COMMUNITY HERBAL MONOGRAPH ON
PLANTAGO AFRA
L. ET
PLANTAGO INDICA
L., SEMEN
To be specified for the individual finished product.
Traditional use
With regard to the marketing authorisation
application of Article 10a of Directive
2001/83/EC as amended
With regard to the registration application of
Article 16d(1) of Directive 2001/83/EC as
amended
Plantago afra
L. (
Plantago psyllium
L.) or
Plantago indica
L. (
Plantago arenaria
Waldstein
and Kitaibel), semen (psyllium seed)
•
Herbal substance
- ripe, whole, dry seeds
•
Herbal preparation
- powdered herbal substance
Traditional use
Herbal substance or herbal preparation in solid
dosage forms such as granules or powders for oral
use.
The pharmaceutical form should be described by
the European Pharmacopeia full standard term.
4.1.
Therapeutic indications
Well-established use
Traditional use
Herbal medicinal product
a)
for the treatment of habitual constipation;
b)
in conditions in which easy defaecation with
soft stool is desirable, e.g. in cases of painful
defaecation after rectal or anal surgery, anal
fissures or haemorrhoids.
1
The material complies with the Ph. Eur. monograph.
2
The declaration of the active substance(s) should be in accordance with relevant herbal quality guidance.
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4.2.
Posology and method of administration
Well-established use
Traditional use
Posology
Oral use
Adolescents over 12 years of age, adults, elderly
25 - 40 g herbal substance or corresponding
amount of herbal preparation
(daily dose) in 3
single doses
Children from 6 to 12 years of age
Half to two-thirds of the adult dose (12 - 25 g
herbal substance or corresponding amount of
herbal preparation, daily dose) in 3 single doses
Method of administration
Mix approximately x g of the [pharmaceutical
form] (amount corresponding to 1 g herbal
substance) with at least 30 ml of water, milk, fruit
juice or similar aqueous liquid; stir briskly and
swallow as quickly as possible. Alternatively the
herbal substance can be taken and swallowed with
sufficient quantity (at least 30 ml per g of herbal
substance) of water, milk, fruit juice or similar
aqueous liquid; then maintain adequate fluid
intake. The product should be taken during the day
at least ½ to 1 hour before or after intake of other
medicines. The effect starts 12 - 24 hours later.
Warning: Not to be taken immediately prior to
bed-time.
Duration of use
If the constipation does not resolve within 3 days,
a doctor or a pharmacist should be consulted.
See also section 4.4 Special warnings and
precautions for use.
4.3.
Contraindications
Well-established use
Traditional use
Psyllium seed should not be used by patients with
a sudden change in bowel habit that persists for
more than 2 weeks, undiagnosed
rectal bleeding
and failure to defaecate following the use of a
laxative.
Psyllium seed should also not be used by patients
suffering from abnormal constrictions in the
gastro-intestinal tract, with diseases of the
oesophagus and cardia, potential or existing
intestinal blockage (ileus), paralysis of the
intestine, or megacolon, diabetes mellitus, which
is difficult to regulate.
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This product should not be taken by patients, who
have difficulty in swallowing or any throat
problems.
Patients with known hypersensitivity to the active
substance should not use psyllium seed and its
preparations.
4.4.
Special warnings and precautions for use
Well-established use
Traditional use
As there is insufficient experience available, use is
not recommended in children below the age of
6 years. Laxative bulk producers should be used
before using other purgatives if change of nutrition
is not successful.
Psyllium seed should not be used by patients with
faecal impaction and symptoms such as abdominal
pain, nausea and vomiting unless advised by a
doctor because these symptoms can be signs of
potential or existing intestinal blockage (ileus).
If abdominal pain occurs or in cases of any
irregularity of faeces, the use of psyllium seed
should be discontinued and medical advice must
be sought.
A sufficient amount of liquid should always be
taken e.g. 30 ml of water per 1 g of herbal
substance.
In the package leaflet, the patient is informed
about the following warning:
Warning
Take each single dose of this product with at least
x ml (x is to be replaced by the amount which
corresponds to 30 ml per 1 g of the herbal
substance or corresponding amount of the herbal
preparation) of water or similar aqueous fluid.
