Community herbal monograph on
Hamamelis virginiana
L.,
cortex
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
Hamamelis virginiana
L., cortex;
Hamamelidis cortex (hamamelis bark)
i)
Herbal substance
Not applicable
ii)
Herbal preparations
-
Dried comminuted herbal substance
-
Tincture (Ratio of herbal substance to
extraction solvent 1:10), extraction solvent
ethanol 45% v/v
-
Dry extract (DER 5-7.7:1), extraction
solvent ethanol 30% m/m
Well-established use
Traditional use
Comminuted herbal substance for decoction for
oromucosal and anorectal use.
Herbal preparations in semi-solid dosage forms
for cutaneous use.
Herbal preparations in semi-solid or liquid dosage
forms for anorectal use.
Herbal preparations in solid dosage forms for
rectal use.
2 “Hamamelidis cortex” consists of the dried bark from the stems, branches and twigs of
Hamamelis virginiana
L. (Fam.
Hamamelidaceae), collected in spring. It contains not less than 4.0% of hide-powder precipitable tannins, expressed as
pyrogallol and calculated with reference to the dried drug.
3 The declaration of the active substance(s) for an individual finished product should be in accordance with relevant herbal
quality guidance.
Community herbal monograph on Hamamelis virginiana L., cortex
EMA/HMPC/114583/2008
Page 3/7
Well-established use
Traditional use
Herbal preparations in liquid dosage forms for
oromucosal use.
The pharmaceutical form should be described by
the European Pharmacopoeia full standard term.
4.1.
Therapeutic indications
Well-established use
Traditional use
a)
Traditional herbal medicinal product for relief
of minor skin inflammation and dryness of the
skin.
b)
Traditional herbal medicinal product for
symptomatic relief of itching and burning
associated with haemorrhoids.
c)
Traditional herbal medicinal product used as a
mouthwash and gargles for relief of minor
inflammation of mucous membranes of the
oral cavity.
The product is a traditional herbal medicinal
product for use in the specified indications
exclusively based upon long-standing use.
4.2.
Posology and method of administration
Well-established use
Traditional use
Posology
Indication a)
Adolescents, adults and elderly
Cutaneous use
Tincture in a strength corresponding to 5-10% in
semi-solid preparations, several times daily.
Dry extract (5-7.7:1; ethanol 30% m/m) in a
strength corresponding to 1.3% as an ointment,
several times daily.
The use in children under 12 years of age is not
recommended (see section 4.4 ‘Special warnings
and precautions for use’).
Community herbal monograph on Hamamelis virginiana L., cortex
EMA/HMPC/114583/2008
Page 4/7
Well-established use
Traditional use
Indication b)
Adults and elderly
Anorectal use
Tincture in a strength corresponding to 5-10% in
semisolid and liquid preparations, several times
daily.
Comminuted herbal substance as a decoction:
5-10 g/250 ml, up to 3 times a day as
impregnated dressings.
Dry extract (5-7.7:1; ethanol 30% m/m) in a
strength corresponding to 1.3% as an ointment,
several times daily.
Rectal use
Suppositories containing 66 mg of dry extract
(5-7.7:1; ethanol 30% m/m), one suppository
two or three times daily.
The use in children and adolescents under
18 years of age is not recommended (see section
4.4 ‘Special warnings and precautions for use’).
Indication c)
Adolescents, adults and elderly
Tincture (1:10), ethanol 45% v/v (diluted 1:3,
with water): 2-4 ml, three times daily for gargles.
Comminuted herbal substance to be used as a
decoction, for gargles: 2-3 g up to 3 times daily.
The use in children under 12 years of age is not
recommended (see section 4.4 ‘Special warnings
and precautions for use’).
Duration of use
Indications a) and c)
If the symptoms persist for more than 1 week
during the use of the medicinal product, a doctor
or a qualified health care practitioner should be
consulted.
Community herbal monograph on Hamamelis virginiana L., cortex
EMA/HMPC/114583/2008
Page 5/7
Well-established use
Traditional use
Indication b)
If the symptoms persist for more than 2 weeks
during the use of the medicinal product, a doctor
or a qualified health care practitioner should be
consulted.
Method of administration
Cutaneous use.
Oromucosal use.
Rectal use.
Anorectal use.
4.3.
Contraindications
Well-established use
Traditional use
Hypersensitivity to the active substance(s).
4.4.
Special warnings and precautions for use
Well-established use
Traditional use
Indication a)
The cutaneous use in children under 12 years of
age has not been established due to lack of
adequate data.
Indication b)
The use in children and adolescents under
18 years of age has not been established due to
lack of data.
If rectal bleeding occurs a doctor should be
consulted.
Indication c)
The use in children under 12 years of age has not
been established due to lack of data.
If symptoms persist or worsen during the use of
the medicinal product, a doctor or a qualified
health care practitioner should be consulted.
For tinctures 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.
Community herbal monograph on Hamamelis virginiana L., cortex
EMA/HMPC/114583/2008
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4.5.
Interactions with other medicinal products and other forms of
interaction
Well-established use
Traditional use
None reported.
4.6.
Fertility, 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 effect on the ability to drive and
use machines have been performed.
4.8.
Undesirable effects
Well-established use
Traditional use
Allergic contact dermatitis has 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.
Community herbal monograph on Hamamelis virginiana L., cortex
EMA/HMPC/114583/2008
Page 7/7
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.
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.
6 June 2011
Community herbal monograph on Hamamelis virginiana L., cortex
EMA/HMPC/114583/2008
Page 8/7
Assessment Report
I.
REGULATORY STATUS OVERVIEW
...................................................................................3
II.
ASSESSMENT REPORT
...........................................................................................................6
INTRODUCTION
............................................................................................................................... 7
II.1.1
Description of the herbal substance (s), herbal preparation(s) or combinations thereof
....... 7
II.1.2
Information on period of medicinal use in the Community regarding the specified
indication
II.1.2.1
13
Type of tradition, where relevant
..................................................................................... 15
II.1.2.2
Evidence regarding the indication/traditional use
......................................................... 15
II.1.2.3
Evidence regarding the specified strength /posology
..................................................... 19
II.1.2.4
Evidence regarding the route of administration
............................................................. 24
II.1.2.5
Evidence regarding the duration of use
........................................................................... 24
II.1.2.6
Overall conclusion on the traditional medicinal use
...................................................... 24
II.2
............................................................................................................. 26
II.2.1
Pharmacology
...................................................................................................................... 26
II.2.2
Pharmacokinetics
................................................................................................................. 32
II.2.3
Toxicology
........................................................................................................................... 32
II.2.3.1
Overall conclusions on Toxicology
................................................................................... 33
II.3
....................................................................................................................... 34
II.3.1
Clinical Pharmacology
........................................................................................................ 34
II.3.1.1
Pharmacodynamics
........................................................................................................... 34
II.3.1.2
Pharmacokinetics
.............................................................................................................. 38
II.3.2
Clinical Efficacy
.................................................................................................................. 38
II.3.3
CLINICAL SAFETY
.......................................................................................................... 42
II.3.3.1
Patient exposure
................................................................................................................ 42
II.3.3.2
Adverse events
................................................................................................................... 42
II.3.3.3
Serious events and deaths
................................................................................................. 42
II.3.3.4
Laboratory findings
.......................................................................................................... 42
II.3.3.5
Safety in special populations and situations.
................................................................... 42
II.3.3.6
Overall conclusions on safe use
........................................................................................ 43
ANNEXES..................................................................................................................................................47
II.5
II.4
...................................................................................................... 43
II.6
RAMUNCULUS DESTILLATUM
....................................................................................................... 47
............................................................................................................ 47
LITERATURE REFERENCES
EMEA 2010
2/47
I.
REGULATORY STATUS OVERVIEW
MA: Marketing Authorisation;
TRAD: Traditional Use Registration;
Other TRAD: Other national Traditional systems of registration;
Other: If known, it should be specified or otherwise add ‘Not Known’
Member State
Regulatory Status
Austria
MA
TRAD
Other TRAD
Other Specify: Medicinal products
Belgium
MA
TRAD
Other TRAD
Other Specify: Combinations
Bulgaria
MA
TRAD
Other TRAD
Other Specify:
Cyprus
MA
TRAD
Other TRAD
Other Specify:
Czech Republic
MA
TRAD
Other TRAD
Other Specify: No Med. Products
Denmark
MA
TRAD
Other TRAD
Other Specify: Medicinal products
Estonia
MA
TRAD
Other TRAD
Other Specify: No Med. Products
Finland
MA
TRAD
Other TRAD
Other Specify: No Med. Products
France
MA
TRAD
Other TRAD
Other Specify:
Germany
MA
TRAD
Other TRAD
Other Specify:
Greece
MA
TRAD
Other TRAD
Other Specify: No Med. Products
Hungary
MA
TRAD
Other TRAD
Other Specify: No Med. Products
Iceland
MA
TRAD
Other TRAD
Other Specify:
Ireland
MA
TRAD
Other TRAD
Other Specify: Medicinal products
Italy
MA
TRAD
Other TRAD
Other Specify: Medicinal products
Latvia
MA
TRAD
Other TRAD
Other Specify: Combinations reg.
Liechtenstein
MA
TRAD
Other TRAD
Other Specify:
Lithuania
MA
TRAD
Other TRAD
Other Specify:
Luxemburg
MA
TRAD
Other TRAD
Other Specify:
Malta
MA
TRAD
Other TRAD
Other Specify:
The Netherlands
MA
TRAD
Other TRAD
Other Specify:
Norway
MA
TRAD
Other TRAD
Other Specify:
Poland
MA
TRAD
Other TRAD
Other Specify:
Portugal
MA
TRAD
Other TRAD
Other Specify: Medicinal products
Romania
MA
TRAD
Other TRAD
Other Specify:
Slovak Republic
MA
TRAD
Other TRAD
Other Specify:
Slovenia
MA
TRAD
Other TRAD
Other Specify:
Spain
MA
TRAD
Other TRAD
Other Specify: Medicinal products
Sweden
MA
TRAD
Other TRAD
Other Specify:
United Kingdom
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.
1
Not mandatory field
EMEA 2010
3/47
Austria
:
Ointment containing per 1 g, 50 mg of liquid extract (1:1), extraction solvent ethanol 45% V/V;
Aqua Hamamelidis cooling gel.
Belgium
: For oral use (herbal tea), authorisation date 1961-1962; no clear indication
For rectal use (suppositories): authorisation date 1965 (combination with lidocaine,
triclosan…): indication: hemorrhoids
For cutaneous use (ointments): authorisation date 1961-1962 (combination with
Aesculus
, local
anaestetic, antiseptic,
Viburnum
, …) : indication : hemorrhoids, “protective” , bleeding nose..
Czech Republic
: there is not registered any herbal medicinal product containing
Hamamelis
Denmark
:
Hamamelis virginiana
L., fresh leaf and twig distillate (water steam distillate) (1:1.6); 0.5 g
extract (HEL)/100 g ointment
Estonia
: No medicinal product containing hamamelidis folium is authorised in.
Finland
: No herbal medicinal product containing
Hamamelis
.
Germany
:
Hamamelidis folium
: WEU (In the market at least since 1976).
For adults and adolescents over 12 years old.
1)
Liquid extract (1:1), extraction solvent ethanol 45% V/V. Ointment, containing 50 mg of liquid
extract per 1 g of ointment. For cutaneous use 1 string of ointment 2-3 times daily.
For treatment of small skin lesions and minor inflammation of the skin. For relief of disorders in the
beginning of haemorrhoids disease.
2)
Liquid extract (1:1), extraction solvent ethanol 30% m/m. Gel, containing 2.5 g liquid extract per
25 g of gel. For cutaneous use. 1 string of ointment several times daily. For supporting treatment of
superficial skin lesions.
3)
Liquid extract (1:2), extraction solvent ethanol 60% V/V. Suppositories, containing 400 mg of
extract. For rectal use. 1 Suppository two times daily. For relief of disorders as: itching, burning,
slight bleeding in haemorrhoids grade I and II.
4)
Liquid extract (1:2), extraction solvent ethanol 60% V/V. Ointment, containing 200 mg liquid
extract per 1g ointment. For cutaneous use: 1 string of ointment two times daily. For relief of
itching, weeping and burning in the beginning of haemorrhoids disease as soon as inflammation
(i.e.: anal-eczema) and superficial skin lesions in the anal region.
5)
Liquid extract (1:2), extraction solvent ethanol 60% V/V. Suppositories, containing 400 mg of
extract. For rectal use. 1 suppository two times daily, in case of heavy discomfort temporarily
1 suppository three times a day. For relief of: itching, weeping and burning in the beginning of
haemorrhoids disease as soon as inflammation of mucosa in the anal region.
Risks: 1-5): In many cases a short irritation and slight burning is possible. Very seldom allergic reaction
could occur.
The products are in the market as authorised products. No pharmacovigilance actions taken on medicinal
products containing the herbal substance.
The Herbal substance (Hamamelidis folium) is only available in combination products. There are
6 authorised products 4 (2-3 ingredients); 1 (4-5) and 1 >5.
There is also 1 German Standard Marketing Authorisation product. A herbal tea (single ingredient) for the
preparation of poultices, for gargling and for rinsing of the oro-pharynx. For supporting treatment in
superficial skin lesion at minor inflammation of the skin and mucosa.
Hamamelidis destillatum:
WEU (1-2) In the market since 2007; 3-5) at least since 1976). For adults and
adolescents over 12 years old.
1-5) Distillate of fresh
Hamamelis virginiana
L. leaves and branches (1:1.12-2.08), distillation agent
ethanol 6% m/m.
EMEA 2010
4/47
1), 2) and 4) Ointment, 100 g of ointment containing 6.25 g distillate, for cutaneous and mucosal use.
Several times daily, thinly to the affected regions. Minor skin lesions, minor inflammation
of skin and mucosa. For relief of disorders in the beginning of haemorrhoids disease.
3) Liquid, 100g (=102 ml) containing 25 g distillate. For cutaneous use: apply several times daily
undiluted to the affected regions. For oromucosal use: In case of gums bleeding add 1 measuring
spoon (=5 ml) liquid to the mouthwash. Minor skin lesions and inflammation of skin and gums.
5) Cream, 100 g containing 5.35 g destillate. For cutaneous and mucosal use. Apply several times
of skin and mucosa.
Risks: 1-5): In many cases a short irritation and slight burning is possible. Very seldom allergic reaction
could occur.
The products are in the market as authorised products. No pharmacovigilance actions taken on medicinal
products containing the herbal substance.
There is also 1 product in combination (2-3 ingredients).
Hamamelidis cortex: WEU (1-2) In the market at least since 1976). For adults and adolescents over 12
years old.
1)
Ointment, containing 129 mg dry extract per 10 g ointment. Dry extract (5-7.7:1), extraction solvent
ethanol 30% m/m. For cutaneous use 1 string of ointment of 1-2 cm length, 2-3 times a day. For
amelioration of disorders as itching, burning, slight bleeding in haemorrhoids disease, grade I and II
and inflammation, and slight skin lesion at the anus.
2)
Suppository, containing 66 mg dry extract. Dry extract (5-7.7:1), extraction solvent ethanol 30%
m/m. For rectal use 1 suppository 3 times daily. For amelioration of disorders as itching, burning,
slight bleeding in haemorrhoids disease grade I and II. Inflammation and slight skin lesion at the
anus.
Risks: 1-2): In many cases a short irritation and slight burning is possible. Very seldom allergic reaction
could occur.
The products are in the market as authorised products. No pharmacovigilance actions taken on medicinal
products containing the herbal substance.
The Herbal substance (Hamamelidis cortex) is only available in combination products. There are
3 authorised products (2-3 ingredients).
There is also 1 German Standard Marketing Authorisation product. A herbal tea (single ingredient) for the
preparation of poultices, for gargling and for rinsing of the oropharynx. For supporting treatment in
superficial skin lesion at minor inflammation of the skin and mucosa.
Greece
: There is not registered any herbal medicinal product containing
Hamamelis
Hungary
: No herbal medicinal product containing
Hamamelis
.
Ireland
: Four products which contain hamamelis distillate of fresh
Hamamelis virginiana
L. leaves and
branches (1:1.12-2.08), distillation agent ethanol 6% m/m.authorised as medicines in Ireland and
one adverse reaction has been reported [i.e. conjunctivitis case associated]. No 'herbal' products
have been authorised containing it though!
Italy
: Cream, 100 g containing 5.35 g distillate (1:1,6); Distillate of fresh
Hamamelis virginiana
L. leaves
and branches (1:1.12-2.08), distillation agent ethanol 6% m/m.
Latvia
: Only combinations.
Spain
: Cream, 100 g containing 5.35 g distillate (1:1,6); Distillate of fresh
Hamamelis virginiana
L.
leaves and branches (1:1.12-2.08), distillation agent ethanol 6% m/m.
EMEA 2010
5/47
daily at regular intervals thinly to the affected regions. Superficial skin lesions, minor inflammation
II.
