Achillea (Millefolii herba)

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Authorisation details
Latin name of the genus: Achillea
Latin name of herbal substance: Millefolii herba
Botanical name of plant: Achillea Millefolii L.
English common name of herbal substance: Yarrow
Status: P: Draft published
Date added to the inventory: 31/10/2007
Date added to priority list: 10/01/2008
Outcome of European Assessment: Community herbal monograph
Additional Information:

Product Characteristics - Assessment Report
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ations thereof .3
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preparations ... 8
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ance(s), herbal
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5.1. Overview of toxicological/safety data from clinical trials in humans.......................... 20
5.2. Patient exposure .............................................................................................. 20
5.3. Adverse events and serious adverse events and deaths ......................................... 20
5.4. Laboratory findings .......................................................................................... 21
5.5. Safety in special populations and situations ......................................................... 22
5.6. Overall conclusions on clinical safety ................................................................... 23
6. Overall conclusions .......................................................................................................... 23
Annex .................................................................................................................................. 23
Assessment report on Achillea millefolium L., herba
1. Introduction
1.1. Description of the herbal substance(s), herbal preparation(s) or
Herbal substance(s)
- The whole or cut dried flowering top
s of yarrow, Achillea millefolium
This definition can be found in:
European Pharmacopoeia 6 ed. (2008) Yarrow
Extra Pharmacopoeia Martindale
XXV. Edition (Todd RG 1976)
Herbal Medicines (Newal CA et al. 1996), (Barnes J at al. 2007)
WHO Monographs (Volum
e 4, 2009)
ESCOP Monographs (Supplement 2009)
- Fresh or dried aerial (aboveground) part collected during the flowering season of Achillea millefolium
This definition can be found in:
Pharmacopoea Hungarica Editio VI. Tomus III, 196
Hagers Handbuch der Pharm
azeutischen Praxis 1969 (Kern W.)
German Comission E Monograph 1990
British Herbal Pharmacopo
eia 1996 (dried aerial parts)
British Herbal Comp
endium Volume 1, 1992 (dried aerial parts)
WHO Monographs (Volume 4, 2009)
ESCOP Monographs (Supplement 2009)
Assessor’s comment: MLWP decided to use the definition of European Pharmacopoeia 6 th ed. (2008)
Yarrow on it March meeting 2010.
Herbal preparation(s)
Communited herbal substance as infusion for tea preparation (Augustin B 1948, Todd RG 1967,
BHP 1974, R . 1984, German Commission E monograph 1990, Blumenthal M et al. 1990,
Wren RC 1988, Bisset NG 1994, Newal CA et al. 1996, Hänsel R et al. 1992, Bradley R 1992)
ácz G et al
Expressed juice (1:1) from fresh herb (Blumenthal M et al. 1990, Hänsel R et al. 1992)
Liquid extract (1:1), extraction solvent: ethanol 25% (V/V) (Wren RC 1988, Bradley R 1992, Newal CA
et al. 1996, BHP 1974)
Tincture (1:5), extraction solvent: ethanol 45% (V/V) (Bradley R 1992, Newal CA et al. 1996, BHP
Assessment report on Achillea millefolium L., herba
Combinations of herbal substance(s) and/or herbal preparation(s) including a descri
vitamin(s) and/or mi
assessed, where applicable.
ption of
neral(s) as ingredients of traditional combination herbal medicinal products
Millefolii herba is a frequent component of combinations mainly for mild cramp-like, gastrointestinal
complaints, catarrh and lost of appetite.
1.1.1. Phytochemical characteristics
Achillea millefolium L. s.l. is a cytogeneti
The genus Achillea consists of about 140 perennial herbs native to the Northern
cally, morphologically, and chemically polymorphic aggregate.
Principal components of the herbal substance
oils, mostly linalool,
composed of guaianolides,
achillifolin, millefin); flavonoids (apigenin, luteolin, isorhamnetin, rutin); amino acids (alanine,
ic, salicylic);
ne, choline);
ponins; sterols (β-sitosterol); sugars (dextrose, glucose,
histidine, leucine, lysine); fatty acids (linoleic, palmitic, oleic); phenolic acids (caffe
vitamins (ascorbic acid, folic acid); alkaloids and bases (achiceine, achilleine, betai
alkanes (tricosane); polyacetylenes; sa
mannitol, sucrose); and coumarins (Blumenthal M 2000).
According to the literature the pharmacological effects are mainly due to the e
and other sesquiterpene lactones, phenolic compounds such as dicaffeoylquinic ac
However, according to the two below mentioned articles these components can be
different quantity in the different plant materials.
ssential oil, proazulenes
ids and flavonoids.
found in very
Benedek B et al. (2007 a) developed a SPE-HPLC/UV method that allows quantification of the phenolic
constituents in the different taxa in oder to evaluate their contribution to the chemotaxonomy of
European taxa of the A. millefolium group. The investigated species displayed differences in the
quantitative and qualitative composition of phenolic acids and flavonoids. Hence, they seem to be of
chemotaxonomic significance, especially for the distinction of the diploid taxa. Combining the obtained
results with the data of the sesquiterpene analyses they can give a comprehensive insight into the
distribution of those pharmacologically relevant plant constituents in the A. millefolium group.
In their study Benedek B et al. 2008 revealed that the quality of 40 commercial drug samples was very
heterogenous and only 50% of the samples met the standards of the European Pharmacopoeia.
Assessment report on Achillea millefolium L., herba
Yarrow contains 3-4% condensed and hydrolysable tannins; 0.3-1.4% volatile
borneol, camphor, β-caryophyllene, 1.8-cineole, and sesquiterpene lactones
mainly achillicin (a proazulene), achillin, leucodin, and germacranolides (dihyd
1.2. Information about prod
ucts on the market in the Member States
Regulat y status ove
Member Stat
Regulatory Status
Comments (not
mandatory field)
Other TRAD
Ot er Specify: Only in combination.
Other TRAD
Other Speci
Other TRAD
Other Specify:
Other TRAD
her Specify: No products.
Czech Republic
Other TRAD
Ot er Specify: + in combination
Other TRAD
her Specify:
Only in combination
Other TRAD
Ot er Specify: Only in combination
Other TRAD
her Specify:
Other TRAD
Other Specify: No products.
MA 5
Other TRAD
her Specify:
Other TRAD
Other Speci
Other TRAD
Other Specify: “Healing products”
Other TRAD
Other Specify:
Other TRAD
Other Specify: No products.
Other TRAD
Other Specify: No products.
Other TRAD
Other Specify:
Other TRAD
Other Specify:
Other TRAD
Other Specify:
Other TRAD
Other Specify:
Other TRAD
Other Specify:
The Netherlands
Other TRAD
Other Speci
Other TRAD
her Specify:
No products.
Other TRAD
Other Specify:
Other TRAD
Other Specify:
Other TRAD
Other Specify:
Slovak Republic
Other TRAD
Other Specify: Only in combination.
Other TRAD
Other Specify: No products.
Other TRAD
Other Specify: No products.
Other TRAD
Other Specify: No products.
United Kingdom
Other TRAD
Other Specify:
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’
Assessment report on Achillea millefolium L., herba
This regulatory overview
products in the MSs concerned.
is not legally binding and does not necessarily reflect the legal status of the
Table I. Product n the ma
s o
rket as provided by the Member s
Active substance
Pharmaceutical f rm
Poso y
Legal status
Millefolii herba (names of
the products: řebříč
čaj, řebříčková nať)
oral use: for s
treatment of m
intes-tinal comp
loss of appetite
oromucosal use:
tomatic treatm
and thr
ts, at
for or
and to
al, oromucosal
pical use
ral use: 1.5 g (1
n)/250 ml of
s 2 – 3 times
dailyfor oromucosal and
in t
or symp-
of minor
he mouth
(2 –
se: 3 to 4.5
a spo
ng water/15
r tre
everal times daily (as a
bath or poultice)
atment of
3 te
ons)/ 250
ml of boili
Tincture from Millefo
herba (1:5), extra
in the
ntestinal tract, loss of
ts like
4 x dail
g) l
y 4.
