For short term use in cases of constipation.

Posology

The maximum daily dose of hydroxyanthracene derivatives is 30 mg. On average,

this is equivalent to 10 g (= 2 measuring spoonfuls or 2 sachets) of Agiolax Granules.

Dosage for adults and adolescents over 12 years of age:

One to two measuring spoonful(s) (or 1 – 2 sachet(s)) of Agiolax Granules once

daily, to be taken with plenty of liquid after the evening meal.

The correct individual dose is the smallest required to produce a comfortable

soft-formed motion.

 

Pediatric population

Agiolax should not be used in children under 12 years of age (see Section 4.3).

Method of administration and Duration of use:

The granules should be swallowed unchewed with plenty of liquid (a quarter of

a litre).

When other medicinal products are used concomitantly, it is recommended to

take this product 30 minutes to one hour later.

At best, Agiolax should be taken in the evening. The effect occurs after 8 to

12 hours. The laxative should not be used for longer than 1 to 2 weeks and not

be taken at higher doses.

Hypersensitivity to the active substances or to any of the excipients listed in Section 6.1. Pathological stenosis in the gastro-intestinal tract or the oesophagus; ileus or atonia of the intestine; acute inflammatory bowel disease, such as Crohn's disease, ulcerative colitis, appendicitis; abdominal pain of unknown origin; dysphagia; severe dehydration states with water and electrolyte depletion; children under 12 years of age; patients with difficult to control diabetes mellitus.

If any cardiac glycosides, anti-arrhythmic agents, medicines eventually leading

to QT interval prolongation, diuretics, adrenocortical steroids and/or liquorice

root are administered concomitantly, Agiolax shall be taken under medical

supervision only.

Like all laxatives Agiolax shall not be taken without consulting a doctor by

patients suffering from coprostasis (impaction of the faeces) or undiagnosed

acute or persisting intestinal disorders (such as abdominal pain, nausea and

vomiting) because these symptoms may be signs of threatening or manifest ileus.

If laxatives need to be used every daily, the cause of constipation should be

determined. Long-term use of laxatives (for more than two weeks) shall be

avoided.

Any intake of laxatives beyond the recommended treatment period may worsen

bowel function and lead to laxative addiction. Agiolax should only be used if

constipation cannot be resolved by means of changes in diet or the administration

of bulk forming agents.

 

When Agiolax is administered to incontinent adults, patient and the caretakers

should be informed that the hygienic pads should be changed more frequently to

prevent extended skin contact with faeces.

Patients with kidney disease should pay special attention to any disorders in the

electrolyte balance.

In order to reduce the risk of ileus medicines inhibiting the bowel function (such as

opiates) shall be taken in combination with Agiolax under medical supervision

only.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose

malabsorption, galactose intolerance, lactase deficiency or

saccharase-isomaltase deficiency should not take Agiolax.

In case of chronic use/abuse, potassium deficiency may potentiate the action of

cardiac glycosides and may cause an interaction with anti-arrhythmic agents and

medicines used for cardioversion (e.g., quinidine) as well as products leading to

QT interval prolongation. Potassium loss may be aggravated by combination

with diuretics, adrenocortical steroids and liquorice root.

The absorption of concomitantly administered medicines such as minerals,

vitamins (vitamin B12), cardiac glycosides, coumarin derivatives,

carbamazepine and lithium may be retarded. Therefore, an interval of

30 minutes up to one hour should always be allowed between taking Agiolax

and other medicines.

Concomitant use of Agiolax and thyroid hormones shall require medical

monitoring since the thyroid hormone dose may need to be adjusted.

Diabetic patients will also need medical supervision since adjustment of

antidiabetic therapy may be required.

There are no or limited amount of studies on the use of Agiolax in pregnant

women. Further experience in pregnant women do not indicate any risk of

malformation or reveal any foetal/neonatal toxicity of the active substances

provided that Agiolax is taken according to the dosage instructions. Animal

studies are insufficient with regard to reproductive toxicity (see Section 5.3).

As a precautionary measure, it is preferable to avoid the use of Agiolax during

the first trimester of pregnancy. Otherwise, Agiolax may only be used for a short

 

time, if constipation cannot be resolved by a change of habit or diet, or by the

administration of bulk forming agents.

It is unknown whether components of the active substances or their metabolites

are excreted in human milk. Small amounts of active metabolites (such as rhein)

are excreted in human milk. A risk to the newborns/infants cannot be excluded.

Agiolax should not be used during breast-feeding.

Adequate studies with Agiolax with regard to fertility are not available.

 

Agiolax has no influence on the ability to drive and use machines.

