<0.025) in nine of ten patients, with 70% patients having a reduction of at least 50%. Attack intensity was reduced by 38.7% at 6 weeks (p<0.005) and by 62.6% at 12 weeks (p<0.004) in ten of ten patients, with 70% of patients having a reduction of at least 50%. Attack duration decreased by 67.2% at 6 weeks (p<0.001) and by 76.2% at 12 weeks (p<0.00l) in ten of ten patients. Two patients were excluded for reasons unrelated to treatment.
Author’s conclusions: the remarkable efficacy of the combination product in this trial is not only reducing the frequency of migraine attacks but also pain intensity and duration. Further investigation of this therapy in a
Guideline for the
To provide physicians and allied health care professionals with guidelines for the
Feverfew in rheumatoid arthritis
Feverfew in rheumatoid arthritis: a double blind, placebo controlled study.
Feverfew is reputed by folklore to be effective in arthritis. Forty one female patients with symptomatic rheumatoid arthritis received either dried powdered feverfew
(C3dg), rheumatoid factor titre, immunoglobulins (IgG, IgA, IgM), functional capacity, and patient and observer global opinions. One patient (placebo) withdrew after three days and was not included in the analysis. Treatment and placebo groups (20 patients each) were well matched at entry. No important differences between the clinical or laboratory variables of the groups were observed during the six week period. This study therefore shows no apparent benefit from oral feverfew in rheumatoid arthritis (Pattrick et al. 1989).
4.2.3. Clinical studies in special populations (e.g. elderly and children)
Compositae dermatitis from airborne parthenolide
Feverfew is a member of the European Compositae plant family that are suspected of causing airborne contact allergy. Its most important allergen is the sesquiterpene lactone PN. A study was designed to:
(i) assess the allergenicity of
4.3. Overall conclusions on clinical pharmacology and efficacy
Based on the totality of evidence, including clinical trials and systematic reviews, feverfew should not be considered as definitely effective (grade B evidence) nor as established safe in
5. Clinical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trials in humans
Feverfew was well tolerated in the included trials, and adverse events were generally mild and reversible. Controlled studies have demonstrated no effect on blood pressure, heart rate or body weight after 6 months of regular consumption of encapsulated dried feverfew leaf (Johnson et al. 1985). Two studies (Johnson 1985; Murphy 1988) reported a higher incidence of adverse events during treatment with placebo than with feverfew. Feverfew did not appear to affect blood pressure, heart rate, body weight or haematological and biochemical safety parameters (Pittler 2004).
During the study conducted in 1985 by Johnson at the City of London Migraine Clinic, roughly 10% of patients who were switched to placebo after taking feverfew for several years appeared to experience a genuine
It was a small study including seventeen patients that were already using the plant by eating fresh leaves of feverfew daily as prophylaxis against migraine in the period before the beginning of the clinical investigation.
In another study conducted by Pfaffenrath et al. (2002), the incidence of adverse events was similar for all treatment groups.
Chewing feverfew leaves produces sometimes a more general inflammation of the oral mucosa and tongue, accompanied by swelling of the lips and occasionally loss of taste. In Johnson’s 1983 survey of 300 feverfew users, mouth ulceration (aphthous ulcers) from chewing fresh leaves was reported by 11.3% of users, prompting discontinuance of treatment by some. Mouth ulceration is a systemic reaction to Tanaceti Parthenii observed only in subjects chewing fresh leaves; it requires discontinuation of the product. Inflammation of the mouth and tongue with swelling of the lips appears to be a local reaction that may be overcome by using encapsulated herb products (WHO monograph 2004).
Abdominal pains and indigestion have been reported for feverfew users who chewed the leaves over a period of years. Although
The frequency of chromosomal aberrations and sister chromatid exchanges was determined from lymphocyte cultures established from blood samples. Samples had been taken over a period of several months in 30 migraine patients who had daily taken leaves, tablets or capsules of feverfew for more than 11 consecutive months. They were compared to 30 feverfew
5.2. Patient exposure
Feverfew has been ingested continuously by large numbers of people without indication of any chronic toxicity effects (Dennis 1998). Anderson et al. (1988) found no substantial differences in the frequency of chromosomal aberrations and sister chromatid exchanges in lymphocytes, or in the mutagenicity of urine, in tests comparing migraine patients who used feverfew leaves, tablets or capsules chronically with
Sesquisterpene lactones such as the feverfew constituent and PN are also known to cause contact dermatitis (Dennis 1998, Johnson 1983).
5.3. Adverse events and serious adverse events and deaths
Allergy to Tanacetum and other plants from the Compositae family
Parthenium dermatitis, in its classical form, is known as airborne contact dermatitis and primarily affects the exposed areas and the flexures. Other clinical patterns are a seborrheic pattern, widespread dermatitis and exfoliative dermatitis.
