COMMUNITY HERBAL MONOGRAPH ON
PASSIFLORA INCARNATA
L., HERBA
To be specified for the individual finished product.
Well-established use
Traditional use
With regard to the marketing authorisation
application of Article 10(a) of Directive
2001/83/EC as amended
With regard to the registration application of
Article 16d(1) of Directive 2001/83/EC as
amended
Passiflora incarnata
L., herba (passion flower)
i) Herbal substance
Fragmented or cut, dried aerial parts
ii) Herbal preparations
Herbal substance for tea preparation
Liquid extract (1:8 ; extraction solvent 25%
ethanol)
Liquid extract (1:8 ; extraction solvent 45%
ethanol)
Liquid extract (1:1 ; extraction solvent 25%
ethanol)
Liquid extract (1:1 ; extraction solvent 70%
ethanol)
iii) Corresponding dry extracts
Well-established use
Traditional use
Herbal substance or herbal preparations in solid
or liquid dosage forms for oral use.
The pharmaceutical form should be described by
the European Pharmacopoeia full standard term.
1
The material complies with the Ph. Eur. monograph (ref. 01/2005:1459).
2
The declaration of the active substance(s) for an individual finished product should be in accordance with
relevant herbal quality guidance.
©
EMEA 2007
2/6
4.1.
Therapeutic indications
Well-established use
Traditional use
Traditional herbal medicinal product for relief of
mild symptoms of mental stress and to aid sleep.
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
Adolescents over 12 years of age, adults
0.5-2 g of herbal substance as powder 1-4 times
daily.
To make an infusion, pour 150 ml of boiling
water over 1–2 g of herbal substance. Steep for 10
minutes. To be taken 1-4 times daily.
2-4 ml of liquid extract (1:8 ; extraction solvent
25% ethanol) up to 4 times daily.
2 ml of liquid extract (1:8 ; extraction solvent
45% ethanol) up to 3 times daily.
0.5-2 ml of liquid extract (1:1 ; extraction solvent
25% ethanol) up to 4 times daily.
2 ml of liquid extract (1:1 ; extraction solvent
70% ethanol) up to 3 times daily.
Corresponding doses of dry extracts.
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
If the symptoms persist during the use of the
medicinal product, a doctor or a qualified health
care practitioner should be consulted.
Method of administration
Oral use.
©
EMEA 2007
3/6
4.3.
Contraindications
Well-established use
Traditional use
Hypersensitivity to the active substance.
4.4.
Special warnings and precautions for use
Well-established use
Traditional use
The use in children under 12 years of age is not
recommended because data are not sufficient and
medical advice should be sought.
For liquid extracts containing ethanol, the
appropriate labelling for ethanol, taken from the
‘Guideline on excipients in the label and package
leaflet of medicinal products for human use’,
must be included.
4.5.
Interactions with other medicinal products and other forms of interaction
Well-established use
Traditional use
Although no clinical data about interactions with
synthetic sedatives are available, concomitant use
with synthetic sedatives (such as
benzodiazepines) is not recommended unless
advised by a doctor.
4.6.
Pregnancy and lactation
Well-established use
Traditional use
Safety during pregnancy and lactation has not
been established.
In the absence of sufficient data, the use during
pregnancy and lactation is not recommended.
4.7.
Effects on ability to drive and use machines
Well-established use
Traditional use
May impair ability to drive and use machines.
Affected patients should not drive or operate
machinery.
©
EMEA 2007
4/6
4.8.
Undesirable effects
Well-established use
Traditional use
One case of hypersensitivity (vasculitis) and one
case of nausea and tachycardia have been
reported. The frequency is not known.
If other adverse reactions not mentioned above
occur, a doctor or a qualified health care
practitioner should be consulted.
Well-established use
Traditional use
No case of overdose has been reported.
5.1.
Pharmacodynamic properties
Well-established use
Traditional use
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
5.2.
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.
P
RECLINICAL 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.
©
EMEA 2007
5/6
Well-established use
Traditional use
Not applicable.