ASSESSMENT REPORT
Hamamelis virginiana
L cortex
Hamamelis virginiana
L., folium
Hamamelis virginiana
L., folium et cortex out ramunculus destillatum
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)
Hamamelis
virginiana
L., cortex (hamamelis bark)
Hamamelis
virginiana
L., folium ( hamamelis leaf)
Hamamelis
virginiana
L., folium et cortex aut
ramunculus destillatum (leaf and bark distillate and
twigs distillate)
Herbal preparation(s)
Dried comminuted bark, for tea preparation
Dried or fresh comminuted leaf, for tea preparation
Hamamelidis distillate (1:1.6) ethanol 12%-15%
Hamamelidis distillate (1:1.12-2.08) ethanol 6%
m/m
Tincture (1:10) ethanol 45% V/V (leaf)
Liquid extract (1:1) ethanol 30% m/m (leaf)
Liquid extract (1:1) ethanol 45% V/V (leaf)
Liquid extract (1:1) ethanol 60% V/V (leaf)
Liquid extract (1:2) ethanol 60% V/V (leaf)
Tincture (1:10) ethanol 45% V/V (bark)
Dry extract (5-7.7:1) ethanol 30% m/m (bark)
Pharmaceutical forms
Semi-solid herbal preparation for cutaneous or for
rectal use.
Suppositories liquid dosage forms for ocular use
(eye drops) oromucosal use (gargle).
Rapporteur
Gloria García Lorente
EMEA 2010
6/47
II.1
INTRODUCTION
The aim of this report is to assess the available information on the herbal substances of
Hamamelis
virginiana
L.,
bark, leaf and twigs
and preparations
thereof for the categorisation as products under well-
established use or traditional use and the establishment of the corresponding Community herbal
monographs.
This report is based on a scientific systematic review of the literature (mainly on efficacy and safety) of
Hamamelis virginiana
L. and the documentation provided by the European Medicines Agency completed
by additional searches in biomedical databases and the available articles from references included in
monographs on
Hamamelis virginiana
L.
(Commission E Monographs, 2001; ESCOP, 2003; WHO,
2002), as well as the information provided by Member States.
MEDLINE (1960-2005); TOXNET (Toxline; HSDB); Pubmed Excerpta Medica and Micromedex
databases have been used mainly for bibliographic searches. Due to the limited number of references
obtained, the final strategy for the search was: “Hamameli* or witch hazel”.
This assessment report refers to preparations of
Hamamelis virginiana
L.
as a single ingredient, while
studies performed with combinations are not discussed.
II.1.1
Description of the herbal substance (s), herbal preparation(s) or combinations thereof
Hamamelis virginiana
L. (synonym: witch hazel) is a plant of the
Hamamelidaceae
family. It is a
deciduous, tall shrub, or small tree, branches highly branched, indigenous to the Atlantic coast of North
America, found in damp woods ranging from Nova Scotia to Florida and as far west as Texas. It is
cultivated on a small scale in Europe, though the material of commerce is obtained mainly from the
eastern USA and Canada (Wichtl and Bisset, 1994).
The flowers, bark and leaves of the common, colourful American witch hazel shrub provided tonics and
remedies to Native Americans. Today, natural witch hazel is considered as one of of the few plant
products that meet FDA standards for safety and effectiveness. The plants of the genus
Hamamelis
are
unusual because they bear their blossoms and fruits together, at the very same time of the year, usually in
autumn or winter. Flowers of
Hamamelis virginiana
L. are ribbon-like clusters of yellow, orange, or red
petals; the adjacent seed capsules, from the previous year’s blossoms, which eject two black seeds when
they burst.
According to Laux (1993),
Hamamelis virginiana
L. has the following synomyms
: Hamamelis
macrophylla Pursh, H. androgyna Walt, H. coryfolia, H. dioica, Trilopus dentate, T. nigra,
T. rotundifolia,
and
T. virginiana.
Hamamelis bushes are very similar in appearance to the hazelnut (
Coryllus avellana
), which can also lead
to confusion during harvesting period. The two plants can be distinguished anatomically and analytically.
“Hamamelidis folium” consists of the dried or fresh leaves of
Hamamelis virginiana
L. It contains not less
than 3% of tannins, expressed as pyrogallol (C
6
H
6
O
3
; M
r
126.1) and calculated with reference to the
dried drug. The material complies with the monograph of the European Pharmacopoeia 6.1, [monograph
(04/2008:0909)]. Leaves are about 7 to 15 cm long, brittle, dark green or brownish-green, alternate,
stipulate, broadly oval or rhomboid ovate; short-petiolated about 1 to 1.5 cm long, margin coarsely crenate
or sinuate, apex acute or rounded, base cordate and unequal and venation pinnate, lateral veins straight,
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
Rev.2)
EMEA 2010
7/47
prominent on the under surface, each ending in a marginal crenation; trichomes stellate, scattered or under
surface, numerous on young leaves. Flowers thread-like, golden-yellow; appear in axillary clusters as
leaves fall in autumn and at about the same time as fruits ripen from blossoms of the previous year.
“Hamamelidis cortex” consists of the dried bark from the stems, branches and twigs of
Hamamelis
virginiana
L. (Fam.
Hamamelidaceae
), collected in spring. It contains not less than 4.0% of hide-powder
precipitable tannins, expressed as pyrogallol (C
6
H
6
O
3
; M
r
126.1) and calculated with reference to the
dried drug.
Stems and fruits are present in small amounts; stems pale reddish-brown or greyish-brown, smooth or
slightly warty and up to about 4 mm thick, with alternate leaf scars; fruit a woody capsule, about 15 mm
long when mature, splitting at the apex into 2 halves each containing a single black seed. Odour is not
marked; the taste is bitter and astringent.
“Hamamelidis ramunculus (twigs)” have structures called buds, leaf scars and bundle scars that can differ
for different species. Hamamelis twig is the herbal substance used in the preparation of hamamelis water,
or as Witch Hazel as described in USP monograph.
Chemical constituents of herbal substances
The leaf contains 3-10% tannins (a mixture of catechins, gallotannins, plus cyanidin and delphinidin type
proanthocyanidins), mainly hamamelose (Wichtl, 1989); catechins, mainly (+)-catechin, (+)-gallocatechin,
(-)-epicatechin gallate, (-)-epigallocatechin gallate; phenolic acids (caffeic and gallic acids); flavonoid
galactosides and glucuronides; flavonoids such as kaempherol, quercetin, quercitrin, and isoquercitrin
(Hänsel et al, 1993; ESCOP, 1997; Sagareishvili, TG. et al,. 1999; Kaul, R et al. 2001). 0.01-0.5% volatile
oil (Meyer-Buchtela, 1999; Wichtl, 1989), among which 40% are aliphatic alcohols, 25% carbonyl
compounds, 15% aliphatic esters, and a maximum of 0.2% safrol (Wichtl and Bisset, 1994). According to
Hager, the leaves contain a small amount of hamamelitannin. The “hamamelin” reported in the literature
for witch-hazel leaf is a preparation obtained by precipitating a concentrated alcoholic extract of powdered
leaves.
Witch hazel bark contains 8-12% tannins (minimum content recommended of 4% tannins). Cortex tannins
are qualitatively similar to folium tannins, but have a higher content of hamamelitannin (1-7%), followed
by monogalloylhamamelose, free gallic acid, condensed catechin tannins, and small amount of flavonols;
approximately 0.1% volatile oil with a very complex composition (Hänsel et al, 1993; Wichtl, 1996;
Meyer-Buchtela, 1999; Wang et al, 2003). The bark contains significantly higher levels of
phenylpropanoids and sesquiterpenoids in the volatile fractions compared to the leaves, which contain
higher amounts of monoterpenoids. The bark is richer in hydrolysable tannins and the leaves mainly
contain condensed tannins.
Herbal preparations
Herbal preparations are obtained from dried or fresh leaves and/or the dried bark of the trunk and twigs of
Hamamelis virginiana
L. (Fam.
Hamamelidaceae
). The following herbal preparations have been proposed
by Member States or cited in the literature search:
Dried comminuted herbal substance, for tea preparation (decoction), official in the standard license
monographs (Banz, 1998; Braun et al, 1997; DAC, 1986; Wichtl and Bisset, 1994) and German Drug
Codex (1986). Herbal tea preparation (decoction) 5-10 g/250 ml or 2-3 g/150 ml (decoction 10-15 min).
Powdered herbal substance (a green to greenish-brown powder possessing the diagnostic microscopic
characters, odour and taste of the crude drug as described in the European Pharmacopoeia).
Tincture (1:10; ethanol 60%)
Tincture (bark) (1:10; ethanol 45% V/V)
Tincture (leaf or bark) (1:10; ethanol 45% V/V)
Tincture (leaf) (1:10; ethanol 55% V/V)
Liquid extract (leaf) (1:1; ethanol 30% m/m).
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Liquid extract (leaf) (1:1; ethanol 45% V/V).
Liquid extract (leaf) (1:1; ethanol 60% V/V).
Liquid extract (1:2; ethanol 60% V/V).
Liquid extract (leaf) (1:3), extraction solvent ethanol 62% V/V (Gracza, 1987)
Dry extract (cortex) (5-7.7:1; ethanol 30% m/m).
Hamamelis water (Hamamelis distillate): Aqua hamamelidis. Distilled Witch Hazel; Witch Hazel USP;
Liquor Hamamelidis. Several preparations, similar but not equivalent, obtained from different processes
and called with different names are referring to hamamelis wate.
Leaves, bark and twigs collected in spring are used for the production of water distillates. Aqua
hamamelidis is a clear colourless liquid; the odour is characteristic. Their acidity or alkalinity is neutral or
slightly acid to litmus solution. Its weight per ml at 20ºC is 0.976 g to 0.982 g. The residue on
evaporation, not more than 0.025% w/v, the residue being dried to constant weight at 105ºC. The alcohol
content is from 13 to 15% v/v of ethyl alcohol, determined by the method included in BP Codex.
Preparations:
Distillate of fresh
Hamamelis virginiana
L. (leaves and branches) (1:1.12-2.08), distillation agent
ethanol 6% m/m. Used as an ointment with 100 g of ointment containing 6.25 g distillate.
Distillate prepared from dried twigs (1:2; ethanol 14-15% v/v).
Chemical constituents of hamamelis preparations.
Polyphenols
Tannins are a broad class of complex phenolic compounds of molecular weight between 500 and 3000.
The biological importance of tannins is attributed to their ability to bind and precipitate mainly proteins
but also alkaloids. Tannins have been defined as “phenolic natural products that precipitate proteins from
their aqueous solutions”. There are two types of tannins, the hydrolyzable tannins, which, upon acidic,
alkaline, or enzymatic hydrolysis produce glucose and phenolic acids; and the condensed tannins
(proanthocyanidins), which are flavan-3-ol polymers. Condensed tannins can occur as galloyl esters.
Hydrolizable tannins are polyesters of glucose, and upon hydrolysis, they release the sugar, and either
gallic acid, hexahydroxydiphenic acid, or both, the latter acid rapidly lactonizes to ellagic acid (which
explains the traditional terminology of ellagitannins). Oligomer hydrolysis also yields compounds with
three or four aromatic rings, whose structures vary depending on the nature of the bond between
monomers.
Tannins are generally extracted with a water and acetone mixture. The polymeric proanthocyanidins and
high molecular weight gallotannins remain in the aqueous phase.
The therapeutic activity of tannins is mainly due to the astringency, and result from their affinity for
proteins. Externally, they waterproof the external layers of the skin and mucosas, thus protecting the
underlying layers; they also have a vasoconstrictor effect on small superficial vessels. By limiting fluid
losses, tannins enhance tissue regeneration in case of superficial burn or wound.
Generally speaking tannins are enzyme inhibitors. They block 5-lipoxygenase; they inhibit angiotensin
converting enzyme, hyaluronidase activation, and the glucosyl-transferases of microorganisms involved in
the formation of cavities; ellagitannins and complex tannins inhibit protein kinase C.
Tannins especially the hydrolysable ones inhibit the peroxidation induced by ADP and ascorbic acid in rat
hepatic mitochondria. In vitro they are radical scavengers and inhibitors of superoxide ion formation, and
some of them inhibit lipoxygenase in rat peritoneal granulocytes.
(Bruneton 1999
)
The main characteristic constituent of
Hamamelis virginiana
L. is hamamelitannin, a mixture of the α- and
β- forms of (2´, 5-di-O-galloyl-hamamelose), its molecular structure bears two gallate moeities and a
sugar unit, hamamelose. Wang et al (2003) developed an HPLC method for the determination of
hamamelitannin, catechins, and gallic acid from witch hazel bark, twig, and leaf. The concentrations in
the bark for hamamelitannin, gallic acid, (+)-gallocatechin, and (+)-catechin were 4.77, 0.59, 0.22, and
0.39% (wt/wt), respectively. Hamamelitannin and catechins were also detected in the leaves at
concentrations of < 0.04% (wt/wt).
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Hamamelitanin
Proanthocyanidins are also present including: procyanidin dimers such as catechin-(4α→8)-catechin,
3-O-galloyl-epicatechin-(4 β →8)-catechin and epicatechin-(4 β →8)-catechin-3-O-(4-hydroxy)benzoate;
prodelphinidins such as epigallocatechin-(4 β →8)-catechin, 3-O-galloyl-epigallocatechin-(4 β →8)-
catechin and 3-O-galloyl-epigallocatechin-(4 β →8)-gallocatechin, and proanthocyanidin oligomers
consisting of 4-9 catechin-gallocatechin units, some of which are 3-O-galloylated.
Other constituents include flavan-3-ols such as (+)-catechin, (+)-gallocatechin, (-)-epicatechin-3-O-
gallate, and (-)-epicatechin-3-O-gallate, di- and tri-O-galloyl hamameloses and related
4-hydroxybenzoates, pentagalloylglucose, gallic acid and about 0.5% volatile oil. Hexen-2-ol, hexenol,
α and β –ionones, eugenol, safrole and sesquiterpenes.
Epicatechin (4beta->8) epicatechin (Procyanidin B2)
Polymeric proanthocyanidins were isolated from an acetone-water (7:3) extract from hamamelis bark in
yields of about 5% by Dauer et al (2003), Touriño et al (2008). Terminal chain units were catechin and
gallocatechin in a constant ratio of 95:5. All chain extension units were completely galloylated at position
0-3, while chain terminating units were not galloylated. Predominant interflavan linkages were 4→8-
bonds.
According to Vennat et al (1992), proanthocyanidins, phenolic acids and flavonoids have been identified
in leaf extracts. Ollivier et al (1992) studied on the biotransformation of polyphenols in
Hamamelis
virginiana
L. leaves and had shown variations on the qualitative and quantitative determination of gallic
acid and ethyl gallate in hamamelis leaves according to the extraction solvent used. In water, only gallic
acid was present; both were found in solutions containing 10-70% of ethanol (m/m). For hydroalcoholic
solutions up to 80% (m/m) their rate was negligible. Polyphenols are modified by conjugated action of
enzymes and solvents. Gallic acid is produced by hydrolysis of tannins while ethyl gallate is an artifact
obtained by esterification of gallic acid in hydroalcoholic solutions.
Hydroxycinnamic acids and flavonoids (e. g. myricetin, leucodelphinidin, quercetin, kaempferol, and
gallic acid ) are found mainly in the leaves of
Hamamelis virginiana
L
.
(Besset et al, 1986).
Phenolic compounds from leaves of
Hamamelis virginiana
L. were studied by Sagareishvili (1999), where
kaempferol, quercetin, trifolin, kaempferol 3-O-β-D-glucuronide, quercetin 3-O-β-D-glucuronide were
isolated.
Several pharmacological activities, including anti-phlogistic, antiviral (Erdelmeier et al, 1996),
antimutagenic (Dauer et al, 1998) and cell proliferation stimulating effects (Deters et al, 2001) have been
attributed to proanthocyanidins.
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Volatiles
According to Engel et al, (1998), the composition of the volatile fraction obtained by water distillation
from the leaves and bark of
Hamamelis virginiana
L., and determined in detail by GC-MS, consists in
about 175 (leaves) and 168 (bark) identified compounds or at least partly characterized on the basis of a
computerized database (SeKoMS). The dominating substances were represented by a homologous series
of alkanes, alkenes, aliphatic alcohols, related aldehydes, ketones, and fatty acid esters. Significant
differences in the terpenoid and phenylpropanoid patterns of the products obtained from the bark and
leaves are apparent: whereas the product of bark distillation was found to typically contain
phenylpropanoids and mainly sesquiterpenoids, that obtained from the leaves included some distinct
monoterpenoids detected in comparably higher amounts. The chemical composition of the volatiles, when
taken together with the absence of specific accumulation sites of lipophilics, emphasizes the definition
"volatile fraction" rather than essential oil.
Reporting the same data, Engel et al (1998) stated “bark of young twigs” but Hartisch (1997) stated
“young twigs tips were coarsely milled and then steam distilled”. The volatile fraction (0.009% of the
crude drug on the dry weight basis) contained about 160 compounds: aliphatic hydrocarbons (45.4% , of
which nonacosane 6.9%, heptacosane 5.4%), sesquiterpenes (20.2% of which α- ylangene 11.1% , trans-
nerolidol 2.73%) , monoterpenes (8.3%, of which linalool 2.0%), phenylpropanoids (7.5%, of which trans-
anethole 3.3%, eugenol 2.4%), aldehydes (6.1%, of which nonanal 2.7%) and small amounts of many
other compounds (British Herbal Compendium, 2006).