The trend of the clinical pattern is changing. The classic airborne contact dermatitis may change to photodermatitis resembling chronic actinic dermatitis or mixed pattern dermatitis. The allergens responsible for contact dermatitis are sesquiterpene lactones and are present in the oleoresin fraction of the leaf, the stem and the flower, and also in the pollen. The allergens can be extracted in various solvents (such as acetone, alcohol, ether and water) and then used for patch testing. The acetone extract of T. parthenium is better than the aqueous extract in eliciting contact sensitivity. The treatment of T. parthenium dermatitis is mostly symptomatic. Topical steroids, antihistamines and avoidance of T. parthenium are the mainstay of treatment for localised dermatitis. Systemic corticosteroids and azathioprine are frequently needed for severe or persistent dermatitis (Sharma et al. 2007).
A case of specific, delayed hypersensitivity induced by repeated contact with a wild form of feverfew in a
Compositae dermatitis occurred in a
A positive patch test reaction was found for feverfew and other Compositae plants. The eruption resembled atopic dermatitis morphologically but was prominent on the palms and face and dramatically spared the area of the boy’s feet covered by his shoes (Guin & Skidmore 1987).
Around 80% of patients with prurigo nodularis are atopic, even in the absence of eczema, and in 20%, the condition starts after an insect bite. The association of contact dermatitis with prurigo nodularis was documented in a study of 32 patients, 25 of whom had positive patch tests, including to ragweed. Three case reports of
A second patient, a
same calming moisturizer. It is thought that both of these eruptions are a result of contact dermatitis from the Compositae plant family (Killoran et al. 2007).
5.4. Laboratory findings
No data available.
5.5. Safety in special populations and situations
Occupational or direct exposure has caused eczema and allergic dermatitis.
Feverfew cross reacts with Tansy, Yarrow, Marguerite, Aster, Subflower, Laurel and Liverwort (PDR monograph 2007).
Withdrawal and rebound
Some theoretical potential risks have been suggested:
–feverfew inhibits platelet aggregation and it has been suggested that caution should be used in patients treated with other inhibitors of platelet aggregation such as aspirin and dipyridamole (PDR monograph 2007);
–moderate risk of bleeding may result by interactions with anticoagulants, low molecular weight heparins, thrombolytic agents and antiplatelet agents (PDR monograph 2007);
–moderate risk of adverse reactions (i.e. gastrointestinal, renal effects) may result by interactions with nonsteroidal
However, no drug interaction has been reported in people taking feverfew.
Use in pregnancy and lactation
In view of its traditional reputation for emmenagogic effect and to affect the menstrual cycle (Herbal Medicines 2007), feverfew preparations should not be consumed by pregnant or lactating women.
Use in children and adolescents
Because of lack of information on the plant’s effect, it has to be advised that children and adolescents should not be treated with feverfew.
5.6. Overall conclusions on clinical safety
Data from clinical studies show that feverfew is well tolerated and adverse events were generally mild and reversible. In view of its traditional reputation for emmenagogic effect, feverfew preparations are contraindicated in pregnant or lactating women. Because of the lack of data, feverfew treatment is not recommended in children and adolescents. Moderate risks may result from interactions with drugs or substances influencing blood coagulation and platelets aggregation. Rebound symptoms may appear after stop taking feverfew. Exposure to feverfew may cause eczema and allergic dermatitis.
6. Overall conclusions
Tanacetum parthenium, also known as “feverfew”, is a member of the Compositae family and it has been described since ancient times as having beneficial medicinal effects. The plant parts used for medicinal use are the dried leaves or the dried aerial parts.
Several investigations support feverfew’s traditional medicinal uses. Feverfew herbal medicinal products for migraines have been available for more than 30 years in the European Union and the medicinal use of feverfew for migraine and headaches in Europe is well documented for centuries. The sesquiterpene lactone parthenolide is considered the main active constituent. Parthenolide inhibits platelet aggregation and platelets serotonin release. It has also been shown that parthenolide has antinflammatory effects through the inhibition of
Feverfew appears to be safe and well tolerated for the indication proposed and side effects are generally mild and reversible. Despite the wide use, no serious adverse reaction was reported. The analysis of data from clinical studies shows that side effects associated with its use such as nausea, heartburn, constipation, flatulence, abdominal bloating and diarrhoea are rarely reported and their frequency is similar to that of placebo. The occurrence of frequent mouth ulceration has been reported, but it has successively become clear that it is associated with chewing of feverfew fresh leaves. Such events are not reported from clinical studies in which feverfew was encapsulated. This may be plausible because such preparations do not come into contact with the Langerhans cells of the skin oral mucosa. Potential problems of sensitisation caused by allergens can be avoided by the use of capsules.
The proposed medicial use for Tanaceti parthenii herba is:
“Traditional herbal medicinal product for the prophylaxis of migraine headaches”.
Due to the lack of sufficient data on long term use and based on the knowledge that prolonged intake can provoke rebound effects when feverfew is withdrawn, the duration of use of two months seems to be suitable for