7 September 2007
©
EMEA 2007
6/6
Assessment Report
1.
INTRODUCTION
1.1
D
ESCRIPTION
Passiflora incarnata
L., herba is the dried aerial parts of
Passiflora incarnata
L.
It may contain flowers and fruits [European Pharmacopoeia].
Passiflora incarnata
L., herba extract is the dry extract of
Passiflora incarnata
L.,
herba, prepared with ethanol (40% – 90% v/v) or methanol (60% v/v), or acetone
(40% v/v), and containing a minimum of 2.0% flavonoids, expressed as vitexin
[European Pharmacopoeia].
2.
TRADITIONAL MEDICINAL USE
2.1
I
NFORMATION ON PERIOD OF MEDICINAL USE IN THE
C
OMMUNITY REGARDING THE
SPECIFIED INDICATION
Passiflora incarnata
L., herba has been used in Europe for the relief of mild symptoms of mental
stress and to aid sleep. The medicinal use has been documented continuously in recognised handbooks
dating
e.g.
from 1938, 1958, 1977 and 2003 [Madaus, 1938; Hoppe, 1958; List and Hörhammer, 1977;
ESCOP, 2003]. It is often used in combinations with other sedative herbal substances.
2.2
T
YPE OF TRADITION WHERE RELEVANT
European phytotherapy.
2.3
B
IBLIOGRAPHIC
/
EXPERT EVIDENCE ON THE MEDICINAL USE
Medicinal use of
Passiflora incarnata
L., herba for the relief of mild symptoms of mental stress and to
aid sleep has been recorded
e.g.
in the following handbooks:
Lehrbuch der Biologischen Heilmittel
[Madaus, 1938].
Daily dose:
30-50 drops or 0.250-0.375 g fresh
plant material (“Teep”-tablets) before bedtime.
Duration of use
: No information.
Martindale Extra Pharmacopoeia
[Todd, 1967].
Single dose
: liquid extract (1 in 1): 0.5-1 ml; tincture
(1 in 5): 0.5-2 ml.
British Herbal Pharmacopoeia
(1976). Dosage (3 times daily): 0.25-1 g (powder or infusion);
0.5-1 ml liquid extract (1:1 in 25 % alcohol); 0.5-2 ml tincture (1:8 in 45% alcohol).
Hagers Handbuch
[List and Hörhammer, 1977].
Single dose
: 2 g as infusion.
Hagers Handbuch
[Hänsel
et al.
, 1994].
Daily oral dose
: 4 – 8 g of the crude drug or the
corresponding amount of the extract. For tea: 15 g crude drug in 150 ml of water. Used mostly in
combinations with
Valeriana officinalis
L., root,
Humulus lupulus
L., cone or
Melissa officinalis
L.,
leaf. Also combinations with
Pimpinella anisum
L., fruit,
Lavandula angustifolia
Mill., flower,
Citrus aurantium
L., flower or
Mentha piperita
L., leaf are used.
Duration of use
: No information.
British Herbal Compendium
[Bradley, 1992].
Daily oral dose
: crude drug: 2 – 8 g. Liquid extract
(1:1, 25% ethanol) 2 – 8 ml. Tincture (1:8, 25% ethanol) 8 – 16 ml.
Duration of use
: No information.
Herbal Drugs and Phytopharmaceuticals
[Wichtl, 2004)].
Daily oral dose
: 6 g.
Duration of use
:
No information.
Herbal Medicines. A guide for healthcare professionals
[Barnes
et al.
, 1996].
Daily oral dose
:
crude
drug: 1,25 – 8 g. Liquid extract (1:1, 25 % ethanol) 1.5 – 3.0 ml. Tincture (1:8, 45 % ethanol)
1.5 – 6.0 ml.
Duration of use
: No information.
© EMEA 2008
2/9
Handbook of Medicinal Herbs
[Duke, 2002].
Daily oral dose
: 2 – 8 g.
Duration of use
:
No information.
ESCOP Monograph
(2003).
Daily oral dose
: crude drug: 2 – 8 g. As infusion: crude drug 10 g.