The following convention has been used for the classification of side effects in

terms of frequency:

Very common: ≥ 1/10

Common: ≥ 1/100 to < 1/10

Uncommon: ≥ 1/1,000 to < 1/100

Rare: ≥ 1/10,000 to < 1/1,000

Very rare: < 1/10,000

Not known: Frequency cannot be estimated from the available data.

Hypersensitivity reactions such as pruritus, urticaria, localised or generalised

exanthema, rhinitis, conjunctivitis, bronchospasm and - in isolated cases –

anaphylactic shock may occur.

Moreover, flatulence, abdominal pain and spasm as well as diarrhoea may be

experienced, in particular in patients suffering from irritable bowel syndrome.

In general, these complaints are usually caused due to individual overdosage and

therefore, a dose reduction is necessary.

Meteorism may occur - mainly in case of insufficient fluid intake – that may be

associated with the risk of ileus, oesophagus obstruction and constipation of

stool. The frequency of these side effects cannot be estimated from the available

data.

In case of long-term use, disorders in the water and electrolyte balance may be

developed resulting in albuminuria and haematuria. Furthermore, pigmentation

of the intestinal mucosa (Pseudomelanosis coli) may occur which, as a rule, is

reversible after discontinuation of the product.

Degradation products of senna pods may cause a harmless red-brownish

discoloration of urine.

 

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the product is

important. It allows continued monitoring of the benefit/risk balance of the

medicinal product. Healthcare professionals are asked to report any suspected

adverse reactions via:

To report side effect(s):

 

Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

Fax: +966-11-205-7662

SFDA Call Center: 19999

E-mail:npc.drug@sfda.gov.sa

Website: https://ade.sfda.gov.sa/

 

Other GCC states:

Please contact the relevant competent authority.

Painful intestinal spasms and severe diarrhoea may occur as the main symptoms

of case of overdosing or abuse of stimulating laxatives resulting in losses of fluid

and electrolytes which should be replaced.

Diarrhoea may especially cause potassium depletion, which may lead to cardiac

disorders and muscular asthenia, particularly where cardiac glycosides,

diuretics, adrenocorticosteroids or liquorice root are being taken at the same

time.

Overdosage of bulk-forming products - such as Ispaghula seeds – may cause

abdominal discomfort, flatulence and intestinal obstruction.

Supportive treatment should include the intake of generous quantities of liquid.

The electrolyte level – in particular the potassium level – should be monitored.

This is particularly important in case of elderly patients.

Chronic ingested overdoses of anthranoid-containing medicinal products may

lead to toxic hepatitis.

Pharmacotherapeutic group: Laxatives

ATC Code: A06AB56

 

Swelling and bulking agents from Ispaghula seeds and seed husks (Indian flea

seed, Indian flea seed husks) physiologically enhance intestinal passage by

producing an increased volume of intestinal contents through their water binding

capacity and bulking properties thus producing a stretch stimulus and

accelerating intestinal passage. The swollen mass of mucilage softens the stools

and improves gliding properties.

The action of Ispaghula drugs on colon motility is supported by senna glycosides

(sennosides) from senna pods.

1,8-dihydroxyanthracene derivatives possess a laxative effect. In case of

sennosides or their active metabolite in the large intestine (rhein anthrone) this

effect is mainly based on an influence on the motility of the large intestine

(stimulation of peristaltic contractions and inhibition of local contractions)

resulting in accelerated colonic transit and - due to reduced contact time – in

reduced fluid absorption. In addition, water and electrolytes are secreted by

stimulation of active chloride secretion. The onset of action of anthracene

derivatives can be expected with a delay of approximately 8 - 12 hours.

 

Systemic studies on the kinetics of drug preparations are not available.

However, is can be expected that the aglyca contained in the drug product are

absorbed in the upper gut already.

The β-linked glycosides are prodrugs which are neither split nor absorbed in the

upper gut. They are converted by the bacteria enzymes of the large intestine into

rhein anthrone. Rhein anthrone is the laxative metabolite. Systemic availability

of rhein anthrone is extremely low. In animal experiments, less than 5 % were

excreted in form of the oxidized, partly conjugated products rhein and sennidine.

Most of rhein anthrone (approx. 90 %) is excreted in faeces bound to the

intestinal contents as polymers.

Active metabolites, e.g. rhein, pass in small amounts into human milk.

Animal experiments demonstrated that placental passage of rhein is small.

 

Available preclinical safety data on Agiolax is incomplete. Based on extensive

medical experience gained over many years, the safety of use in humans has

been sufficiently proved. The AMES test did not reveal any relevant mutagenic

potential of Ispaghula seeds and husks. The available mutagenicity data on

senna pods are incomplete.

