COMMUNITY HERBAL MONOGRAPH ON
EQUISETUM ARVENSE
L., HERBA
To be specified for the individual finished product.
Well-established use
Traditional use
With regard to the registration application of
Article 16d(1) of Directive 2001/83/EC as
amended
Equisetum arvense
L., herba (horsetail herb)
i) Herbal substance
Not applicable
ii) Herbal preparations
a)
comminuted herbal substance
b)
expressed juice (1 : 1.6-2.0)
c)
liquid extract (1 : 4 - 5) extraction solvent:
ethanol 31.5 % (m/m)
d)
liquid extract (1 : 5) extraction solvent:
ethanol 96 % (V/V)/water/sweet wine
(16.5/13.5/70) (m/m)
e)
liquid extract (1 : 5.5) extraction solvent:
sweet wine/ethanol 96 % (V/V)
(91/9) (m/m)
f)
dry extract (4 - 7 : 1) extraction solvent:
water
g)
dry extract (7.5 - 10.5 : 1) extraction
solvent: ethanol 70 % (V/V)
Well-established use
Traditional use
Herbal preparation in solid or liquid dosage forms
or as herbal tea for oral use.
The pharmaceutical form should be described by
the European Pharmacopoeia full standard term.
1
The dried material complies with the Ph. Eur. monograph (ref. 0/2005:1825)
2
The declaration of the active substance(s) for an individual finished product should be in accordance with
relevant herbal quality guidance.
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4.1.
Therapeutic indications
Well-established use
Traditional use
Traditional herbal medicinal product to increase
the amount of urine to achieve flushing of the
urinary tract as an adjuvant in minor urinary
complaints.
The product is a traditional herbal medicinal
product for use in specified indication exclusively
based upon long-standing use.
4.2.
Posology and method of administration
Well-established use
Traditional use
Posology
Adolescents over 12 years of age, adults
ii)
Herbal preparations
Single dose
a)
-
comminuted herbal substance for tea
preparation: 2 - 3 g herbal substance into
250 ml boiling water
-
comminuted herbal substance : 570 mg herb
b)
expressed juice from fresh herb (1 : 1.6-2.0):
20 ml
c)
liquid extract (1 : 4 - 5) extraction solvent
ethanol 31.5 % (m/m): 20 drops
d)
liquid extract (1 : 5) extraction solvent:
ethanol 96 % (V/V)/water/sweet wine
(16.5/13.5/70) (m/m): 30 - 40 drops
e)
liquid extract (1 : 5.5) extraction solvent:
sweet wine/ethanol 96 % (V/V) (91/9) (m/m):
25 drops
f)
dry extract (4 - 7 : 1) extraction solvent:
water : 185 mg
g)
dry extract (7.5 - 10.5 : 1) extraction solvent:
ethanol 70 % (V/V): 200 - 225 mg
Daily dose
: 3 single doses
Maximum daily dose
: 4 single doses
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The use is not recommended in children under
12 years of age (see section 4.4. Special warnings
and precautions for use)
Duration of use
Herbal preparations are traditionally used over a
period of 2 to 4 weeks. See also 4.4. Special
warnings and precautions for use
If the symptoms persist after one week during the
use of the medicinal product, a doctor or a
qualified health care practitioner should be
consulted.
Method of administration
Oral use.
For preparations other than tea preparations
ensure appropriate fluid intake.
4.3.
Contraindications
Well-established use
Traditional use
Hypersensitivity to the active substance.
Conditions where a reduced fluid intake is
recommended (e.g. severe cardiac or renal
diseases).
4.4.
Special warnings and precautions for use
Well-established use
Traditional use
The use is not recommended in children under
12 years of age because of the lack of available
experience.
If complaints or symptoms such as fever, dysuria,
spasm or blood in urine occur during the use of
the medicinal product, a doctor or a qualified
health care practitioner should be consulted.
For liquid extracts containing ethanol the
appropriate labelling for ethanol, taken from the
‘Guideline on excipients in the label and package
leaflet of medicinal products for human use’,
must be included.
4.5.
Interactions with other medicinal products and other forms of interaction
Well-established use
Traditional use
None reported.
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4.6.
Pregnancy and lactation
Well-established use
Traditional use
Safety during pregnancy and lactation has not
been established.
In the absence of sufficient data the use during
pregnancy and lactation is not recommended.
4.7.
Effects on ability to drive and use machines
Well-established use
Traditional use
No studies on the ability to drive and use
machines have been performed.
4.8.
Undesirable effects
Well-established use
Traditional use
Mild gastrointestinal complaints and allergic
reactions (e.g. rash) have been reported. The
frequency is not known.
If other adverse reactions not mentioned above
occur, a doctor or a qualified health care
practitioner should be consulted.
Well-established use
Traditional use
No case of overdose has been reported.
5.1.
Pharmacodynamic properties
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
5.2.
5.2 Pharmacokinetic properties
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
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5.3.
Preclinical safety data
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended, unless
necessary for the safe use of the product.
Tests on reproductive toxicity, genotoxicity and
carcinogenicity have not been performed.
Well-established use
Traditional use
Not applicable.
3 July 2008
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Assessment Report
TABLE OF CONTENTS
I.
REGULATORY STATUS OVERVIEW
.......................................................................................... 3
II.
ASSESSMENT REPORT FOR HERBAL SUBSTANCE(S), HERBAL PREPARATION(S)
OR COMBINATIONS THEREOF WITH WELL-ESTABLISHED USE AND/OR TRADITIONAL
USE
........................................................................................................................................................... 5
II.1
I
NTRODUCTION
............................................................................................................................... 6
II.1.1
Description of the herbal substance(s), herbal preparation(s) or combinations thereof
...... 6
II.1.2
Information on period of medicinal use in the Community regarding the specified
indication
............................................................................................................................................... 8
II.2
N
ON
-C
LINICAL
D
ATA
.................................................................................................................. 17
II.2.1
Pharmacology
..................................................................................................................... 17
II.2.1.1
Overview of available data regarding the herbal substance(s), herbal preparation(s)
and relevant constituents thereof
..................................................................................................... 17
II.2.1.2
Assessor’s overall conclusions on pharmacology
....................................................... 29
II.2.2
Pharmacokinetics
................................................................................................................ 30
II.2.2.1
Overview of available data regarding the herbal substance(s), herbal preparation(s)
and relevant constituents thereof
..................................................................................................... 30
II.2.2.2
Assessor’s overall conclusions on pharmacokinetics
.................................................. 30
II.2.3
Toxicology
........................................................................................................................... 30
II.2.3.1
Overview of available data regarding the herbal substance(s)/herbal preparation(s) and
constituents thereof
.......................................................................................................................... 30
II.2.3.2
Assessor’s overall conclusions on toxicology
............................................................. 32
II.3
C
LINICAL
D
ATA
........................................................................................................................... 33
II.3.1
Clinical Pharmacology
........................................................................................................ 33
II.3.1.1
Pharmacodynamics
...................................................................................................... 33
II.3.1.2
Pharmacokinetics
......................................................................................................... 34
II.3.2
Clinical Efficacy
.................................................................................................................. 35
II.3.2.1
Dose response studies
.................................................................................................. 35
II.3.2.2
Clinical studies (case studies and clinical trials)
......................................................... 35
II.3.2.3
Clinical studies in special populations (e.g. elderly and children)
............................. 35
II.3.2.4
Assessor’s overall conclusions on clinical efficacy
.................................................... 35
II.3.3
Clinical Safety/Pharmacovigilance
..................................................................................... 35
II.3.3.1
Patient exposure
.......................................................................................................... 35
II.3.3.2
Adverse events
............................................................................................................ 36
II.3.3.3
Serious adverse events and deaths
............................................................................... 36
II.3.3.4
Laboratory findings
..................................................................................................... 38
II.3.3.5
Safety in special populations and situations
................................................................ 38
II.3.3.6
Assessor’s overall conclusions on clinical safety
........................................................ 40
II.4
A
SSESSOR
’
S
O
VERALL
C
ONCLUSIONS
......................................................................................... 40
III.
ANNEXES
...................................................................................................................................... 41
III.1
C
OMMUNITY
H
ERBAL
M
ONOGRAPH
...............................................................................................
III.2
L
ITERATURE
R
EFERENCES
...............................................................................................................
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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’
Member State
Regulatory Status
Comments
2
Austria
MA
TRAD
Other TRAD
Other Specify:
Belgium
MA
TRAD
Other TRAD
Other Specify:
Not known
Bulgaria
MA
TRAD
Other TRAD
Other Specify:
No preparations
Cyprus
MA
TRAD
Other TRAD
Other Specify:
Not known
Czech Republic
MA
TRAD
Other TRAD
Other Specify:
Denmark
MA
TRAD
Other TRAD
Other Specify:
Estonia
MA
TRAD
Other TRAD
Other Specify:
Not known
Finland
MA
TRAD
Other TRAD
Other Specify:
France
MA
TRAD
Other TRAD
Other Specify:
Not known
Germany
MA
TRAD
Other TRAD
Other Specify:
Greece
MA
TRAD
Other TRAD
Other Specify:
Not known
Hungary
MA
TRAD
Other TRAD
Other Specify:
Not known
Iceland
MA
TRAD
Other TRAD
Other Specify:
Not known
Ireland
MA
TRAD
Other TRAD
Other Specify:
No preparations
Italy
MA
TRAD
Other TRAD
Other Specify:
Not known
Latvia
MA
TRAD
Other TRAD
Other Specify:
Not known
Liechtenstein
MA
TRAD
Other TRAD
Other Specify:
Not known
Lithuania
MA
TRAD
Other TRAD
Other Specify:
Luxemburg
MA
TRAD
Other TRAD
Other Specify:
Not known
Malta
MA
TRAD
Other TRAD
Other Specify:
Not known
The Netherlands
MA
TRAD
Other TRAD
Other Specify:
Not known
Norway
MA
TRAD
Other TRAD
Other Specify:
No information
Poland
MA
TRAD
Other TRAD
Other Specify:
Not known
Portugal
MA
TRAD
Other TRAD
Other Specify:
No preparations
Romania
MA
TRAD
Other TRAD
Other Specify:
Not known
Slovak Republic
MA
TRAD
Other TRAD
Other Specify:
Not known
Slovenia
MA
TRAD
Other TRAD
Other Specify:
Not known
Spain
MA
TRAD
Other TRAD
Other Specify:
Not known
Sweden
MA
TRAD
Other TRAD
Other Specify:
1
This regulatory overview is not legally binding and does not necessarily reflect the legal status of the products in
the MSs concerned.