Tincture (1:8) 4 – 16 ml.
Duration of use
: No restriction.
PDR for Herbal Medicines
(1998).
Daily oral dose
: 3 teaspoons (~ 6 g) for tea preparation.
Duration of use
: No information.
Acupuncture & Médicine traditionelle chinoise
[Weniger and Anton, 1996].
Daily oral dose
: 6 – 9 g
for tea preparation. Powdered crude drug: 0.5 – 1 g.
Duration of use
: No information.
Drogenkunde
(Hoppe, 1958).
Daily oral dose
: No information.
Duration of use
: No information.
Précis de Matière Médicale
[Paris and Moyse, 1981]
.
Daily oral dose
: tincture or fluid extract 2 – 5 g
(unclear if this amount relates to the crude drug).
Duration of use
: No information.
Phytothérapie. Les données de l´évaluation
[Bruneton, 2002].
Daily oral dose
: No information.
Duration of use
: No information.
The Complete German Commission E Monographs
[Blumenthal
et al.
, 1998].
Daily oral dose
: 4 – 8 g.
Equivalent
amount of preparations.
Duration of use:
No information.
Herbal Medicine, expanded Commission E monographs
[Blumenthal
et al.,
2000].
Daily oral dose
:
4 – 8 g. Equivalent
amount of preparations.
Duration of use
: No information.
Dry extracts (5-7:1) prepared by 60% methanol have been on the German market since 1992
(Information from Germany).
Liquid extract (1:1 in 70% ethanol) has been on the market in Germany since at least 1978.
Daily oral dose
: 3 times 2 ml (Information from Germany).
No information on medicinal use of acetone extracts have been found in the literature or received from
the Member States.
Medicinal and traditional use for the relief of mild symptoms of mental stress and to aid sleep is also
described in a number of reviews [Bizet, 1998; Brasseur and Angenot, 1984; Lutomski
et al.
, 1981;
Meir, 1995]. Only one reference [Lutomski
et al.
, 1981] contains information on dosage and quotes
the information from Commission E and ESCOP. None of the reviews contains any information on the
duration of use. An extensive review of the botany, chemistry pharmacology and clinical use of plants
of the genus
Passiflora
, including
Passiflora incarnata
has been published [Dhawan
et al.
, 2004].
2.4
A
SSESSOR
’
S OVERALL CONCLUSION ON THE TRADITIONAL MEDICINAL USE
Traditional medicinal use of
Passiflora incarnata
L., herba in the form of powdered herbal substance,
herbal tea or ethanol extracts, for the relief of mild symptoms of mental stress and to aid sleep is well
documented in a number of handbooks. The requirement for medicinal use of at least 30 years
(15 years within the Community) according to Directive 2004/24/EC is considered fulfilled.
A:
The daily dosage ranges from 0.5 – 8 g of herbal substance as powder.
B:
For herbal tea, a daily dosage of 1 – 8 g of herbal substance is used to make an infusion.
C:
For liquid extracts (1:8, extraction solvent 25% ethanol), the dose range 8 – 16 ml daily in divided
doses is documented.
D:
For liquid extracts (1:8, extraction solvent 45% ethanol), the dose range 2 – 6 ml daily in divided
doses is documented.
E:
For liquid extracts (1:1, extraction solvent 25% ethanol), a daily dose ranging between 0.5 and
8 ml is documented.
© EMEA 2008
3/9
F:
For liquid extracts (1:1, extraction solvent 70% ethanol), a daily dose of up to 3 times 2 ml is
documented.
Extracts prepared with acetone are included in the European Pharmacopoeia but data on traditional use
(30 years) of these extracts have neither been found in the literature, nor reported by Member States.
Methanol extracts are also included in the European Pharmacopoeia and have been authorised in
Germany since 1992. As the required 30 years of medicinal use have not elapsed, acetone and
methanol extracts cannot be included in a Community herbal monograph.
2.5
B
IBLIOGRAPHIC REVIEW OF SAFETY DATA OF THE TRADITIONAL HERBAL MEDICINAL
The following two major electronic databases were searched on 20 June 2006 with the search term
“passiflora”. Results:
PubMed: 160 references obtained.