3 ml (= 4.
At least since
solvent: ethanol 31.
iquid containing
100% tin
V/V, oral liquid; (D )
Expressed juice (1:0
0.85) from fresh Mill
d; (DE)
Digestive co
mild spasms in the gastro-
ts like
5 ml liquid
g 100%
express d juice
At least since
herba; oral liqui
intestinal tract, l
oss of
Expressed juice (1
0.93) from fre
sh Millefolii
.84- Digestive
mild spasms in the gastro-
ts like
2 x
daily 10
ml li
At least since
1990 (already
authorized in
the former
containing 100%
herba oral liquid; E)
intestinal tract, l
s of
d juice
l (29 V/V
oral solution; (HU)
Treatment of infl
disorders of stom
colon, appetize
ch and
3x30 dr
small vo
f fluid,
en before meals
ps daily in a
lume o
Since 1995
190 mg finely chopp
Millefolii herba
coated tablet; (HU)
Digestivum, spasm
oliticum, 3x3-4
coated tablets
(corresponding to 3x
570-760 mg herbal
Since 1996
Herbal substance
(millefolii herba) as
herbal tea. (PL)
Traditional herbal medicinal
product for treatment loss
of appetite and dyspeptic
complaints (mild, spastic
gastrointestinal discomfort)
Topical use: small superficial
epidermal excoriation
Oral use: (infusion) 3.5
g of herbal substance in
½ glass of bolding
water 2 – 3 times daily
Topical use: Infusion
should be prepared in
the same way
More than 30
Assessment report on Achillea millefolium L., herba
for o
tea spoo
boiling wa
topical use: fo
minor skin infla
Digestive comp
mild spasms
x daily
20 g extract
Millefolii herba
80 g ethano
1.3. Search and assessment methodology
The assessment report of Millefolii herba is based on the following literature resourc
- Monographs:
(Volume 4 2009), Hagers Handbuch (Hansel R et al. 1992), Expanded Commission
(Blumenthal 2000).
ESCOP Monographs (Supplement 2009). WHO Monographs on Selected Medicinal Plants
E Monograph
- Articles and references retrieved from data bases (Pubmed, Toxnet) or internet s
until the end of 2009. The term of Achillea mille
ources (e.g. Google)
folium was searched.
Articles and data that were found to be relevant for assessment are included in the list of references.
2. Historical data on medicinal use
2.1. Information on period of medicinal use in the Commun
tures for
n name is a corruption of the
been derived from
es of Greek mythology, which was fabled to have had his wounds treated by topical use of the
erived from the many segments of its foliage. The ancient
ry herb – an ointment made from it was used as vulnerary
drug on battle wounds. Yarrow flower was formerly official in United States Pharmacopoeia.
a for fevers and wound healing (Karnick
Additionally, it is listed in the Indian Ayurvedic Pharmacopoei
CR 1994).
European National pharmacopoei
al monographs:
Hungarian Pharmacopoeia 6 Edition Volume III (1967)
Extra Pharmac
opoeia Martindale Twenty-fifth edition (1967)
British Herbal Pharmacopoeia (BHP) 19
74, 1996
Polish herbal compendium (1978)
German Pharmacopoeia (DAB 10) (mentioned by Bisset NG 1994)
ch, French, Romanian Pharmarmacopoeias (mentioned by Newal CA et al. 1996)
Other monographs:
Hungarian Herbal Drugs (Augustin B et al. 1948)
German Commission E monograph (1990)
Hagers Handbuch (Kern W et al. 1969, Hänsel R et al. 1992 )
Potter’s New Cyclopedia of Botanical Drugs and Preparations (Wren RC 1988)
Assessment report on Achillea millefolium L., herba
According to Blumental M et al. (2000) yarrow has been used as medicine by many cul
hundreds of years (Budavari S 1996, Zeylstra H 1997). Its English commo
Anglo-Saxon name gearwe ; the Dutch, yerw . The genus name Achillea may have
the Achill
herb. The species name millefolium is d
Europeans called it Herba Militaris , the milita
2.2. Information on
traditional/current indications and specified
Evidence regarding the indic
ation/traditional use
In Belgium (cited
Circulaire No. 367 of July 1991
dermatological affection.
in Bradley PR 1992):
: Traditionally used topically as soothing antipruriginous application for
In France (cited in Bradley PR 1992):
Bulletin Officiel No.90/22
Taken orally: traditionally used in symptomatic treatment digestive disorders such
bis: Achillée millefeuille, sommité fleurie
as: epigastric
distension; Sluggishness of digestion; belching; flatulence as adjuvant treatment for painful
t of spasmodic colitis.
Traditionally used topically as soothing and antipruriginous application for derma
protective treatment for cracks, grazes, chaps and against insect bites.
tological ailments, as
In Germany:
As aromatic, somatic, adstringents, choleretic, in problems of menstruation, bleeding for
15-20:200), expressed juice from
y as chamomile
Internally: loss of appetite; dyspeptic complaints such as mild, spasmodic disturbances i
gastrointestinal region. In hip baths: painful, cramp-like conditio
part of female pelvis) (German Commission E monograph 1990, Hänsel R et al. 1992).
n the
n of psychosomatic origin (in the lower
r aromatic for loss of
he skin and mucous
membranes, for healing wounds. In folk medicine, the drug is often employed as haemostyptic, e.g. in
ration (baths)
bleeding from haemorrhoids, and in problems of menstruation and to remove perspi
(Bisset NG Herbal drugs and Phytopharmaceuticals 1994, Hänsel R et al. 1992).
llefolii herba in case of dysmenorrhoea is mentioned e.g. in the Madaus handbook (1938)
up to now also in recent editions of handbooks on phytotherapy (e.g. Fintelmann 2002 Lehrbuch
on comminuted herbal
In Romania (Rácz G et al. 1984):
It is used in the inflammation of the mucous membrane of the stomach, gastric-
catarrh of the colon. It i
, duodenal ulcer,
s used externally for bathing of baby, of patients with eczema and as rinse in
In UK:
Diaphoretic, stimulant, and haemostatic (Todd G Extra Pharmacopoeia Martindale 1967)
Indications: feverish conditions, common cold; digestive complaints. Other uses: loss of appetite,
hypertension, menstrual irregularities. It used topically for slow-healing wounds and skin inflammation.
(Newal CA Herbal Medicines 1992, Bradley PR British Herbal Compendium 1992, British Herbal
Pharmacopoeia 1983, 1990, Wren RC Potter’s New Cyclopedeia of botanical drugs and Preparations
1988, First published in 1907).
Assessment report on Achillea millefolium L., herba
haemorrhoids, varicose vein, as diuretic by hypertension, diaphoretic, liver trouble,
abortifacient, pertusis, lung tuberculosis, haematoma, as in infusum (
fresh herb for spring-cure. Externally it used for healing wounds and ulcers similarl
(Kern W et al . Hagers Handbuch 1969).
Gastrointestinal complaints (inflammation, diarrhoea, flatulence, cramps), as bitte
appetite, and for stimulation of bile secretion. Externally: inflammation of t
The use of Mi
der Phytotherapie). In this reference also the use of the infusion (1 spo
substance per cup, several times a day) is mentioned.
ve system and the
the folk medicine it has been used in female diseases, especially in the climacteric
period, the drug is often employed as haemostyptic in bleedings from intestine, uterus, lung or nose
(Augustin B 1948).