2
Not mandatory field
©
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Member State
Regulatory Status
Comments
2
United Kingdom
MA
TRAD
Other TRAD
Other Specify:
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II.
ASSESSMENT REPORT FOR HERBAL SUBSTANCE(S), HERBAL
PREPARATIONS OR COMBINATIONS THEREOF WITH TRADITIONAL USE
Equisetum arvense
L., herba
BASED ON ARTICLE 16D(1) AND ARTICLE 16F AND 16H OF DIRECTIVE 2001/83/EC AS
AMENDED (TRADITIONAL USE)
Herbal substance(s) (binomial scientific name of
the plant, including plant part)
Equisetum arvense
L., whole or cut dried, sterile
aerial parts of the plant
Herbal preparation(s)
a)
comminuted herbal substance
b)
expressed juice (1 : 1.6 - 2.0)
c)
liquid extract (1 : 4-5) extraction solvent:
ethanol 31.5 %
d)
liquid extract (1 : 5) extraction solvent:
ethanol 96 % (V/V)/water/ sweet wine
(16.5:13.5 : 70) (m/m)
e)
liquid extract (1 : 5.5) extraction solvent:
sweet wine: ethanol 96 % (V/V) (91 : 9)
(m/m)
f)
dry extract (4 - 7 : 1) extraction solvent:
water
g)
dry extract (7.5-10.5 : 1) extraction solvent:
ethanol 70 % (V/V)
Herbal preparation in solid or liquid dosage forms
or as herbal tea for oral use.
Pharmaceutical forms
The pharmaceutical form should be described by
the European Pharmacopoeia full standard term.
Rapporteur
Dr Werner Knöss
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II.1
I
NTRODUCTION
II.1.1
Description of the herbal substance(s), herbal preparation(s) or combinations thereof
the plant
Herba Equiseti is known under the synonyms:
German: Equisetum-arvense-Kraut, Kannenkraut, Pferdeschwanzkraut,
Schachtelhalmkraut, Scheuerkraut, Tannenkraut, Zinnkraut;
English.: Herb of field horse-tail, Herb of horse-tail;
French.: Herbe de prêle, Herbe de champs;
Italian: Erba d'equiseto dei campi;
Spanish.: Yerba de cola de caballo,
Croatian: Zelen preslice,
Czech Republic: Preslicova nat,
Danish: Agerpadderokke,
Lituanian: Asiukliu zole,
Norvegian: Kjerringrokk.
The drug consists of the whole or cut dried sterile aerials parts of
Equisetum
arvense
L. The primary stem of horsetail is hollow and about 1-3.5 mm thick,
separated by nodes into 2-6 cm long segments (internodes) with about 6-19, but
generally 9-13 pronounced, longitudinal ridges. The main stem and lateral
branches are green to greyish green, rough and brittle. The herb is almost
odourless. The taste is insipid, grates between the teeth when chewed.
Equisetum is widely distributed throughout the temperate zones of the northern
hemisphere. The material of commerce is imported of China, as well as from
eastern and south-eastern European countries.
3
According to the ‘Procedure for the preparation of Community monographs for traditional herbal medicinal
products’ (EMEA/HMPC/182320/2005 Rev.2) and the ‘Procedure for the preparation of Community
monographs for herbal medicinal products with well-established medicinal use (
EMEA/HMPC/182352/2005
)
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It contains about 10 % inorganic constituents with two-third silicic acid (or
silicates respectively) of with 10 % are water-soluble. Flavonoids (0.2 -0.9 %)
are present with mostly caempferol and quercetin glycosides and their malonyl
esters. There are apparently two chemotypes. Asian and North American
varieties contain luteolin-5-glycoside, which is absent from European plants.
Also caffeic acid derivates and small amounts of a styrylpyrone glycoside,
polyenic acid, sterols, rare dicarboxylic acids and traces of alkaloids including
nicotin have been detected. The supposed saponin-complex which has previously
been known as “equisetonin”, has been identified as a mixture of sugars and
flavonoids (Wichtl M, 2004). Schneider (1989) also proposed to cancel
“Equisetonin” from the list of compounds of Equisetum arvense.
•
comminuted herbal substance
•
expressed juice (1 : 1.6 – 2.0)
•
dry extract (4 - 7 : 1) extraction solvent: water
•
dry extract (8 - 10 : 1) extraction solvent: ethanol 70 % (V/V)
•
dry extract (7.5-10.5 :1) extraction solvent: ethanol 70 % (V/V)
•
liquid extract (1 : 4 - 5) extraction solvent: ethanol 31,5 %
•
liquid extract (1 : 5) extraction solvent: ethanol 96 % (V/V)/water/ sweet
wine (16.5 : 13.5 : 70) (m/m)
•
liquid extract (1 : 5.5) extraction solvent: sweet wine: ethanol 96 % (V/V) (91
: 9) (m/m)
•
extract from fresh herb (1 : 9) extraction solvent water
(Sweet wine is monographed in the German Pharmacopoea EB 6.)
For combination products there is often lack of 30 years of tradition, unclear
composition (unclear number of composition partners, unclear content of
composition partner) or unclear declaration of the extracts. Because of the
number of composition partners an extrapolation to a plausible dosage for a
4
According to the Guideline on the clinical assessment of fixed combinations of herbal substances/herbal
preparations (EMEA/HMPC/166326/2005)
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single preparation is not possible. Therefore the combinations of horsetail are
not proposed for the monograph/list.
II.1.2
Information on period of medicinal use in the Community regarding the specified
indication
The following herbal substances and herbal preparations are since a period of 30 years on the
European market and are proposed for the monograph on traditional use.
i)
comminuted herbal substance
ii)
expressed juice (1 : 1.6 - 2.0)
iii)
liquid extract (1 : 4-5) extraction solvent: ethanol 31.5 %
iv)
liquid extract (1:5) extraction solvent: ethanol 96 % (V/V)/water/ sweet
wine (16.5:13.5:70) (m/m)
v)
liquid extract (1:5,5) extraction solvent: sweet wine: ethanol 96 % (V/V)
(91 : 9) (m/m)
vi)
dry extract (4-7 : 1) extraction solvent: water
vii)
dry extract (7.5-10.5 : 1) extraction solvent: ethanol 70 % (V/V)
The dry extract (8-10 : 1) extraction solvent: ethanol 70 % (V/V) is included in
the dry extract (7.5-10.5 : 1) extraction solvent: ethanol 70 % (V/V).
Posology and indications of the traditional herbal substance and preparations of horsetail:
•
comminuted herbal substance in tablets
Indication: traditionally used to promote the renal elimination of water
5
Only applicable to traditional use
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Posology: 3 times daily 3 coated tablets with 190 mg herb
Single dose: corresponding to 570 mg herbal substance
Daily dose: corresponding to 1.71 g herbal substance
•
comminuted herbal substance for tea preparation
Indication:
Czech Republic
:
Oral use: adjuvant in treatment of kidney and urinary tract inflammation and infections.
Topical use: for compresses and ablution of superficial wounds with tendency to poor
healing, for lavage in case of nose bleeding.
Croatia:
oral use: diuretic
Lituania
: oral use: for improvement diuresis
Germany:
Commission E monograph, published 18.09.1986: Equisetum herba:
Oral use: Posttraumatic and static oedema, irrigation therapy in bacterial and inflammatory
diseases of the lower urinary tract and the renal gravel.
Topical use: supportive treatment for poorly healing wounds.
Posology for oral use:
Germany
: Daily dose 6 g herbal substance. (3 times daily an infuse of 2 g herbal substance or
4 times daily 1.5 g herbal substance)
Single dose: corresponding to 2 g herbal substance
Daily dose: corresponding to 6 g herbal substance
Croatia
: 3 times daily a tea preparation of 1 tea spoon herb (ca. 2 g) in 250 ml water
Czech Republic
: 2-3 times daily a tea preparation of 1 tea spoon herb (ca. 2 g) in 250 ml
water
Lithuania
: 3 times daily a tea prepared with 3-5 g herbal substance
Conclusion:
Range of posology: Daily dose: 4-15 g herbal substance
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Recommendation: The most common posology of all countries is 3 times daily a tea
prepared with 2-3 g herbal substance (Daily dose: 6-9 g herbal substance)
Posology for topical use as compresses
:
Germany: 10 g herbal substance in 1 l hot water.
Czech Republic: 1 table spoon herbal substance in 250 ml water.
•
expressed juice (1 : 1.6-2.0)
Indication
Oral use: Posttraumatic and static oedema. Irrigation therapy in bacterial and inflammatory
diseases of the lower urinary tract and the renal gravel.
Topical use: supportive treatment for poorly healing wounds.
Posology for oral use
:
2-3 times daily 20 ml (single dose corresponding 11 g fresh herb, daily dose corresponding
22-33 g fresh herb)
Posology for topical use as compresses:
40 ml expressed juice in 500 ml water (corresponding 22 g fresh herb)
•
liquid extract (1 : 4 - 5) extraction solvent: ethanol 31.5 %
Indication:
Oral use: Traditionally used to promote the renal elimination function.
Posology for oral use
: 3 times daily 20 drops (single dose corresponding to 0.155 g herbal
substance, daily dose corresponding to 0.465 g herbal substance).
•
liquid extract (1:5) extraction solvent: Ethanol 96 % (V/V)/water/ sweet wine
(16.5:13.7:70) (m/m)
Indication
: Oral use: Traditionally used to promote the renal elimination function.
Posology for oral use
: 3 - 4 times daily 30-40 drops (single dose corresponding to 0.2 g
herbal substance, daily dose corresponding to 0.6-1.04 g herbal substance).
•
liquid extract (1 : 5.5) extraction solvent: Sweet wine: ethanol 96 % (V/V) (91:9) (m/m)
Indication
: Oral use: Traditionally used to promote the renal elimination function.
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Posology for oral use
: 3 times daily 25 drops (single dose corresponding to 0.2 g herbal
substance, daily dose corresponding to 0.6 g herbal substance).
•
dry extract (4 - 7 : 1) extraction solvent: water
Indication:
Oral use: Irrigation therapy for bacterial and inflammatory diseases of the lower
urinary tract and renal gravel.
Posology for oral use
: 3 times daily 185 mg (single dose corresponding to 2 g herbal
substance, daily dose corresponding to 6 g herbal substance) or 2 times daily 272 mg (single
dose corresponding to 2 g herbal substance, daily dose corresponding to 6 g herbal
substance).