Taking this product without adequate fluid may
cause it to swell and block your throat or
oesophagus and may cause choking. Intestinal
obstruction may occur if adequate fluid intake is
not maintained. If you experience chest pain,
vomiting, or difficulty in swallowing or breathing
after taking this product, seek immediate medical
attention. The treatment of debilitated patients
requires medical supervision. The treatment of
elderly patients should be supervised.
4.5.
Interaction with other medicinal products and other forms of interaction
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Well-established use
Traditional use
Enteral absorption of concomitantly administered
medicines such as minerals, vitamins (B 12),
cardiac glycosides, coumarin derivatives,
carbamazepine and lithium may be delayed. For
this reason the product should not be taken ½ to 1
hour before or after intake of other medicinal
products.
If the product is taken together with meals by
insulin dependent diabetic patients it may be
necessary to reduce the insulin dose.
Use of psyllium seed concomitantly with thyroid
hormones requires medical supervision because
the dose of the thyroid hormones may have to be
adjusted.
In order to decrease the risk of gastrointestinal
obstruction (ileus) psyllium seed should be used
together with medicinal products known to inhibit
peristaltic movement (e.g. opioids, loperamide)
only under medical supervision.
4.6.
Pregnancy and lactation
Well-established use
Traditional use
No restriction.
Laxative bulk producers should be used before
using other purgatives if change of nutrition is not
successful.
4.7.
Effects on ability to drive and use machines
Well-established use
Traditional use
Not relevant.
4.8.
Undesirable effects
Well-established use
Traditional use
Flatulence may occur with the use of the product,
this generally disappears in the course of the
treatment. Abdominal distension and risk of
intestinal or oesophageal obstruction and faecal
impaction may occur, particularly if swallowed
with insufficient fluid.
Due to the allergic potential of psyllium, patients
must be aware of reactions of hypersensitivity
including very rare anaphylaxis-like reactions.
If other adverse reactions not mentioned above
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occur, a doctor or a pharmacist should be
consulted.
Well-established use
Traditional use
Overdose with psyllium seed may cause
abdominal discomfort, flatulence and possibly
intestinal obstruction. Adequate fluid intake
should be maintained and management should be
symptomatic.
5.1.
Pharmacodynamic properties
Well-established use
Traditional use
Pharmacotherapeutic group: Laxatives – Bulk
Producers
ATC-Code: A 06 AC
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
Specific data on psyllium are not available but the
mode of action seems to be similar for all laxative
bulk producers.
The active ingredient in psyllium seed consists of
the ripe, whole, dry seeds of
Plantago afra
L
.
(Plantago psyllium
L
.)
or
Plantago indica
L.
(
Plantago arenaria
Waldstein and Kitaibel).
Psyllium seed is particularly rich in alimentary
fibres and mucilages. Psyllium seed is capable of
absorbing up to 10 times its own weight in water.
Psyllium seed consists of 10 - 12% mucilage
polysaccharides, which are located in the
episperms. It is partly fermentable (
in vitro
72%
unfermentable residue) and acts by hydration in
the bowel. Gut motility and transit rate can be
modified by psyllium through mechanical
stimulation of the gut wall as a result of the
increase in intestinal bulk by water and the
decrease in viscosity of the luminal contents or by
contact with rough fibre particles. When taken
with a sufficient amount of liquid (at least 30 ml
per 1 g of herbal substance) psyllium produces an
increased volume of intestinal contents due to its
highly bulking properties and hence a stretch
stimulus, which triggers defaecation; at the same
time the swollen mass of mucilage forms a
lubricating layer, which makes the transit of
3
Scientific data available do not always differentiate the investigated preparations exactly whether the
investigated herbal substance was ispaghula husk or seed or psyllium seed and often indicate "psyllium" as
investigated herbal substance. If a differentiation was not possible the term "psyllium" is used.
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intestinal contents easier.
Progress of action
: Psyllium seed usually acts
within 12 to 24 hours after single administration.
Sometimes the maximum effect is reached after 2
to 3 days.
5.2.
Pharmacokinetic properties
Well-established use
Traditional use
The material hydrates and swells to form a
mucilage because it is only partially solubilised.