Literature data on the content of these components fluctuate between 0.01% and 0.5% referred to the leaf
drug and 0.1% for the bark. Safrole was also found at a level of < 0.2% in hamamelis leaf oil.
The study of distilled water of
Hamamelis virginiana
L. permitted the identification of volatile
components and relative changes under the effects of different storage conditions (Messerschmidt, 1971;
Martelli et al, 1977, 1978 and 1979). Among identified compounds were phenylacetaldehyde, linalool
oxide, guaiacol, and geranylacetone. Storage of the oil with addition of ethanol or storage at
-20
º
C resulted in no changes in the oil.
Combinations of herbal substance(s) and/or herbal preparation(s)
Hamamelis preparations aresometimes used in combinations with other herbal substances (herbal
preparations), such as
Hydrastis canadensis
L.,
Ruscus aculeatus
L., or
Aesculus hippocastanum
L.
This assessment report refers exclusively to the use of hamamelis preparations as single ingredient
products.
Vitamin(s)
Not applicable
Mineral(s)
Not applicable
Pharmacopoeias’ references
The European Pharmacopoeia (1997)
There is a monograph on Hamamelidis folium in the European Pharmacopoeia
(Hamamelis leaf. Eur.
Pharm 6.1, monograph 04/2008:0909).
The herbal substance
consists of the whole or cut, dried leaf of
Hamamelis virginiana
L., containing minimum 3% of tannins, expressed as pyrogallol (C
6
H
6
O
3
;
M
r
126.1) (dried drug), and has the macroscopic and microscopic characters described under identification
tests.
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The leaf is green or greenish-brown, often broken, crumpled and compressed into more or less compact
masses. The lamina is broadly ovate to obovate; the base is oblique and asymmetric and the apex is acute
or, rarely, obtuse. The margins of the lamina are roughly crenate or dentate. The venation is pinnate and
prominent on the abaxial surface. Usually, four to six pairs of secondary veins are attached to the main
vein, emerging at an acute angle and curving gently to the marginal points where there are fine veins often
at right angles to the secondary veins.
The powder is brownish-green, it shows fragments of abaxial epidermis with wavy anticlinal walls;
abaxial epidermis with stomata mainly paracytic; star-shaped covering trichomes, either entire or broken,
composed of four to twelve unicellular branches which are united by their bases, elongated, conical and
curved, usually up to 250 µm long, thick-walled and with a clearly visible lumen with contents often
brown in colour; fibres are lignified and thick-walled, isolated or in groups, and they are accompanied by
a sheath of prismatic calcium oxalate crystals; small, cylindrical parenchymatous cells of palisade;
irregular-shaped cells of spongy mesophyll; sclereids, frequently enlarged at one or both ends, 150 µm to
180 µm long, whole or fragmented; fragments of annular or spiral vessels; isolated prisms of calcium
oxalate.
It may contain no more than 7% of stem pieces and maximum and not more of 2% of other foreign matter,
determined on 50 g. Loss on drying, not more than 10.0%, determined on 2.000 g of powdered drug by
drying in an oven at 100 °C to 105 °C for 4 h. Total ash, not more than 7.0%. Ash insoluble in
hydrochloric acid, not more than 2.0%. Botanical identity must be confirmed by TLC as well as
macroscopic and microscopic examinations. Assay: determination of tannins in herbal drugs. Action and
use: Astringent.
Real Farmacopea Española , 3ª ed. 3.0 (1997)
Hamamelis, hoja de,
monografía 01/2005, 0909. (Ph. Eur. monograph 0909)
British Pharmacopoeia (2007)
Hamamelis leaf.
BP, 2007, Vol 1: 1007. (Ph. Eur. monograph 0909). Currently, there is no monograph for
Hamamelis water in BP.
British Pharmacopoeia (1932)
Hamamelis leaves.
BP, 1932: 201
Extractum Hamamelidis Liquidum.
BP, 1932: 170
1000 g of moderately coarse powder hamamelis and alcohol 45% V/V sufficient to produce 1000 ml.
Exhaust the hamamelis by percolation with alcohol (45%), and reserve the first 850 ml of the percolate;
remove the alcohol from the remainder of the percolate and evaporate the residue to a soft extract.
Dissolve this in the reserved portion, and add the sufficient alcohol (45%) to produce the required volume.
Set aside for not less than twelve hours; filter. Alcohol content 32 to 40% V/V of ethyl alcohol. Doses:
2 to 4 ml.
German Drug Codex (1986)
Witch hazel is listed in the
German Drug Codex
, approved in the Commission E monographs, and the tea
infusion is officially included in the standard license monographs (Banz 1998; Braun et al, 1997; DAC,
1986; Wichtl and Bisset, 1994). Witch hazel leaf and bark are used in some haemorrhoidal teas and
antiphlebitis drugs. Several witch hazel mono-preparations and combinations products are available in
various dosage forms, including ointments, suppositories, coated tablets, and tinctures.
Hamamelidis folium (Hamamelisblätter, DAC 86). The German Drug Codex requires for witch hazel leaf
not less than 5.0% tannins, precipitated with hide powder (DAC, 1986; Wichtl and Bisset, 1994).
The German standard license requires that the leaf comply with the quality requirements of the German
Drug Codex monograph.
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Preparations: Suppositoria Hamamelidis (Hamamelidis-Stuhlzäpfchen) EB 6: ‘Aus 50T
Hamamelisextrakt’. Hamamelis suppositories BPC 79.
Herbal tea preparation (decoction): 5-10 g /250 ml. 2-3 g/150 ml (decoction for 10 min).
Liquid extract (1:1) ethanol 45%, 3 times daily, 2-4 ml. Extractum hamamelidis EB 6: 0.1 g.; Extractum
hamamelidis fluidum EB 6: 5.0 g, as an haemorrhoidal cream 10%.
Pharmacopoeial grade witch hazel bark consists of the dried bark from stems and branches of
Hamamelis
virginiana
L. collected in spring. The bark is required a content of not less than 9.0 % tannins, precipitable
with hide powder (DAC, 1986; Wichtl and Bisset, 1994), and not less than 20% ethanol (45%) soluble
extractive.
Hamamelidia aqua (Hamamelisrindenwasser); Aqua Hamamelidis corticis (Monographiensammlungen:
EB-6); Aqua Hamamelidis; Liquor Hamamelidis.
Preparations: Unguentum Hamamelidis (Hamamelissalbe, EB6)
The mother tincture (1:10) and liquid dilutions thereof, are also official in the German Homeopathic
Pharmacopoeia (GHP), prepared from different plants of plants including the fresh leaves, the fresh bark
from roots and branches, as well as the mixture of bark from the branches with tips of the shoots. The
GHP also includes a monograph for an ethanolic decoction of the dried bark from stems and branches as
pyrogallol (GHP, 1993).
USP 31/ NF 26 (2008)
Witch hazel
is the clear, colourless distillate prepared from recently cut and partially dried dormant twigs
of
Hamamelis virginiana
L. It is prepared by macerating a weighted amount of the twigs in water for
24 hours in about twice their weight of water. Then it is distilled until not less than 800 ml and not more
of 850 ml of clear, colourless distillate is obtained from each 1,000 g of the twigs taken, which is followed
by the addition of 150 ml of alcohol to each 850 ml of distillate, and thorough mixing. It has a tannins
limit of 0.03 mg tannic acid per ml, a pH between 3.0 and 5.0, and alcohol content of 14.0-15.0% of
ethanol, and is official in the current USP (USP-31- NF 26, 2008).
Pharmacopoeia Helvetica VII (1987)
Hamamelidis Extractum Liquidum Normatum. Syn. Extractum Hamamelidis folium alcohol content
28-35% V/V. Quantified extract with a tannin content of 3.5-4.5%.
II.1.2
Information on period of medicinal use in the Community regarding the specified
indication
Witch hazel preparations have a long history of traditional use in North America. The bark aqueous
infusion was used in aboriginal medicine to treat haemorrhages, inflammations and haemorrhoids
(Millspaugh, 1974). Pharmacopoeias and handbooks list the therapeutic uses as an astringent and anti-
inflammatory product for the treatment of minor skin injuries, local inflammation of skin and mucous
membranes; for bruises and localized inflamed swellings; to treat vascular disorders including
hemorrhoids, varicose veins, phlebitis and other conditions associated with poor venous tone or
congestion; menorrhagia and metrorrhagia; diarrhea; as a protective against oxidative stress and ultraviolet
radiation. Mainly Hamamelidis aqua has been reported in medicinal use for many decades.
The decoction was used in poultices for painful swellings and tumours (Grieve, 1979). The alcoholic
fluidextract form became official in the United States Pharmacopoeia in 1882 (Millspaugh, 1974). Native
Americans applied poultices of hamamelis leaves and barks as a remedy for haemorrhoids, wounds, insect
bites, painful tumours and ulcers (Duke, 1985). Today, the external use of witch hazel is well known for
the astringency associated with the tannin content of its leaves and bark. In Europe, tannin rich witch hazel
extracts made from the leaf and bark are used.
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K. Hering (1800-1880), a German doctor is thought as the first who has used
Hamamelis virginiana
L. in
medical treatment in USA. At that time, a “Pond’s Extract” of hamamelis was already known, which T.
Pond learned from an Oneida Indian tribe in 1840. This extract was sold under the name “Golden
Treasure”. In the course of time Pond modified the production process, using an aqueous distillate of
hamamelis twigs, known as “hazaline” (Laux, 1993).
In folk medicine, the drug is used in menorrhagia and dysmenorrhea as a haemostatic, and there are
similar uses in homeopathy. Total extracts, such as hamamelis extracts or distillates from flowering
branches freshly collected (“hazeline” witch hazel water), dry extracts of the leaves (“green hamamelin”
and bark (“brown hamamelin”) are applied in the form of infusions, ointments, or suppositories, far more
often than herbal teas made from the leaves or bark. Therapeutically, they are used for their astringent,
antiseptic and haemostatic properties, and especially as venotonic, properties which have been
demonstrated in animal experiments (Wichtl, 1994).
An hamamelis ointment containing a distillate of leaves and bark, has been commercially available in
Germany since 1878 (Gäble, 1978).
The
British Pharmacopoeia of 1932 included a monograph on
Extractum Hamamelidis Liquidum
. This
liquid extract was obtained by percolation of 1000 g of moderately coarse powder hamamelis and alcohol
45%. The final ethanol content was 32 to 40% V/V and the recommended dose: 2 to 4 ml.
The medicinal use of hamamelis has been reported by Gathercoa & Wirth, 1936 (WHO monographs,
2002).
The herbal substance and some herbal preparations of hamamelis have also been mentioned in Hager’s
Handbuch (List and Horhammer, 1969-1979).
The alcoholic fluid extract (Witch Hazel water distillate (1:2) became official in the United States
Pharmacopoeia in 1882 (Millspaugh, 1974). The FDA has approved as an OTC drug “witch hazel water”,
made from the steam distillate of the twigs containing about 14-15% alcohol in water, with a small
amount of the essential oil of the plant.
In USA witch hazel is used in several OTCs in astringent and haemostatic preparations in combination
with Aloe.
An alcoholic tincture (1:10 w/v, in 55% ethanol V/V) of the bark, including the root bark, is classified in
the Homeopathic Pharmacopoeia of the United States as an OTC Class C drug (HPUS, 1992), as well.
Witch hazel does not have GRAS status. However, it is freely available as dietary supplement in the USA
under DSHEA legislation (1994 Dietary Supplement Health and Education Act).
Witch hazel has been defined as an astringent active ingredient in OTC skin protecting medical products,
for relief of minor skin irritations due to insect bites, minor cuts, minor scrapes and in OTC anorectal
products. These OTC products, in a suitable form for topical administration, are generally recognized as
safe and effective. The FDA, however, advises “that based on evidence currently available, there is
inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the
specified uses” (USP 30/ NF 25, 2007).
Hamamelis
virginiana
L.
preparations are used in cosmetics (skin lotions, nourishing creams, pre- and
after-shaves etc) as well, while it is also used topically in veterinary medicine, as a solution or as an
ointment in combination with other herbal preparations to promote wound healing of minor injuries of the
skin, for treatment of skin inflammations, ulcerations and dermatoses. The medicinal products contain
2.5 to 10.8% (W/W) of an extract of the leaves and are applied 1 to 2 times daily for 2 to 3 days (CVMP
Reports for
Hamamelis virginiana
L. mother tincture and dilutions thereof, which are intended for use in
all food-producing animals, use in veterinary homeopathy, EMEA/MRL/358/98-final; and
EMEA/MRL/689/99-final).
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II.1.2.1
T
YPE OF TRADITION
,
WHERE RELEVANT
American traditional medicinal use: Witch hazel distillate from twigs is official in the United States
Pharmacopoeia- National Formulary (USP23-NF18, 1995- June 1999).
European traditional use: Witch hazel leaf is official in European Pharmacopoeia since 1997.
ESCOP monographs, 2003.
II.1.2.2
E
VIDENCE REGARDING THE INDICATION
/
TRADITIONAL USE
Agencia Española de Medicamentos y Productos Sanitarios (AEMPS, 2007)
Hamamelidis distillate, 10%: “Temporary relief of eye irritation or discomfort due to various causes
(smoky atmospheres, sustained visual effort, swimming in the sea or swimming baths, etc)”.
Hamamelidis distillate (1:1.6) 5% Ointment: “Temporary relief of haemorrhoids symptoms”
Afssaps Avis aux fabricants… Bulletin officiel nº 86/20 bis (1986); (1990)
Hamamelis virginiana
leaf (feuilles d´hamamélis, feuilles du noisetiere la sorcière): Listed in
Médicaments à base de plantes.
Nº 7: “Traditionally used in subjective symptoms of chronic insufficiency such as sensation of heavy legs
and in haemorrhoids symptoms”.
Nº 16: Traditionally used as a gargle in inflammation of the mouth and throat.
Afssaps monograph : cahiers de l’Agence n° 3(1998)
Hamamelis virginiana
leaf (feuilles d´hamamélis, feuilles du noisetierde la sorcière): Listed in
Médicaments à base de plantes.
“Traditionally used in subjective symptoms of chronic insufficiency such as sensation of heavy legs and in
haemorrhoids symptoms”.
“Traditionally used in the case of eye irritation or discomfort due to various causes (smoky atmospheres,
sustained visual effort, swimming in the sea or swimming baths, etc)”.
British Herbal Medicines Association, British Herbal Compendium Vol II (2006)
Hamamelis bark (Hamamelidis Cortex)
Indications: None adequately substantiated by pharmacological or clinical studies. Uses based on
experience or tradition.
External: Small wounds, skin injuries and bruises, local inflammation of skin and mucous membranes;
haemorrhoids and varicose veins complaints.
Internal: Diarrhoea, mucus colitis, haemorrhoids.
Regulatory status in UK: Medicinal products are accepted for general sale, internal or external use.
Permitted by Council of Europe as food flavouring, category N3 (this category indicates that there is
insufficient information available for an adequate assessment of potential toxicity).
Hamamelis leaf
Indications: None adequately substantiated by pharmacological or clinical studies. Uses based on
experience or tradition
External: Minor skin injuries, local inflammation of skin and mucous membranes, bruises; varicose vein
complaints and haemorrhoids.
A hamamelis leaf extract (not defined) appears to be beneficial in the topical treatment of dermatitis
atopica.
Internal: Diarrhoea, colitis.
Regulatory status in UK: Medicinal products are accepted for general sale, internal or external use.
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Permitted by Council of Europe, as food flavouring, category N3.
Hamamelis water
The BPC 1973 monograph and the USP monograph for witch hazel water are broadly similar.
Indications: None adequately substantiated by pharmacological or clinical studies. Uses based on
experience or tradition: hamamelis water is used to alleviate minor affections of the skin such irritation,
roughness, or soreness. It has also been employed when diluted, as a constituent of eye lotions.
Topical use: Minor sores, inflammation or irritations of the skin such as cuts, grazes, insect bites,
dermatitis, slight burns or scalds and sunburn; bruises and sprains, muscle pains; external haemorrhoids,
varicose vein complaints; as a mouthwash for inflamed mucosa or bleeding gums; as a nasal plug for
nosebleeds; as an eyewash for conjunctivitis and sore or tired eyes.
Regulatory status in UK: Medicinal products are accepted for general sale, internal or external use.
Food: Not used in foods.
Witch hazel is not on the UK General Sale List.
British Herbal Pharmacopoeia (1983)
Hamamelis leaf indications: Diarrhoea, mucus colitis, haematemesis, haemoptysis, haemorrhoids.
Topical bruises, localised inflamed swellings.
British Pharmaceutical Codex (1973)
Witch hazel leaf
Actions and Uses: hamamelis has astringent properties and its preparations are used in the treatment of
haemorrhoids. It is used in toilet preparations.
Preparations: Hamamelis dry extract BPC; Hamamelis liquid extract BPC; Hamamelis ointment, BPC;
Hamamelis suppositories.
Hamamelis water.
Uses: Hamamelis water is used to alleviate minor affections of the skin such irritation, roughness, or
soreness. It has also been employed when diluted, as a constituent of eye lotions.