•
dry extract (8-10 : 1) extraction solvent: ethanol 70 % (V/V),
Indication:
Oral use: Irrigation therapy for bacterial and inflammatory diseases of the lower
urinary tract and renal gravel.
Posology for oral use
: 3 times daily 200 mg (single dose corresponding to 1.8 g herbal
substance, daily dose corresponding to 5.4 g herbal substance).
•
dry extract (7.5-10.5 : 1) extraction solvent: ethanol 70 % (V/V),
Indication:
Oral use: Irrigation therapy for bacterial and inflammatory diseases of the lower
urinary tract and renal gravel.
Posology for oral use
: 3 times daily 225 mg (single dose corresponding to 2 g herbal
substance, daily dose corresponding to 6 g herbal substance).
The following list shows combinations containing horsetail, existing on the European market,
and their indications.
•
Equiseti herba extract (4:1) extraction solvent: ethanol 70 % (corresponding to 540 mg
herb) and an extract of dandelion herb and root (Taraxacum officinale) solvent unknown,
corresponding to 600 mg of plant (Uvalette® of Denmark, not 30 years of tradition, no
clinical data for well established use)
Indication: Herbal medicinal product for the increase of the diuresis in minor oedemas
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•
(Equisetum arvense L., herba) 13 g/100g in a fixed combination product with other
herbal substances in a herbal tea (Horsetail Salus tea (Denmark), not 30 years of
tradition, no clinical data for well established use, unclear composition)
Indication: Herbal medicinal product for the increase of the diuresis, especially in
situations with irritations in the urinary system.
•
Echinamin® (Denmark): Unclear composition and indication
•
135 mg Equiseti fruct. extr. sicc. resp. (5 : 1), extraction solvent unknown and 120 mg
Tarataci rad. extr. sicc. resp. (5 : 1) extraction solvent unknown (from Finland: not 30
years tradition)
•
Indication: Minor enhancing effect on urinary secretion.
•
Equiseti herba dry extract, ext. solvent: aqua purificata; DER= (4.7-5.7 : 1) combined
whith Uvae ursi folii extractum siccum, and other supportive active ingredients Betulae
folii extractum siccum and Ononidis radicis extractum siccum. (Product from Croatia,
unclear composition, more than 15 years on the market, but unclear if 30 years traditional
use)
Indication: Uncomplicated urinary infections, urinary tract disorders relief with
prescribed medicines
•
Equiseti herba dry extract (other data not available) combined with Juniperus communis
(fruit), Arctostaphylos uva ursi (leaf), Pepper fruit, Petroselenium sativum (aerial),
Ananas comusus, and Potassium Citrate (from Croatia, unclear composition)
Indication: Improvement and health maintenance of urinary tract
•
Herbal tea – Visci albi herba 40 g, Hyperici herba 20 g, Crataegi folium cum flore 16.5 g,
Crataegi fructus 10 g, Equiseti herba 7.5 g, Menthae piperitae herba 2 g, Melissae herba 2
g, Matricariae flos 2 g/100 g of the herbal tea. On the market in Czech Republic since
1969 – for oral use
Indication: In presclerotic states, as an adjuvant in mild forms of hypertension.
•
Herbal tea – Filipendulae ulmariae herba 450 mg, Equiseti herba 150 mg, Violae
tricoloris herba 225 mg, Harpagophyti radix 150 mg, Salicis cortex 225 mg, Solidaginis
virgaureae herba 150 mg, Callunae herba 150 mg/tea bag – on the market in Czech
Republic since 1999 – for oral use
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Indications: As an adjuvant for inflammatory and degenerative diseases of the locomotor
apparatus (rheumatism, arthrosis, arthritis and gout), adjuvant therapy in flu like
symptoms
•
Herbal tea – Uvae ursi folium 375 mg, Matricariae flos 150 mg, Sambuci nigrae flos 150
mg, Equiseti herba 300 mg, Myrtilli herba 225 mg, Solidaginis virgaureae herba 150 mg,
Thymi herba 150 mg/tea bag - on the market in Czech Republic since 1989, for oral use,
Indications: As an adjuvant therapy in acute and chronic infections and inflammations of
the urinary tract
•
Equisetum arvense (unknown extract) and Taraxacum officinale (unknown extract),
unknown composition, is approved as a natural remedy in Sweden with the following
indication: “Traditionally used to relieve a sensation of swelling, for example due to PMS
(premenstrual syndrome)”.
•
Germany: On the German market there are many combination products containing
horsetail as mild diuretics. The average number of combination substances is 3-5. The
main combination substances are Betulae folium, Urticae herba, Solidaginis herba,
Juniperi fructus, Ortosiphonis folium and Ononidis radix. Two extracts [Equiseti herba
dry extract (6 - 8 : 1) extraction solvent: water and Equiseti herba dry extract (4 - 6 : 1)
extraction solvent: water] are combined with crude drug.
•
Austria: In Austria Equiseti herba is authorised / registered only in homoeopathics, in a
herbal combination with Plantago and Thyme (Pneumopan - Sirup) for the treatment of
cough, and in several tea preparations (in combination with other herbal substances) for
mild urinary tract disorders.
Documentation of tradition in the European context:
Horsetail has an old tradition in the European context. [Madaus 1938] describes horsetail as
an “additional important area of this medicine is diseases of the urinary organs”. He notes,
that horsetail is mentioned in phytotherapeutical books since the 16
th
Century. He gives
detailed information about old European literature to the traditional medicinal use in a lot of
different indications, for example Magnus 12
th
century, in Germany (Agricola, 16
th
century,
Kneipp 19
th
century), in Poland and Russia at the beginning of the 20
th
century.
Equisetum arvense is described detailed in a lot of newer phytotherapeutical books, for
example Bézanger-Beauquesne (1986, 1990), British Herbal Medicine Association (1996,
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2003), Duke JA (1985, 2002), Garnier (1961), Hänsel (1993), Hager ROM (2003, 2006),
Hoppe (1975), LaGow PDR for Herbal Medicines (2004), Paris (1976), Saint-Paul (1980),
Van Hellemont (1986) and Wichtl (2003, 2004).
Hiermann (2006) describes as traditional indications for the oral use, to promote the
elimination of water in catarrhs of kidneys and bladder, as an haemostyptic at nose, stomach,
lung and strong menstruation, as an adjuvant in the treatment of tuberculosis, fissured nails
and loss of hair. Horsetail was traditionally used in form of a bath at gynaecological diseases,
rheumatic diseases, gout, and treatment of poorly healing wounds, tumescence and break of
bones.
It is interesting that the characteristics from the traditional use in the indications involving the
plant’s inorganic content of silicon, the potential to heal broken bones, connective tissue and
nail injuries in patients needing remineralisation, and to treat osteoporosis, led to the French
patent application for the use of silicon compounds isolated from E. arvense (Hamon, 1992).
Only a few of these traditional uses of horsetail have been introduced into Pharmacopoeias or
accepted collections in the European countries:
Great Britain
:
•
Equisetum. In: British Herbal Pharmacopoeia Part One, British Herbal
Medicinal Association, 1976, 75.: dried herb, or infusion or decoction of the
dried herb (thrice daily the single dosage: 1-4 g), liquid extract (1 : 1) in 25
% alcohol (thrice daily the single dosage 1-4 ml): Indications: Enuresis,
prostatic disease, cystitis with haematuria, urethritis. Specific indications:
Inflammation or benign enlargement of the prostate gland; urinary
incontinence; enuresis of children
•
Equisetum. In: Ainley Wade, Martindale The Extra Pharmacopoeia, 27
th
Ed,
Pharmaceutical Society of Great Britain 1977, 1754.: Dried herb: Weak
diuretic
Germany:
•
Herba Equiseti. Ergänzungsbuch zum Deutschen Arzneibuch 6. Ausgabe,
DAV Stuttgart, 1953, 244-245
•
Equiseti herba, Schachtelhalmkraut, Monographie der Kommission E. In:
Bundesanzeiger Nr. 173 vom 18.09.1986. (Equisetum herba. Commission E
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monograph, published in Bundesanzeiger Nr. 173, 18.09.1986 and
Blumenthal, 1998):
Orally: Comminuted herbal substance for tea preparation and other oral galenic
combinations; Dosage: Corresponding to 6 g herbal substance daily.
Indications: Posttraumatic and static oedema. For irrigation therapy in bacterial
and inflammatory diseases of the lower urinary tract and the renal gravel.
External use: Comminuted herbal substance for tea preparation and other galenic
combinations; Dosage: 10 g herbal substance in 1 l water. Indication: supportive
treatment for poorly healing wounds.
•
Schachtelhalmkraut Standardzulassung No. 1239.99.99 published
12.03.1986 (Equivalent to: Schachtelhalmkraut. In: Braun R
Standardzulassungen für Fertigarzneimittel, DAV Stuttgart Govi Verlag
GmbH Frankfurt 2004): dried herb for tea preparation;
Dosage: three times daily the single dose: an infusion of 2 teaspoons (ca. 2 g)
herb in 150 ml hot water.
Indication: Posttraumatic and static oedema. For irrigation therapy in bacterial
and inflammatory diseases of the lower urinary tract and the renal gravel.
External use: comminuted herbal substance for tea preparation and other galenic
combinations; Dosage: 10 g herbal substance in 1 l water. Indication: Supportive
treatment for poorly healing wounds.
Belgium:
•
Circulaire Nr. 367 1990: Equisetum arvense, herba. Indication: Traditionally
used to promote the renal elimination of water, although its activity has not
been proven in accordance with the current evaluation criteria for medicines
(Bradley, 1992).
France:
•
Agency Instructions No. 3 (Bulletin Officieal Nr. 19/22, 1990): Equisetum
arvense: Therapeutic Indications Nr.
045: Traditionally used to promote renal and digestive elimination functions
085: Traditionally used as an adjuvant in slimming diets/to assist loss of weight,
complementary to dietary measures.
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151: Traditionally used to promote renal elimination of water
Switzerland:
•
Equiseti herba. Pharmacopoea Helvetica, Verlag Eidgenössische
Drucksachen- und Materialzentrale Bern 1971: Equisetum arvense L.: dried
herb: Indication: “Species diureticae”
Europa:
•
Conseil de l Europe, (1989): Equisetum arvense L. :Glycolic extract
E/D=2:1; Dosage up to 10 per cent in products of massage, skin restoring
elasticity (striae, wrinkles) antiperspirants, hair lotions (hair loss), greasy
skins; remineralisating agent, antihaemorrhagic, disinfiltrating agent, tissue
drainage.