Polysaccharides, such as those which dietary
fibres are made of, must be hydrolysed to
monosaccharides before intestinal uptake can
occur. The sugar residues of the xylan backbone
and the side chains of psyllium are joined by ß-
linkages, which cannot be broken by human
digestive enzymes.
Less than 10 % of the mucilage gets hydrolysed in
the stomach, with formation of free arabinose.
Intestinal absorption of the free arabinose is
approximately 85
% to 93 %.
To varying degrees, dietary fibre is fermented by
bacteria in the colon, resulting in production of
carbon dioxide, hydrogen, methane, water, and
short-chain fatty acids, which are absorbed and
brought into the hepatic circulation. In humans,
psyllium reaches the large bowel in a highly
polymerised form that is fermented to a limited
extent, resulting in increased faecal concentration
and excretion of short-chain fatty acids.
Not required as per Article 16c(1)(a)(iii) of
Directive 2001/83/EC as amended.
5.3.
Preclinical safety data
Well-established use
There are only data for ispaghula husk and
psyllium without defining the exact test
preparation available.
Single dose toxicity
The LD50 in rats was greater than the highest dose
tested corresponding to 3,360 mg/kg ispaghula
husk administered by gavage of an aqueous
suspension. The LD50 in mice was greater than
the highest dose tested corresponding to
2,940 mg/kg ispaghula husk also administered by
gavage of an aqueous suspension. These studies
were conducted prior to the establishment of good
laboratory practices.
Subchronic toxicity
Psyllium was fed to rats at levels high as 10 % of
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.
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the diet for periods up to 13 weeks (three 28-day
studies, one 13-week study). Psyllium
consumption ranged from 3,876 to
11,809 mg/kg/day. Because the absorption of
psyllium is very limited, histopathological
evaluations were limited to the gastrointestinal
tract, liver, kidneys and gross lesions without
observing any treatment-related effect. Effects
considered to be biologically significant and
related to psyllium supplementation were lower
serum total protein, albumin, globulin, total iron-
binding capacity, calcium, potassium, and
cholesterol; and higher aspartate transaminase
(AST) and alanine transaminase (ALT) activities
relative to control. Several of these effects are
considered to be secondary effects to others. The
reasons for the lower serum total protein, albumin
and globulin are not clear, but the absence of any
increases in urinary protein, any evidence of
gastrointestinal pathology, which could account
for protein loss, and any differences in growth or
feed efficiency in psyllium fed rats may give
evidence that there are no adverse effect of
psyllium on protein metabolism.
Reproductive toxicity
A rat multigeneration reproduction/teratology
study showed no evidence of any adverse effects
of psyllium on reproduction or development.
Psyllium as 0, 1.25, or 5% (w/w) of the diet was
administered in a standard (NIH-07) rat and mouse
meal diet
ad libitum
through gestation of the third
generation.
A segment II study in rabbits also showed no
evidence of any adverse effect. Psyllium as 0, 2.5,
5 or 10% (w/w) of diet was administered in a
purine certified rabbit chow diet for days 2 - 20 of
gestation.
Genotoxicicity and carcinogenicity
Tests on genotoxicity and carcinogenicity have not
been performed.
Well-established use
Traditional use
Not applicable.
26 October 2006
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Assessment Report
T
ABLE OF CONTENTS
I.
Introduction
3
II. Clinical Pharmacology
3
II.1 Pharmacokinetics
3
II.2 Pharmacodynamics
II.2.1 Mode of action
4
II.2.2 Interactions
5
III. Clinical Efficacy
6
III.2 Clinical studies
6
III.2.1 Laxative effect
6
III.2.2 Effect on blood lipids levels
7
III.3 Clinical studies in special populations
7
III.3.1 Use in children
7
III.3.2 Use during pregnancy and lactation
7
III.4 Traditional use
8
I.1 Preclinical Safety
8
I.2 Clinical Safety
8
IV.2.1 Undesirable effects
8
IV.2.2 Contraindications
9
IV.2.3 Special warnings and precautions for use
9
IV.2.4 Interactions with other medicinal products and other forms of
interactions
9
V. Overall conclusions
9
Community herbal monograph
annex
References
annex
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4
III.1 Dosage
6
I. Safety
8
I.