German Drug Codex (1986)
Witch hazel is listed in the
German Drug Codex
, approved in the Commission E monographs, and the tea
infusion is officially included in the standard license monographs (Banz, 1998; Braun et al, 1997; DAC,
1986; Wichtl and Bisset, 1994). Witch hazel leaf and bark have been used in some haemorrhoidal teas and
anti-phlebitis drugs. Several witch hazel mono-preparations and combinations products are available in a
variety of dosage forms, including ointments, suppositories, coated tablets, and tinctures.
Hamamelis herbal medicinal products are traditionally used in the form of herbal tea, as astringent in
supportive therapy for acute diarrhoea, as a gargle in inflammation of the mouth and throat, especially
when accompanied by inflammation of the gums.
In folk medicine the drug is used in menorrhagia as a haemostatic and in dysmenorrhoea, and there are
similar uses in homeopathy. Extracts (of the leaves and bark) and distillates are applied in the form of
infusions, ointments, or suppositories, far more often than teas, for their astringent, antiseptic and
haemostatic properties, and especially for their ability to increase blood vessel tonus. It is used against
haemorrhoids, varicose veins, local inflammation of the mucous membranes with swelling and superficial
skin damage, and in body and face lotions (Bisset et al, 1994).
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USP 30/ NF 25 (2007)
Witch hazel has been defined as an astringent active ingredient in OTC skin protectant drug products for
relief of minor skin irritations due to insect bites, minor cuts, minor scrapes and OTC anorectal products.
These OTC products in a suitable form for topical application are generally recognized as safe and
effective. The FDA, however, advises “that based on evidence currently available, there is inadequate data
to establish general recognition of the safety and effectiveness of these ingredients for the specified uses”.
ESCOP Monograph (ESCOP, 2
nd
ed. 2003)
Hamamelis water
Therapeutic indications:
External use: “Treatment of bruises, skin irritations, sunburn, insect bites, external haemorrhoids. Minor
inflammatory conditions of the skin and mucosa”.
Hamamelis bark
Therapeutic indications:
Internal use: “Inflammations of mucous membranes of the oral cavity”.
“Short term symptomatic treatment of diarrhoea”
External use: “Haemorrhoids, minor injuries and local inflammations of the skin”
“Symptomatic treatment of problems related to varicose veins, such as painful and heavy
legs”.
Hamamelis leaf
Therapeutic indications:
Internal use: “Symptomatic treatment of complaints related to varicose veins, such as painful and heavy
legs, and of haemorrhoids”.
External use: “Bruises, sprains and minor injuries of the skin, local inflammations of the skin and mucosa,
haemorrhoids, relief of symptoms of
neurodermitis atopica
and feeling of heavy legs”.
Witch hazel leaf and bark (Hamamelisblätter und –rinde)
Witch hazel leaf and bark are covered by positive Commission E monographs and both have the following
applications: “Mild damage to the skin (minor skin wounds), local inflammation of the skin and mucous
membranes, haemorrhoids and varicose veins.”
WHO Monographs on selected medicinal plants. Volume 2 (World Health Organization, 2002)
Folium et Cortex Hamamelidis.
Medicinal uses supported by clinical data:
Topically for minor skin lesions, bruises and sprains, local
inflammation of the skin and mucous membranes, haemorrhoids and varicose veins.
Uses described in pharmacopoeias and in traditional systems of medicine:
Topically as a haemostat.
Uses described in folk medicine, not supported by experimental or clinical data:
Treatment of colitis
diarrhoea, dysentery, dysmenorrhoea, eye inflammations, haematuria, kidney pains, neuralgia, nosebleeds
and excessive menstruation, and as tonic.
Martindale, The complete drug reference (35
th
edition, 2007)
Hamamelis, Witch hazel, Amamelide.
Hamamelis has astringent properties. It is used in preparations for the symptomatic relief of haemorrhoids.
Hamamelis water is used as a cooling application and has been applied as a haemostatic.
EMEA 2010
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Commission E Monograph (1985, correction 1990)
Hamamelis from various parts of the plant is used in herbal or homeopathic preparations for a variety of
disorders.
Non-prescription Product Therapeutics (2
nd
edition, 2006)
Hamamelis water:
Includes references to different preparations of Witch hazel 50%, with glycerine, water, or aloe
barbadensis, as astringent products suitable for external use in case of haemorrhoids.
A product for insect bites/stings which contains Witch hazel distilled 100% and some astringents, is used
for the relief of pain and swelling caused by insect bites.
Handbook of Non-prescription Drug (15
th
edition, 2006)
Therapeutic uses: Witch hazel has been used both externally and internally although it is currently
recommended only for external use.
Dosage and Administration Guidelines: Witch hazel preparations are applied topically, as needed for the
described disorders.
Safety: Oral use may cause stomach irritation and liver damage. Topical use may result in contact
dermatitis.
Most commercially available Witch hazel preparations are mixture of alcohol 14% in water with only a
trace amount of the volatile water.
Clinical evidence: Little clinical trial data are available. Witch Hazel’s astringent effects are useful for
treating minor skin injuries and relieving the itch, irritation, and pain of haemorrhoids and after anal
surgery.
Table 1. Summary of Indications (short description)
FOLIUM
CORTEX
AQUA/
DESTILLATUM
AEMPS
Haemorrhoids
Eye irritation
AFSSAPS-
(Avis 1986)
Haemorrhoids, Heavy legs,
Gargle, mouth & throat
Eye irritation
AFSSAPS-
(Cahiers 1998)
Haemorrhoids
Heavy legs
Eye irritation
British Herbal
Compendium
External use:
Skin & mucous
inflammation, small
wounds / skin injuries,
atopic dermatitis (extract
not defined)
Haemorrhoids
Bruises, varicose veins,
External use:
Small wounds/skin injuries,
Skin & mucous
inflammation,
Haemorrhoids,
Bruises, varicose veins,
Skin irritation,
roughness, soreness,
cuts, wounds, insect
bites, dermatitis,
sunburns,
Haemorrhoids,
Bruises, varicose
veins
Gargle, mouth &
throat
Eyewash
Internal use: Diarrhoea/
colitis
Internal use: Diarrhoea/
colitis , Haemorrhoids
British
Pharmaceutical
Codex
Haemorrhoids
Minor skin irritation
Eyewash
EMEA 2010
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British Herbal
Pharmacopoeia
Skin inflammation,
Local inflamed swellings
Haemorrhoids,
Bruises,
Internal use: Diarrhoea/
colitis.
Minor skin irritation
Eyewash
Commission E
Skin & mucous minor
inflammation, minor skin
injuries
Haemorrhoids,
varicose veins
Skin & mucous minor
inflammation, minor skin
injuries
Haemorrhoids,
varicose veins
ESCOP
Internal use:
Haemorrhoids,
varicose veins, heavy legs
External use:
Local skin inflammation
Haemorrhoids,
Heavy legs,
Gargle mouth & throat
External use:
Minor inflammation
skin & Mucous
membranes.
Skin irritation,
sunburns, Insect bites,
Haemorrhoids
Bruises
External use:
skin & mucous
inflammation, minor skin
injuries.
Neurodermitis atopica
Haemorrhoids,
Heavy legs, Bruises
Internal use: Diarrhoea
German Drug
Codex
Local inflamed swellings.
Damaged skin
Haemorrhoids,
Flebitis, varicose veins.
Menorrhagia,dysmenorrhea
Gargle, mouth & throat
Internal use: Diarrhoea
Local inflamed swellings
Damaged skin
Haemorrhoids,
Flebitis, varicose veins.
Menorrhagia, dysmenorrhea
Gargle, mouth & throat
Internal use: Diarrhoea
Martindale
Haemorrhoids
Haemorrhoids
Haemorrhoids
USP 30
Gargle, mouth & throat
Minor irritation skin
Insect bites, cuts,
Haemorrhoids,
WHO
Skin & mucous
inflammation,
Haemorrhoids,
Heavy legs, Bruises
Skin & mucous
inflammation,
Haemorrhoids,
Heavy legs, Bruises
Haemorrhoids
Trad. Use: dysmenorrhoea
Diarrhoea/colitis
Eye irritation
Nosebleeds
Trad. Use: dysmenorrhoea
Diarrhoea/colitis
Eye irritation
Nosebleeds
II.1.2.3
E
VIDENCE REGARDING THE SPECIFIED STRENGTH
/
POSOLOGY
Agencia Española de Medicamentos y Productos Sanitarios (AEMPS, information, 2007)
Hamamelidis distillate 10%, eye drops: Single dose 2 drops/each eye, 3-6 times a day.
EMEA 2010
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British Herbal Medicines Association, British Herbal Compendium Vol II (2006)
Hamamelis bark (Hamamelidis cortex)
External use: Semi-solid and liquid preparations containing the equivalent 5-10% of bark; as impregnated
dressings, lotion or mouthwash, diluted tincture of hamamelis (1:10, 45% ethanol) or decoction of 5-10 g
of bark to 250 ml of water.
Internal use: Tincture, 2-4 ml or an infusion of 2 g of dried bark, three times daily. In suppositories, an
amount equivalent to 0.1-1 g of dried bark, up to three times daily.
Hamamelis leaf
External use, hamamelis ointment BPC 1973 (10% by weight of hamamelis liquid extract BPC 1973 in an
ointment base); semi-solid and liquid preparations containing the equivalent 5-10% of leaf; for
impregnated dressings and rinses, decoctions of 5-10 g of leaf to 250 ml of water, or 20 ml of tincture
diluted to 100 ml.
Local use for mouthwashes: as a decoction of 2-3 g in 150 ml of water, several times daily.
Hamamelis suppositories BPC 1973 (200 mg of hamamelis dry extract BPC 1973 in a suitable base) or,
more generally, suppositories containing the equivalent of 0.1-1 g of dried leaf.
Internal use, three times daily: dried leaf, 2 g or by infusion; hamamelis liquid extract BPC 1973 (1:1,
45% ethanol), 2-4 ml three times daily.
Hamamelis water
Topical use: undiluted hamamelis water for applications to cuts, grazes, insect stings, other skin
complaints and haemorrhoids, as a mouthwash, and in a saturated cotton wool swab as a nasal plug for
nosebleeds, or to place over eyelids; for compresses, undiluted or diluted 1:3 with water; in semi-solid
preparations, 20-30%.
As an eyewash use diluted hamamelis water, 10 drops to an eyebath half-filled with water.
German Drug Codex (1986)
Hamamelis folium (Hamamelisblätter. DAC 86; Wichtl and Bisset, 1994). Preparations: Suppositoria
Hamamelidis (Hamamelidis-Stuhlzäpfchen) EB 6: ‘Aus 50T Hamamelisextrakt’. Hamamelis suppositories
BPC 79.
Herbal tea preparation (decoction) 5-10 g/250 ml 2-3 g/150 ml (decoction 10 min).
Liquid extract (1:1) Ethanol 45%, 3 times daily, 2-4 ml. Extractum hamamelidis EB 6: 0.1 g.; Extractum
hamamelidis fluidum EB 6: 5.0 g, as a hemorrhoidal cream 10%.
Hamamelidia aqua (Hamamelisrindenwasser); Aqua Hamamelidis corticis (Monographiensammlungen:
EB-6); Aqua Hamamelidis; Liquor Hamamelidis.
Preparations: Unguentum Hamamelidis (Hamamelissalbe, EB.6), according to Pharmacopoeial grade
(DAC, 1986; Wichtl and Bisset, 1994)
British Herbal Pharmacopoeia (1983)
Adults and elderly: Dried hamamelis leaf 2 g (or by infusion) three times daily.
Liquid extract 1:1 in 45% alcohol. Dose 2-4 ml.
Hamamelis water BPC for local application.
ESCOP Monograph (ESCOP, 2
nd
ed. 2003)
Hamamelis water
For compresses: hamamelis water undiluted or diluted 1:3 with water; in semisolid preparations, 20-30%.
Apply as often as required.
For mucosa: hamamelis water undiluted or diluted with water, several times daily.
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Hamamelis bark
Internal use: 2-10 g of the drug daily as a decoction, used as a mouthwash, or 2-3g daily as a tea.
2-4 ml of tincture, used diluted as a mouthwash 3 times daily.
Other preparations: the equivalent of 0.1-1g of the drug, 1-3 times daily
External use: 5-10 g of the drug as a decoction in 250 ml of water.
Extracts in semi-solid preparations corresponding to 20-30% of the drug.
Hamamelis leaf
Internal use: 2-3 g of the drug daily as a infusion, or 2-4 ml of liquid extract (1:1, 45% ethanol), three
times daily.
External use: Extracts in semi-solid or liquid preparations, containing 5-10% of the drug.
Decoctions, 5-10 g of drug in 250 ml water, for compresses or washes.
Ointment containing 10% of liquid extract.
It has to be noted that the ESCOP Monograph considers only the available data on
Hamamelis virginiana
L. preparations as a single ingredient.
Commission E Monograph (1998)
Internal use:
(mucous membranes): Several times daily, corresponding to 0.1-1g of drug in preparations,
or witch hazel water undiluted or diluted with water.
2-3 g of the drug daily as a infusion, or 2-4 ml of liquid extract (1:1, 45% ethanol), Three times daily.
External use
: Water steam distillate (witch hazel water) undiluted or diluted 1:3 with water.
Extracts in semi-solid or liquid preparations, containing 5-10% of the drug.
Decoctions, 5-10 g of drug in 250 ml water, for compresses or washes.
Ointment containing 10% of liquid extract.
For poultices, 20-30% in semisolid preparations.
WHO Monographs on selected medicinal plants. Volume 2 (World Health Organization, 2002)
External use: steam distillate, undiluted or diluted 1:3 with water to make poultices; 20-30% in semisolid
preparations.
Extracts: in semisolid and liquid preparations corresponding to 5-10% of the crude drug. Decoctions, from
5-10 g of drug to 1 cup (250 ml) water for poultices and wound irrigation.
Rectal suppositories, 1-3 times daily the quantity of a preparation corresponding to 0.1-1.0g crude drug,
Hamamelidis water undiluted or diluted 1:3 with water.
Other preparations, several times daily, corresponding to 0.1-1.0 g drug in preparations or witch hazel
water undiluted or diluted with water.
Posology in children
Good tolerance and lack of adverse effects have been reported for hamamelis ointment (Hametum) for
temporary relief of minor skin injuries such as diaper skin rash, nevertheless such kind of treatment
should be monitored by medical supervision to avoid other clinical complications (Candida
infections).There are not adequate clinical data on the paediatric use of other hamamelis preparations.
Elderly:
Same posology as recommended for adults.
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Table 2. Summary of recommended Posologies.
FOLIUM
CORTEX
AQUA/
DESTILLATUM
AEMPS
External use:
Distillate 10%, eye
drops. 2 drops/each
eye, 3-6 times daily
AFSSAPS-
(Avis 1986)
-------------------
AFSSAPS-
(Cahiers 1998)
-------------------
British Herbal
Compendium
External use:
Hamamelis ointment (10%
by weight of liquid extract
BPC in an ointment base)
Semisolid or liquid
preparations corresponding
to 5-10% leaf.
Herbal tea (decoction):
5-10 g dried leaf for
compresses and rinses, or
20 ml tincture diluted to
100 ml.
Herbal tea (decoction):
2-3 g, several times a day
for mouthwashes.
External use:
Semisolid or
liquid preparations
corresponding to 5-10%
bark.
As compresses, lotion or
mouthwash, diluted tincture
(1:10; 45% ethanol), or
herbal tea (decoction):
5-10 g dried bark up to three
times a day
External use:
Hamamelis water
undiluted or diluted
1:3 with water, in
semisolid preparations
20-30%
As an eyewash, 10
drops of diluted (with
water) hamamelis
water.
Internal use:
Tincture
(1:10; 45% ethanol), 2-4 ml
Herbal tea: 2 g dried bark up
to three times a day,
Suppositories 200 mg
hama. extract or equivalent
to 0.1-1 g of dried leaf.
Internal use:
2 g dried leaf,
hama. liquid extract 1:1;
45% ethanol), 2-4 ml, three
times daily
British
Pharmaceutical
Codex
-----------------
------------------
British Herbal
Pharmacopoeia
2g herbal tea: 2 g, three
times a day.
Liquid extract (1:1, 45%
ethanol) 2-4 ml
------------------
Commission E
Internal use:
Preparations
corresponding to 0.1-1 g
dried leaf, several times
daily.
Herbal tea (infusion) 2-3 g
drug daily
2-4 ml liquid extract (1:1,
45% ethanol) three times
daily
Internal use:
Preparations
corresponding to 0.1-1 g
dried leaf, several times
daily.
Herbal tea (infusion) 2-3 g
drug daily
2-4 ml liquid extract (1:1,
45% ethanol) three times
daily
External use:
Hamamelidis water
undiluted or diluted
(1:3) with water
EMEA 2010
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External use:
extracts in
Semisolid or liquid
preparations, containing
5-10% of the drug
Herbal tea (decoction):
5-10 g/250 ml (compresses
or washes).
Ointment containing 10%
of liquid extract
Poultices: 20-30% in
semisolid preparations
External use:
extracts in
Semisolid or liquid
preparations, containing
5-10% of the drug
Herbal tea (decoction):
5-10 g/250 ml (compresses
or washes).