•
Current Pharmacopoeial Monographs: Equisetum Stem Ph. Eur. 01/2008:
1825 corrected 6.0. In European Pharmacopoeia, 6.0 Vol 2 Council of
Europe, 2008, 1794-5.
For horsetail herb a period of at least 30 years in medical use as requested by Directive
2004/24/EC for qualification as a traditional herbal medicinal product is fulfilled.
Altogether the literature data support the traditional use for the following indications:
Oral use:
i)
Traditionally used to promote renal elimination function
ii)
Posttraumatic and static oedema
iii)
For irrigation therapy in bacterial and inflammatory diseases of the lower urinary
tract and the renal gravel/kidney and bladder stones
The topical use is based only on one preparation (expressed juice 1:1.6-2.0) and the German
Commission E monograph (Willuhn, 1995). Therefore this indication is not recommended for
the monograph.
Assessor’s comments:
From the above mentioned indications only the following indications are appropriate for use
without the supervision of a medical practitioner for diagnostic purposes or for prescription
or monitoring of treatment:
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Oral use: Traditionally used to promote renal elimination function.
Diuretics are a group of drugs that block normal solute reabsorption (not water reabsorption
directly) along the nephron, inducing solute diuresis.They decrease the extra cellular fluid
volume, and are primarily used to produce a negative extra cellular fluid balance. The data
for efficacy of horsetail are not appropriate to document a diuretic mechanism of activity
with a negative extracellular fluid balance. Therefore the following wording is proposed:
Oral use: Traditional herbal medicinal product to increase the amount of urine to achieve
flushing of the urinary tract as an adjuvant in minor urinary complaints.
II.2
N
ON
-C
LINICAL
D
ATA
II.2.1
Pharmacology
II.2.1.1
Overview of available data regarding the herbal substance(s), herbal preparation(s) and
relevant constituents thereof
(e.g. primary pharmacodynamics, secondary pharmacodynamics, safety pharmacology,
pharmacodynamic interactions)
In-vitro tests:
Antioxidant effect:
Amarowitcz (2004): Different ethanolic extracts from the roots of wild liquorice (Glycyrrhiza
lepidota), narrow-leaved echinacea (Echinacea angustifolia), senega (Polygala senega),
leaves of bearberry (Arctostaphylos uvae-ursi) and aerial parts of two varieties of horsetail
(Equisetum spp.) (dry extract, DER unclear, extraction solvent 95 % ethanol) were prepared
and evaluated for their free-radical scavenging capacity and their antioxidant activity by a
number of chemical assays. Assays employed included a beta-carotene-linoleic acid
(linoleate) model system, reducing power, scavenging effect on the DPPH free radical and
capacity to scavenge hydroxyl free radicals (HO), by use of electron paramagnetic resonance
(EPR) spectroscopy. The bearberry-leaf extract, followed by horsetail exhibited the highest
antioxidant activity based on the tests performed. The polyphenolic constituents appear to be
responsible, at least in part, for the extract's radical-scavenging capacity.
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method in order to visualize the inhibition of the DPPH, superoxide and hydroxyl radicals. E.
arvense had by comparison with reference molecules, e.g. vitamin E and quercetin only low
antioxidant properties. Antioxidant effects were correlated with the total amount of phenolic
compounds contained in the extracts. Also measured were the
anti-inflammatory
activities of
the 16 water-soluble fractions, by evaluating inhibition of lipoxygenase activity. E. arvense
belonged to the group with the second highest activity. (IC50 1.5 mg/ml). Equisetum arvense
showed for high concentrations (> 0,5 mg/ml) a significant
antiproliferative effect
on the
proliferation of melanoma B16 cells.
Inhibitory activity on nitric oxide synthesis in LPS-activated macrophages:
Ryu (2003): Nitric oxide (NO) produced in large amounts by inducible nitric oxide synthase
(iNOS) is known to be responsible for the vasodilation and hypotension observed in septic
shock and inflammation. Inhibitors of iNOS, thus, may be useful candidates for the treatment
of inflammatory diseases accompanied by overproduction of NO. The authors prepared
extracts (“stem bark and woody plant material were extracted with MeOH, dispersed in water
and extracted with ethyl ether”) of woody 23 different plants, including E. hyemale and
screened the inhibitory activity of NO production in lipopolysaccharide (LPS)-activated
macrophages after the treatment of these extracts. Among 83 kinds of plant extracts, 23 kinds
of extracts showed potent inhibitory activity of NO production above 60% at the
concentration of 80 mcg/ml. Some of potent extracts showed dose dependent inhibition of
NO production of LPS-activated macrophages at the concentration of 80, 40, 20 mcg/ml.
Artemisia iwayomogi, Machilus thunbergii, Populus davidiana and Populus maximowiczii
showed the most potent inhibition (above 70%) at the concentration of 40 mcg/ml. Inhibitory
activity of NO production was concentrated to nonpolar solvent fractions (ethyl ether and/or
ethyl acetate soluble fractions) of Artemisia iwayomogi, Machilus thunbergii and Morus
bombycis. E. hyemale showed a potent inhibition above 50.1 %.
Antimicrobial effects:
Heisey (1992): Extracts (1 : 1) (v/v), extraction solvent methanol/dichlormethan (1 : 10)
(g/ml) from 54 plant species, including E. arvense, were tested for antimicrobial activity
against E. coli, Staph. aureus, Strept. mutans, Candida albicans, Fusarium oxysporum and
Trichophyton rubrum. Antimicrobial activity was noted in extracts of Celastrus scandens,
Chamaebatia foliolosa, Cheledonium majus, Chenopodium ambrosioides, Digitaria
sanguinalis, Echinochloa crusgalli, Ginkgo biloba, Juglans nigra, Juniperus virginiana,
Kalmia latifolia, Lindera benzoin, Oenothera biennis, Rhus glabra, Pelargonium xhortorum
and Thuja occidentalis. In a secondary screen, 10 of the above were tested against Bac.
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cereus, Erwinia carotovora, Micrococcus luteus, Proteus vulgaris, Strept. salivarius, Asp.
niger, Pen. notatum, Pythium ultimum, Rhizopus nigricans and Sacch. cerevisiae. Equisetum
arvense showed no antimicrobial activity.
Aswal (1984): 292 Plant extracts (not described) were tested for antibacterial, antifungal,
antiprotozoal, anthelmintic, antiviral, antifertility (abortifacient and contraceptive),
neuromuscular blocking, cytostatic, sedative, vulnerary, hypoglycemic, respiratory,
cardiovascular, spasmolytic, analgesic, utertonic, hypothermic, anticonvulsant, diuretic and
antiinflammatory effects. LD50s were also determined. Organisms used included E. coli,
Strept., Ps., Klebs., Proteus, Candida, Cryptococcus, Asp., Entamoeba, Nippostrongylus,
Vaccinia virus, and Ranikhet disease virus. E. arvense was tested for antibacterial, antifungal,
antiprozoal and antiviral activity. It showed no activity. The LD50 was > 1000 mg /kg i.p. in
mice.
Antibacterial activity:
Kloucek (2005): Nine ethanol extracts of Brunfelsia grandiflora (Solanaceae), Caesalpinia
spinosa (Caesalpiniaceae), Dracontium loretense (Araceae),
Equisetum giganteum
(Equisetaceae), Maytenus macrocarpa (Celastraceae), Phyllanthus amarus (Euphorbiaceae),
Piper aduncum (Piperaceae), Terminalia catappa (Combretaceae), and Uncaria tomentosa
(Rubiaceae), medicinal plants traditionally used in Callería District for treating conditions
likely to be associated with microorganisms, were screened for antimicrobial activity against
nine bacterial strains using the broth microdilution method. Among the plants tested,
Phyllanthus amarus and Terminalia catappa showed the most promising antibacterial
properties, inhibiting all of the strains tested with minimum inhibitory concentrations (MICs)
ranging from 0.25 to 16 mg/ml. The extract from aerial part of Piper aduncum was
significantly more active against Gram-positive (MICs ranging from 1 to 2 mg/ml) than
against Gram-negative bacteria (MICs>16 mg/ml).
Antifungal activity:
Guerin (1984): 41 Plant extracts (water extract of Equisetum arvense herba (1:6))were tested
against 9 fungi species. Extracts of Piper methysticum, Illicium verum, Rhamnus frangula,
Ruscus aculeatus, Hibiscus sabdariffa, Tamarindus indica, Eschscholtzia californica, Zingiber
officinale, Tilia cordata and Viola tricolor were found to have antifungal activity against 1 or
more of Sacch. pastorianus, Candida albicans, Rhizopus nigricans, Asp. niger, A. Fumigatus,
Botrytis cinerea, Penicillium digitatum, Fusarium oxysporum and Trichophyton
mentagrophytes, in vitro. P. methysticum extract was active against all 9 fungi. Other extracts
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tested were from Fucus,
Equisetum
, Cupressus, Acorus, Allium, Salix, Betula, Castanea,
Urtica, Humulus, Beta, Peumus, Erysimum, Raphanus, Hypericum, Aesculus, Vitis, Cassia,
Trigonella, Lespedeza, Lotus, Melilotus, Medicago, Glycyrrhiza, Alchemilla, Crataegus,
Rosa and Spiraea species. E. arvense showed no antifungal activity.
Parihar (2002): The antifungal properties of the aqueous and acetone extracts of pinnules,
petioles and rhizomes of Adiantum lunulatum; stems and roots of
Equisetum ramosissimum
;
and leaflets, petioles and rhizomes of Marsilea minuta against Candida albicans were studied
in vitro. All the tested plants exhibited antifungal properties against C. albicans, although the
inhibitory properties of the extracts varied depending on the type of extract and plant part
used. The aqueous stem extract of E. ramosissimum recorded the highest inhibitory effect.
Antiviral effect:
Husson (1986): A test for antiviral properties using cell cultures and the results with a series
of plant extracts (alcoholic (content unclear) extract of fresh plant of E. arvense (5 : 1)) are
described. Equisetum arvense showed an antiviral effect.
Suganda (1983): Ethanolic extracts of 41 species of plant indigenous to France were screened
for antiviral activity. Extracts of Matricaria chamomilla, M. inodora and Anthyllis vulneraria
inhibited in vitro replication of human polio virus type 2 and human herpes virus type 1.
Extracts of Bryonia dioica inhibited human polio virus replication. E. arvense had no antiviral
effect.