Introduction
This assessment report reviews the scientific data available for psyllium seed (
Plantago afra
L. et
Plantago indica
L., semen), primarily the clinical data. This report was prepared on the basis of the
assessment report of ispaghula husk and ispaghula seed because available scientific data do not always
differentiate precisely the investigated preparations i.e. whether the investigated herbal substance was
ispaghula husk, ispaghula seed or psyllium seed and often indicate “psyllium” as the investigated
herbal substance. If a differentiation was not possible, use was made of the term “psyllium”. In the
more recent investigations ispaghula husk was used predominantly. When ‘Plantago psyllium’ is
mentioned, it is not sure whether the investigated herbal substance is
Plantago psyllium
or
Plantago
ovata
.
The literature presented by the European Scientific Cooperative on Phytotherapy (ESCOP) and
supporting the monograph “Psyllii Semen” (Psyllium seed) (ESCOP Monographs, second edition
2003) was also taken into account.
Constipation is a common complaint in 1 – 6% of the middle-aged population and 20 – 80 % of the
elderly people, and may be treated by laxatives. Functional constipation is the most common type
without any specific etiology (1). The most commonly used laxatives are either stimulant laxatives
(containing anthracenic derivatives from senna, frangula or cascara), lubricant laxatives (e.g. mineral
oils) or bulk forming agents such as ispaghula husk and psyllium seed.
Psyllium seed is a natural substance and belongs to the bulk forming agents. It is used:
a)
for the treatment of habitual constipation,
b)
in conditions in which easy defaecation with soft stool is desirable, e.g. in cases of painful
defaecation after rectal or anal surgery, anal fissures and haemorrhoids.
These indications are scientifically substantiated by the pharmacological effects of psyllium seed.
Preparations of psyllium seed have to be regarded as herbal medicinal products with a “well-
established medicinal use” with respect to the application of Directive 2001/83/EC of the Parliament
and of the Council on the Community code relating to medicinal products for human use as amended.
II.
ClinicalPharmacology
II.1 Pharmacokinetics
Please refer to the assessment report on ispaghula husk.
Psyllium seed consists of the ripe, whole, dry seeds of
Plantago afra
L. (
Plantago psyllium
L.) or
Plantago indica
L. (
Plantago arenaria
Waldstein and Kitaibel). The herbal subtance has to comply
with the monograph “Psyllium Seed” of the European Pharmacopoeia (ref. 01/2005:0858).
Psyllium seed only contains approximately 10 – 12 % mucilage polysaccharides (2, 3) in the
epidermis, consisting of xylose, galacturonic acid, arabinose and rhamnose residues (4). These
ingredients suggest that the mucilage polysaccharides are similiarly structured as in Plantago ovata.
But the fraction of galacturonic acid and rhamnose is twice as high as in ispaghula husk. Psyllium seed
does not contain starch as ispaghula seed does.
Conclusion
The pharmacokinetics of psyllium are essentially those of an inert unabsorbed substance, with only
small amounts of monosaccharides becoming available for systemic absorption through limited
digestion of the few available α-linkages and fermentation by colonic bacteria.
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II.2
Pharmacodynamics
II.2.1 Mode of action
•
Laxative effect
The active ingredients are the mucilages like in ispaghula husk and seed. The European
Pharmacopoeia monograph requests that the swelling index should be ‘not less than 10’. High-quality
psyllium seeds are capable of absorbing 14 to 19 times their own weight of water (2, 3).
The mode of action seems to be similiar to that of ispaghula husk and seed. Psyllium seed increases
the volume of intestinal contents by binding fluid, resulting in increased faecal weights and decreased
viscosity of the luminal contents. This leads to a physical stimulation of the gut. The intraluminal
pressure is decreased and colonic transit is accelerated. At the same time the swollen mass of mucilage
forms a lubricating layer, which eases the transit of intestinal contents.
•
Effect on diarrhoea
There are no specific data available for psyllium seed.
•
Effect on blood lipids levels
There are no specific pharmacological data available for psyllium seed.
•
Effect on blood glucose levels
Psyllium seed may influence the glucose metabolism in the same way as ispaghula husk and seed do.