Ointment containing 10% of
liquid extract
Poultices: 20-30% in
semisolid preparations
ESCOP
External use:
Extracts in semisolid or
liquid preparations,
containing 5-10% of the
drug
Herbal tea (decoction):
5-10 g drug daily (for
compresses or washes)
Ointment 10% liquid
extract
drug daily
0.1-1 g herbal drug,
1-3 times daily
Internal use:
Herbal tea
(infusion)2-3 g drug/ daily
2-4 ml liquid extract (1:1,
45% ethanol) three times
daily
External use:
Extracts in
semisolid or liquid
preparations, containing
20-30% of the drug
Herbal tea (decoction):
5-10 g/250 ml
External use:
Undiluted or diluted
1:3 with water;
semisolid prepara
tions, 20-30%, several
times daily
Internal use:
Herbal tea (infusion)2-3 g
drug daily
2-4 ml tincture (diluted,
mouth wash)
0.1-1 g herbal drug,
1-3 times daily
German Drug
Codex
External use:
Ointment
hamamelis extract BPC
(10% by weight in an
ointment base).
Herbal tea (decoction):
5-10 g/250 ml or 2-3 g/150
ml, several times daily.
External use:
Hamamelidis aqua
(cortex)
Unguentum
Hamamelidis.
Internal use:
herbal tea:
2g x 3 times daily.
Liquid Extract (1: 1, 45%
ethanol), 2-4 ml x 3 times
daily.
Suppositories hamamelis
extract BPC (200 mg
extract in a suitable base) or
containing equivalent to
0.1-1 g of dried leaf.
Martindale
-------------------------
------------------------
-----------------------
USP 30
------------------------
-----------------------
EMEA 2010
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WHO
External use:
Semisolid or
liquid preparations,
containing 5-10% of the
drug
Herbal tea (decoction):
5-10 g/250 ml.
Internal use:
suppositories,
corresponding to 0.1-1.0 g
crude drug
External use:
Undiluted or diluted
1:3 with water;
semisolid preparations
20-30%, several times
daily.
External use:
1.
Skin/mucosae (irritation/inflammation). Wounds. Insect bites.
2.
Haemorrhoids
3.
Heavy legs/varicose veins. Bruises
4.
Gargle & mouth & throat
5.
Eye irritation/eye lotion
Internal use:
6.
Diarrhoea/colitis
7.
Haemorrhoids
8.
Heavy legs/varicose veins. Bruises
10.
Nosebleed
II.1.2.4
E
VIDENCE REGARDING THE ROUTE OF ADMINISTRATION
The oromucosal, cutaneous and rectal applications, have been proposed for hamamelis preparations in the
recommended traditional indications.
II.1.2.5
E
VIDENCE REGARDING THE DURATION OF USE
It is recommended not to take oral preparations for more than 1 month. In case of external application, it
might be used for a longer time.
II.1.2.6
O
VERALL CONCLUSION ON THE TRADITIONAL MEDICINAL USE
Based on the information obtained from Member States and the literature search, it can be concluded that
the following extracts and uses fulfil the criteria for traditional use:
Hamamelis water:
1) Distillate prepared from fresh leaves and bark (1: 1.12-2.08; ethanol 6% m/m)
2) Distillate prepared from dried twigs (1:2; ethanol 14-15% v/v)
A)
Traditional Herbal Medicinal Product for relief of minor skin inflammation and dryness of the skin.
Distillates (1, 2) in a strength corresponding to 5-30% in semi-solid preparations, several times a day.
External use
B)
Traditional Herbal Medicinal Product for the temporary relief of discomfort due to dryness of the eye
or to exposure to wind and sun. Eye drops: Distillate (2) diluted (1:10), 2 drops each eye, 3 to 6 times a
day.
Hamamelis bark:
1) Comminuted herbal substance for herbal tea
2) Tincture (1:10; ethanol 45% v/v
)
and
corresponding dry extracts
3) Dry extract (5-7.7:1; extraction solvent ethanol 30% m/m)
EMEA 2010
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9.
Menorrhagia. Dysmenorrhoea
External use
A)
Traditional Herbal Medicinal Product for relief of minor skin inflammation and dryness of the skin.
Tincture in a strength corresponding to 5-10% in semi-solid preparations, several times a day.
Dry extract in a strength corresponding to 1.3% in semi-solid preparations, several times a day.
B)
Traditional herbal medicinal product for symptomatic relief of itching and burning associated with
hemorrhoids.
Tincture in a strength corresponding to 5-10% in semi-solid preparations, several times daily.
Comminuted herbal substance as decoction: 5-10 g / 250 ml, up to 3 times a day in impregnated
dressings.
Suppositories containing 66 mg of dry extract (5-7.7:1; ethanol 30% m/m) One suppository, two or
three times a day.
C)
Traditional Herbal Medicinal Product for (mouthwash and gargles) relief of minor inflammation of
mucous membranes of the oral cavity. 2-3 g of herbal substance as herbal tea (decoction) for using as a
mouthwash, up to three times a day.
Hamamelis leaf:
Dried comminuted herbal substance for herbal tea
- Tincture (fresh leaf) (1:10; ethanol 45% v/v)
- Liquid extract (fresh leaf) (1:1; ethanol 45% v/v)
- Liquid extract (dried leaf) (1:1; ethanol 30% m/m)
- Liquid extract (dried leaf) (1:2; ethanol 60% v/v)
A)
Traditional herbal medicinal product for relief of minor skin. inflammation and dryness of the skin.
Tincture or liquid extracts (1:1) in a strength corresponding to 5-10% in semisolid or liquid
preparations, several times daily.
Liquid extract (1:2; ethanol 60% V/V) in a strength corresponding to 20% as semi-solid preparation
B)
Traditional herbal medicinal product for symptomatic relief of itching and burning associated with
hemorrhoids.
Tincture or liquid extracts in a strength corresponding to 5-10% in semisolid and liquid preparations,
several times daily.
Liquid extract (1:2; ethanol 60% V/V) in a strength corresponding to 20% as a semi-solid preparation,
several times daily.
Comminuted herbal substance as decoction: 5-10 g/250 ml, up to 3 times a day in impregnated
dressing
Suppository containing 400 mg of liquid extract (1:2; ethanol 60% v/v), 2-3 times a day.
C)
Traditional Herbal Medicinal Product for (mouthwash and gargles) relief of minor inflammation of
mucous membranes of the oral cavity.
2-3 g of comminuted herbal substance as herbal tea (decoction) for using as a mouthwash, up to three
times a day.
Tincture (1:10) in 45% ethanol (diluted (1:3) with water) 2-4 ml, three times daily as gargle
EMEA 2010
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II.2
NON-CLINICAL
DATA
II.2.1
Pharmacology
Venotonic activity
Hamamelis has been used as venoconstrictor substance but there are not well performed experimental tests
to demonstrate this effect. Balansard et al (1970)
described a method derived from the technique of
Laewen-Trendelenburg. The method was not intended for the study of the venotonic activity since it was
not possible to eliminate the arterioconstrictive activity typical of certain substances which manifest their
effect simultaneously by increasing the venous tone and an arterial vasoconstriction. The method consists
in per fusing at a constant pressure
via
the aorta the rear part of the rabbit a substance provided that it was
soluble in water or in a water solvent mixture which does not precipitate in dextran. A catheter is
introduced into the abdominal aorta and a second into the superior vena cava following heparinization
(5 mg/kg/ i.v.). The arterial activity of the hamamelis fraction (condensed tannins) has been tested on an
isolated aortic segment The arterial vasoconstriction of the hamamelis fraction is weak and initial kinetics
are very slow when compared with kinetics of the adrenergic type. A decrease in blood supply was
observed after intra-arterial administration of the distillate. This effect was not influenced by concomitant
administration of adrenergic, adrenolytic or myotonic drugs (Balansard, 1970, 1972).
The venotonic effects of leaf preparations (steam distillate, tincture or alcohol extract) were tested by
measuring the blood supply to the rear paw of rabbits (Bernard, 1972).
Neugebauer (1948) studied the similarity of effects between
Hamamelis virginiana
and
Corylus avellana
.
For monitoring the haemostatic effect determined the bleeding time for the rabbit ear according to the
method of Fleisch and Tripod. The preparations studied had an ethereal oil content of 0.015% on average,
and manufactured by distillation from fresh leaves previously treated with alcohol and water. Both the
distillate and the ethereal oil produced a positive reduction in bleeding time and an acceleration of blood
coagulation, as demonstrated by experiments with the hollow-bead capillary method of Schultz.
Vasoconstrictor activity
A randomized, placebo controlled study assessed the vasoconstrictive effects of an aqueous propylene
glycol extract of hamamelis in 30 volunteers. The hamamelis extract used was a hydroglycolic extract
(water/propylenglycol 50:50), obtained from hamamelis leaves. A thermometric method is proposed in
this study. The extract produced a significantly reduction in skin temperature as compared with the
placebo (Diemunsch and Mathis, 1987).
Astringent activity
Hamamelis leaves and bark contain tannins. Although tannins may be responsible for the astringent and
styptic properties, the distilled product contains almost no active tannins. Alcohol provides the astringent
effect. When applied to broken skin or mucous membranes, hamamelis products induce protein
precipitation that tightens up superficial cell layers and shrinks colloidal structures. This action, in turn,
causes capillary vasoconstriction, decreasing vascular permeability and inflammation (Lamont Hume and
Strong, 2006).
In vitro
experiments
The phenolic constituents of hamamelis, particularly the tannins (e.g. hamamelitannin), aldehydes and
oligomeric proanthocyanidins are responsible for its astringent activity. Similar to other astringent drugs,
application of hamamelis preparations to the skin and mucosa in low concentrations sealed cell
membranes and reduced capillary permeability. Higher concentrations precipitated proteins and thickened
colloidal tissue, forming a thin membrane in the wound region, and slightly compressed the skin tissue
EMEA 2010
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beneath it. Alcohol hamamelidis extracts showed strong astringent action, the bark extract is slightly
superior to the leaf extract (Laux, 1993, Vennat 1988, Hänsel 1993)
The astringent effect of a tincture (1:3; 62% ethanol) prepared from fresh hamamelis bark was
demonstrated with hide powder (Gracza, 1987)
In vivo
experiments
The healing effect of hamamelis distillate was compared with hydrogen peroxide on skin damaged by
application of dichlorodiethyl sulfide (mustard gas) in various animal models. The distillate was more
effective than hydrogen peroxide in reducing the occurrence of pus in the affected skin areas.
Furthermore, subsequent treatment of the purulent skin areas with a 20% Hamamelidis ointment reduced
the incidence of suppuration as compared with hydrogen peroxide treatment.
Anti-inflammatory activity
Hamamelis extracts and isolated chemical constituents have shown anti-inflammatory activity
in vitro
and
in vivo
.
In vitro
experiments
Anti-inflammatory effects of polyphenols isolated from hamamelis stem and twig bark were evaluated in
human polymorphonucleocytes (PMNs) and human macrophages. With the exception of hamamelitannin,
all the tested substances inhibited the synthesis of platelet activating factor (PAF) in human PMNs.
Dimeric galloylated proanthocyanidins showed the strongest effects. The synthesis of leukotriene B
4
in
PMNs was inhibited by the tested substances. Oligomeric proanthocyanidins had stronger activity than
hamamelitannin, which had the weakest effect (Hartisch et al, 1996).
In the lyso-PAF: Acetyl-CoA acetyltransferase assay, hamamelitannin proved to be ineffective, but in the
same assay other potent candidates are represented by the group of B-type proanthocyanidins. A range of
compounds from hamamelis bark had a inhibitory effect on 5-lipoxygenase, hamamelitannin and the
galloylated proanthocyanidins showed greater potency than other substances; With IC50 values ranging
from 1.0 to 18.7 µM. Structure-activity relationships regarding the in vitro inhibitory potency of the
polyphenols in the biological assays were discussed
(Hartisch et al, 1997).
According to Deters et al (2001), polysaccharides and proanthocyanidins from hamamelis bark could
influence on human skin keratinocyte proliferation and differentiation of cultured human keratinocytes,
and influence on irritated skin. While the polysaccharide fraction, consisting mainly of arabinans and
arabinogalactans, did not have effect human keratinocytes, the proanthocyanidins strongly increased the
proliferation of the cells, while the differentiation was not influenced significantly. Within a preliminary
cumulative in vivo study on SLS-irritated skin, proanthocyanidins were proven to reduce trans-epidermal
water loss and erythema formation. Furthermore, a clinical scoring indicated that procyanidins can
influence irritation processes significantly
.
In vivo
experiments
Intra-peritoneal administration of a 70% ethanol extract of hamamelis leaf (200 mg/kg body weight)
significantly inhibited the chronic phase of carrageenan-induced rat footpad oedema (Duwiejua et al,
1994).
A aqueous ethanolic extract of hamamelis bark (ethanol 70%) showed a significant anti-inflammatory
effect (43% inhibition of oedema; p<0.05) in the croton oil ear oedema test in mice when applied topically
at 250µg per ear. This effect was shown to be mainly due to proanthocyanidins of molecular weight
≥3kDa (69% inhibition at 250µg per ear; p<0.05) obtained from this extract subjected to ultrafiltration
(UF) and identified by TLC, HPLC. Proanthocyanidins also exhibit significant antiviral activity against
Herpes simplex virus type 1 (HSV-1). In addition, the UV-conc. displayed radical scavenging properties,
inhibited α-glucosidase as well as human leukocyte elastase (HLE). With the exception of the antioxidant
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potential and the inhibition of HLE-action the lower molecular fraction possessed weaker activities and
contained mainly hamamelitannin, catechin, and unidentified constituents (Erdelmeier et al, 1996).
Studies by Brown and Dattner (1998), presented witch hazel preparations as useful in the treatment of
atopic dermatitis or pruritus (Millikan et al, 2003).
The aqueous ethanolic extracts of
Polygonum bistorta
L.,
Guaiacum officinale
L. and
Hamamelis
virginiana
L. were screened for their anti-inflammatory activity. Administered (100 and 200 mg/kg body
weight, p.o.) before the induction of carrageenan rat paw oedema, extracts of
P. bistorta
significantly
suppressed both the maximal oedema response and the total oedema response, while
H. virginiana
was
inactive and
G. officinale
was only active a 200 mg/kg. (Duwiejua et al, 1994).
In vitro Antibacterial activity
An aqueous extract of the leaves of hamamelis inhibited the growth of
Escherichia coli
(MIC 0.4 mg/ml),
Staphylococcus aureus
(MIC 0.4 mg/ml),
Bacillus subtilis
(MIC 1.1mg/ml) and
Enterococcus faecalis
(MIC 3.0mg/ml). Aqueous extracts of the bark inhibited the growth of
Escherichia coli
,
Staphylococcus
aureus
,
Bacillus subtilis
and
Enterococcus faecalis
(MIC for all 10.0 mg/ml) (Brantner et al, 1994, WHO
monograph).
The antimicrobial activity of a distillate of Aqua Hamamelidis (USP) (90%) and urea (5%) formulated as
a topical dermatological preparation was studied in vitro by the agar diffusion test showed inhibition of
Staphylococcus aureus
and
Candida albicans
, among other organisms. Comparison with earlier studies of
chlorhexidine digluconate and fuchsine, hamamelis distillate and urea were relatively weak. (Leyden et
al, 1979).
Lauk et al (2003), studied the antibacterial activity of some medicinal plant extracts against
periodontopathic bacteria, such as:
Porphyromonas gingivalis, Prevotella ssp, Fusobacterium nucleatum,
Capnocytophaga gingivalis, Veilonella parvula, Eikenella corrodens, Peptoscoccus micros
and
Actinomyces odontolyticus
among which the methanol extract of
H. virginiana
was shown to possess an
inhibiting activity (MIC≥2048 mg/L) against all the tested species except for
Prevotella sp
.
Antiviral activity
Hamamelitannin and proanthocyanidins obtained from a hydroethanolic extract of
Hamamelis virginiana
L., bark subjected to ultrafiltration exhibited
in vitro
antiviral activity against Herpes simplex virus type
1(HSV-1) in monkey kidney cells. After 2-3 days the ED
50
of hamamelitannin for antiviral activity was
26 µg/ml, compared to 6.3 µg/ml for a fraction consisting mainly of oligomeric to polymeric
proanthocyanidins and 0.42 µmol/ml for acyclovir as positive control (Erdelmeier et al, 1996).
Radical scavenging effects
The activity of active-oxygen scavengers such as superoxide anion radicals, hydroxyl radicals, singlet
oxygens and lipid peroxides in 7 plant extracts among which
Hamamelis virginiana
L. was examined in
detail by both ESR spin-trapping and malondialdehyde generation. Furthermore, the active-oxygen
scavenging activity of extract was evaluated using a murine dermal fibroblast culture system.
Hamamelis
virginiana
L. extract was found to have strong active-oxygen scavenging activity of and protective
activity against cell damage induced by active oxygen and it could be proposed as potent plant extract
with potential application as anti-aging or anti-wrinkle material for the skin.