Toxline: 37 references obtained in Toxline Core on PubMed and 68 references in Toxline Special.
Out of these references 1 case report on ventricular tachycardia was retrieved. The case concerned a
34-year old male [Fisher
et al.
, 2000]. One case of hypersensitivity vasculitis in connection with
Passiflora
extract intake has also been reported [Smith
et al.
, 1993]. No other signals of safety concern
were identified throughout these searches.
2.5.1
Patient exposure
Products containing
Passiflora incarnata
L., herba are currently available in most Member States. The
products have various regulatory statuses. A considerable patient/consumer exposure must be
anticipated although no exact figures can be given.
2.5.2
Adverse events
Hypersensitivity is possible in very rare cases [ESCOP, 2003]. One case of hypersensitivity vasculitis
has been reported [Smith
et al
., 1993].
2.5.3
Serious adverse events and deaths
One case of ventricular tachycardia accompanied by severe nausea, vomiting, drowsiness and
prolonged QT interval required hospital admission for cardiac monitoring and intravenous fluid
therapy [Fisher
et al.
, 2000]. The daily ingested dose corresponded to 1.5 g respectively 2 g crude drug
during 2 days. Causality cannot be assessed with certainty due to incomplete data.
2.5.4
Safety in special populations and situations
2.5.4.1
Intrinsic (including elderly and children)/extrinsic factors
No data available.
2.5.4.2
Drug-drug interactions and other interactions
No clinical data available.
2.5.4.3
Use in pregnancy and lactation
No data available.
2.5.4.4
No data available.
© EMEA 2008
4/9
SUBSTANCE
2.5.4.5
Drug abuse
No data available.
2.5.4.6
Withdrawal and rebound
No data available.
2.5.4.7
Effects on ability to drive or operate machinery
Theoretically, products containing
Passiflora incarnata
L., herba may cause drowsiness. The ability to
drive a car or to operate machinery may be reduced. If affected, patients should not drive nor operate
machinery [ESCOP, 2003]. Excessive doses may cause sedation [Barnes
et al.
, 1996].
2.5.4.8 Contraindications
Hypersensitivity to the active substance.
2.5.5
Non-clinical safety data
Overview of available data regarding Passiflora incarnata L., herba preparation(s)
Acute toxicity:
Extracts
: mice,
i.p
., 900 mg/kg. LD
50
: oral: >15 g/kg (mice and rats),
i.p.
: 3510 mg/kg (rats),
3140 mg/kg (mice),
s.c.
: >10 g/kg (rats), 8300 mg/kg (mice) [Committee of experts on cosmetic
products, 2001].
Maltol
: LD
50
s.c.
, mice 820 mg/kg [Hänsel
et al
., 1994],
i.p.
, mice 820 mg/kg, [Committee of experts
on cosmetic products, 2001].
Ethylmaltol
: LD
50
i.p.
, mice 910 mg/kg [Committee of experts on cosmetic products, 2001].
and relevant constituents thereof
Repeated dose toxicity:
Hydroethanolic extract, male rats, oral, 10 ml/kg body weight = 5 g/kg dried herb, 21 days, no change
in weight, rectal temperature and motor coordination (ESCOP, 2003). An oral daily dose of 600 mg/kg
for 4 weeks did not give any toxic symptoms in rats [Weniger and Anton, 1996].
Genotoxicity:
No genotoxic effects in the diploid strain
Aspergillus nidulans
D-30 of 1.30 mg/ml of a fluid extract
(16.2% dry matter, 0.32% ethanol) [ESCOP, 2003].
No information on carcinogenicity, reproductive and developmental toxicity is available.
2.5.6
Assessor’s overall conclusions on safe use
The non-clinical information indicates that the acute and repeated dose toxicity is low. As there is no
information on reproductive and developmental toxicity the use during pregnancy and lactation cannot
be recommended. Minimum required data on mutagenicity (Ames test) are not available.