Assessor’s comments:
A lot of in vitro test have been performed in order to examine the mechanism of the effects
which attribute to the use in diseases of the urinary tract. From the in vitro tests the
antioxidant effect may contribute to the efficacy. The anti-inflammatory activity could be at
least in part due to the presence of compounds with antioxidant activity. E. arvense shows in
the majority of tests performed an antioxidant activity for which the polyphenolic constituents
appear to be responsible. The tests show that other Equisetum species (E. telmateia, E.
ramosissimum) may be more potent antioxidants.
Equisetum arvense showed no antimicrobial activity in the tests performed. Additionally E.
arvense showed no reproducible antiviral and antifungal effect. An antimicrobial
contribution to the efficacy is implausible.
Anticancer and antithrombin activity:
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Goun (2002): A chromogenic bioassay was utilized to determine the antithrombin activity of
the methylene chloride and methanol extracts prepared from forty-five plants of Russia,
including E. arvense. Mouse leukemia cells (L1210) were utilized to screen these extracts
(“200 g plants, dry weight extracted in sequence with methylen chloride (24 h) and ethanol”),
for activity against cancer. The results indicated that eight plant extracts demonstrated 90 %
or higher activity in the inhibition of thrombin. Also, nine methanol extracts demonstrated
activity of 90 % or higher in the inhibition of mouse leukemia L1210 cells. The methylen
cloride extracts of E. arvense demonstrated high activity against both thrombin and cancer
(84/99 %). The ethanol extracts of E. arvense demonstrated 45/38 % activity against
thrombin and mouse leukemia L1210 cells.
Assessor’s comments:
The anticancer effect and antithrombin activity correspond with the traditional use as
anticancer preparation and in hematopoietic diseases. A negative point of the study is the
fact that the DER of the extracts and the ethanol content (%) is not described clearly. The
results show a strong dependence of the effect from the used vehicle methylene chloride or
ethanol. The methylene chloride extract had approximately the double power in the
anticancer activity as compared with the ethanolic fraction. The results indicate that the lipid
fraction may contribute to the effect. A water extract, or an ethanolic water extract were not
tested. For the clinical relevance additional in vivo studies must be conducted. The effects
must be taken into consideration at the toxicological assessment.
Hepatoprotective activity:
Oh (2004): The hepatoprotective activity-guided fractionation of the MeOH extract of
Equisetum arvense L. (Equisetaceae) resulted in the isolation of two phenolic petrosins,
onitin (1) and onitin-9-O-glucoside (2), along with four flavonoids, apigenin (3), luteolin (4),
kaempferol-3-O-glucoside (5), and quercetin-3-O-glucoside (6). Among these, compounds 1
and 4 exhibited hepatoprotective activities on tacrine-induced cytotoxicity in human liver-
derived Hep G2 cells, displaying EC(50) values of 85.8 +/ -9.3 microM and 20.2 +/- 1.4
microM, respectively. Silybin, used as a positive control, showed the EC(50) value of 69.0
+/- 3.3 microM. Compounds 1 and 4 also showed superoxide scavenging effects (IC(50) =
35.3 +/- 0.2 microM and 5.9 +/- 0.3 microM, respectively) and DPPH free radical scavenging
effect (IC(50) of 35.8 +/- 0.4 microM and 22.7 +/- 2.8 microM, respectively). The authors
concluded that these results support the use of this plant for the treatment of hepatitis in
oriental traditional medicine.
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Katalinic (2006): The total phenolic content and related total antioxidant capacity of 70
medicinal plant infusions was analyzed. Aqueousus extracts were prepared as infusion, (3 g
of the herb with 200 ml boiled water). The total phenolics were measured by Folin-
Ciocalteau assay. The total antioxidant capacity was estimated by Ferric
Reducing/Antioxidant Power (FRAP) assay. To make a practical comparison of the relative
antioxidant potential of phenolics extracted from selected medicinal plants, the phenol
antioxidant coefficient (PAC) was calculated for each infusion. There was a significant linear
correlation between total phenolic content and FRAP. The best results were obtained for
Melissae folium infusions. Equisetum herba had a Phenol antioxidant coefficient of 2.5 (The
PAC was ranging from 1.1 to 3.9).
Nagai (2005): Water extract and ethanol extract from top and body portions of field horsetail
Equisetum arvense (tsukushi) were prepared, and the antioxidative activity was investigated
using four different methods. (5 g herb were extracted by 5 volumes water or ethanol
(unknown concentration), devaporated and solved in 1 ml ethanol (unknown concentration).
0.1 and 1.0 sample solutions were used.) The contents of total phenolic components were
richer in the ethanol extract fractions of each portion than in the water extracts. The protein
contents were much lower in ethanol extract fractions than in water extract fractions. The
ethanolic fractions had antioxidative activities, similar to that of 5 mM ascorbic acid. Water
extracts of both portions showed high superoxide anion radical-scavenging activities.
Hydroxyl radicals were effectively scavenged by ethanol extracts. The authors concluded that
field horsetail (tsukushi) is rich in vitamins C and E. Moreover it contains high levels of
copper and zinc. These are essential elements for superoxide dismutase to act against active
oxygen species.
Stajner (2006): The scavenger activities of Equisetum arvense, Equisetum ramosissimum and
Equisetum telmateia above ground parts phosphate buffer (pH 7) aqueous extracts (1 g of
fresh plant material in 5 ml 0,1 mol/l K2HPO4) were evaluated using three different methods:
DPPH assay, ESR and NO radical inhibition assay. The total reducing power was determined
by FRAP assay. The E. telmateia extract demonstrated the most relevant scavenger and
antioxidant properties. ESR signal of DMPO-OH radical adducts in the presence of E.
telmateia phosphate buffer (pH 7) extract was reduced to 98.9 %, E. ramosissimum 97.8 %
and Equisetum arvense 73.5 %.
Trouillas (2003): The paper presents the antioxidant, anti-inflammatory and antiproliferative
capabilities of 16 plants, including E. arvense. The biological properties of the water-soluble
fractions (“5 g of hydroalcoholic plant extracts were extracted by 50 ml water addition”)
were measured. Antioxidant properties were evaluated by the electron spin resonance (ESR)
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Selenium content:
Lovkova (1993): A total of 192 plant species belonging to 44 families were screened for their
selenium contents. The highest selenium contents were found in the rhizomes of Siberian
liquorice [Glycyrrhiza sp.] (1.12 mug/g DM), the leaves of ash gum [Myrtaceae] (0.64 mu/g),
the buds of weeping birch [Betula sp.] (0.70 mug/g), and the shoots of common melilot
[Melilotus], joint fir [Ephedra sp.] and meadow horsetail [Equisetum arvense](0.80, 0.68 and
0.60 mug/g, respectively). Based on plant and soil analyses, the highest coefficients of
biological accumulation, defined as the ratio of plant selenium content versus soil selenium
content, were calculated for ash gum (53.3) and meadow horsetail (30.0). It is suggested that
these species might be of therapeutic value in the treatment of selenium deficiency.
Assessor’s comment:
The results of the studies on Selenium content and the hepatoprotective activity do not
highlight any specific activity for the relevant indication or safety concerns.
Pharmacological interactions:
Schauss (2006): A bacterial reverse mutagenicity assay has shown that Urologic (TM), a
dietary supplement containing Crateva nurvala bark extract and standardized Equisetum
arvense (composition unknown), is non-mutagenic in all six strains. To determine if Urologic
is a potential inducer of human cytochrome P450 (CYP1A2 and CYP3A4), an assay using
immortalized human hepatocytes (Fa2N-4 cells) found a lack of interference of P450
cytochromes as preliminary evidence of its safety when taken with other medications.
Scott (2006): High-throughput enzyme inhibition screening assays were used to quantify the
effect of ethanol extracts (1:5) extraction solvent ethanol: water 55 % (v/v)) of 2 accessions
of 10 North American (NA) botanicals against the activity of the human cytochrome P450s:
CYP3A4, CYP19, and CYP2C19. The fluorescence readings were measured by a Cytofluor
4000 Fluorescence Measurement System plate reader with excitation and emission at 485/20
and 535/25 with two gains (50 and 75). In addition, phytochemical biomarkers within each
extract were identified and quantified using HPLC-MS or GC. Extracts containing
uncharacterized phytochemicals were identified taxonomically. The overall objective was to
describe the relationship between types and quantities of phytochemicals in ethanol extracts
and their ability to inhibit CYP activity. The top three inhibitors of CYP3A4 were Gaultheria
procumbens L. leaf > Rhodiola rosea L. root > Arctostaphylos uva-ursi L. Spreng leaf; of
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CYP19 were R. rosea root > Rhododendron groenlandicum (Oeder) Kron & Judd leaf > A.
uvae-ursi leaf; and of CYP2C19 were Achillea millefolium L. leaf and flower > Vaccinium
sp. L. leaf > Polygala senega L. root. Equisetum arvense L. leaf, Arctium lappa L. root, and
P. senega root had the lowest effect on CYP3A4 and CYP19 activity. Furthermore, the
concentration of certain phytochemical markers varied significantly between accessions (i.e.,
rosarin and essential oils), suggesting that the extent of metabolic inhibition is directly
dependent upon the concentration of bioactive constituents in an extract.
Assessor’s comments:
The two studies have shown contradictory results. Since Schauss (2006) describes results of a
combination preparation with limited data to the extracts, the results of the study from Scott
(2006) are of more interest. They show a low inhibitory effect on CYP3A4 and CYP19
activity. The data have to be taken into consideration at the risk assessment of clinical
interactions. (see II.3.3.5.2)
In-vivo tests
Diuretic effect:
The diuretic effect of E. arvense was tested in older in vivo studies. In a study published in
1912 an E. arvense preparation showed a diuretic effect on dogs about 15-20 % compared
with water [Cow, 1912].
About 650 diuretic trials on rats were prepared by Wachter (1938). The diuretic effect of a 6
% infuse was tested in 210 rats. Compared with water, after 30 minutes the effect was about
196 % higher, after 45 min 79 % and after 60 min about 39 %. The speed of the elimination
of urine was much higher in the tea group compared with the water group. A negative fluid
balance after 4 hours could not be determined. The author concluded that horsetail is a fast
and good diuretic. Similar were the experiments of Kreitmair (1936 and 1953) and Herre
(1937).
Lower diuretic effects of an E. arvense decoct were shown by Volmer (1937, 1939, 1940,
1941) on 55 mice (39 % diuretic effect), 20 rats (13 % diuretic effect), 20 rabbits (23-50 %
diuretic effect and about 30 % chloride). The authors compared the collected urine of 24
hours of the tea group with the water group. The content of 0,948 % chloride in Equisetum
arvense was considered.