Hamamelitannin inhibited the production of superoxide anion radicals
(IC 1.38
50
µmol/l) and hydroxyl
50
µmol/l) in murine dermal fibroblasts, as measured by electron spin resonance
spectrometry and showed significant protective activity at minimun concentrations of 50 µM, while the
corresponding figure for gallic acid was 100 µM. Pre-treatment of fibroblasts with hamamelitannin
enhanced cell survival. The superoxide-anion scavenging activity of the compounds in terms of its IC
50
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radicals (IC 5.46
values, which represent the concentration giving 50% inhibition of active oxygens generated, was
evaluated by ESR spin-trapping. Hamamelitannin and gallic acid protected murine dermal fibroblasts
against damage induced by superoxide anion radicals (IC
50
= 1.31
±
0.06 µM) and (IC
50
= 1.01
±
0.03
µM) respectively, compared with 23.31 µmol/l for ascorbic acid and Propyl gallate (1.41 μM). In
hydroxyl radical scavenging, hamamelitannin gave the lowest IC
50
value (5.46 μM) among the
compounds treated, the values of gallic acid and propyl gallate were 78.04 and 86.46 μM, respectively.
For singlet oxygen scavenging, the IC was 45.51
Hamamelitannin exhibits potent superoxide-anion scavenging activity. Its high affinity for cells or
membranes may be an important factor for protecting cells against active oxygen species. The author
screened the active components using the superoxide dismutase like activity (SOD-like activity) as an
indicator. The
Hamamelis virginiana
L. extract showed a strong SOD-like activity.
The extracts (leaf and bark) were extracted with ethanol 50%, and the bark extract showed higher activity
than the leaf one. The study confirmed through further isolations procedures that the SOD-like activity
was due to the hamamelitannin. Hamamelitannin showed also inhibitory activity on depolymerization of
hyaluronic acid; synergistic activity on antioxidation of dl-alpha-tocopherol; protecting activity on cell
injury induced by active oxygens and an in vivo suppressive activity on peroxidation in guinea pig skin.
(Masaki et al, 1993, 1994, 1995).
Witch hazel (
Hamamelis virginiana
L.) bark extract and hamamelitannin, the major active component of
witch hazel bark, were shown to possess a strong ability to scavenge peroxynitrite (ONOO-) and it was
suggested that it might be developed as an effective peroxynitrite scavenger for the prevention of ONOO-
involved diseases (Choi et al, 2002)
.
Touriño et al (2008) showed that
Hammamelis virginiana
L. bark is a rich source of tannins. They, by
extraction and solvent fractionation, generated fractions rich in pyrogallol-containing polyphenols
(proanthocyanidins, gallotannins, gallates).
The mixtures were highly active as free radical scavengers. The antiradical efficiency of the fractions was
evaluated by the DPPH stable radical method (hydrogen donation and electron transfer) and HNTTM
(electron transfer). These fractions were also able to reduce the newly introduced TNPTM radical,
meaning that they included some highly reactive components. Witch hazel phenolics protected red blood
cells from free radical –induced haemolysis and were mildly cytotoxic to 3T3 fibroblasts and HaCat
keratinocytes. They also inhibited the proliferation of tumoral SK-Mel 28 melanoma cells at lower
concentrations than grape and pine procyanidins. The high content in pyrogallol moieties may be
responsible of its effects on skin cells. The authors hypothesize that the final putative antioxidant effect of
polyphenols may be in part attributed to the stimulation of defense systems by mild prooxidant challenges
provided by reactive oxygen species generated through redox cycling.
The abundance of pyrogallol groups appears to play a major role in the antioxidant/prooxidant effects os
hamamelis phenolics (Touriño et al, 2008).
Tumour necrosis factor-alpha (TNF) inhibitory activity
The effect on TNF-mediated cell death of hamamelitannin and consequently
H. virginiana
extracts has
been also reported (Habtemariam, 2002) by assessing the TNF-mediated EAhy926 endothelial cell death
and adhesiveness to monocytes. One to 100 µM concentrations of hamamelitannin inhibited the TNF-
mediated endothelial cell death and DNA fragmentation in a dose-dependent manner. 100% protection
against TNF-induced DNA fragmentation and cytotoxicity was obtained for hamamelitannin
concentrations higher than 10 µM.
The protective effect of hamamelitannin was comparable with that of a related compound epigallocatechin
gallate while gallic acid was a weak protective agent (<40% protection). The cytoprotection assay
(Habtemariam et al, 1997) has been used to study the effect of protective agents (hamamelitannin, gallate
or epigallocathechin gallate) on TNF-mediated cytolysis. The order of potency in inhibiting the TNF-
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50
µM for hamamelitannin, 69.81
µM for gallic acid and
66.66 µM for propyl gallate. (Masaki et al, 1993, 1994, 1995)
mediated cytolysis was: hamamelitannin> epigallocathechin gallate > gallate. These data are in agreement
with previous reports which revealed that compounds with catecholic functional moeity could inhibit the
TNF-mediated apoptosis and cytotoxicity in the murine fibroblast, L929 cells. In parallel with the
cytotoxicity results, the study suggests that hamamelitannin inhibited the TNF-induced DNA
fragmentation in a concentration dependant manner. As shown for catechol and flavonoid compounds a
post receptor mechanism of action: i.e. an action mediated neither trough direct interaction with TNF nor
with TNF receptors has been suggested. The study demonstrated that hamamelitannin inhibits the
cytotoxic effects of TNF without altering its effects on endothelial adhesiveness And these may inhibit the
TNF-mediated apoptosis and cytotoxicity or its protective effect against UVB-induced cell damage but do
not permit to establish the concrete mechanism of action and hence awaits further research The observed
anti-TNF activity of hamamelitannin may explain the haemostatic use of
H. virginiana
in traditional
medicine and its claimed use as a protective agent for UV radiation. (Habtemariam et al, 2002
).
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Table. 3. Non-clinical studies
PHARMACOLOGY FOLIUM
CORTEX
AQUA/
DESTILLATUM
Venotonic activity
Bernard,
(1972)
Neugebauer
(1948)
Balansard (1970,
1972)(condensed
tannins)
Vasoconstrictor
activity
Diemunsch &
Mathis (1987)
(Aqueous
propylene glycol
extract)
Astringent activity
Gracza (1987)
(tincture 1:3; 62%
ethanol)
Laux et al 1993
(Hamamelitannin;
folium & cortex
extract)
Antiinflammatory
activity
Duwiejua M
et al (1994)
(ethanolic
extract 70%)
Hartisch et al (1996,
1997)
(proanthocyanidins,
hamamelitannin
)
Deters et al (2001)
(proanthocyanidins,
polysaccharides)
Brown & Dattner
(1998)
Millikan et al
(2003)
Erdelmeier et
al(1996) (ethanolic
extract 70%)
Antibacterial activity
Brantner et al
(1994)
(aqueous
extract)
Erdelmeier et al
(1996)
(hamamelitannin,
proanthocyanidins)
Lauk et al
(2003)(methanol
extracts)
Radical scavenging
effects
Choi et al (2002)
(hamamelitannin)
Masaki et al
(1993,1994, 1995)
(hamamelitannin)
Tumour necrosis
factor alpha (TNF)
inhibitory activity
Habtemariam et al
(2002)
(hamamelitannin)
Antimutagenic activity
Dauer et al (1998)
(tincture (1:5) and a
methanolic extract
(1:5))
Genotoxic and
antigenotoxic effects
Dauer et al (2003)
(tannins, catechin,
hamamelitanin,
proanthocyanidin
low and high
molecular fractions)
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Assessor’s comments
Most of the tests have been performed on pure isolated components of hamamelis such as:
hamamelitannin, polyphenols, proanthocyanidins and gallic acid.
Venotonic, astringent, antibacterial, antiviral, antioxidative and scavenging mainly in vitro activities have
been reported.
The in vivo anti-inflammatory effects of two hydroethanolic extracts (ethanol 70% v/v), from the leaves
and the bark respectively, have been also reported.
II.2.2
Pharmacokinetics
According to the definition of HMP, the total preparation (e.g: Hamamelidis destillatum) must be regarded
as the active substance. This involves a mixture of numerous constituents. The active constituents have not
yet been clearly defined and many compounds are only contained in very small concentrations or defy
analytical detection due to their chemical structure or their ubiquitous occurrence (polymeric phenols) No
single constituent has been defined as therapeutically active marker and consequently, no appropriate
pharmacokinetic studies are available.
Witch hazel extracts locally applied in therapeutic amounts do not penetrate into the deeper layers of the
skin because of the astringency of their ingredients, and they are therefore not absorbed into the blood
circulation (Fachinfo Posterine ® Salbe, 1997)
II.2.3
Toxicology
Hamamelis virginiana
L. distillate was one of the substances studied in the Carcinogenesis Bioassay
Program by the National Toxicology Program of the National Cancer Institute in 1981; thus relatively
reliable data on hamamelis can be found both in original articles and extensive analyses of this program
(Haseman et al, 1984, 1987; Woodruff et al, 1985).
Acute and subchronic toxicity
The oral administration of 10-20 g (single dose) of hamamelis preparation (not specified) showed no toxic
effect in mice and rats. The LD
50
(rats) on oral administration could not be found. A daily oral intake of
100 mg/kg body weight for three months produced no abnormalities in rats (Bernard et al, 1972
).
The
i.v.
administration of different aqueous solutions of a liquid extract of Hamamelis (unknown
declaration) 0.2-0.4 g extract/kg bw
to dogs (8.5 kg) has shown a marked arterial hypotension, with lethal
doses from 0.6 to 0.8 g/kg bw. The lethal dose after a slow administration in the intrafemoral arteria was
of 0.5 to 1.2 g/kg bw
(
Mercier & Vignoli, 1936).
Genotoxicity
Mortelmans et al (1986) included data of
Salmonella
mutagenicity results of 270 coded chemicals,
encompassing 329 tests performed by three laboratories under contract to the NTP. The
Salmonella
/
mammalian microsome assay was used to test chemicals in up to five strains TA1535; TA1537; TA98;
TA100 in the presence and absence of rat and hamster liver S9. Tests performed after Jan 1983 included
the strain TA97 replacing TA1537. Hamamelis water was negative in all tests.
In a study by McGregor et al (1988), eighteen chemicals were tested for their mutagenic potential in the
L5178Y tk+/- mouse lymphoma cell forward mutation assay. Cultures were exposed to the chemicals for
4h, and cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT),
3
μ
g/ml. The chemicals were tested at least twice. Witch hazel was not identified as a mutagen. [PMID:
3338442, PubMed - indexed for MEDLINE]
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Witch hazel was evaluated for the induction of sex-linked recessive lethal mutations in Drosophila
melanogaster by the National Toxicology Program. Canton-S wild-type males were treated with
concentrations of the witch hazel that result in approximately 30% mortality. Following treatment, males
were mated individually to 3 harems of Basc virgin females to produce 3 broods for analysis. The
concentrations of witch hazel tested by injection (500 ppm) or feeding (500 ppm) were negative in this
assay (Woodruff et al, 1985).
Carcinogenicity
The results of approximately 86 chronic studies in rodents were published as technical repots by Huff et al
(1984, 1985). The studies consist in two years feeding or gavage experiments involving groups of 50 male
and female Fischer -344/N rats and B6C3F
1
mice (Haseman et al, 1984, 1987).
Hamamelis water (68916-39-2) is considered as showing no carcinogenic effects after dermal application
50% or 100% in deionized water 5 d/wk. Witch hazel was tested at EGG and SRI and gave a reproducible
dose response, EGG, EGG ( +. –) and SRI, SRI (–.–). Both samples were returned to Radian Corporation
for analysis and comparison with the parent repository sample where it was found that all three samples
gave identical HPLC tracings. This ruled out the possibility of a mutagenic contaminant in the EGG
sample. The possibility of a contamination or mislabeled samples was ruled out by the analysis of the
remainder sample which gave negative results. Technical reports classified hamamelis as a non-
carcinogen. However, the study was considered inadequate and no formal report was prepared.
Antimutagenic activity
In the Ames mutagenicity test, a tincture (1:5) and a methanolic extract (1:5) of hamamelis bark dose
dependently inhibited 2-nitrofluorene-induced mutagenicity in
Salmonella typhimurium
TA98, by 60%
and 54% respectively at 100 μl/plate. The mechanism of antimutagenic action was also studied. The
proanthocyanidins did not act as bioantimutagens, but rather as direct-acting desmutagens. Tannin-free
samples did not display any inhibition. It was demonstrated that the antimutagenic effect increased with
increasing degree of polymerisation of proanthocyanidins, the most active fraction consisting of catechin
and gallocatechin oligomers with and average degree of polymerization of 9.2 (Dauer et al, 1998) .
Reproductive and development toxicity.
There is not information on reproduction toxicity.
II.2.3.1
O
VERALL CONCLUSIONS ON
T
OXICOLOGY
Limited information is available on toxicology of herbal preparations of hamamelis. Details of the
preparations used in the studies reported are usually lacking. There are only few studies with
Hamamelis
virginiana
L. distillate, fractions of hamamelis preparations and isolated compounds such as
hamamelitannin.
Reliable data from tests on genotoxicity are only available for Hamamelidis aqua preparations, which are
devoid of genotoxic activity. Although the definite carcinogenicity NTP study has not been formally
reported, it can be provisionally concluded that hamamelis water is not carcinogenic. Nevertheless,
according to the studies of hamamelis water preparations, the external application of hamamelis water
probably poses a very low or absent genotoxic or carcinogenic risk.
The safe use of hamamelis distillates has been accepted by the MLWP and HMPC, taking into account the
data in the AR toxicology section (II.2.3) and all available data for the therapeutic indications for
cutaneous use as well as the short-term duration recommended for treatments. As the requirements have
been found to be fulfilled, a positive decision has been taken for the preparation of a List entry on
hamamelis leaf and bark or twigs distillate.
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II.3
CLINICAL
DATA
II.3.1
Clinical Pharmacology
II.3.1.1
P
HARMACODYNAMICS
Anti-inflammatory activity
Although
Hamamelis virginiana
L. has long been used in the traditional treatment of skin diseases, there
are few controlled clinical studies defining the extent of its anti-inflammatory action.
Topical herbal drugs have for centuries been used for treating skin ailments. Although they are currently
widely accepted by patients, their scientific esteem among dermatologists in particular is limited. In a
review
of the efficacy and safety of anti-inflammatory agents used in dermatology, with >100 references,
a variety of herbal drugs for topical application were reviewed by Hoermann et al, (1994). Hamamelis
preparations looked particularly well documented. While the final proof of efficacy in common
dermatoses such as atopic dermatitis was found still lacking, is the authors found fairly ample evidence for
their activity against cutaneous inflammation in man, as may be deduced from experiments with normal
volunteers and unwanted effects related to the drug are virtually absent. The authors concluded that in
particular dermatitis and related disorders can be considered potential indications for topical herbal anti-
inflammatory drugs (Hoermann et al, 1994).
In a randomized, placebo controlled study Sorkin (1980) assessed the vasoconstrictive effects of an
aqueous propylene glycol extract of hamamelis in 30 healthy volunteers. The extract produced a reduction
in skin temperature as compared with the placebo. The anti-inflammatory effects of a hamamelis ointment
containing 25 g aqueous distillate /100 g ointment base (about 4 g of drug) were analysed in five patients
with dermatoses and 22 healthy volunteers were examined. 44 fluvographic curves were obtained, of
which 23 were recorded under the verum product under its ointment base.
Fluvography involves the measurement of the thermal conductivity of the skin, this being as a factor in
linear proportion to skin circulation. Fluvography measurements indicated that in both groups the
ointment reduced the thermal conductivity of the skin due to vasoconstriction, suggesting a mild anti-
inflammatory activity. These data were confirmed by trans-cutaneous oxygen measurements.
The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug
concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion
with/without Phosphatidylcholine (PC) in an experimental study (two randomized double blind studies).
The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base
preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in
24 healthy volunteers and two tested experiences. Skin blanching was quantified by visual scoring and
chromometry. Drug effects were compared with one another and with an untreated control area, as well as
with any action due to the vehicle.
UV-induced erythema at 24h was best suppressed hydrocortisone cream and standard low dose hamamelis
PC-cream while chamomile cream appeared inactive. Hydrocortisone appeared superior to both
hamamelis vehicle, hamamelis cream (without PC) and chamomile extract. Though the cellophane tape
stripping Seventy five µl of each test preparation was applied to five test areas in random order, and
another remained untreated and served for control. Twelve subjects received the low dose hamamelis
cream and the corresponding vehicle as well as chamomile cream (Group 1) and 12 volunteers received
hydrocortisone cream, hamamelis PC-creams (low and high dose), the corresponding vehicle and O/W
vehicle-2(Group 2). Skin colour was determined after 4, 8 and 24 h by chromametry. The erythematous
reaction to the stripping of the horny layer faded rapidly. Thus, only the changes in the skin redness 4 and
8 hours after stripping and drug application were suitable for the analysis of drug effects. Comparing the
effects of the active preparations, hydrocortisone appeared superior to PC-creams in 9 of 12 tests
according to the visual scores and chromametry data (p<0.1).
Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone 1% (P≤ 0.05).
Inflammation was also less pronounced following lower dose hamamelis PC-cream and chamomile cream.