The proposed indications for the monograph:
Indications based on products on the markets for more than 30 years:
1) Traditional herbal medicinal product used in temporary loss of appetite.
nal product for symptomatic treatment of mild, spasmodic gastro-intestinal
complaints including bloating, and flatulence.
4) Traditional herbal medicinal product for treatment of small superficial wound.
Indications based on literature:
3) For sym
ptomatic treatment of minor spasm associated with menstrual periods.
Evidence rega
rding specified substances/preparations
Herbal substance
Not applicable.
Herbal preparations
In the literature
9, Hansel R et al.
2, BHP 1974, 1983, Augustin B et al. 1948, Rácz G et al. 1984, German Commission E monograph
l CA et al. 1996, Bradley R 1992, Bisset NG 1994, Newal
1990, Wren RC 1988, Bisset NG 1994, Newa
CA et al. 1996)
Liquid extract (1:1), extraction solven
1992, Newal CA et al. 1996)
t: ethanol 25% (V/V) (BHP 1974, Wren RC 1988, Bradley R
Tincture (1:5), extraction solvent: ethanol 45% (V/V) (BHP 1974, Bradley R 1992,
Newal CA et al.
Products on the market for more than thirty years
Communited herbal substance
Expressed juice (1:0.65-0.85) from fresh herb
Expressed juice (1:0.84-0.93) from fresh herb
Assessor’s comment: These two expressed juice were drawn together in one preparation according to
the suggestion of Subgroup discussion in May 2010:
Expressed juice (DER 1:0.6-0.9) from fresh herb
Tincture (ratio of herbal substance to extraction solvent 1:5), extraction solvent: ethanol 31.5% (V/V)
Assessment report on Achillea millefolium L., herba
In Hungary:
Millefolii herba belongs to the bitter substances, because it stimulates the digesti
metabolism. In
2) Traditional herbal medici
Communited herbal substance as infusion for tea preparation (Kern W et al. 196
2.3. Specified strength/posology
for relevant prepar
/route of administration/duration of use
ations and indications
Indication 1) and 2)
Comminuted herbal substance as infusion for tea preparation:
Three times daily: 2-4 g (Todd RG 1967, Bradley PR 1992, Hänsel R et al. 1992)
Daily dose: 4.5 g of yarrow herb (German Commission E monograph 1990, Bisset NG 199
Wording of the package insert, from the German Standard Licence:
Hot water (ca. 150 ml) are
passed through a tea strainer. Unless otherwise prescribed, a cup of freshly prepare
warm three or four times a day betw
poured over two teaspoonfuls (2-4 g) of Yarrow and after 10 minutes
d infusion is drunk
een meals (in Bisset NG 1994, Hänsel R et al. 1992).
Single dose: 1.5 g (Kern W 1
Herbal tea: 3.5 g of herbal substance as infusion in ½ glass of boiling water 2-3
on the market more than 30 years i
times daily (products
n Poland).
Expressed juice f
rom fresh herb:
DER: 1:0.6-0.9; 3 x daily 5 ml liquid containing 100% expressed juice (product on the market
more than 30 years)
DER: 1:0.8–1.0; 2 x daily 10 ml liquid containing 100% expressed juice (product on the market
more than 30 years)
Assessor’s comment: These two expressed juice were drawn together in one pre
the suggestion of Subgrou
paration according to
p discussion in May 2010:
Expressed juice (DER: 1:0.6-0.9) from fresh herb 5-10 ml twice or three times da
tract (1:1) , extraction solvent: ethanol 25% (V/V): 2-4ml three times daily (Wren 1988,
Bradley R 1992, Newal CA et al. 1996 , BHP 1974)
Tincture (1:5) , extraction solvent: ethan
Newal CA
ol 45% (V/V): 2-4 ml three times daily (Bradley R 1992,
et al. 1996 , BHP 1974)
Tincture (1:5) , extraction solvent: ethanol 31.5% (V/V) 4 x daily 4.3 ml (= 4.2
market more than 30 years)
g) (products on the
Indication 3)
inuted herbal substance per cup, as infusion several times a day (the Madaus handbook
1938, Fintelmann 2002 Lehrbuch der Phytotherapie)
Indication 4)
Herbal substance as herbal tea (infusion) 3.5 g of herbal substance in ½ glass of boling water 2 – 3
times daily (products on the market more than 30 years in Poland)
The proposed posology for the monograph
Oral use
i) Herbal substance
Not applicable
Assessment report on Achillea millefolium L., herba
Liquid ex
1 spoon comm
ii) Herbal preparati
Indication 1) and 2)
a) 2-4 g comminuted herbal substance as infusion three or four times a day between meals
b) Expressed juice from fresh herb (1:0.6-0.9) 5-10 ml twice or three times daily
c) Liquid extract (1:1), extraction solvent: ethanol 25% (V/V): 2-4 ml
three times daily
d) Tinctur
e (1:5), extraction solvent: ethanol 45% (V/V)
e) Tincture (1:5), extraction solvent: ethanol 31.5% (V/V) 4 x
daily 4.3 ml (= 4.2 g)
Indication 3)
1-2 g comminuted herbal substance per cup, as infusion 2-3 times daily
Cutaneous use
Indication 4)
3.5 g of comminuted herbal substance as infusion applied as cold compresses
2-3 times daily
3. Non-
Clinical Data
3.1. Overview of available pharmacological data regarding the herb
substance(s), herbal preparation(s) and relevant constituent
s thereof
In vitro studies
Anti-inflammatory activity
An extract of yarrow herb, prepared as 0.2 mg/ml of a lyophilized cold water extract,
% inhibition of platelet activating factor (PAF)-induced exocytosis of elastase f
The same extract (0.2 mg/ml) showed 21±2% activity in a test for inhibition of
prostaglandins from 14 C-arachidonic acid (Tunón H et al. 1995).
produced 41±2
rom human neutrophils.
the biosynthesis of
udy was to test a
rts of Achillea
millefolium L. s.l in in vitro-protease inhibition assays for understanding the mechanisms of anti-
ylquinic acids
activity of the plant. The extract and the flavonoid fraction inhibited HNE showing IC(50) values of
approximately 20 microg/ml, whereas the DCQA fraction was less active (IC(50)=72 microgram/ml).
The inhibitory activity on MMP-2 and -9 was observed at IC(50) values from 600 to 800 microgram/ml,
whereas the DCQA fraction showed stronger effects than the flavonoid fraction and the extract. The
authors concluded that the in vitro antiphlogistic activity of Achillea was at least partly mediated by
inhibition of HNE and MMP-2 and -9 (Benedek B et al. 2007).
inflammatory action. Furthermore, two fractions enriched in flavonoids and dicaffeo
(DCQAs), respectively, were also tested in order to evaluate their contribution to the anti
An inhibitory effect of the water soluble fraction of a hydro-alcoholic extract of Achillea millefolium was
measured with the value of IC 50 =1.25 mg/ml on soybean 15-lipoxygenase assay (IC 50 =concentration
which gave 50% inhibition) (Trouillas P et al. 2003).