No diuretic effect was detected by Jaretzky (1938, 1940) and Breitwieser (1939).
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Assessor’s comments:
The results of Wachter (1938) indicate a faster excretion of the urine and no negative fluid
balance. The results of Volmer (1937) indicate a diuretic mechanism with negative cellular
fluid volume, and the data from Jaretzky (1938, 1940) and Breitwieser (1939) do not show
any effect. In summary the mechanism of the diuretic activity of Equisetum arvense is not
known, but a low diuretic effect was shown in three different animal species.
Pérez Gutierrez (1985): Chloroform extracts of 4 Equisetum spp. (20 g herb /250 ml
chloroform, vacuum evaporated, suspended in ml water; single dose 50 mg extract /kg mice,
corresponding ca. 4 mg herb/kg mice ) were compared for activity with standard diuretics in
studies with mice. The most active was in E. hiemale [hyemale] var. affine, followed by E.
fluviatile, E. giganteum and E. myriochaetum. E. hiemale was a more effective diuretic than
any of the three standards. The tested dosage showed significant increase in sodium,
potassium and chloride excretion, as well as a rise in the urine pH level. The authors
concluded that the mechanism of action may be similar to that of hydrochlorothiazide.
Assessor’s comments:
From the point of view of the wide traditional use, different Equisetum species have been
used as diuretics. The study indicates that the E. species have different potential in diuretic
activity. The current study does not analyze E. arvense, the relevant E. species used in
Europe. It cannot be concluded whether other E. species might be more potent diuretics.
Antiurolithiasic effect:
Grases (1994): The effects of seven plants that have been applied to prevent and treat kidney
stone formation (Verbena officinalis, Lithospermum officinale, Taraxacum officinale,
Equisetum arvense
, Arctostaphylos uvae-ursi, Arctium lappa and Silene saxifraga) have been
studied using 12 female Wistar rats for each plant. The studied herbs were given by infusion.
E. arvense infusion was prepared from 3 g herb/l water. Variations of the main urolithiasis
risk factors (citraturia, calciuria, phosphaturia, pH and diuresis) have been evaluated. No
relevant difference was found in diuresis. None of the studied infusions affect calciuria and
citraturia values. The authors concluded that beneficial effects caused by these herb infusions
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on urolithiasis can be attributed to some disinfectant action, and tentatively to the presence of
saponins. Some solvent action can be postulated with respect to uric stones or heterogeneous
uric nucleus, due to the pH -increasing capacity of some herb infusions.
Assessor’s comments: The results of the study do not support the use for prevention and
treatment in kidney stone formation. The results are also contrary to the use as diuretic.
From the point of view that only 12 rats were tested for each plant, the results are only of
minimal value.
Antinociceptive and anti-inflammatory properties:
Do Monte (2004):
In this study antinociceptive and anti-inflammatory effects of
hydroalcoholic extract of stems from Equisetum arvense (“the dried stems were extracted
with 50 % ethanol-water, the ethanol was evaporated and the extract was stored in the
concentration of 5 %”) in mice were evaluated. The extract (10, 25, 50 and 100 mg kg-1,
i.p.), reduced the writhing induced by acetic acid in 49, 57, 93 and 98 %, respectively,
compared with the control group treated with saline. In the formalin test, 50 and 100 mg kg-1
(i.p.) extract reduced the licking activity in 80 and 95 % of the animals in the first phase, but
in the second phase only the latter dose diminished the licking time (in 35% of the animals).
In both phases, naloxone failed to revert the analgesic effect of the extract.
In the hot-plate test, the extract at 100 and 200 mg kg-1 did not change the latency to licking
or jumping. In the carrageenan-induced rat paw oedema, the extract at 50 mg kg-1 reduced
the paw oedema 2 h (25 %) and 4 h (30 %) after carrageenan administration. The dose of 100
mg kg-1 caused reduction of the paw oedema (29 %) only 4 h after carrageenan
administration. The authors concluded that this extract exhibits an antinociceptive (analgesic)
effect in chemical models
of nociception which is not related to the opioid system, as well as
significant
anti-inflammatory
properties.
Assessor’s comments:
The results of the studies may contribute to the plausibility of the traditional global use in
diseases of the urinary tract (not for the use as diuretic). The anti-inflammatory effect may
contribute to the traditional topical use.
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Sedative and anticonvulsant effects:
Dos Santos (2005): The hydroalcoholic extract of Equisetum arvense (HAE) (“the dried
stems were extracted with 50 % ethanol-water, DER unclear”) tested i.p. at the doses of 200
and 400 mg/kg showed a significant activity on the open-field, enhanced the number of falls
in the rota-rod reducing the time of permanence in the bar and increased the sleeping time (46
% and 74 %) in the barbiturate-induced sleeping time. On the contrary, in the elevated plus
maze, the doses of 50, 100 and 150 mg/kg did not affect the evaluated parameters. HAE
presented anticonvulsant and sedative effects.
In the pentylenetetrazole-seizure test the hydroalcoholic extract of Equisetum arvense
increased the first convulsion latency, diminished the severity of convulsions, reduced the
percentage of animals which developed convulsion (50% and 25 %) and protected animals
from death.
An acute toxicity study showed that in rats the extract at doses of 2 and 5 g /kg i.p. induced
mortality in 12 % and 37,5 % of the animals. Because the LD50 values were higher than 5
g/kg, the extract was considered as non-toxic.
A phytochemical analysis detected the presence of tannins, saponins, sterols and flavonoids.
Cognitive enhancement effects:
Dos Santos Junior (2005)(2) has investigated if the chronic administration of the
hydroalcoholic extract of stems from
Equisetum arvense
(HAE) reverses the cognitive
impairment in aged rats; moreover the in vitro antioxidant properties were evaluated. The
chronic administration of HAE at dose of 50 mg/kg, i.p. improved both short- and long-term
retention of inhibitory avoidance task and ameliorated the cognitive performance in reference
and working memory version of the Morris Water Maze. No differences were found between
all three groups of young controls, aged controls and EHA-treated animals with regard to the
open field and elevated plus maze tests. No toxicity manifestations were observed during the
treatment for eight weeks. In vitro assays revealed that HAE diminished the thiobarbituric
acid reactive substances as well as the nitrite formation, but did not alter the catalase activity.
Thus, the cognitive enhancement effects of the HAE may be attributed, at least in part, to the
antioxidant action.
Assessor’s comments:
The anticonvulsant, sedative and enhancement effects were examined
intraperitoneally
. The
effects were dose dependent. The i.p. administration is one point to make it impossible to
extrapolate the data to the human use. A further point is the unknown dosage because the
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extract is not described in detail. The DER of the administered extract is unknown. The
relevance for the clinical use is to be examined in the clinical assessment.
The results of the studies conducted by the Brazil investigators referring the anticonvulsant,
sedative and enhancement effects do not highlight any specific activity for the relevant
indication. Under clinical conditions the symptoms were not described. In summary it is
proposed not to include the effects in the text referring the “use of machines” or “special
warnings”.
Tumor-damaging capacity
:
Belkin (1952): Materials from 30 plants, used as diuretics, were tested at a single
subcutaneous dose for necrotisizing capacity against Sarcoma 37 implanted in CAF1 mice.
Four preparations were used for each plant material: An aqueous suspension, an olive-oil
suspension, an alcohol extract, and an acid extract.
From E. arvense was used the aqueous suspension (1mg/g mouse), olive-oil suspension
(1mg/g mouse), alcoholic extract ((1mg/g mouse) and an acid extract (0.02 ml pro g mouse,
0.01 ml acid extract represents about 5 mg per g of the original plant material).
Materials from 12 plants produced grossly and histologically demonstrable damage. A
relatively pronounced effect was induced with: Dioscorea villosa, Oxydendrum arboreum and
Spiraea ulmaria. Tumor damage of lesser degree was exhibited by 9 other plants: Apocynum
androsaemifolium, Asparagus officinalis, Capsella bursa-pastoris,
Equisetum arvense
, E.
hyemale, Hydrangea arborescens, Juniperus communis, Parietaria officinalis, and
Polytrichum juniperum. E. arvense aqueous suspension, olive-oil suspension, alcohol extract
showed no tumour damaging capacity. The acid extract showed “a lesser degree of induced
effect”.
Assessor’s comments: The results for E. arvense aqueous suspension, olive-oil suspension
and alcohol extract are negative. The effect of the acid extract was equivocal.. The tests were
performed with a subcutaneous single dose. The results do not highlight any specific activity
for the relevant indication or safety concerns on the oral use.
Hypoglycaemic effect:
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Cetto (2000): The hypoglycaemic effect of water extracts as well as of butanolic extracts
prepared from the aerial parts of Equisetum myriochaetum was examined in streptozotocin-
induced diabetic rats. A single oral administration of the water extract (WE) at doses of 7 and
13 mg/kg and of the butanol extract (BE) at doses of 8 and 16 mg/kg significantly (P<0.001)
lowered the plasma glucose levels in diabetic rats within three hours of administration. As a
reference drug, glibenclamide was used and showed, at a dose of 3 mg/kg, similar
hypoglycaemic effects to the tested extracts. Three kaempferol glucosides and one caffeoyl
glucoside were isolated from the drug and were shown to be the main constituents in both
extracts.
Assessor’s comments:
The hypoglycaemic effect was realized by oral administration of aqueous extracts. The result
is to be considered in the clinical assessment.(See II.3.1.1.2)
II.2.1.2
Assessor’s overall conclusions on pharmacology
Indication: Oral use: Traditionally used to promote renal elimination function
Assessors comments:
A diuretic is any drug that tends to increase the flow of urine from the body. Diuretics also
decrease the extracellular fluid volume and are primarily used to produce a negative
extracellular fluid balance.
In summary the data for the efficacy of horsetail are not appropriate to document a diuretic
aaction with a negative extracellular fluid balance. The results of Wachter (1938) indicate a
faster excretion of the urine and no negative fluid balance. The results of Vollmer (1937)
indicate a diuretic mechanism with negative cellular fluid volume and the data of Jaretzky
(1938, 1940) and Breitwieser (1939) did not show any effect. Since then no in-vivo studies
addressing the diuretic effect of E. arvense have been performed.
For horsetail it is shown that saponins, which are regarded as effective diuretic constituents
in the literature, are absent. Pharmacological and pharmacokinetical data of flavonoids and
other phenolics as possible effective constituents have been presented. Flavonoids and the
high potassium content may contribute to the efficacy.
Therefore the following wording is proposed:
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Oral use: Traditional herbal medicinal product to increase the amount of urine to achieve
flushing of the urinary tract as an adjuvant in minor urinary complaints.