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As expected, the results have demonstrated the anti-inflammatory activity of hamamelis PC-cream, which
appeared more active than hamamelis cream (Korting et al, 1993).
The anti-inflammatory efficacy of an aftersun lotion with 10% hamamelis distillate, the vehicle and a prior
after sun formulation were tested in 30 healthy volunteers using a modified UVB erythema test as model
of inflammation. The main indication for the lotion is the alleviation of the symptoms accompanying by
mild sunburn. Chromametry and visual scoring were used to determine the degree of erythema in the
treated fields and an untreated, irradiated control field 7, 24 and 48 h after irradiation. The erythema
suppression in the test sites treated with hamamelis tended to increase with longer treatment times. The
erythema suppression ranged from approximately 20% of 7 h to 27% at 48 h in the hamamelis fields. A
suppression of 11-15% was recorded in the fields treated with the other lotions. Significant differences
were noted between hamamelis and these lotions. Hamamelis distillate in a conventional O/W cream did
not prove effective. The results provide evidence for the topical use of hamamelis distillate for the
treatment of minor inflammatory skin diseases which do not need treatment with potent corticosteroids.
The authors stated that, in particular the relief of the symptoms associated to the sunburn inflammation, is
a suitable indication for aftersun lotion with hamamelis (Korting, 1993).
The anti-inflammatory activity of hamamelis in experimental irritation models were explored in
15 healthy volunteers. Irritation test caused by Sodium lauryl sulphate (SLS) on 4 test sites on both volar
forearms. SLS was applied once a day for ½ hour. 4 symmetrical test sites were tested: a distillate of Aqua
Hamamelidis (USP) (90%) and urea (5%) formulated as a topical dermatological preparation
vs
untreated;
the product containing Hamamelidis Aqua
vs
the product without hamamelis; hamamelis extract USP
vs
extract and hydrocortisone 1% in the above mentioned speciality without hamamelis and hydrocortisone.
Stratum corneum water content (corneometry), transepidermal water loss (TEWL, Tewameter), cutaneous
blood flow (Laser Doppler), and skin redness (Chromameter, a *value) were determined at baseline and
after at 7 days (Gloor et al, 2001).
Eighteen subjects underwent the dithranol (anthralin) irritation test for 3 days. An erythema was produced
by application of 1% dithranol for 10 minutes. The product containing hamamelis against the product
without hamamelis, and one site untreated. Cutaneous blood flow (Laser Doppler) and skin redness
chromameter were determined at baseline and after 3 days.
In both irritation models, hamamelis produced significant reductions in cutaneous blood flow and skin
redness compared with the vehicle. In the SLS irritation test, TEWL and stratum corneum water the
effects were mainly due to the vehicle that contained both glycerol and urea. Hamamelis USP was
ineffective on all measures. Hydrocortisone 1% had similar effect on cutaneous blood flow and had also
significant hydrating effect. The vehicle in the formulation is fundamental for having an effective product.
(Gloor et al, 2001).
Clinical trials data regarding the efficacy in eczema patients are conflicting (Swoboda et al, 1991; Korting
et al, 1995). However it has been possible to demonstrate a beneficial effect of hamamelis preparations in
inflammation induced by UV light (Korting et al, 1993, Hughes-Formella et al, 1998). The efficacy of
three lotions with 10% hamamelis distillate obtained from different suppliers, two hamamelis free vehicles
(vehicle 1: distillate replaced with 85% water and 15%ethanol and vehicle 2: hamamelis distillate replaced
by water) and three comparators (dimethindene maleate 0.1% gel, hydrocortisone 1% cream and
hydrocortisone 0.25% lotion) were tested in 40 volunteers (19-50 years of age), in a modified UV
erythema test with three dosages (1.2, 1.4 and 1.7 MED, Individual minimal erythemal dosage
determined). Chromametric measurement of redness and visual assessment were performed 24, 48 and 72
h after the induction of erythema. The hydrocortisone formulations were most effective in erythema
suppression. An anti-inflammatory effect was noted for all three hamamelis lotions as well as for the
vehicles. In this study the best results for all three hamamelis formulations were found at 1.4 MED.
Antihistamine dimethindene maleate 0.1% gel did not prove to be more effective than the hamamelis
lotions as well as the vehicles, this failure observed was in accordance with the available literature since
antihistamines have usually found to be ineffective in this model when applied after irradiation
(Hughes-
Formella et al, 2002).
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Vasoconstriction
A randomized, placebo controlled study assessed the vasoconstrictive effects of an aqueous propylene
glycol (water/propylenglycol 50:50) extract of hamamelis leaves in 30 volunteers in three arms.
A thermometric method is proposed in this study. The extract produced a significant reduction in skin
temperature as compared with placebo (Diemunsch & Mathis, 1987).
Antimicrobial activity
The antimicrobial activity of a distillate of
Hamamelis
(Aqua
Hamamelidis
), United States Pharmacopoeia
(USP) 23, and urea (5%) formulated as a topical dermatological preparation was studied. The study was
conducted in 15 healthy volunteers. In vivo, the occlusion and expanded flora tests produced consistent
results. The occlusion and expanded flora tests were described by Leyden et al (1979). The occlusion test
involved the application of a commercial water impermeable cling film, following the test solution
application, having it in place for 24 hours and then the bacteriological test was performed. The expanded
flora test involved 24-hour film treatment as described for the occlusion test but without prior test solution
application.
The distillate showed significant antimicrobial activity on aerobes. The simple occlusion test showed the
same tendency, but results were not significant. Formulations of hamamelis distillate and urea are mainly
used for their anti-inflammatory, hydrating and barrier stabilizing effects in dermatitis maintenance
therapy. The antimicrobial activity of such products is considered an added benefit. The antimicrobial
activity is particularly welcome in the management of atopic dermatitis and intertrigo because the
organisms involved in the pathogenesis of these conditions are susceptible to the hamamelis preparations
(Gloor et al, 2002)
Anti-aging activity
Typical symptoms of skin aging are tautness and itching, which may eventually lead to exsiccation
eczema. This study investigated the safety and efficacy of hamamelis ointment for skin care and symptom
relief in patients with dry aging skin.
An open-label clinical study was performed with a hamamelis ointment for studying dry aging skin in 89
patients at a minimum age of 50 years. Patients were treated with Hametum ointment, applied twice daily
for a period of four weeks. Primary variables of the study were sebumetric and corneometric
measurements, secondary visual score of dryness symptoms such as tautness, roughness or itching. The
outcome after a period of 4 weeks of application was a significant and clinically relevant improvement of
skin sebum content and moisture. Improvement of symptoms was statistically significant for all tested
variables. Pronounced effect was already present after 2 weeks of treatment. Scaling and fissures were
clearly reduced and symptoms like tautness, roughness and itching improved. Skin tolerability was
regarded as very good. Hametum wound healing ointment contains 6.25 mg distillate from fresh leaves
and twigs of
H. virginiana
(1:1.6) as active ingredient. The effect could be attributed to the ointment base
which protects the skin from moisture loss in the form of a superficial layer, but also to the healing-
promoting action of the hamamelis distillate contained in the ointment. (Welzel et al, 2005; Hartmann,
2005)
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Table 4. Clinical References
Author
Design(D)/
Indication(I)
Test substance
Test criterion
Posology/
Duration
of use
Year
Sorkin B
(D): open against base,
intraindiv.
Comparison.
Volunteers (N=20)
Ointment
Blood flow in the
skin (Fluvography)
1980
(I): Atopic eczema
(N=5)
Diemunsch
AM
D) Randomized,
controlled
Intraindividual
comparison
Extract (water/
propylene glycol)
Skin temperature
Thermometric
method
1987
(I)
Volunteers (N=30)
(II)
Moore W
James DK
(D): Double blind,
randomized, placebo-
controlled.
Hamamelis water
BPC
Pain swelling,
oedema (Patient and
doctor)
1989
(I) Postepisiotomy care
(n=266)
Korting HC D): Double blind,
multiple control,
intraindiv. comparison.
(n=12)
(I) Inflammation
models in volunteers
(cell stripping)
-phosphatidylcho-
line-containing ham.
distillate
(PC-Cream) or ham.
ketone
-cream without PC
- hydrocortisone 1%
- Chamomile extract
Visual appearance.
(multiple sum score)
Chromametry
4, 8, 12h
test
1993
Korting HC D): Double blind,
multiple control,
intraindiv. comparison.
(n=24)
(I) Inflammation
models in volunteers
(erythema UV
irradiation)
-phosphatidylcholine
containing ham.
distillate (PC-Cream)
or ham. ketone
-cream without PC
- hydrocortisone 1%
- Chamomile
extract
Visual appearance.
(multiple sum score)
Chromametry
24, 48h
1993
Korting HC (D) Randomized,
double-blind, placebo
controlled.
(I) Inflammation
models in volunteers.
UV induced Erythema
(N=40)
aftersun Lotion
10% ham. distillate
Inflammation
induced by UV light
1993
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Gloor M
(N=18)
Experimental irritation
model: Dithranol
(anthralin)
Hamamelidis Aqua
+ Urea
3 days
2001
Gloor M
(N=15)
Experimental irritation
model: Sodium Lauryl
sulphate (SLS)
Hamamelis
ointment;
Base ointment;
Hamamelidis
extract USP
Hydrocortisone 1%
Corneometry/
Transepidermal
water loss/
Cutaneous blood
flow/Skin redness
(chromameter)
7days.
SLS once
a day for
½ hour +
study
products
2001
Gloor M
Occlusion and
expanded flora tests
Hamamelidis Aqua
+ Urea
Dermatitis/Anti-
septic effects
24 h
2002
Hughes-
Formella
BJ
Erythema suppression.
antinflammatory effect
Finn chamber
(N=40)
Aftersun Lotion,
ham. distillates,
lotion base
Inflammation
induced by UV light
24, 48,
72h
2002
Welzel J
(D) Open, clinical
study
(N=89)
Hametum ointment Dry aging skin
4 Weeks 2005
II.3.1.2
P
HARMACOKINETICS
No data available.
II.3.2
Eczema
Hamamelis preparations could be proposed in the maintenance therapy for atopic eczema, particularly as
follow up to treatment with steroidal anti-inflammatory agents. The low toxicity of hamamelis and the
absence of known undesirable effects, support a favourable risk/benefit ratio for this preparation
containing hamamelis distillate. Hamamelis water led to a significant reduction in erythema compared to
the vehicle (p=0.00001) and untreated irradiated skin (p=0.00001) (Hughes-Formella et al, 1998).
A randomized double blind comparison study assessed the efficacy of ointments containing either a
standardized extract of the dried leaves or bufexamac in the treatment of 22 patients with bilateral,
moderately or severe endogenous eczema. Patients were treated three times daily for an average of 17 ± 5
days (Treatment duration between 5 to 22 days). Comparison of the patients’ forearms showed that both
treatments reduced the severity of symptoms such as desquamation of the skin, redness, itching,
infiltration and lichenification, with desquamation showing the highest reduction (55%). No differences
were observed in the global assessment of the therapy or the severity of symptoms between treatments
(Swoboda et al, 1991).
A randomized, double-blind, placebo controlled trial lasting 14 days compared the efficacy of three
creams containing either a hamamelis distillate (5.35 g hamamelis distillate with 0.64 ketone/100 g) 0.5%
hydrocortisone cream or a drug-free vehicle in 72 patients for the symptomatic treatment, and reductions
in severe atopic eczema (∆ values of the sum scores) were evaluated. Effects were compared using
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3
In case of traditional use the longstanding use and experience should be assessed.
Wilkinson’s test. All treatments significantly reduced the incidence of itching, scaling and erythema after
1 week of treatment. Hydrocortisone proved superior to hamamelis distillate. The cream containing
hamamelis distillate did not differ from the vehicle. The results showed that the therapeutic outcome using
the hamamelis preparation was not better than following the base preparation (Korting et al, 1995).
A case of accidental skin injury caused by leakage of sodium hypochlorite solution from the rubber dam
during root canal preparation is reported. The patient developed a skin rash followed by scab formation
which required medical treatment with topical
Hamamelis virginiana
extract for 2 weeks, with full
recovery (Ahmet et al, 2004).
The efficacy of two hamamelis ointments (differing only in the ointment base) containing 25 g aqueous
distillate/100 g ointment base (equivalent to about 4 g drug), for the treatment of endogenous eczema
(neurodermatitis) and toxic degenerative eczema (attrition eczema) was compared in a placebo controlled,
double blind study (the placebo was not described) in 80 patients. Symptomatic improvements in itching,
redness, burning sensation and desquamation of the skin were observed in 36 patients after 28 days of
treatment with endogenous eczema with both hamamelis preparations after treatment for 39 days (Pfister,
1981).
In a pilot study of 37 patients with endogenous eczema a cream containing a hamamelis leaf extract was
applied twice daily for two weeks. Following treatment, considerable improvement in symptoms like such
as inflammation and itching was noted in 24 patients (Wokalek, 1993)
In a multicenter, prospective paediatric cohort study on the efficacy and tolerability of hamamelis
ointment, children of different age groups (27 days to 1 year; 1 to 5 years; 6 to 11 years of age) suffering
from superficial skin lesions/ diaper skin rash/ or other local inflammations of skin and mucous
membranes were treated in a randomized manner at a ratio of 3:1 with either an hamamelis ointment and
dexpanthenol. The recommended individual observation was 7 to 10 days; dosage was based on the
recommendations of the treating physician.
309 patients were enrolled into the study (hamamelis ointment: 231; dexpanthenol: 78). Both therapeutic
groups showed comparable initial values. The efficacy of both therapeutic treatments could be proven for
all three diagnoses with statistically significant and clinically relevant improvement of the total score
between the beginning and the end of treatment (p< 0.0001 in each case). Within the three age groups, the
total score for the skin diseases investigated improved in both therapeutic treatments without statistically
relevant differences between the comparative cohorts. In total, 83.5% of the doctors and 83.1% of the
parents considered the efficacy of hamamelis ointment as excellent or good (Dexpanthenol: 83.3% and
80.7%). Tolerability of hamamelis ointment was assessed as excellent or good by 99.1% of the doctors
and 98.2% of the parents (Dexpanthenol: 97.4% and 92.3%).
Hamamelis ointment could be considered effective and safe as a temporary treatment for certain skin
disorders in children up to 11 years of age in minor skin injuries, diaper dermatitis, or localized
inflammation of skin (Wolff et al, 2005). Regarding the safety in this study: 12 out of 309 children
experienced adverse events, 1 out of 78 in the dexpanthenol treatment (conjunctivitis) and 11 out of 231 in
the hamamelis treatment group (confusion, head lice, cough/allergic reaction, fungal
infection/deterioration, otitis, erythema increased, rhinopharyngitis, burning sensation, super-infection,
diaper candidiasis, and obstructive bronchitis). The authors considered only two adverse events as
potentially drug related, i.e.: erythema and burning sensation. A series of physical, chemical, enzymatic
and microbial changes related to diaper’s holding of urine and faeces are considered responsible for diaper
dermatitis. In this situation, antifungal and antibacterial products should be avoided and not to be used, as
it is known that bacterial infection does not have a role in diaper dermatitis and the normal microflora
should be preserved, while the antimicrobial activity of hamamelis preparations could be an explanation
for some of these events.
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Antihemorrhoidal efficacy
Witch hazel extracts, high in tannins and volatile oils, have a long therapeutic tradition and are used
primarily for its astringent, anti-inflammatory and local haemostatic effects. In folk medicine hamamelis
has been used for poor venous conditions, including the treatment of haemorrhoids. A few studies have
shown that witch hazel water relieves itching, burning and other discomforts when applied to anorectal
area. The substance is judged safe and effective in concentrations 10 to 50% (cream 50%); it can be
applied after each bowel movement or up to 6 times daily (Zimmerman, 1993).
A randomized double blind three limb study, of 21 days duration, compared the efficacy of rectal
ointments containing either a hamamelis liquid extract, bismuth subgallate or a local anaesthetic in the
treatment of 90 patients with acute stage 1 haemorrhoidal symptoms. The local anesthetic was presented
in two control ointments which also contained either policresulen or fluocinolone acetonide. After 21 days
of treatment, all four ointments were equally effective in improving: pruritus, bleeding, burning sensation
and pain. All three ointments proved highly effective. Both during the course of treatment and at the final
examination; no major differences were to be found between the three groups (Knoch 1992; Barnes et al,
2007).
The study of Steinhart (1982) considered corticoid-free preparations suitable for conservative long-term
treatment of symptoms associated to anorectal complaints such as haemorrhoids which may lead to
bleeding, itching, burning and pain. The study compared the efficacy of Hametum ointment to an
hamamelis reference preparation in 70 patients of both sexes. After a four weeks treatment 60% of
symptoms disappeared in the ointment group; in the reference group, this percentage was 30%.
Episiotomy pain
In a randomized clinical trial involving 300 mothers patients undergoing episiotomy, the efficacy of three
topical agents (Epifoam, hamamelis water and ice) was investigated to determine their effects on pain,
bruising and oedematous swelling. Data were collected in 266 women for immediate postnatal evaluation.