Assessment report on Achillea millefolium L., herba
As various proteases, for instance human neutrophil elastase (HNE) and matrix met
(MMP-2 and -9), are associated with the inflammatory process, the aim of the st
methanolic [20% (V/V)] lyophilized extract (DER: 2.75:1) of powdered aerial pa
Anti-oxidant effects
Anti-oxidant activity of the water-soluble fraction from a hydro-alcoholic extract of
was demonstrated in the 1.1-diphenyl-2-picrylhydrazyl (DPPH) scavaging test
the hydroxyl radical scavenging test IC 50 =0.26 mg/ml) and in the superoxide ra
(IC 50
correlated with the total amount of phenolic compounds contained in the extr
Infusions of pulverized flower heads of various Achillea ( Asteraceae ) species prote
increased catalase, superoxid dismutate and glutation peroxidase activities, as
glutathione content of the cells and decrease in lipid peroxidation (Konyalioglu S an
Steam-distilled and non-stilled plant material from yarrow (A. millefolium L .)
solvents of different polarity and resulting fractions were evaluated for their radic
by the DPPH, NBT/hypoxanthine superoxide, and OH/luminol chemiluminescence methods and for
was extracted with
al scavenging activity
their antioxidant activity by the β-carotene blenching test. The total phenolic content was also
ons. In general, the
ioxidant and radical
The in vitro antioxidant activities of the essential oil and methanol extracts of Achillea mil
subsp. millefolium Afan. were investigated by Candan et al. GC-MS analys
in the identification of 36
terpineol, beta-pinene, and borneol were the principal components comprising
strongly reduced the diphenylpicrylhydrazyl radical (IC(50)=1.56 micro g/ml) an
radical scavenging effect in the Fe(3+)-EDTA-H(2)O(2) deo
It also inhibited the non-enzymatic lipid peroxidation of rat liver homogenate (IC(5
g/ml). The polar phase of the extract showed antioxidant activity (Candan F et al
is of the essential oil resulted
compounds constituting 90.8% of the total oil. Eucalyptol, camphor, alpha-
60.7% of the oil. The oil
d exhibited hydroxyl
xyribose system (IC(50)=2.7 micro g/ml).
0)=13.5 micro
. 2003).
Anti-proliferative activity
The above mentioned water-soluble fraction from a hydro-alcoholic extract of Achill
showed anti-proliferative effect on B16 mouse melanoma cells after two days of gr
cell proliferation at 0.05-0.1mg/ml concentration (Trouillas P et al. 2003).
ea millefolium
owth. It inhibited
ea millefolium was
th arrest in G2/M
1, which in turn inhibits
uld explain casticin
er cells, and a sub-G1
accumulation occurs in the cell cycle. Moreover, following a transient transfection with Bcl-2, MN1 cells
are resistant to casticin. According to the authors a number of features suggest that casticin could be
important in cancer therapy. Indeed, Pgp over expressing cells are not resistant to casticin, and its cell
killing effect is observed even in p53 mutant or null cell lines (Haidara K et al. 2006).
The antiproliferative activities of n-hexane, chloroform, aqueous-methanol and aqueous extracts of the
aerial parts of the Achillea millefolium aggregate on three human tumour cell lines were investigated
by means of MTT assays. The chloroform-soluble extract exerted high tumour cell proliferation
inhibitory activities on HeLa and MCF-7 cells, and a moderate effect on A431 cells; accordingly, it was
subjected to detailed bioactivity-guided fractionation. As a result of the multistep chromatographic
Assessment report on Achillea millefolium L., herba
Achillea millefolium
(IC 50 =0.13 mg/ml), in
dical scavenging test
=0.82 mg/ml). Other 15 plant extracts were tested as well, and the antioxidant effects were
acts (Trouillas P et al.
cted human
hrocytes and leucocytes against hydrogen peroxide-induced oxidative damage. This was shown by
well as by reduced
d Karamrenderes C
determined by the Folin-Ciocalteu method. Both remarkably high phenolic content and radi
scavenging activities were found for the ethyl acetate and dichloromethane fracti
distilled plant material was found to exhibit a higher phenolic content as well as ant
scavenging activities than the non-distilled material (Parejo I et al. 2002).
The mechanism of anti-tumour activity of the flavonoid casticin, derived from Achill
studied by Haidara K et al. (2006). Casticin anti-tumour activity results in cell grow
and in apoptotic death. As a tubulin-binding agent (TBA), casticin induces p2
Cdk1. Moreover, casticin appears to down regulate cyclin A. These observations co
induced G2/M arrest. Following casticin exposure, Bcl-2 depletion occurs in canc
purifications (VLC, CPC, PLC, gel filtration), five flavonoids (apigenin, luteolin, centa
and artemetin) and five sesquiterpenoids (paulitin, isopaulitin, psilostachyin C, desacetyl
sintenin) were isolated and identified by spectroscopic methods. The antiprolife
demonstrated that centaureidin is the most effective constituent of the aerial parts
growth inhibitory activities were observed especially on HeLa (IC(50) 0.0819 micro
(IC(50) 0.1250 microm) cells. Casticin and paulitin were also highly effective aga
cell lines (IC(50) 1.286-4.76 microm), while apigenin, luteolin and isopauli
active (IC(50) 6.95-32.88 microm). Artemetin, psilostachyin C, desacetylmatri
not display antiproliferative effects against these cell lines (Csupor-Löffler B et al. 2008).
ureidin, casticin
matricarin and
rative assay
of yarrow: high cell
m) and MCF-7
inst all three tumour
tin proved to be moderately
carin and sintenin did
A lyophilized
hepatoma activity (
of proliferation was 55% on non-hepatitis B virus cell lines and 20% on hepatitis B
L-T et al. 2002).
Estrogenic activity
showed oestregenic
0 -5 mg/ml and 2.8
erved with compounds
.9 x 10 -3 mg/ml) and
and luteolin, the
udied for their ability to activate
ceptors (ERalpha, ERbeta) using transiently transfected cells. On the basis of
their results the authors suggest that apigenin can stimulate ERs-dependent biological pathways,
receptors, alpha and
have a very slight effect on beta and does not
of A. millefolium
although with a smaller potency as compared with the endogen hormone. Both
beta, can be activated by apigenin. Luteolin seems to
seem to activate alpha at all. However the role of apigenin in emmenagogic effects
as traditionally reported- can not be defined on this basis (Innocenti G et al. 2007).
Antispasmodic activity
Antispasmodic activity on isolated rabbit intestine has been documented for flavono
fraction of the aerial parts of yarrow (Hoerhammer L 1962).
yarrow ( Achillea millefolium
cetin and two flavonoid metabolites were investigated on
ed the highest
µmol/L, respectively.
effects on contractility of the terminal ilea. From the results on the spasmolytic activity of the flavonoid
fraction, the glycosides and respective aglycones it was concluded by the author that in tea prepared
from yarrow the concentration of flavonoidsis high enough to exert a spasmolytic effect in gut, which is
mainly caused by blockade of the calcium inward current, but additionally also by mediator-
antagonistic effects (Lemmens-Gruber et al. 2006).
In isolated rabbit jejunum preparations, a 70% methanolic extract of the aerial parts of Achillea
millefolium (DER: 5.5:1) caused a concentration-dependent (0.3-10 mg/mL) relaxation of both
spontaneous and K + -induced contractions as well as shifting the Ca ++ concentration-response curves to
the right, similar to that caused by verapamil (Yaeesh S et al. 2006).