In summary the pharmacological data support the traditional indication but they are not
sufficient to demonstrate well established use. The pharmacological effects and efficacy are
only plausible on the basis of long standing use and experience (traditional use) (Veit, 1994).
The following wording is recommended in the monograph:
“Not required as per Article 16c(1)(a)(iii) of Directive 2001/83/EC as amended.”
II.2.2
Pharmacokinetics
II.2.2.1
Overview of available data regarding the herbal substance(s), herbal preparation(s) and
relevant constituents thereof
(e.g. absorption, distribution, metabolism, elimination, pharmacokinetic interactions with
other medicinal products)
II.2.2.2
Assessor’s overall conclusions on pharmacokinetics
In vivo data on pharmacokinetics are absent. See II.3.1.2
II.2.3
Toxicology
II.2.3.1
Overview of available data regarding the herbal substance(s)/herbal preparation(s) and
constituents thereof
(e.g. single/repeat dose toxicity, genotoxicity, carcinogenicity and reproductive and
developmental toxicity, local tolerance, other special studies)
Single and repeat dose toxicity:
Aswal (1984): The LD50 for an undefined extract of E. arvense was > 1000 mg /kg i.p. in
mice.
Maeda (1997): The effects of dietary field horsetail (Equisetum arvense L.) powder on lipid
components were examined in male Sprague-Dawley rats fed on a 20 % casein diet with or
without cholesterol (0.5 % cholesterol and 0.15 % sodium cholate) for 14 days. The rats were
given free access for diet. The ingestion of E. arvense L. powder, 0.4 or 4.0 %, did not
influence food intake or growth. However, a cholesterol diet with E. arvense L. at 4 % caused
dermatitis at the neck, head and back in about 20-65 % of the rats. This dermatitis was
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reversed when the diet was changed to a standard commercial pelleted diet. There were no
apparent effects on serum or liver lipids in the rats fed with E. arvense L. irrespective of the
dietary cholesterol. Serum immunoglobulin E (IgE) concentrations, measured by enzyme-
linked immunoassay, revealed that the induction of IgE may not necessarily be involved in
the dermatitis caused by the intake of E. arvense L. It was concluded that the ingestion of
large amounts of E. arvense L. as cooking material is not recommended for those on a
cholesterol-rich diet.
Dos Santos (2005): The acute toxicity study of the hydroalcoholic extract of Equisetum
arvense (HAE) (“the dried stems were extracted with 50 % ethanol-water, DER unclear”)
showed that in the dose of 2 and 5 g /kg i.p. rat the extract induced mortality in 12 % and
37.5 % of the animals. Because the LD50s was higher than 5 g/kg the extract was considered
as non-toxic. The author noted that chronic administration of the dose utilized in the study
did not result in toxicity which may support the intense, chronic and popular use.
Dos Santos (2005)(2):
No toxicity manifestations were observed during treatment of eight
weeks of HAE (hydroalcoholic extract of stems from Equisetum arvense, DER unclear) at a
dose of 50 mg/kg, i.p. in rats.
Genotoxicity:
Joksic (2003): The authors assessed the in vitro cytogenetic effects of extracts of the
commonly used medicinal plants Equiseti herba, Ononidis radix, and Uvae ursi on irradiated
human blood lymphocytes. They examined the acquired micronucleus formation in
unirradiated and irradiated samples of cultured blood lymphocytes using the cytochalasin
block micronucleus test (CBMN).
An alcoholic extract of
Equiseti herba
had weak clastogenic properties, increasing the yield
of micronuclei in unirradiated samples and reducing the level of radiation-induced
micronuclei in a concentration-dependent manner. In the control, unirradiated samples,
36.8% of micronuclei were centromere-positive (MNC+), while in the irradiated ones the
percentage of MNC+ ranged from 10.8-15.3%, indicating a clastogenic mechanism for the
micronuclei formation.
Schauss (2006):
A bacterial reverse mutagenicity assay has shown that Urologic (TM), a
dietary supplement containing Crateva nurvala bark extract and standardized Equisetum
arvense, is non-mutagenic in all six strains investigated.
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Other toxicity studies have not been performed
II.2.3.2
Assessor’s overall conclusions on toxicology
Single/repeat dose toxicity, genotoxicity, carcinogenicity and reproductive and
developmental toxicity, carcinogenicity, reproductive and developmental toxicity, local
tolerance or other special studies do not exist according to the state of the art and the relevant
guidelines. The few data are only results from studies with other intention. The cited studies
give less information on the acute and chronic toxicity since the DER of the extracts is
unclear and the route of administration was mostly i.p. and not oral.
In the cytochalasin block micronucleus test (CBMN) an alcoholic extract of Equiseti herba
had weak clastogenic properties, increasing the yield of micronuclei in unirradiated samples
and reducing the level of radiation-induced micronuclei in a concentration-dependent manner
(Joksic, 2003). The study was performed to detect the mechanism of action of the tested
plants. The blood from only one person was tested. In the highest concentration 4.2 % of cells
had micronuclei. In the range of 4-5 % the test is often cut off. The effect is in the borderline
range.
In an in vivo study (Belkin, 1952) E. arvense aqueous suspension, olive-oil suspension or
alcohol extract did not show any tumour damaging capacity. The acid extract showed “a
lesser degree of induced effect”. In animals, in the chronic administration of the
hydroalcoholic extract of stems from Equisetum arvense in rats no toxicity manifestations
were observed during treatment (Dos Santos 2005(2)).
The dermatitis caused by the intake of E. arvense in a cholesterol-rich diet is not relevant
with respect to the therapeutic use. The rats consumed E. arvense powder in “free access”. In
Japan E. arvense is consumed as food.
In summary the data on toxicity are insufficient. Therefore for horsetail a traditional
monograph and no list entry are recommended.
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II.3
C
LINICAL
D
ATA
II.3.1
Clinical Pharmacology
II.3.1.1
Pharmacodynamics
II.3.1.1.1 Overview of available data regarding the herbal substance(s)/herbal preparation(s)
including data on constituents with known therapeutic activity.
Lemus (1996): A 10 % infusion of Equisetum bogotense (collected in San Juan de Pirque,
Chile) was administered to 25 healthy volunteers at a single daily dose equivalent to 0.75 g
plant/person for 2 consecutive days during a 6-day study. Effects on water balance and
urinary biochemical parameters were determined. The infusion showed a significant diuretic
effect. The analysis of urinary electrolytes showed a significant increase in sodium,
potassium and chloride excretion with respect to the control group, but within normal
physiological limits. No adverse effects were noted.
Revilla (2002): The hypoglycaemic effect of a water extract from aerial parts (0.33 g/kg) of
Equisetum myriochaetum was analyzed in 11 recently diagnosed type 2 diabetic patients. A
single dose of this extract was orally administered. Glucose and insulin were determined at 0,
30, 60, 90,120 and 180 min after administration. The same patients served as the control
group and received only coloured water as placebo. The administration of the extract
significantly reduced the blood glucose levels of the type 2 diabetic patients within 90, 120
and 180 min. There were no significant changes in the insulin levels. The results demonstrate
that the water extract of the aerial parts of E. myriochaetum shows a hypoglycaemic effect in
type 2 diabetic patients, starting 90 min after its administration.
Sparavigna (2006) : Two clinical trials were carried out with a new formulation based on
Equisetum arvense and a sulfur donor in a hydro-alcoholic solution, with the aim to evaluate
the efficacy and preventive activity of this new formulation on nail alterations. For the first
study, 36 women with nail plate alterations applied the test product every night on the nails of
one hand, randomly assigned for 28 days. The results demonstrated a significant reduction in
longitudinal grooves as well as an 85% reduction in patients reporting lamellar splitting of
treated nails, while no significant change was observed in untreated controls. In the second
study, 22 women with nail plate alterations applied the test product randomly on the nails of
one hand only, on alternating days, preferably in the evening, for 14 days. After drying, a
common nail polish was applied on the finger nails of both hands and removed by an organic
solvent every other day before the application of the next product . The results from this
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study showed a significant decrease (P< .001) of lamellar splitting compared to baseline with
the test product (82 % of cases).
II.3.1.1.2 Assessor’s overall conclusions on pharmacodynamics
Clinical pharmacological data of Equisetum arvense preparations do not exist. The
plausibility of the efficacy is based on the traditional medicinal use and supported by the non
clinical data.
One Study with a different Equisetum species, E. bogotense, showed a diuretic effect
(Lemus, 1996). The clinical study is consistent with results of in-vivo studies that indicate
that the E. species have different potential in diuretic activity. The current study does not
analyze E. arvense, the relevant E. species used in Europe.
A human study on Equisetum (E. myriochaetum) showed a hypoglycaemic effect (Revilla,
2002). It is a disadvantage that the study was conducted only with one single dose, and the
analyzed product contains a different Equisetum species. In summary the data are consistent
with the in vivo data, based on Equisetum myriochaetum. General data on the base of other
plant species are not considered in the labelling. From the traditional use of E. arvense no
clinical hypoglycaemic effects are reported.
The study by Sparavigna (2006) has been conducted with a new formulation. The results are
not relevant for the traditional use indications.
II.3.1.2
Pharmacokinetics
II.3.1.2.1 Overview of available data regarding the herbal substance(s)/herbal preparation(s)
including data on constituents with known therapeutic activity.
Graefe, 1999): Flavonoids and hydroxycinnamic acids are polyphenolic compounds present
in our daily diet in form of tea and vegetables as well as in herbal remedies used in
phytomedicine. In order to examine the metabolism and renal excretion of these compounds a
standardized extract from horsetail (Equisetum arvense) was administered to 11 volunteers
following a flavonoid-free diet for 8 days. 24 h urine samples were collected and analyzed by
HPLC-DAD. The putative quercetin metabolites, 3.4-dihydroxyphenylacetic acid or 3,4-
dihydroxytoluene could not be detected in urine in any sample. The endogenous amount of
homovanillic acid, generally regarded as one of the main quercetin metabolites, was 4 +/- 1
mg/d and did not increase significantly. Hippuric acid, the glycine conjugate of benzoic acid,
increased twofold after drug intake. Thus, the degradation to benzoic acid derivatives rather
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than phenylacetic acid derivatives seems to be a predominant route of metabolism. The
results of this pilot study should give rise to additional pharmacokinetic investigations in
humans.