Due to delayed intestinal absorption of carbohydrates, the glucose metabolism is influenced by the
reduction of peak levels of blood glucose.
Frati-Munari AC
et al.
1985
(5) performed three oral glucose tolerance tests in eight healthy
volunteers as follows: I) glucose alone (control test), II) glucose mixed with 10 g of powder of
“Plantago psyllium mucilage”, and III) 10 g of mucilage were given 30 minutes before glucose. In the
test with mucilage mixed with glucose, significant (p<0.05) lower peak of serum glucose and insulin
were observed. Blood glucose was 20.5 +/- 22.1 mg/dl (1.13 +/- 1.22 mmol/l) lower at 60 minutes
than control test, blood glucose was also lower 9.2 +/- 14.2 mg/dl (0.51 +/- 0.78 mmol/l) at 120
minutes in the same test, but did not reach statistically significance (p>0.05). Serum insulin values had
a parallel course with glucose. Previous ingestion of the mucilage did not modify basal nor subsequent
glucose values.
Frati-Munari AC
et al.
1989
(6) assessed the effect of different doses of “Plantago psyllium
mucilage” on glucose tolerance test. Four oral glucose tolerance tests were performed in eight healthy
volunteers. Glucose load (75 g) was mixed with 0 (control test), 10, 20 and 30 g of mucilage. Serum
glucose levels were measured at 0, 30, 60, 120 and 180 minutes. Maximum peak of glucose at 30
minutes, and the area under curve of glucose were significantly lower in the test with 20 and 30 g of
mucilage than in the tests with 0 and 10 g. Blood glucose after additional ingestion of 20 g of mucilage
was 11.8 +/- 14.3 mg/dl lower at 30 minutes than after ingestion of 10 g and 14.3 mg/dl +/- 16 mg/dl
lower at 60 minutes (p<0.05). Blood glucose after additional ingestion of 30 g of mucilage was 6.1 +/-
5.3 mg/dl lower at 30 minutes than after ingestion of 20g and 18 +/- 15.4 mg/dl lower at 30 minutes
and 15 mg/dl +/- 17.1 mg/dl lower at 60 minutes than after ingestion of 10 g (p<0.01). There was a
significant relationship (r = 0.44, p<0.025) between the dose of “Plantago psyllium mucilage” and its
attenuating effect of hyperglycaemia.
Frati-Munari AC et al. 1998
(7) evaluated the effect of acarbose and “Plantago psyllium mucilage”
on glycaemic index (GI) of bread. Twelve patients with non-insulin-dependent diabetes mellitus
(NIDDM) and ten healthy volunteers were studied. Three meal tests with an intake of 90 g white bread
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(50 g of carbohydrates) were performed on each subject. In one test, 200 mg of acarbose was given,
while 15 g of Plantago psyllium mucilage was given in another test, and only bread was ingested in
the control test. Serum glucose and insulin concentrations were measured every 30 min from 0-180
min. Net area under curve (AUC) concentrations of glucose and insulin, GI (AUC glucose with bread
plus treatment / AUC glucose with bread alone x 100) and insulin index (AUC insulin with bread plus
treatment / AUC insulin with bread alone x 100) were calculated. In NIDDM patients, AUC glucose in
the test with acarbose (1.9 +/- 0.7 mmol/L) and with Plantago psyllium (4.3 +/- 1.2 mmol/L) were
significantly lower than in the control test (7.4 +/- 1.5 mmol/L) (p<0.01). GI of bread plus acarbose
was 26 +/- 13, and of bread with Plantago psyllium, 59 +/- 10 (p<0.05). AUC insulin and insulinic
index behave similiarly. In healthy individuals, AUC glucose and GI did not significantly change with
the treatments; however, insulinic index with acarbose was 17 +/- 16 and with Plantago psyllium was
68 +/- 15 (p<0.05). The authors concluded that adding acarbose or Plantago psyllium to meals may
reduce glycaemic index of carbohydrate foods and may help diabetic control.
In another publication (8)
Frati-Munari AC
investigated Metamucil®, which he also defined as
Plantago psyllium mucilage.
It is therefore not sure if the above-mentioned investigations are performed with ispaghula husk or
psyllium seed.