While no carcinogenicity studies with Ispaghula seeds and husks are available,

studies on the carcinogenicity of senna pods with senna extract in rats were

 

conducted. Compared to the control group, oral doses of up to 300 mg/kg BW

administered for 104 weeks did not lead to a higher incidence of tumor rates in

both genders. The product under investigation contained 1.83 % of sennosides

A-D (calculated as the total of the individual identified compounds), equivalent

of approximately 1.59 % of potential total rhein determined by way of

computation, 0.11 % potential aloe-emodin and 0.014 % of potential emodin.

With regard to reproductive toxicology, results obtained from animal studies are

inadequate.

Moreover, data is available in the literature on senna pods products or its isolated

active constituents, e.g. rhein or sennosides A and B, as well as on Ispaghula

seeds and husks.

Subacute/chronic toxicity

In a 90-day rat study, senna pods were administered at dose levels from

100 mg/kg up to 1,500 mg/kg. The tested drug contained 1.83% sennosides A-D,

1.6% potential rhein, 0.11% potential aloe-emodin and 0.014 % potential

emodin. Epithelial hyperplasia of the large intestine of minor degree,

hyperplastic lesions of the forestomach epithelium, dose-dependent tubular

basophilia and epithelial hypertrophy of the kidneys without functional affection

as well as dark discoloration of the renal surface were seen. All these changes

were largely reversible. A no-observable-effect-level (NOEL) could not be

obtained in this study.

Sennosides were tested for their toxicity at doses up to 500 mg/kg of BW in dogs

for 4 weeks and up to 100 mg/kg of BW in rats for 6 months. No toxic activity

was displayed.

Ispaghula seed husk was fed to rats at levels high as 10% of the diet for periods

up to 13 weeks (three 28-day studies; one 13-week study). Ispaghula

consumption ranged from 3.876 to 11.809 g/kg/day. While effects on serum

protein, albumin, globulin, iron-binding capacity, calcium, potassium,

cholesterol and the activities of aspartate transaminase and alanine transaminase

were seen at higher dosages, the absence of any increases in urinary protein, any

effects on the growth or the feed efficiency suggest that ispaghula seed husk has

no effect on protein metabolism. Because the absorption of ispaghula seed husk

is very limited, histopathological evaluations were limited to the gastrointestinal

tract, liver, kidneys and gross lesions without observing any treatment-related

effect.

Reproductive toxicity

There was no evidence of any embryolethal, teratogenic or foetotoxic actions in

rats or rabbits after oral treatment with sennosides. Furthermore, there was no

effect on the postnatal development of young rats, on rearing behaviour of dams

or on male and female fertility in rats. Data for herbal preparations are not

available.

 

In a study on fertility, embro-foetal development and pre- and postnatal

development (2-generation study) ispaghula husk (0, 1, 2.5, or 5% (w/w) of the

diet) was administered to rats. For fertility, foetal development and teratogenesis

the NOAEL was 5% of the diet, while for offspring growth and development the

NOAEL was given with 1% of the diet based on reductions in pup weights.

Genotoxicity and carcinogenicity

Several genotoxicity/carcinogenicity tests were conducted with a liquid extract

from tinnevelly senna pods. While positive results were obtained from two

in vitro tests (AMES test, chromosomal aberration test), another in vitro test

(HPGRT test) as well as an in vivo test (micronucleus test) yielded negative

results.

A specified senna extract was given orally for 2 years to male and female rats;

no carcinogenic effects were seen. The extract investigated contained

approximately 40.8% of anthranoids from which 35% were sennosides,

corresponding to about 25.2% of potential rhein, 2.3% of potential aloe-emodin

and 0.007% of potential emodin and 142 ppm free aloe-emodin and 9 ppm free

emodin. Furthermore, another 2-year study on male and female rats and mice

with emodin gave no evidence of carcinogenic activity for male rats and female

mice; and equivocal evidence for female rats and male mice.

Talc, Gum Arabic, E 172 (coloring agent), Solid paraffin, Viscous paraffin,

Caraway oil, Peppermint oil, Sage oil, Sucrose (sugar).

1 measuring spoonful (or 1 sachet) contains approximately 1.05 g of sucrose

(sugar), equivalent to 0.09 bread units (BU).

Not applicable.

3 years After first opening the tin, Agiolax can be used for 6 months

Store below 30ºC, in a dry place.

Tightly close the tin after each use!

Original packs of 250 g of brown granules (tin with screw cap).

A measuring spoon (medical device, CE 0481) is supplied with the tin with

screw cap. The manufacturer of the medical device is Madaus GmbH.

 

No special requirements