Assessment report on Achillea millefolium L., herba
decoction (approx. 5:1) from yarrow ( Achillea millefolium L. ) was evaluated for anti-
cytotoxicity) on five human liver cancer cell lines; at 2mg/ml the average inhibition
virus cell lines (Lin
Dry methanolic and 10%-methanolic extracts of the aerial parts of A. millefolium
activity in transgenic MCF-7 cells. The lowest effective concentrations were 8.57 x 1
x 10 -4 mg/ml respectively (p<0.01). Positive oestrogenic effects were also obs
isolated from the 10%-methanolic extract: apigenin (2.5 x 10 -4 mg/ml) luteolin (8
their 7-O–glucosides (3.9 x10 -5 mg/ml and 3.4 x10 -5 mg/ml respectively). Apigenin
most important estrogenic compounds among those tested, were st
alpha or beta oestrogen re
The spasmolytic activity of a flavonoid fraction of a commercial sample of
L. s.l), its main flavonoids as well as quer
isolated guinea-pig ilea. The aglycones quercetin, luteolin and apigenin exhibit
antispasmodic activities with IC 50 values of 7.8 µmol/L, 9.8 µmol/L and 12.5
Rutin and the flavonoid metabolites homovanillic and homoproto-catechuic acid showed no si
Choleretic effect
c extract of the
cynarin (1,3-
ts revealed a dose-
stimulated bile flow more effectively than the single compound cynarin. Due to their polar structure,
ntitatively extracted into teas and tinctures; hence, according to the authors,
s of yarrow.
these compounds are qua
they seem to be the choleretic active principles in the traditional application form
Antimicrobial activity
A lipophilic extract of aerial parts of Achillea millefolium (hexane: ether: m
DER approx. 11:1) has been tested for antimicrobial activity in a disk diffusio
bacteria ( Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pse
and Salmonella enteritidis
broad spectrum of antimicrobial activity against all tested strains (Stonajovic G
ethanol=1:1:1 solvent,
n assay against five
udomonas aeruginosa
) and two fungi ( Aspergillus niger and Candida albicans ). Extract possessed a
et al. 2005).
fresh plant (Acchillea millefolium ) exhibited antimicrobial activity
against Mycobacterium phlei, but not against fungi or Gram-positive or Gram-negative bacteria
(Dornberger K and Lich H 1982).
A 95% methanolic extract of powered arial parts of yarrow (Achillea millefolium
different strains of the Gramm-negative ba
L.) inhibited 15
cterium Helicobacter pylori with MICs in the range 1.56-100
microg/mL (Mahady GB et al. 2005).
The in vitro antimicrobial activities of the essential oil and methanol extracts of Achillea millefolium
subsp. millefolium Afan. (Asteraceae) were investigated. The oil showed antimicro
Streptococcus pneumoniae , Clostridium perfringens, Candida albicans, Mycobacter
Acinetobacter woffii and Candida krusei while water-insoluble parts of the methan
exhibited slig
bial activity against
ium smegmatis,
olic extracts
ht or no activity (Candan F et al. 2003).
Haemostyptic activity
A 5% m/V hot water infusium of yarrow ( Achillea millefolium) significantly short
time (a test of blood coagulation) in human plasma to 43% of that of the refer
sodium chloride (p<0.001). The flowering herb had the highest hamostypic activity, whereas presse
juice significantly prolonged blood coagulation (p<0.05 to p<0.001) (Sellerber
ened recalcification
ence substance, 0.9%
g U and Glasl H 2000).
In vivo studies
study, the efficacy of herbal extracts of Thymus vulgaris (thyme) and Achillea millefolium
(yarrow), propolis hydroalcoholic extract and systemic glucantime against cutaneous leishmaniasis in
Balb/c mice we evaluated. A total of 45 mice were randomised into five groups each including nine
mice. They were treated with pure ethanol 70 degrees, systemic glucantime, Achillea millefolium
hydroalcoholic extract, Thymus vulgaris hydroalcoholic extract and propolis hydroalcoholic extract for
six weeks. The statistical tests including student t-test were used for analysis. Mean of ulcer size
reduction were -17.66, -22.57, 43.29, 36.09 and 43.77% for the alcohol, glucantime, yarrow, thyme
and propolis groups, respectively. The results were suggestive that Thymus vulgaris , Achillea
millefolium and propolis hydroalcoholic extracts were significantly more effective in reduction of ulcer
size as compared with glucantime (p = 0.006, 0.002 and 0.008, respectively) (Nilforoushzadeh MA et
al. 2008).
Assessment report on Achillea millefolium L., herba
In their work Benedek B et al. (2006) investigated a fraction from a 20% methanoli
arial part of yarrow enriched in dicaffeoylquinic acids (48%) and luteolin-7-
(3.4%) on its choleretic effect in the isolated perfused rat liver (IPRL) compared to
DCCA), the main choleretic compound of Cynara scolymus L. IPRL experimen
dependant increase in bile flow (23-44-47%) by the Achillea fraction. Choleresis was two- to
higher than that of cynarin. The combined effect of DCCAs and luteolin-7-O
A 95%-ethanolic extract, from
In this
Analgesic effects
The aim of the study of Noureddini M et al. was to assess the analgesic effects of aqueous extract (AE)
of Achillea millefolium L. in the rat’s formalin test. Oral administration of differen
and 320 mg/kg) induced a dose-dependent antinociception, both in the first and
formalin test. The results of the present study support the proposal t
analgesic effects. These
that its activity may be resulted from its central action (Noureddini M, Rasta V 2
t doses of AE (80, 160
second phases of the
hat Achillea millefolium L. has
findings justify the traditional use of the plant for treating pain and suggest
Anti-inflammatory effect
An aqueous extract of the dry flower heads of Achillea millefolium has been fou
inflammatory activity as measured by the yeast–induced mouse paw oedema test. Fracti
respectively fot the same doses (40 mg/kg body weight) of indomethacin and phenyl
concentrate is water-soluble, nonsteroidal and has a very low order of toxicity. P
studies show this active fraction to be mixture of protein-carbo-hy
A dry 80%-ethanolic extract from the aerial parts of yarrow ( Achillea millefolium
at 100 mg/kg, inhibited oedema in the carrageenan-induced rat paw oedema test
compared to 45% by indometacin at 5 mg/kg. (p<0.01) (Mascolo N et al. 1987).
L) administered orally
by 29% (p<0.05)
Gastro-protective effects
Seven days after induction of chronic gastric lesions in rats by acetic acid a hot (70º
(yield 36%, approximately DER: 2.8:1) from the aerial part of yarrow ( Achillea
administered orally at 100 or 300 mg/kg/day for 7 d
dependent healing effect
started 1 day after injection of acetic acid did not prevent the formulation of gastric u
treatment of rats with the extract one hour before induct
dose-dependent protective effect (p <0.05, ED 50 = 936 mg/kg). Gastric lesion
indometacin one hour after subcutaneous administration of the extract were si
<0.05) only the highest dose tested, 2000 mg/kg (Cavalcanti AM et al. 2006).
C) water extract
millefolium L), was
ays. Compared to controls a significant and dose-
was observed (p <0.05, ED 50 = 32.4 mg/kg). However, the same treatment
lcers. Oral pre-
ion of acute gastric lesions by ethanol had a
s induced by
gnificantly reduced (p
Hepato-protective effect:
A dry extract of aerial parts of yarrow (5.5:1, 70% methanol) administered intr
300, and 600 mg/kg body weight exerted a protective effect against D-
galactosamine+lipopolysaccharide-induced hepatitis in mice, significantly and dose-de
reducing plasma ALT and AST levels in treated animals compared to controls (p
histopathology an absence of congestion and focal necrosis was observed in trea
dose-dependent improvement in cellular swelling an
a-peritoneally at 150,
<0.05). In liver
ted animals, with
d the number of apoptotic cells. Pre-treatment of
the animals with the extract reduced mortality from 100% to 40% (Yaeesh S et al. 2006).
The antihepatotoxic activity of dry extracts of yarrow ( Achillea millefolium L), of varying polarity
(following extraction with chloroform, methanol or water) was evaluated in rats treated with carbon
tetrachloride or paracetamol as toxicants. Liver function was assessed by determining the levels of
serum glutamic oxalacetate transaminase (ALAT) and serum glutamic pyruvic transaminase (ASAT),
increases indicating necrosis of the liver. Intraperitoneal administration of the extract at 50 mg/kg
reduced ALAT/ASAT levels by 50-96% in carbon tetrachloride-treated animals and 41-91% in
paracetamol-treated animals (p <0.05) (considering the difference in levels between untreated and
toxicant-treated animals as 100%) (Gadgoli C et al. 1995).