II.2.2 Interactions
Because of their pharmacodynamic properties, all bulk forming laxatives may delay the enteral
absorption of concomitantly administered medications. Psyllium seed should therefore be taken at
least ½ to 1 hour before or after intake of other medicinal products.
There are no specific data on interactions between psyllium seed and other medicinal products.
Because of the similiar structure of the active ingredients of psyllium seed to that of ispaghula seed
and husk, it is assumed that psyllium seed interacts with the same medicinal products as ispaghula
husk. Resulting from the assessment of data on interactions available for ispaghula husk, the following
information should be included in the product information of psyllium seed containing medicinal
products:
- Enteral absorption of concomitantly administered medicines such as minerals (e.g lithium), vitamins
(B 12), cardiac glycosides, coumarin derivates, and carbamazepine may be delayed. For this reason
the product should not be taken ½ to 1 hour before or after intake of other medicinal products.
- If the product is taken together with meals in the case of insulin dependent diabetics it may be
necessary to reduce the insulin dose.
- Use of psyllium seed concomitantly with thyroid hormones requires medical supervision because the
dose of the thyroid hormones may have to be adjusted.
- In order to decrease the risk of gastrointestinal obstruction (ileus) psyllium seed should only be used
together with medicinal products known to inhibit the peristaltic movement (e.g. opioids,
loperamide) under medical supervision.
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III.
Clinical Efficacy
III.1 Dosage
There are no dose-finding studies available.
As a laxative for adults, elderly and children over 12 years of age, experts (9) recommend 10 – 30 g
daily in 1 – 3 single doses.
Considering that there are no clinical data indicating a definite daily dose, that psyllium seed has
nearly 25 % to 45 % of the water-binding capacity of ispaghula husk (see above) and that the
recommended dosage for ispaghula husk is 7 – 11 g in 1 – 3 single doses daily, this recommendation
seems to be too low and has to be increased. The Committee on Herbal Medicinal Products (HMPC)
therefore recommends a range of 25 – 40 g herbal substance or corresponding amount of herbal
preparation as a daily dose and it should be taken in 3 single doses because the amount of the fluid
administered with a single dose is otherwise too high.
III.2 Clinical studies
III.2.1 Laxative effect
Numerous clinical practice summaries, dating back to as early as 1935, recommended the use of fibre
supplementation for the management and treatment of chronic constipation. Between 1976 and the
present, numerous studies involving over 900 patients have been published; they evaluated the effects
of psyllium intake on symptoms of constipation in a population specifically identified as “chronically
constipated” and meeting the definition of less than three bowel movements per week for more than
3 months.
These studies were predominantly carried out with ispaghula husk; in other cases the investigated
herbal substance was not exactly defined.
These studies are described in the assessment report on ispaghula husk.
Weis M 1996
(10) administered a preparation made from “Plantago psyllium” to 63 patients suffering
from chronic functional constipation for a period of 20 days. The tolerance of the preparation was
satisfactory in 55 patients (87%), including 49 (89 %), who reported a favourable effect, i.e. problem-
free defaecation and regression or disappearance of meteorism. A statistically significant decline of
serum cholesterol occurred. In 14 patients (25%) a weight loss of more than 1 kg was observed. With
regard to these facts, the author concluded that the preparation can be considered suitable for the
treatment and probably also the prevention of chronic functional constipation and as an adjuvant in the
treatment of hyperlipoproteinaemia type II, in particular when associated with obesity.
Conclusion
The use of psyllium seed as a laxative is mainly based on experts’ testimony and scientifically
substantiated by the pharmacological data on ispaghula whose structure of mucilages may be similiar
to the structure of the mucilages of psyllium seed. The above-mentioned investigation is an
uncontrolled study and the information provided is too limited to decide if the study was well-
designed or not. Because of the different amount and swelling index, a higher dosage for psyllium
seed than that of ispaghula is required as explained above.
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III.2.2 Effect on blood lipids levels
As already mentioned above,
Weis M 1996
(10) detected a statistically significant decline of serum
cholesterol in his uncontrolled investigation.
Conclusion
The clinical data are insufficient to mention a specific indication.