Conventional clinical safety data are virtually absent. However, longstanding medicinal use and
experience of
Passiflora incarnata
L., herba has been documented within the Community. During this
time, no clear clinical signals that
Passiflora incarnata
L., herba is harmful under normal conditions of
use have been identified. As no data on use in children are available, products containing
Passiflora
incarnata
L., herba cannot be recommended for use in children below the age of 12 years.
© EMEA 2008
5/9
3
3.1
O
VERVIEW OF THE PHARMACOLOGICAL EFFECTS OF
P
ASSIFLORA INCARNATA
L.,
HERBA PREPARATIONS AND RELEVANT CONSTITUENTS THEREOF
Constituents
:
Flavonoids
, mainly
C
-glycosides of apigenin and luteolin,
e.g.
isovitexin, isoorientin and their
2"-β-
D
-glucosides, schaftoside, isoschaftoside, vicenin-2 and swertisin, with considerable variation in
qualitative and quantitative composition according to source [Hänsel
et al
., 1994; Bradley, 1992;
Wichtl, 2004; Barnes
et al.
, 1996; ESCOP, 2003; PDR for herbal medicines, 1998; Weniger and
Anton, 1996].
Maltol
which, however, may be an artefact [Hänsel
et al
., 1994; Bradley, 1992; Barnes
et al.
, 1996;
ESCOP, 2003; Weniger and Anton, 1996].
Essential oil
in trace amounts comprising more than 150 components [Hänsel
et al
., 1994; Bradley,
1992; Wichtl, 2004; Barnes
et al.
, 1996; ESCOP, 2003; PDR for herbal medicines, 1998; Weniger and
Anton, 1996].
Gynocardin
(a cyanogenic glycoside) [Hänsel
et al
., 1994; Bradley, 1992; Wichtl, 2004; ESCOP,
2003; PDR for herbal medicines, 1998; Weniger and Anton, 1996].
β-carboline alkaloids
(e.g. harman, harmol, harmalol) may be present in traces. However, these
alkaloids are undetectable in most commercial materials [Hänsel
et al
., 1994; Bradley, 1992; Wichtl,
2004; Barnes
et al
., 1996; ESCOP, 2003; PDR for herbal medicines, 1998; Weniger and Anton, 1996].
A tri-substituted benzoflavone derivative
[Dhawan
et al.
, 2004].
A number of early pharmacological studies have been reviewed by Hänsel
et al
., [1994], most of
which are said to be of poor quality. Newer studies are reviewed in the ESCOP monograph [2003],
which indicate a sedative effect in rodents of hydroethanolic extracts, including reduction of
spontaneous locomotor activity and prolongation of pentobarbital-induced sleeping time at doses of
50 – 400 mg/kg administered intraperitoneally or
per os
. The authors conclude that the available
pharmacodynamic studies generally support, with some conflicting results, the empirically
acknowledged sedative and anxiolytic effects of passion flower but it is not yet clear which
constituents are responsible for these effects.
A tri-substituted benzoflavone derivative, comprising a benzene ring fused at positions 6, 7 of a
flavone compound has recently been isolated and claimed to be the main bioactive phyto-constituent
of
Passiflora incarnata
. It exhibits significant anxiolytic activity at an oral dose of 10 mg/kg in mice.
It also causes reversal of morphine tolerance in mice (dose 10 – 100 mg/kg), prevention of nicotine
addiction in mice (10 – 20 mg/kg), prevention of Δ
9
-THC dependence and tolerance in mice (10 – 20
mg/kg) and prevention of ethanol dependence in mice (10 – 50 mg/kg). The compound was also found
to counteract dependence on benzodiazepines in mice and to increase libido in aged rats and to prevent
loss of libido induced by ethanol, Δ
9
-THC or nicotine. The authors postulate that the mechanism for
all these effects is inhibition of the enzyme aromatase (a member of the cytochrome P-450 family),
resulting in inhibition of the metabolic conversion of androgens to oestrogens thereby increasing free
testosterone and decreasing free oestrogen [Dhawan
et al.
, 2004].