Assessment report on Achillea millefolium L., herba
nd to possess anti-
nation has
lted in the isolation of a material which reduces inflammation by 35% compared to 44% and 26%
butazone. This
hysical and chemical
drate complexes (Goldberg AS et al.
3.2. Overview of available pharmacokinetic data regardi
substance(s), herbal preparation(s) and
ng the herbal
relevant constituents thereof
There are no pharmacokinetic data available.
3.3. Overview of available toxicolo
gical data regarding the herbal
bal preparation(s) and constituents thereof
Single dose toxicity
Yarrow dry extracts of varying polarity (following extraction with chloroform,
non-toxic in mice; the intraperitoneal LD 50 was determined as 1.5 g/kg body weig
methanol or water) were
ht (Gadgoli C et al.
Non-fasted rats of both sexes were treated with a single dose of hot water extract (yield 36%,
t doses of 3 and
e observational period of
(Cavalcanti AM et al. 2006).
lution, yield 18%,
dy weight no
changes in behaviour were apparent during a 6-hour observation period and no mortality after 24
. 2006).
hours (Yaeesh S et al
According to a safety assessment for its use in cosmetics, the oral and subcutaneo
mice of yarrow, Achillea millefolium. L. extract (2% flowers in propylene glycol and
1 g/kg (Anonymous 2001).
us LD 50 values in
water) were both
Repeated dose toxicity
ith a hot water extract (yield 36%, approximately
the aerial part of yarrow ( Achillea millefolium L) in doses 0.3-1.2 g/kg, p.o./day or
vehicle (water, 10 ml/kg/day) for 28 or 90 consecutive days. Rats were observed throughout the study
tudy, fairly extensive pathological,
ations from controls
th the extract
nd did not exceed
for morbility, mortality and vital signs and in the end of the s
histopathological and biochemical investigations were carried out. Occasional devi
or reference values were observed, but none of the changes observed after treatments wi
were correlated with dose or time of exposure in neither female nor male animals a
the reference range of variation (Cavalcan
ti AM et al. 2006).
Genotoxity studies
No adequate genotoxicity studies have been performed with Millefolii herba.
vidence of genotoxicity in
tation and Recombination Test (SMART). Quercetin and rutin, two flavonols
present in beverages of plant origin, exhibited weak genotoxic activity in somatic cells of Drosophila .
The standard herbal teas (infusions) were prepared by adding 20 g dry tea to 100 ml boiling tap water
and allowing it to draw for 10 min (Graf et al. 1994).
The genotoxicity evaluation of the essential oil of Achillea millefolium was performed at
concentrations of 0.13 microL/mL, 0.19 microL/mL and 0.25 microL/mL with a heterozygous diploid
strain of Aspergillus nidulans, named A757//UT448, with green conidia. A statistically significant
increase of mitotic recombinants due to either the induction of mitotic non-disjunction or crossing-over
was reported after oil treatment with 0.19 microL/mL and 0.25 microL/mL concentrations (de
Sant’anna JR et al. 2009).
Assessment report on Achillea millefolium L., herba
approximately DER: 2.8:1) from the aerial part of yarrow ( Achillea millefolium L) a
10 g/kg perorally or 1 and 3 g/kg intraperitoneally. No toxic symptoms over th
14 days were observed
After intraperitoneal treatment of mice with an extract (70% aqueous-methanol so
approximately DER: 5.6:1) of the arial parts of yarrow ( Achillea millefolium) at 3g/kg bo
Female and male Wistar rats were treated daily w
DER: 2.8:1) from
An herbal tea from Achillea millefolium provided some, albeit inconclusive e
the wing Somatic Mu
on chromosomal
ng it with the
ion at dosages
a-C (5 x 10(-7)
) were exposed to
ells were
ects significantly
rrant cell frequency
Am=249). Regarding
DNA repair inhibition by Ara-C, the Am infusion did not cause a significant reduction in aberrant cell
5.8%; Ara-C+Am=14.4%), These results indicate that the plant infusion per se do
a-C on DNA break
frequency (Ara-C=1
not has clastogenic activity, but can influence the clastogenic action of MMC and Ar
induction, in vitro (Roncada T et al. 2004).
Reproductive toxicity
ntraceptive, and for
perimental animal
s et al. (2003),
uman dose) of
) 1-8 or GD 8-15.
d received an equivalent
ods. On GD 20, rats
ghed and
examined for signs of external, internal or skeletal malformations. The dose used was not materno-
ts were increased in
n GD 1-8 compared
ow on GD 8-15
al or internal
with reduced fetal
toxic. There was no increase in pre- or post-implantation losses. Placental weigh
rats treated with yarrow on GD 8-15 compared to water and ethanol controls and o
to water control foetuses. Body weight was reduced in foetuses exposed to yarr
compared to water control foetuses. There was no difference in incidence of extern
malformations. In conclusion, a 2.8 g/kg b.w. daily dose of yarrow was associated
weight and increased placental weight (Boswell-Ruys CL et al. 2003).
Another study (Dalsenter et al. 2004) evaluated the toxicity of
from leaves of Achillea millefolium L. on reproductive endpoints in Wistar rats. Ad
treated daily with yarrow extract (0.3, 0.6 and 1.2 g/kg/day) during 90 days by or
including reproductive organ weights, sperm and spermatid numbers as well as sperm morphology
were evaluated. No clinical signs of toxicity were detected over the treatment
gain was similar in all groups. A significant increase in the percentage of abnorma
treated with the highest dose of yarrow extract was detected with no other import
the exposure to the aqueous extract
ult male rats were
al gavage. Endpoints
period, and body weight
l sperm in the group
ant changes in the
other reproductive endpoints studied in the male rats. Furthermore, a 3-day treatment of immature
female rats did not show any uterotrophic effects (Dalsenter PR et al. 2004).
on spermatogenesis of 50 Wistar rats by intraperitoneal administration. The animals were divided into
3 experimental groups (10 rats in each group) and control group (10 rat received distilled water) and 1
sham group (10 rats received nothing). At the dose of 200 mg/kg, there was no effect on
spermatogenesis and all of cells had normal arrangement and account. At dose of 400 mg/kg, a
significant difference in cell arrangement and cell count, but after 22 days, on which 5 number of this
group was kept without any extract administration, there was no significant difference between them
Assessment report on Achillea millefolium L., herba
In the present study the action leaves of Achillea millefolium L. (Am) infusion
aberration formation in human lymphocyte system in vitro was assessed, associati
alkylating agent mitomycin C (MMC) and the DNA repair inhibitor cytosine-be
(Ara-C). The cells were cultivated for 72 h and treated continuously with the Am infus
3.5 x 10(-4) g/ml culture medium. Treatments with MMC (0.30 microg/ml) or Ar
microg/ml) were administered after 48 h of cell culture. Each samples (five individual
six treatments (control with PBS; Am; MMC; MMC+Am; Ara-C; and Ara-C+Am) and 100 c
analyzed per cell culture. The used dose of the infusion did not cause clastogenic eff
different to the negative control (control=1%; Am=1.8%). Nevertheless, the abe
after MMC treatment was significantly increased by the Am infusion (MMC=32.4%;
especially when the chromatid break types number was scored (MMC=151; MMC+
Because yarrow has traditionally been used as an abortifacient, emmenagogue, co
stimulating uterine contractions, it is contra-indicated for use in pregnancy. Two ex
studies have addressed reproductive toxicity of yarrow. In a study of Boswell-Ruy
female rats were dosed, orally by gavage using 2.8 g/kg b.w./day (56 times the h
ethanolic solution of a commercial yarrow leaf extract on either gestation days (GD
Two groups of controls were included; the first received water and the secon
dose of ethanol to that found in the yarrow preparation over the two gestation peri
were sacrificed, placentae were weighed, and corpora lutea counted. The foetuses were wei
The effect of hydro-alcoholic extract (200, 400, 800 mg/kg) of Achillea millefolium L. yarrow flowers
and control group, so this dose was reversible. At dose of
as well, but after 22
800 mg/kg a significant effect was observed
days it was not reversible (Takzaree N et al. 2008).