The clinical data available for ispaghula husk and mentioned in the assessment report on ispaghula
husk cannot be extrapolated to psyllium seed because the exact mechanism of action and the involved
active ingredient are still unknown.
III.3 Clinical studies in special populations
III.3.1 Use in children
There are numerous publications, which indicate that the potential health benefits of increased dietary
fibre in childhood outweigh the potential risks, especially in highly industrialised countries (11). A
review of the scientific literature by
Williams CL
et al.
1995
(12) suggests that a small loss of energy,
protein, and fat may occur with a high intake of dietary fibre but that a moderate increase in dietary
fibre is more likely to be helpful than harmful, especially in children with constipation (13). According
to the recommendations from a conference on dietary fibre in childhood, children older than 2 years of
age should increase their daily intake of dietary fibre (increased consumption of a variety of fruits,
vegetables, cereal and other grain product) to an amount equal or greater than their age plus 5 g (e.g.
8 g/day at age 3) (11).
Conclusion
Considering these remarks, laxative bulk producers should be used before using other purgatives in
children, if change of nutrition is not successful. As a general precaution and because clinical data are
lacking, use is not recommended in children below the age of 6 years.
In “Kinderdosierungen von Phytopharmaka” (14), doses for children are calculated on the basis of the
body weight, body height and the body surface and the daily dose for adults (10 to 30 g) indicated in
the German monograph of the Commission E (9). The daily dose for children between 4 – 10 years of
age ranges from 3.7 g to 15.2 g and for children between 10 – 16 years of age from 6.8 to 23.3 g. This
is in line with general recommendations that posology for children from 6 to 12 years of age
corresponds to half to two-thirds of the adult dose.
Given that the recommended dosage for adults has to be marked up (see chapter III.1 Dosage) because
of the swelling index of psyllium seed in comparison to that of ispaghula husk, the recommended
dosage for children is increased as well for the same reason.
The daily dose for children from 6 to 12 years of years recommended by the HMPC is therefore 12 –
25 g herbal substance or corresponding amount of herbal preparation, in 3 single doses.
III.3.2 Use during pregnancy and lactation
There are no recent data available available for the use of ispaghula seed during pregnancy and
lactation.
Bishop C 1978
(15) concluded that bulk-forming laxatives appear to be safe and effective in
pregnancy. The author referred to 2 studies which compared bulk-forming laxatives to irritant
laxatives in antenatal women (see below).
Greenhalf JO et al. 1973
(16) stated that constipation was corrected in a higher percentage of patients
using irritant laxatives but normalisation of bowel habit was similiar (statistically) in all groups (an
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irritant, an emollient/irritant combination, a bulk forming/mild irritant combination, and a bulk
forming agent). The side effects were higher in the irritant group than the bulk forming group.
Fianu S
et al.
1975
(100) compared psyllium hydrophilic mucilloid (ViSiblin®) with irritant laxatives
in 199 pregnant women (plus control patients) and observed no significant differences between irritant
laxatives and psyllium. Psyllium when given to the mothers appeared to have had no effect on the
defaecation of their new-born infants.
Conclusion
The following advice that “Laxative bulk producers should be used before using other purgatives if
change of nutrition is not successful” should appear if the section ‘Pregnancy and lactation’ of the
product information of psyllium seed containing products. Medicinal products should be avoided
during pregnancy and lactation if possible; caution is recommended when administered.
III.4 Traditional use
Please refer to corresponding chapter of the the assessment report on ispaghula husk.
The use of
Plantago psyllium
,
Plantago ovata
and other kinds of Plantago in traditional medicine is
similiar to the use of linseed, but such traditional use is not described as well and so consistently.
Furthermore, no precise posology is mentioned.
None of the uses can therefore be accepted for inclusion in the ‘Community list of herbal substances,
preparations and combinations thereof for use in traditional herbal medicinal products’.
IV.
Safety
IV.1. Preclinical Safety
Please refer to the corresponding chapter of the assessment report on ispaghula husk.
There are only unpublished data available concerning ispaghula husk and psyllium without an exact
definition of the test preparation.