II.3.1.2.2 Assessor’s overall conclusions on pharmacokinetics
Clinical data on absorption, distribution and pharmacokinetic interactions are few. The data
show that flavonoids and hydroxycinnamic acids seem to be predominantly metabolized to
benzoic acid derivates than to phenylacetic derivates.
II.3.2
II.3.2.1
Dose response studies
Not available.
II.3.2.2
Clinical studies (case studies and clinical trials)
Hesse, 1985):
Harntee 400 is recommended for the stone carrier's daily fluid intake
programme. Consitutents include Calendula, Equisetum, Fotniculum, Juniperus, Glycyrrhiza,
Ononidis, Orthosiphonis and Betulus extracts, and arbutin. In 20 calcium oxalate stone
carriers the p.o. treatment with Harntee 400 (TAD) resulted in diuresis and a leveling of
concentration peaks of most urinary parameters investigated. Citric acid elimination in urine
increased, and urine pH stabilized in a range supporting litholysis. No intolerance was noted.
II.3.2.3
Clinical studies in special populations (e.g. elderly and children)
Not available.
II.3.2.4
Assessor’s overall conclusions on clinical efficacy
The data do not fulfil the requirements of a well-established medicinal use with recognised
efficacy and are not eligible for a marketing authorisation. The only clinical study has been
conducted with a combination product in 20 patients only. The efficacy is plausible on the
basis of long standing use and experience.
II.3.3
Clinical Safety/Pharmacovigilance
II.3.3.1
Patient exposure
6
In case of traditional use the long-standing use and experience should be assessed.
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II.3.3.1
Adverse events
The national database of Germany contains 3 reports (database request from 21.06.2007 on
adverse events (AE) connected to preparations with a single herbal preparation containing
horsetail. Subsumed are all horsetail species in all pharmaceutical forms. Two cases refer to
allergic reactions e.g. rash (BfArM case nr. 03015301 and 91009533). The case 91009533
refers to a local allergic reaction after horsetail bath. In the case 03015301 (oral
consumption), because of negative rechallange it was concluded the rash was not related to
the consumption of the E. arvense product.
There is one case of an adverse event of two (elder) people with gastrointestinal reactions as
nausea and diarrhoea and sleep disorder and weariness after horsetail tea consumption
(BfArM case nr.97001924). The patients told their pharmacist that they have also diverse
“complaints of old age”, which are unknown. Also it is unknown if the patients took other
concomitant preparations for these complaints. There is no hint on none-drug related
explanations as infectious diseases. The patients considered the adverse reactions as toxic
reactions. Adulteration with E. palustre was ruled out. It was considered that the intake of
horsetail is not related to the adverse event. The case is insufficiently documented.
The adverse events are labelled: “Mild gastrointestinal complaints and allergic reactions (e.g.
rash) have been reported. The frequency is not known.”
II.3.3.2
Serious adverse events and deaths
Kolettis (2005): The authors report a case of a transient complete atrioventricular block in a
38-year-old man, after intake of a mixture of herbs (not trade name, Ribes nigrum,
Helicrysum italicum, Taraxacum officinale, Uncaria tomentosa, Vitamin C, Vitamin E,
Fumaria officinalis, Melissa officinalis, Equisetum arvense in unclear composition and DER)
for two days, intended to aid cigarette smoking cessation. Since all other causes of
conduction disturbances were excluded, a side effect of the herbal remedy was suspected as
the most likely explanation.
Assessor’s comments:
The patient has a consumption of various other plants preparations with not known medicinal
ingredients (Helicrysum italicum,). From Uncaria tomentosa it is well known that it contains
oxindol alkaloids which are associated to have a negative chronotropic and inotropic
cardiac effect. (Länger,2002). Because of the concomitant plants taken by the patient, a
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causal relationship between the ingestion of Equisetum arvense and the transient complete
atrioventricular block is unlikely.
Whiting (2002): Six patients have been presented with clinical, biochemical and histological
evidence of severe hepatitis after taking herbal remedies. Five patients took a combination of
herbs (one patient took a combination of chaperal, dandelion, Whitania somnifera, horsetail
and Echinacea) and presented with jaundice, fatigue and pruritus. The authors concluded that
healthcare providers and members of the public should be aware of the potential adverse
effects of these remedies.
Assessor’s comment:
A causal relation to horsetail is not probably, because the medication contained other
hepatotoxic plants.
Perazella (2002): Certain medical herbs (such as Equisetum arvense) may induce potentially
life threatening hyperkalemia in patients with underlying risk factors (chronic renal
insufficiency, hypoaldosteronism, and use of other potassium altering medication).
Agustin-Ubide MP 2004]: A patient reported contact dermatitis when preparing a meal from
carrot. She tolerated food ingestion. While she used Equisetum arvense for loss of weight,
she showed a sensation of pharyngeal occupation, cough, breathing difficulty and itching
after the ingestion of cooked carrots. The authors concluded that Equisetum arvense (with a
similar protein as carrots) possibly increased the symptoms.
Assessor’s comments:
Patients with known hypersensitivity to Equisetum arvense and decreased cardiac and renal
function are ruled out under contraindications. Because there is only one case with a
hypothetical relation to horsetail it is proposed not to give information about a possible
increase of the allergy symptoms from carrots under “Special warnings and precautions for
use”:
Other events:
Henderson (1952): The field occurrence of Equisetum poisoning was observed in 3 horses.
Two of these responded favourably to daily subcutaneous injections of 100 mg of thiamine
hydrochloride for 4 days. Similar symptoms were produced in a 2-year old colt fed for 35
days on a ration consisting solely of Equisetum-containing hay from the same field. Thiamine
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injections which were begun after the animal was unable to rise failed to bring about
recovery. In vitro experiments demonstrated that the Equisetum caused an almost complete
destruction of thiamine and of the thiamine content of oats and dried brewer's yeast. The
enzymatic nature of this destruction was indicated.
Assessor’s comments:
In the literature there are reports on a “thiamine like factor” which is discussed to be
responsible for toxicity in animals, particularly in horses, as muscle weakness, weight loss,
abnormal pulse rate, cold extremities and fever, symptoms similar to nicotine poisoning
(Pohl, 1955), (Hamon, 1992), (Jean-Blain, 1973). The Canadian government department
decided that, the manufacturers must prove that their E. arvense products are free of
thiaminase activity, because the “thiamine like factor” destroys thiamine in the stomach of
monogastric animals, including man, which can lead to irreversible brain damage in
thiamine deficient people (Hamon, 1992).
For the toxicity in horses and cows the presence of aconitic acid and the presence of one ore
more alkaloids is discussed by Rapp (1954). Palustrin, an ingredient of E. palustre, is also
dicussed (Frohne, 1984). Veit (1987) noted that 1 % of E. palustre in the hay can cause
heavy damages. The minimal content of alkaloids which are well soluble in water (tea) does
not seem to be the reason for the toxicology of animals, because in humans such adverse
reactions have not been registered.
Enzymes are inactivated by preparing ethanolic extracts or at high temperatures which are
used at the preparation of tea or commercial expressed juice (Fabre, 1993). In Europe
adverse events such as brain damage in thiamine deficient people, or toxic reactions similar
to nicotine poisoning have not been observed.
II.3.3.3
Laboratory findings
No data available.
II.3.3.4
Safety in special populations and situations
No data available.
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II.3.3.4.1
Intrinsic (including elderly and children) /extrinsic factors
No special studies about the use in children under 12 years or elderly exist. For children
under 12 years the use of diuretic drugs in self medication is not appropriate. Therefore the
use for children is not recommended.
II.3.3.4.2
Drug interactions
Validated interaction studies do not exist for horsetail preparations. The Commission E
monograph, published 18.09.1986 for Equisetum herba, gives the information “not known”.
The above mentioned “interaction studies” are insufficient to rule out any interaction.
Clinical interactions with other drugs have not been reported (Mills, 2005).
An in-vitro study gives the information that Equisetum arvense has a low effect on CYP3A4
and CYP19 activity (Scott, 2006). A clinical interaction study was conducted with a
combination of Crateva nurvala bark extract and Equisetum arvense in undefined
composition and dosage. There was a lack of interference with CYP450 (Schauss, 2006).
II.3.3.4.3
Use in pregnancy and lactation
Studies to carcinogenicity, reproductive and developmental toxicity, local tolerance or other
special studies do not exist. In the cytochalasin block micronucleus test (CBMN) Equiseti
herba had weak clastogenic properties. The Commission E monograph, published 18.09.1986
for Equisetum herba, does not give a contraindication in pregnancy and lactation. From the
traditional use no negative clinical observations in pregnancy and lactation exist (Mills,
2005).
In summary, the safety data for use in pregnancy and during lactation are not sufficient;
therefore it is proposed that E. arvense preparations should not be recommended.
The following text is proposed in the monograph:
“In the absence of sufficient data the use during pregnancy and lactation is not
recommended.”
No case of overdose has been reported.
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II.3.3.4.5
Drug abuse
Drug abuse has not been reported
II.3.3.4.6
Withdrawal and rebound
None reported.
II.3.3.4.7
Effects on ability to drive or operate machinery or impairment of mental ability
Not relevant
II.3.3.5
Assessor’s overall conclusions on clinical safety
The efficacy of Equisetum products is plausible on the basis of long standing use and
experience. The traditional use over a long period has shown that E. arvense is not harmful
when it is used in the specified conditions. However a long standing use does not exclude the
possibility that there may be concerns with regard to the product safety. Therefore E. arvense
should not be used in children under 12 years, during pregnancy and lactation, and in patients
suffering from conditions where a reduced fluid intake is recommended (e.g.cardiac or renal
diseases) or in patients with known hypersensitivity to horsetail. Interactions are considered
as clinical irrelevant and are not mentioned in the monograph. Special warnings to
undesirable effects are given. The herbal substance is traditionally used over a period of two
to four weeks. The duration of use is limited to one week if the symptoms persist during the
use of the medicinal product.
II.4
A
SSESSOR
’
S
O
VERALL
C
ONCLUSIONS
Despite of their long tradition, horsetail products do not fulfil the requirements of a well-
established medicinal use with recognised efficacy and an acceptable level of safety..
Horsetail is considered to have an impact on the protection of public health on the basis of the
long medicinal tradition in the specified conditions. Therefore horsetail products may be
considered as traditional herbal medicinal products.
©
EMEA 2008
40/41
III.
ANNEXES
III.1
C
OMMUNITY
H
ERBAL
M
ONOGRAPH ON
E
QUISETUM
ARVENSE
L.,
HERBA
III.2
L
ITERATURE
R
EFERENCES
©
EMEA 2008
41/41
Source: European Medicines Agency
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