Sensitization potential
Sensitization potential was assessed in groups of guinea pigs (Hausen et al. 199
Freund’s complete adjuvant method, by 0.1% and 1% crude extract of the whole
0.1% and 1% crude extract of the flowers. The sensitization potential of the se
alpha-peroxyachifolid was also tested at 0.01% and 0.1% using groups of 10 guin
using a gro
extract were se
sensitizer. Other known yarrow constituents like dehydromatricaria ester and ponti
to play no role.
Cardiac activity
zymes and serum
l group received
line. Base-apex electrocardiogram was recorded up to 2 hours and blood samples for
measuring an extensive array of serum enzymes and electrolytes were collected until 3 days after
rophysiological parameters were observed, whereas
ctrolytes. The authors
2 hours (Rahchamani R
administration. Some occasional changes in elect
Achillea millefolium had no significant effect on serum enzymes and ele
concluded that Achillea millefolium extract increased cardiac contractility after
et al. 2008).
3.4. Overall conclusions on non-clinical data
The above mentioned pharmacological studies made the proposed indica
tions plausible.
The indication of temporary loss of appetite is based on the bitter component(s) of
substance. According to German Pharmacopoeia (1997) the he
of maximum 5000.
the herbal
rbal substance must have a bitter value
The beneficial effect on mild, spasmodic gastro-intestinal complaints including bloating, and flatulence
eretic activity of the
lic (such as
ent of yarrow.
The antispasmodic and analgesic properties of the plant may support its effectiveness in the indication
of symptomatic treatment of minor spasm associated with menstrual periods.
The studies on antimicrobial and antiphlogistic activity may make the wound healing effect plausible.
Adequate tests on reproductive toxicity genotoxicity and carcinogenicity have not been performed.
Three experimental studies on embryotoxicity and reproductive toxicity demonstrate relatively
marginal effects. Guinea pig sensitization tests indicated some sensitization potential for yarrow
extracts and one sesquiterpene lactone component.
Assessment report on Achillea millefolium L., herba
1) in a modified
yarrow plant, and by
squiterpene lactone
ea pigs and at 1%
up of 3 guinea pigs. All animals tested with extracts of the whole plant and with flower
nsitized. Sesquiterpene lactone alpha-peroxyachifolid was identified as a strong
ca epoxide appear
The effects of Achillea millefolium total extract on electrocardiogram, cardiac en
electrolytes in 12 clinically healthy sheep were investigated. The treatment group were ad
intravenously a total extract of Achillea millefolium at a dose 20 mg/kg. The contro
normal sa
c an be supported by the experiments on the inflammatory, antispasmodic and chol
herbal substance . These activities are connected to the sesquiterpenes, pheno
dicaffeoylquinic acids) and flavonoid cont
4. Clinical Data
4.1. Clinical Pharmacology
4.1.1. Overview of pharmacodynamic data regarding the herbal
(s)/preparation(s) including data on relevant constituents
No data available.
4.1.2. Ove
rview of pharmacokinetic data regarding the herbal
eparation(s) including data on relevant constituents
No data available.
4.2. Clinic
al Efficacy
4.2.1. Dose response studies
No data available.
4.2.2. Clinical studies (case studies and clinical trials)
There was no clinical study performed with yarrow herb as a single componen
Only studies with combination products can be found.
bal combination
in. Forty-nine patients
were included for 2 weeks of treatment. Patients were followed until week 8. Forty-four patients
n and 22 with
completed the study. Twenty –two patients were treated with the study medicatio
placebo. The study medication was well tolerated without significant side effects.
The response to the study medication was significant in objective and subjective parameter
maintained partial remission until the end of follow-up. The placebo-treated group
response without a significant difference. In conclusion it was found that the treat
combination for atopic dermatitis does not differ from treatment with placebo
s. Patients
had a similar
ment with tri-herbal
(Shapira MY 2005).
, 90 mg
m, yarrow). Thirty-five patients
who were taking NSAIDs for mild to moderate ostearthrosis underwent a 2-week washout phase before
being randomized to receive Gitadyl (three tablets daily) or ibuprofen (400 mg three times daily)
administered for 2 x 21 days in a double-blind, crossover randomized controlled trial with the double-
dummy technique. Patients were allowed to take dextropropoxyphene as a rescue medication for pain
relief. The number of tablets taken was recorded and used to assess change in condition. The primary
outcome measures of pain (when resting and working) and walking ability were assessed using a
symptom score on a scale of 1–4 (none, mild, moderate, strong). A non-significant trend of symptom
reduction was observed in both groups, with no significant difference between groups. Gastrointestinal
complaints were more frequent in patients treated with ibuprofen (Long L et al. 2001).
Assessment report on Achillea millefolium L., herba
The aim of a randomized, placebo controlled trial was to test the efficacy of tri-her
(Eleutherococcus, Achillea millefolium and Lamium album) on atopic dermatitis
Gitadyl is an herbal preparation containing 110 mg feverfew (Chrysanthemum parthenium)
American aspen (Populus tremuloides) and 60 mg milfoil ( A. millefoliu
4.2.3. Clinical studies in s
pecial populations (e.g. elderly and children)
No data available.
4.3. Overall conclusions on clinical pharmacolog
y and efficacy
As there are no clinical studies, well-established indication can not be suggested.
The traditional use in the proposed indications is plausible taking into consideration the long-standing
d extract, the tincture and the expressed juice from
fresh herb.
5. Clin
ical Safety/Pharmacovigilance
5.1. Overview of toxicological/safety data from clinical trial
s in humans
family. Cases of
erpene lactones (SL)
not been detected. A
therto unknown
anolides of peroxide character. The main SL, identified as a strong sensitizer in guinea pig
tribute marginally
atricaria ester and
ositae -sensitive
(Hausen BM et al.
mile, feverfew, tansy,
udy the
eighteen of 3,851
ingle species of the mixture
ed extracts of chrysanthemums and laurel oil (bay leaf; Lauraceae ) revealed
tions to feverfew (70.1%) and lower responses to chrysanthemums (63.6%),
), chamomile (56.5%), arnica (51.8%), yarrow (51.8%), and the cross-reacting laurel oil
(50.5%). Ten of 85 reacted to arnica alone. The results show that it is important to test Compositae
contain (in contrast to a mixture of
, thiophenes) that may also
contribute to the acquired hypersensitivity. Unrevealed sources of hand and face eczema (including
airborne contact dermatitis) might be diagnosed more frequently (Hausen BM 1996).
extracts in patients with allergic contact dermatitis because these
pure sesquiterpene lactones) other constituents (e.g., polyacetylenes
5.2. Patient exposure
No data available.
5.3. Adverse events and serious adverse events and deaths
None known (German Comission Momograph 1990, Blumenthal M et al. 1998, 2000).