IV.2 Clinical Safety
MacKay EM at al. 1933
(17) reported that, after 125 days on a diet containing 25 % of psyllium seed,
albino rats showed a dark pigmentation of the suprarenal gland, the kidney marrow and the liver. Dogs
showed a grey colour of the kidneys after being fed a diet containing 25% of psyllium seed for 30
days. Similiar effects have not been observed in humans (18). The pigment probably originates from
the black pericarp of
Plantago afra
. When the seeds were extracted with hot water and then fed to the
animals as whole seeds, no pigmentation was observed (17).
In addition, please refer to the assessment report of ispaghula husk.
IV.2.1 Undesirable effects
Flatulence may occur with the use of psyllium seed.
Because
Plantago psyllium
and
Plantago ovata
belong to the same plant family, it is assumed that
Plantago psyllium
also contains allergens. Exposure to these allergens is possible through the oral
route or through contact. Psyllium seed should be considered as a possible cause of anaphylaxis from
laxatives. Reactions of hypersensitivity including anaphylaxis-like reactions may occur very rarely.
Psyllium seed is not to be used by patients with known hypersensitivity to psyllium.
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IV.2.2 Contraindications
Pharmacological data suggest that psyllium seed, like ispaghula husk, lowers peak blood glucose
levels due to delayed intestinal absorption of carbohydrates (see II.2.1 Mode of action). Cases of
diabetes mellitus where insulin adjustment is difficult constitute therefore a contraindication to the
administration of psyllium seed preparations. The following should appear in the product information
of such preparations:
Psyllium seed should not be used by patients with diabetes mellitus, which is difficult to regulate.
Furthermore it may be necessary to reduce the insulin dose, as mentioned under II.2. Interactions, if
the product is taken together with meals by insulin dependent diabetic patients.
Psyllium seed is a bulk forming agent and several other contraindications for this kind of agents must
be respected:
Psyllium seed should not be used by patients with a sudden change in bowel habit that persists for
more than 2 weeks, undiagnosed rectal bleeding and failure to defaecate following the use of a
laxative. Psyllium seed should also not be used by patients suffering from abnormal constrictions in
the gastro-intestinal tract, with diseases of the esophagus and cardia, potential or existing intestinal
blockage (ileus), paralysis of the intestine, or megacolon.
Psyllium seed preparations should not be taken by patients, who have difficulty in swallowing or
who have any throat problems.
Psyllium seed should finally not be used by patients with known hypersensitivity to psyllium.
IV.2.3 Special warnings and precautions for use
There are several warnings to be included in the product information of psyllium seed containing
medicinal products:
Psyllium seed should not be used by patients with faecal impaction and symptoms such as
abdominal pain, nausea and vomiting unless advised by a doctor because these symptoms can be
signs of potential or existing intestinal blockage (ileus).
Furthermore the following advice should be given:
If the constipation does not resolve within 72 hours or if abdominal pain occurs or in case of any
irregularity of faeces, the use of psyllium seed should be discontinued and medical advice must be
sought.
Special warnings for bulk forming agents must be included, too.
IV.2.4 Interactions with other medicinal products and other forms of interactions
See chapter II.2.2.
V.
Overall conclusions
Indication a): For the treatment of habitual constipation
The use of psyllium seed as a laxative is based on experts’ testimony and scientifically substantiated
by the pharmacological data available on the mucilages in ispaghula, which seem to have a similiar
structure to that of the mucilages in psyllium seed. It can be concluded that the use as a laxative is a
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well-established use. The clinical data on ispaghula support the use of psyllium seed as laxative. As
well-designed clinical studies are lacking, the current level of evidence
1
can be identified as level IV.
Indication b): In conditions in which easy defaecation with soft stool is desirable, e.g. in cases of
painful defaecation after rectal or anal surgery, anal fissures and haemorrhoids
The use in conditions in which easy defaecation with soft stool is desirable is scientifically
substantiated by the well-known laxative effects but there are no specific data available. The level of
evidence in this indication is therefore level IV.
1
As referred to in the HMPC ‘Guideline on the assessment of clinical safety and efficacy in the preparation of
Community herbal monographs for well-established and of Community herbal monographs/entries to the
Community list for traditional herbal products/substances/preparations’ (EMEA/HMPC/104613/2005)
©
EMEA 2007
Page 10/10
Source: European Medicines Agency
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