The treatment tested were local application of a cream containing hamamelis water BPC 1973; a reference
cream containing 1% hydrocortisone and a local anesthetic (Epifoam); and ice packs. All three agents
were equally effective at achieving on the first day though one-third of the mothers derived not benefit
from any agent. Ice had a tendency to be better considered. Whilst differences in the incidence resolution
of bruising and oedema were demonstrated, these differences were not reflected in the mothers´ perception
of pain relief. Oral paracetamol and salt baths were also used as needed. The efficacy of all three
treatments appeared to be equal (Moore et al, 1989).
East et al (2007) reviewed in Cochrane database the published and unpublished randomised or quasi
randomised trials (RCTs) that compared localised cooling treatment applied to relieve pain related to
perineal trauma sustained during childbirth. Seven published RCT were included, comparing local cooling
treatment (ice packs, cold gel pads or cold/iced baths) with no treatment, hamamelis water, Pulse
electromagnetic energy (PET), a hydrocortisone/pramoxine foam (Epifoam) or warm baths. The RCTs
reported on a total of 859 women. Ice packs improved pain relief 24 to 72 hours after birth compared with
no treatment. Woman preferred the utility of the gel pads compared with ice packs or no treatment,
although no differences in pain relief were detected between the treatments. None of the treatments
resulted in differences detected in perineal oedema or bruising. Women reported more pain and used more
additional analgesia following the application of ice packs compared with PET. There is only limited
evidence to support the effectiveness of local cooling treatments.
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Table 5. Clinical studies
Author
Design(D)/
Indication(I)
Test substance
Test criterion
Posology/
Duration of
use
Pfister,
(D): Double blind,
randomized, reference
controlled
(I) Atopic eczema (N=36)
Toxic Degenerative Eczema
25 g /aqueous distillate
/100 g ointment base
Neurodermatitis
Various skin
symptoms
28/39 days
1981
Steinhart,
(D): Open, ref. controlled
(I): Anorectal disorders
(n=70)
Hametum ointment
vs hamamelis
reference product
Gen. Symptoms,
rectal examination
findings.
3 times daily
4 weeks
1982
Moore,
James,
(D): Double blind,
randomized, placebo
controlled
(I) Postepisiotomy care
(n=266)
Hamamelis water BPC Pain swelling,
oedema (Patient
and doctor)
1989
Swoboda,
Meurer,
D): Double blind,
randomized, reference-
controlled.
(I)Atopic eczema (N=22)
Hametum ointment.
(Standardized aqueous
distillate)
+ Bufexamac
Neurodermatitis/
eczema
Various skin
symptoms
3 times daily
3 weeks
1991
Knoch,
1991
D): Open; uncontrolled trial
(I) Haemorrhoids (N= 75)
Ointment combination
of fluid extract, base,
bismuth gallate
(corticoid free rectal
ointment)
Acute stage I
haemorrhoidal
complaints:
Bleeding, pain,
itching, burning.
2 times daily
3 weeks
Knoch,
1992
D): Double blind,
randomized, reference
controlled, three arms study
Ointment combination
of fluid extract, base,
bismuth gallate, local
anesthetic
(Eulatin N salbe)
Acute stage I
haemorrhoidal
complaints:
Bleeding, pain,
itching, burning.
21 days
(3/7/14/21d)
twice daily
After 3 days,
improvement of
pruritus,
bleeding.,
burning
sensation and
pain (p<0.001)
(I) Haemorrhoids (N= 90)
Wokalek,
(I) Endogenous eczema.
Inflammation/itching
(N=37)
Cream Ham. leaf
extract
Hamamelis leaf
extract
2 times daily
2 weeks
1993
Korting,
1995
(D) Randomized, double-
blind, placebo controlled.
(N=72)
Ham. distillate cream
Ointment base
0.5% hydrocortisone
(n=36 each group)
Moderate/severe
atopic eczema.
itching, scaling
and erythema
2 weeks
Hughes-
Formella,
1998
Hamamelis distillate
Erythema
maintenance
therapy
Wolff,
2005
(D) Multicenter, prospective
cohort study, (children)
Arms: 27d-1yr; 1-5 yr; 6-11
yr. (N= 309)
Hamamelis ointment
(N=231) /
Dexpanthenol (N=78).
Posology not reported
Superficial skin
lesions/ local
inflammations/
nappy rash
7 to 10 days
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II.3.3
CLINICAL SAFETY
The special feature of
Hamamelis virginiana
L. is that the indications, mode of administration and the
parts of the plant therapeutically used in preparations have always been the same. This simplifies the
toxicological assessment and provides further evidence that hamamelis is effective and safe. A fact worth
mentioning is that
Hamamelis virginiana
L. has been reported as of no toxicological importance.
II.3.3.1
P
ATIENT EXPOSURE
No exact data on patient exposure are available. Hamamelis products are widely used as safe ingredients
in medicinal products and in cosmetics.
II.3.3.2
A
DVERSE EVENTS
Witch hazel preparations are referred in Mayler’s Side Effects of Drugs among the Agents known or
believed to have caused immunological contact urticaria. The patch test concentration and vehicle is 10%
alcohol distillate and the proposed frequency of sensitization is rare (reference SEDA 19, 162).
No significant adverse effects from the ingestion of witch hazel are expected. It may cause irritation of the
stomach in a small number of susceptible individuals and topical application may cause contact allergy in
rare cases (Mills and Bone, 2000).
Allergic contact dermatitis may occur in sensitive individuals. The type of contact reactions to witch hazel
in the older literature is not clear, as patch test were not performed or not reported. Bruynzeel et al (1992)
tested 1032 patients consecutively or randomly chosen, in 6 patch test clinics with a series of 5 popular
ointments. The ointments elicited positive reactions in 11 patients among which 4 were found to react to
an ointment containing 25% extract of hamamelis.
Grandlund (1994) reported a case of a 31 year-old non-atopic woman treated with 1% hydrocortisone-17-
butyrate for dermatitis of the lower limbs. At the same time she started to use an eye gel, after which
developed oedema around the eyes within one week. She stopped the use of the eye gel, but the oedema
spread to the rest of the face and neck, and finally became eczema. The patient showed positive patch test
reactions to the eye gel and to the ingredients: hamamelis distillate and cucumber extract.
Conjunctivitis has been reported by Ireland and Spain for eye drops (hamamelis distillate (1.6:1) the
frequency is not known.
Contraindications (hypersensitivity and allergic potential to be both covered)
Hypersensitivity to the active substance
.
II.3.3.3
S
ERIOUS EVENTS AND DEATHS
None known.
II.3.3.4
L
ABORATORY FINDINGS
No data available.
II.3.3.5
S
AFETY IN SPECIAL POPULATIONS AND SITUATIONS
.
Caution should be exercised with long term oral use due to the presence of tannins. In susceptible patients,
irritation of the stomach may occur occasionally. In rare cases, witch-hazel tannins may cause liver
damage (McGuffin, 1997)
II.3.3.5.1 Intrinsic (including elderly and children)/extrinsic factors
None known.
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II.3.3.5.2 Drug-drug interactions and other interactions
None reported for hamamelis preparations.
Tannins inhibit absorption of minerals and B vitamins.
II.3.3.5.3 Use in pregnancy and lactation
Safety during pregnancy and lactation has not been established definitely. In accordance with general
medical practice and in absence of sufficient data, hamamelis preparations for internal use should not be
used during pregnancy and lactation without medical advice (ESCOP, 2003).
II.3.3.5.4 Overdose
No case of overdose has been reported.
II.3.3.5.5 Drug abuse
None known.
II.3.3.5.6 Withdrawal and rebound
None known.
II.3.3.5.7 Effects on ability to drive or operate machinery
None known.
II.3.3.6
O
VERALL CONCLUSIONS ON SAFE USE
The external application of hamamelis preparations can be regarded as safe, especially at the
recommended doses.
Contact allergic dermatitis has been reported only in rare cases.
Some conjunctivitis cases have been reported during the use of eye drops containing hamamelis (dilution
of hamamelis distillate (1.6:1)), while the frequency is not known.
In view of the results of the preclinical toxicological studies, clinical trials and several decades of
experience of its use in human beings, as well as the degree of satisfaction expressed by the patients, the
hamamelis preparations can be classified as safe and well tolerated medicines
.
II.4
OVERALL
CONCLUSIONS
As is the case for many other plant preparations, consistent scientific data supporting the efficacy of
hamamelis preparations are still limited. Some controlled clinical trials have been performed, some of
them showed positive outcomes but of weak statistical interpretation. The beneficial effect of hamamelis
is primarily supported by traditional use.
Diluted preparations of hamamelis distillate virtually with no tannin content, 14-15% alcohol in water and
a small amount of the essential oil of witch hazel have been widely used in many eye cleansing products.
There are some products of Hamamelis aqua (water steam distillate) (1:1.6), authorised as medicinal
products in different European countries (see I. Regulatory Status Overview), but this provides no
rationale for recommending the use of this preparation under well established use (WEU).
In relation to the cutaneous use of hamamelis, some randomized, placebo controlled studies have been
performed with products containing hamamelis distillate. The results of some of these clinical trials
regarding the efficacy in eczema are conflicting (Hughes-Formella, 2002; Korting, 1995). However, in
two separate laboratories the beneficial effect of hamamelis preparations in inflammation induced by UV
light or tape stripping in human volunteers has been demonstrated (Hughes-Formella BJ, 1998; Korting,
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1993). In both of these studies the anti-inflammatory potency was weaker than for hydrocortisone but
significantly greater than for the vehicle. The efficacy has been demonstrated with concrete products and
related mainly to the excipients used as carriers in the formulations. This is the rationale for not
considering Hamamelidis aqua preparations for WEU.
The plausibility of the traditional cutaneous use of hamamelis distillate and its preparations (semi solid/
solid preparations) is reinforced upon available (non-) clinical pharmacological experiences and based
upon long-standing use, as well.
The assessor’s final conclusion is to recommend only the traditional registration procedure for the
preparations of hamamelis considered in this AR mainly for cutaneous use (skin and external mucosa),
including products containing hamamelis water preparations which are considered as the most extensively
studied.
The oral use of hamamelis preparations such as tincture (1:10) (leaf); tincture (1:10 w/v, in 55% ethanol
V/V) (bark); Liquid extract (1:1) ethanol 45% v/v (leaf) which has been referred and supported by
handbooks and hamamelis monographs ( WHO, Commission E and ESCOP), is not recommended by the
assessor , as there are not products in the market which comply with the conditions required for traditional
herbal medicinal products.
The following extracts: Dry extract with ethanol 80% V/V (DER 5-8.5:1) and dry extract with ethanol
96% V/V (DER 6-9:1), have not been included in the monographs because no adequate information on the
use of either of them was available to the assessor.
Period of traditional use (art. 16a(1)(d)), as laid down in (art. 16(1)(c)), has elapsed for the preparations
included in the monograph. The traditional use outside and inside the European Union has been shown in
detail for much more than 30 years.
Recommended indications for hamamelis leaf or bark for cutaneous use:
Traditional herbal medicinal
product for relief of minor skin, inflammation and dryness of the skin.
Recommended indications for hamamelis leaf or bark preparations for anorectal use:
Traditional herbal medicinal product for symptomatic relief of itching and burning associated with
haemorrhoids.
Recommended indications for hamamelis leaf or bark for oromucosal use
Traditional herbal medicinal product used as a mouthwash and gargle for relief of minor inflammation of
mucous membranes of the oral cavity conditions of the oral mucosa.
Recommended indications for diluted hamamelis distillate/External use
Traditional herbal medicinal product for relief of minor skin inflammation and dryness of the skin.
Traditional herbal medicinal product for the temporary relief of discomfort due to dryness of the eye or to
exposure to wind and sun.
The product is a traditional herbal medicinal product for use in specified indication exclusively based
upon long-standing use.
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Hamamelis bark (Hamamelidis cortex)
Recommended posology
External use
:
Semi-solid and liquid preparations containing the equivalent 5-10% of bark, as often as required. As
impregnated dressings, lotion or mouthwash, decoction of 5-10 g of bark to 250 ml of water.
For cutaneous use:
Tincture (bark) (1:10; ethanol 45% v/v
)
in a strength corresponding to 5-10% in semi-solid preparations,
several times a day.
Dry extract (5-7.7:1; extraction solvent ethanol 30% m/m) in a strength corresponding to 1.3% in semi-
solid preparations, several times a day.
For anorectal use:
Tincture in a strength corresponding to 5-10% in semi-solid preparations, several times daily.
Comminuted herbal substance as decoction: 5-10 g/250 ml, up to 3 times a day in impregnated dressings.
Dry extract (5-7.7:1; extraction solvent ethanol 30% m/m) in a strength corresponding to 1.3% in semi-
solid preparations, several times a day.
For rectal use:
Suppositories containing 66 mg of dry extract (5-7.7:1; ethanol 30% m/m) One suppository, two or three
times a day.
For oromucosal use (mouthwash and gargles):
2-3 g of herbal substance as herbal tea (decoction) for using as a mouthwash, up to three times a day.
Diluted tincture (1:10; ethanol 45% v/v
)
,
2-4 ml, three times a day.
Hamamelis leaf (Hamamelidis folium)
For cutaneous use:
Tincture or liquid extracts (1:1) in a strength corresponding to 5-10% in semisolid or liquid preparations,
several times daily.
Liquid extract (1:2; ethanol 60% v/v) in a strength corresponding to 20% as semi-solid preparation.
For oromucosal use:
Decoctions of 5-10 g of leaf to 250 ml of water (or 2-3 g in 150 ml), for impregnated dressings and rinses,
several times daily.
Tincture (1:10) in 45% ethanol (diluted (1:3) with water) 2-4 ml, three times daily as gargle.
For symptoms associated with hemorrhoids:
Tincture or liquid extracts (1:1) in a strength corresponding to 5-10% in semisolid and liquid preparations,
several times daily.
Liquid extract (1:2; ethanol 60% v/v) in a strength corresponding to 20% as a semi-solid preparation,
several times daily.
Comminuted herbal substance as decoction: 5-10 g/250 ml, up to 3 times a day in impregnated dressing.
For rectal use:
Suppository containing 400 mg of liquid extract (1:2; ethanol 60% v/v), 2-3 times a day.
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Hamamelis distillate (Hamamelidis destillatum)
For cutaneous use: distillates in a strength corresponding to 5-30% in semi-solid preparations, several
times a day.
Eye drops:
Hamamelidis distillate 10% diluted: Single dose 2 drops/each eye, 3-6 times a day.
Route of administration (art. 16a(1)(c))/duration of use
Hamamelis products are mainly recommended for cutaneous application. The average duration of use is
two weeks. In case of application on the eye, the duration of use should be limited to 4 days.
Non clinical safety
Limited information is available on toxicology of herbal preparations of hamamelis. Details of the
preparations used in the studies reported are usually lacking. There are only few studies with Hamamelis
virginiana, destillatum (Hamamelidis Aqua USP), fractions of hamamelis preparations and isolated
compounds such as hamamelitannin.
Reliable data from test on genotoxicity are only available for Hamamelidis aqua preparations.
According to the experience acquired during the prolonged use of hamamelis preparations, the external
application can be regarded as safe.
Clinical Safety
The external application of hamamelis preparations can be regarded as safe at the recommended doses.
Contact allergic dermatitis has been reported only in rare cases.
Conjunctivitis case has been reported for eye drops (dilution of hamamelis distillate (1.6:1)), the
frequency is not known.
In view of the results of the preclinical toxicological studies, clinical trials and several decades of
experience of its use in human beings, as well as the degree of satisfaction expressed by the patients, the
hamamelis preparations can be classified as safe and well tolerated medicines, proved not to be harmful in
the specified conditions of use. Their pharmacological effects or efficacy are plausible on basis of long-
standing use and experience.
These preparations comply the criteria for traditional herbal medicinal products as established in the
Art 16 c(1)(e) of the Directive 2004/24/EC.
The safe use of hamamelis distillates has been accepted by the MLWP and HMPC, taking into account the
data of the AR toxicology section (II.2.3) and all available data for the therapeutic indications for
cutaneous use as well as the short-term duration recommended for treatments. As the requirements have
been found to be fulfilled, a positive decision has been taken for the preparation of a List entry on
hamamelis leaf and bark or twigs distillate.
EMEA 2010
46/47
ANNEXES
II.5
C
OMMUNITY HERBAL MONOGRAPHS ON
H
AMAMELIS VIRGINIANA
L.,
CORTEX
;
H
AMAMELIS VIRGINIANA
L.,
FOLIUM
;
II.6
C
OMMUNITY LIST ENTRY ON
H
AMAMELIS VIRGINIANA
L.,
FOLIUM ET CORTEX OUT
II.7
LITERATURE REFERENCES
4
According to the “Procedure for the preparation of Community monographs for traditional herbal medicinal
products”
(EMEA/HMPC/182320/2005 rev.2)
5
According to the “Procedure for the preparation of Community monographs for herbal medicinal products with
well-established medicinal use”
(EMEA/HMPC/182352/2005 rev.2)
6
According to the “Structure of the Community list of herbal substances, preparations and combinations thereof for
use in traditional herbal medicinal products”
(EMEA/HMPC/100824/2005 rev.2)
EMEA 2010
47/47
Source: European Medicines Agency
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