Assessment report on Achillea millefolium L., herba
use of the comminuted herbal substance, the liqui
Yarrow, Achillea millefolium L., is one of the commonest weeds of the Compositae
allergic contact dermatitis have been described since 1899. Although 10 sesquit
and 3 polyines have previously been identified, the sensitizers of yarrow have
reinvestigation of ether extracts of yarrow revealed the presence of 5 unsaturated hi
sensitization experiments, was named alpha-peroxyachifolid. The minor SL also con
to the sensitizing capacity, while other known yarrow constituents like dehydrom
pontica epoxide appear to play no role. A 5-year follow-up (1985-1990) of Comp
patients showed that more than 50% reacted when tested with an ether extract of
Exacerbation of the patch test sites by irradiation with UV light was never observed
A Compositae plant mixture consisting of ether extracts of arnica, German chamo
and yarrow has been included in the standard series for several years (1985 to 1990) to st
frequency of allergic reactions to Compositae ( Asteraceae ) species. One hundred
tested individuals gave a positive response (3.1%). Further tests with the s
and some additionally test
a high percentage of reac
tansy (60.8%
With allergies to Asteraceae , itching and inflammatory changes in the skin with fo
(yarrow dermati
Rarely allergic reactions with rash, f
external use. Cases of contact dermatitis (“meadow dermatitis”) and cross reacti
Compositae can occur (Hänsel R et al. 1992).
ormation of vesicles and pruritus can occur after internal or
on with other
Allergic reactions to yarrow (e.g. dermatitis) have been documented, and positive patch tests have
ng a
al. 2007).
Several cases of contact allergy have been reported (ESC
OP Supplement 2009).
Numerous reports of allergic contact dermatitis have been published. Direct contac
drug or its preparations may cause hypersensitivity reactions of the skin or mucosa, such
formation of vesicles and pruritus in sensitive individuals (WHO 2009).
t with the crude
as rash,
Compositae dermatitis occurred in a 9-year-old boy with a strong personal and f
Positive patch test reactions were 2+yarro
dermatitis morphologically but was prominent on the palms and face and dram
of the boy's feet covered by his shoes. The condition has always been seasonal,
especially July, and it clears on avoidance of contact. This case is believed to repr
dermatitis to oleoresins of Compositae plants; inhalants as a cause of systemic a
likely to be important in this patient (Guin JD 1987).
amily history of atopy.
w ( Achillea millifolium ). The eruption resembled atopic
atically spared the area
worsening in summer,
esent a contact
ggravation are not
oman began to
ed these dried
trepieces and baskets).
family history of
l examination was normal. Basal spirometry and chest X-ray was normal.
E was 7.94 kU/l.
0-7 mm). Specific
ed an asthmatic
9 kU/l respectively.
Immunoblotting with yarrow flowers revealed several IgE binding bands of 51, 21 and 18 kDa.
s caused by decorative flowers are seldom reported in the literature
Occupational respiratory symptom
(Compes E et al. 2006).
subjects, product formulations containing 2% of extracts of the crude drug
ly not irritating. I provocative testing, patients reacted to Compositae mix that contained
the crude drug, as well as to the crude drug alone. In clinical testing, a formulation containing 0.1%
yarrow extract (propylene glycol and water) was not sensitizer in a maximization test and alcoholic
extracts of aerial parts of A. millefolium did not produce a phototoxic response (Anonymous 2001).
Proposed wording in the monograph:
Hypersensitivity reactions of the skin have been reported. The frequency is not known.
5.4. Laboratory findings
No data available.
Assessment report on Achillea millefolium L., herba
rmation of vesicles
tis) may occur, in which case the treatment must be stopped immediately (Bisset NG
been produced in individuals sensitised to other plants. An instance of yarrow tea causi
generalised eruption in a sensitised individual was reported in 1929 (Barnes J et
Since 5 months after her first contact with dried flowers of yarrow a 44-year-old w
experience rhinitis, asthma and urticaria symptoms in the workplace when she handl
flowers as an instructor of personnel making dried flower arrangements (cen
She had a clinical history of spring seasonal rhino conjunctivitis and asthma but no
atopy. The physica
Methacholine inhalation test was positive with a PC20 of 2.5 mg/ml. Total serum Ig
Skin prick test with aqueous extracts from dried flowers were positive to yarrow (1
Inhalation Bronchial Challenge with aqueous extract of yarrow (1.25 mg/ml) elicit
response with a fall in FEV1 of 31%. Specific IgE (EAST) with yarrow flowers was 0.
In a clinical testing with 20
were general
5.5. Safety in special populations and situations
Contra indications (hypersensitivity and allergic potential to be both cove
Allergy to yarrow and other Compositaes (Blumenthal M 1998, 2000, Breadly R 1992, Hänsel R et al.
1992, Newal CA et al. 1996).
and precautions for use
The use in children and ad
adequate data.
If the s
practitioner should be consulted.
olescents under 18 years of age is not recommended due to lack of
ymptoms worsen during the use of the medicinal product, a doctor or a qualified health care
If signs of skin infection are observed, a doctor or a qualified health care practitioner shou
ld be
For tinctures, extracts containing ethanol the appropriate labelling for ethanol, taken from the
uman use’, must be
Drug interactions
r, the potential for preparations of yarrow to interact with other medicines
particularly those with similar or opposing effects, should be considered.
There is limited evidence from preclinical studies that achilleine, a constituent of yarrow, has
arnes J et al. 2007).
anticoagulant activity, although the clinical relevance of this, if any is not clear (B
Assessor’s comment: “None reported” is written in the monograph as the above m
entioned drug-
ns are only assumptions.
Use in pregnancy and lactation
reputed to be an
ce amounts (0.3%) of
the abortifacient principle thujone. Excessive use should be avoided during lactation (Newal CA et al.
1996, 2007).
Assessor’s comment: Due to lack of adequate data a specific warning is not included in the
tions of yarrow contain only trace amounts of thujone. The herb contains 0.3-
lumenthal M et al. 2000, which may contain 0.3% thujone, see above.
e is 2-4 g three times daily which means 6-12 g/day of the herbal substance with a 0.27-
0.5 mg content of thujone/day. This concentration is probably too low to present a risk to human
standard sentences are suggested in the monograph:
health. The
Safety during pregnancy and lactation has not been established. In the absence of sufficient data, the
use during pregnancy and lactation is not recommended.
No case of overdose has been reported.
Drug abuse
None reported.
Assessment report on Achillea millefolium L., herba
‘Guideline on excipients in the label and package leaflet of medicinal products for h
None documented. Howeve
administered concurrently,
It is frequently considered that yarrow should not be taken during pregnancy. It is
abortifacient and to affect the menstrual cycle, and the volatile oil contains tra
monograph. Prepara
1.4% volatile oil according to B
The daily dos
Effects on ability to drive or operate machinery or impairment of mental abi
No studies on the effect on the ability to drive and use machi
nes have been performed.
5.6. Overall conclusions on clinical safety
The medic
reactions may present a risk but the contra-indication paragraph of the monograp
attention to it.
inal use of yarrow preparation can be considered safe. Only the reported hypersensitivity
h will draw the
The known toxic principle thujone has been documented as a minor component o
concentrations are too low to present a risk to human heath.
f yarrow oil, but the
Dry methanolic and 10%-methanolic extracts of the aerial parts of A. millefolium showed estrogenic
et al. 2007), but in two
here was no increase in pre- or post-implantation losses (Boswell-Ruys
CL et al. 2003).
Since there are insufficient data, the use during pregnancy and lactation is not recommended.
6. Overall conclusions
Yarrow herb has been in medicinal use for a period of at least 30 years as requested by Di
2004/24/EC, thus the requirement for the qualification as a traditional herba
fulfilled (long-standing use dating back to ancient time).
l medicinal product is
The pharmacological studies on the anti-inflammatory, spasmolytic, choleretic, antimicrobial effects of
yarrow may contribute the proposed traditional indications. These properties can be connected to the
rpenes, phenolic (such as dicaffeoylquinic acids) and flavonoid content of the herbal substance.
The benefit-risk balance can be considered positive. The only possible risk, the hypersensitivity
reaction, is taken into consideration, and the patients’ attention is drawn to it properly.
As there are insufficient data, the use during pregnancy and lactation is not recommended.
Assessment report on Achillea millefolium L., herba
activity in an in vitro assay, based on recombinant MCF-7 cells, (Innocenti G
experimental animal studies t

Source: European Medicines Agency

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