Assessor’s comments on pharmacological effects of
Passiflora incarnata
L., herba
Published data on the pharmacodynamics of
Passiflora
extracts and its constituents, particularly the
tri-substituted benzoflavone derivative, give some support to the traditional use of
Passiflora
for the
relief of mild symptoms of mental stress and to aid sleep. The chemical structure of the benzoflavone
derivative does not appear to be known and the amounts of substance present in the herbal
substance/preparations have not been reported in the literature. No data from direct studies of
inhibition of the enzyme aromatase have been found in the literature.
© EMEA 2008
6/9
preparations and relevant constituents thereof
In summary, the doses employed in the animal experiments seem high compared to the doses of
Passiflora
/benzoflavone derivative that humans are exposed to during use of herbal medicinal
products containing
Passiflora
. The mechanism of action cannot, at present, be regarded as clarified.
3.2
C
LINICAL STUDIES
Four clinical studies have been identified in the literature.
In one small pharmacological screening study (12 healthy female volunteers), the effect of a passion
flower extract (1.2 g) was compared with that of placebo and diazepam (10 mg). Alertness was rated
by the subjects on a VAS scale after receiving the medication and after challenge with 100 mg of
caffeine. Diazepam and, to an apparent lesser degree, placebo and passion flower extract, all decreased
mental alertness. The effects of the passion flower extract on qualitative EEG signals could not be
distinguished from placebo [Schulz
et al.
, 1998].
The effect of an extract (45 drops/day) of passion flower on patients with general anxiety was
compared with the effect of oxazepam (30 mg/day) in a study during 28 days. Eighteen patients were
treated with passion flower extract and 18 with oxazepam. Patients were assessed by a psychiatrist at
baseline and days 4, 7, 17, 21 and 28 after the medication started. The score on the Hamilton anxiety
rating scale was the same for both groups on days 0, 21 and 28. The authors concluded that the extract
was equally effective as oxazepam [Akhondzadeh
et al
., 2001a].
Another study by Akhodzadeh
et al
., [2001b] comprised 65 opiate addicts undergoing withdrawal.
Treatment was 60 drops of an extract of passion flower + 0.8 mg of clonidine or placebo + the same
dose of clonidine for 14 days. Both treatments were equally effective with regard to the physical
symptoms of withdrawal. However, the combination of passion flower and clonidine was superior to
clonidine alone with respect to psychological symptoms.
In a randomized, double-blind study in 34 children (between 6 and 13 years of age) recently diagnosed
with ADHD, the efficacy of passion flower tablets was compared with methylphenidate
[Akhondzadeh
et al
., 2005]. Seventeen children were treated with passion flower tablets (0.04
mg/kg/day) for 8 weeks. A control group of 17 children received methylphenidate (1 mg/kg/day). The
primary efficacy parameter was outcome on a parent and teacher ADHD rating scale that has been
extensively used in Iran in school-age children. Both groups improved significantly over the 8 weeks
trial compared to the baseline value. There was no statistically significant difference in treatment
result between the two groups. No placebo group was employed.
3.2.1
Assessor’s comments on the clinical studies
In the first study in 12 healthy volunteers [Schulz
et al.
, 1998], the effect of passion flower could not
be distinguished from that of placebo. No statistical evaluation of the results was performed.
In the second study [Akhondzadeh
et al
., 2001a], major deficiencies in methodology include that the
type of herbal preparation and details of the posology are unclear. Concerning the design of the study,
the number of patients involved (18 treated with passion flower) is too small to provide robust
information. No placebo group was used, but the patients visited a psychiatrist 6 times during the
28 days trial. It appears very reasonable to assume that this extensive contact with a doctor may in
itself have a beneficial effect on patients with general anxiety. In the absence of a placebo group, the
intrinsic effect of the medication cannot be assessed. The trial has been discussed in the literature, and
it has been pointed out that the study was not designed as an equivalence study and conclusions about
efficacy cannot be drawn [Ernst, 2006]. This study does not give conclusive evidence of efficacy of
passion flower extract for treatment of anxiety, but as a pilot study it may be seen as supportive of the
traditional use to relieve mild symptoms of mental stress.
The third study [Akhondzadeh
et al
., 2001b] is a report of the use of passion flower as an adjuvant to
clonidine in the treatment of opiate withdrawal symptoms in opiate addicts. The type of herbal
preparation was not reported. The indication and study population used in this study cannot be
considered relevant for evaluation of the traditional use of passion flower. This is the first report of the
© EMEA 2008
7/9
use of passion flower in the treatment of opiate withdrawal symptoms. Medicinal use of passion
flower in this indication cannot be recognised as well-established nor as traditional in the Community.
In the fourth study [Akhondzadeh
et al
., 2005] the efficacy of passion flower was compared to
metylphenidate in children with ADHD. The type of herbal preparation was not reported, but
apparently the dose (0.04 mg/kg/day) is several orders of magnitude lower than the doses used in
traditional European phytotherapy (approximately 10 - 100 mg/kg/day; 70 kg body weight assumed).
There are a number of limitations of the study, which the authors themselves point out. These include
e.g. the lack of placebo group and the small number of patients involved. The trial must be considered
as a pilot study. This is the first report of the use of passion flower in the treatment of ADHD.
Medicinal use of passion flower in this indication cannot be recognised as well-established/traditional
in the Community.
3.2.2
Assessors overall conclusions on results of clinical studies
Only 4 small clinical studies have been retrieved from literature. They all suffer from serious
deficiencies from efficacy point of view such as too small number of patients involved, lack of
adequate statistical design/treatment of the results, undefined testing medication or therapeutic
indications of doubtful relevance to the traditional medicinal use. The clinical data cannot be
considered to fulfil the criteria required for “well-established medicinal use” according to Directive
2001/83/EC as amended.
4
ASSESSOR’S OVERALL CONCLUSIONS
Traditional medicinal use of
Passiflora incarnata
L., herba for the relief of mild symptoms of mental
stress and to aid sleep has been documented in a number of recognised handbooks. Products
containing
Passiflora incarnata
L., herba are currently available in most Member States. The
requirement for medicinal use of at least 30 years (15 years within the Community) according to
Directive 2001/83/EC as amended is considered fulfilled. Many of the products commercially
available are combination products with other herbal substances/preparations.
The non-clinical information indicates that the acute and repeated dose toxicity is low. Information on
genotoxicity, carcinogenicity, reproductive and developmental toxicity is lacking. Use during
pregnancy and lactation can thus not be recommended.
Insufficient data on use in children are available therefore products containing
Passiflora incarnata
L.,
herba are not recommended for use in children below the age of 12 years.
Conventional clinical safety data are virtually absent, however, longstanding medicinal use and
experience of
Passiflora incarnata
L., herba have been documented within the Community. No
clinical signals that
Passiflora incarnata
L., herba is harmful under normal conditions of use have
been identified.
In view of the empirically acknowledged sedative properties of
Passiflora incarnata
L., herba a
warning for use in connection with driving of cars and operation of machinery is advisable.
Only 4 clinical studies have been reported in the literature. Major methodological deficiencies have
been identified in the trials. The data available are insufficient to document clinical efficacy as
required for products with “well-established medicinal use” according to Directive 2001/83/EC as
amended. Together with available pharmacodynamic studies in animals, however, they do support the
traditional use of
Passiflora incarnata
L., herba, for the relief of mild symptoms of mental stress and
to aid sleep, which altogether may be considered plausible.
Sufficient data to develop a Community herbal monograph on the traditional use of
Passiflora
incarnata
L., herba are available. As the minimum required data on mutagenicity (Ames test) are not
© EMEA 2008
8/9
available, an inclusion to the Community list of traditional herbal substances, preparations and
combinations thereof for use in traditional herbal medicinal producs is not recommended.
© EMEA 2008
9/9
Source: European Medicines Agency
- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.
https://theodora.com/drugs/eu/passiflorae_herba_herbal.html
Copyright © 1995-2021 ITA all rights reserved.