This information is intended for use by health professionals

1. Name of the medicinal product

Ispagel Orange

2. Qualitative and quantitative composition

Each sachet contains 3.5 g ispaghula husk.

Excipient with known effect: Also contains 80.00 mg of aspartame (E951) and 68.81 mg of sodium.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Effervescent granules for oral suspension

4. Clinical particulars
4.1 Therapeutic indications

The treatment of patients requiring a high fibre regime: for example, for the relief of constipation, including constipation in pregnancy and the maintenance of regularity; for the management of bowel function in patients with colostomy, ileostomy, haemorrhoids, anal fissure, chronic diarrhoea associated with diverticular disease, irritable bowel syndrome and ulcerative colitis.

4.2 Posology and method of administration

Posology

Adults and children over 12 years: One sachet morning and evening.

Elderly: There is no indication that dosage needs to be modified for the elderly.

Children aged 12 years and under: Ispagel® Orange should not be used in children aged 12 years and under. Other pharmaceutical forms may be more appropriate for administration to this population.

The last dose should not be taken immediately before going to sleep.

If there has been no bowel movement after three days of treatment the doctor should be consulted.

Method of Administration

Ispagel Orange is intended for oral use as a suspension in a drink of water. The granules should be stirred into a glass of 150 ml of cold water and taken as soon as the effervescence subsides, preferably after meals.

When preparing the product for administration, it is important to try to avoid inhaling any of the powder in order to minimize the risk of sensitization to the active ingredient.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with a sudden change in bowel habit that has persisted more than two weeks.

Undiagnosed rectal bleeding and failure to defecate following the use of a laxative.

Ispagel Orange is contra-indicated in patients suffering from abnormal constrictions in the gastro-intestinal tract, with diseases of oesophagus and cardia, intestinal obstruction, faecal impaction, natural or drug-induced reduction of gut motility and colonic atony such as senile mega-colon.

Patients who have difficulty in swallowing or any throat problems

4.4 Special warnings and precautions for use

Warning on hypersensitivity reactions: In individuals with continued occupational contact to powder of Plantago ovata seeds (i.e. healthcare workers, caregivers) allergic sensitization may occur due to inhalation, this is more frequent in atopic individuals. This sensitization usually leads to hypersensitivity reactions which could be serious (see section 4.8). It is recommended to assess clinically the possible sensitization of individuals at risk and, if justified, to perform specific diagnostic tests. In case of proven sensitization leading to hypersensitivity reactions, exposure to the product should be stopped immediately and avoided in the future (see section 4.3).

If symptoms persist longer than 3 days, the patient should consult a doctor or healthcare professional.

Ispaghula husk 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.

When taken with inadequate fluid amounts, bulk forming agents can cause obstruction of the throat and oesophagus with choking and intestinal obstruction. Symptoms can be chest pain, vomiting, or difficulty in swallowing or breathing.

The treatment of debilitated patients and / or elderly patients requires medical supervision.

In order to decrease the risk of gastrointestinal obstruction ispaghula husk should not be used together with medicinal products known to inhibit peristaltic movement (e.g. opioids) and then only under medical supervision.

The last dose should not be taken immediately before going to sleep since impaired or reduced gastric motility may impair the intestinal passage and then cause sub-obstruction.

Adequate fluid intake should be maintained. Therefore, the product should not be taken dry and should always be taken with at least 150 mL of water or other liquid. The last dose should not be taken immediately before going to sleep since impaired or reduced gastric motility may impair the intestinal passage and then cause sub-obstruction.

Paediatric Population

Use is not recommended in children below 12 years of age.

Important information regarding the ingredients of this medicine

This medicine contains 80.00 mg of aspartame, a source of phenylalanine. Ispagel Orange should not be given to patients with phenylketonuria, as it may be harmful.

Also contains 68.18 mg of sodium per sachet. To be taken into consideration by patients on a controlled sodium diet.

4.5 Interaction with other medicinal products and other forms of interaction

Ispaghula husk and other bulk-forming laxatives may delay or reduce the gastrointestinal absorption of other drugs such as cardiac glycosides, coumarin derivatives, carbamazepine, lithium, or vitamins (such as vitamin B12) and minerals (such as calcium, iron, or zinc). For this reason, the product should not be taken ½ to 1 hour before or after intake of other medicinal products.

Diabetic patients should take ispaghula husk only under medical supervision because adjustment of anti-diabetic therapy may be necessary.

Use of ispaghula husk concomitantly with thyroid hormones requires medical supervision because the dose of the thyroid hormones may have to be adjusted

4.6 Fertility, pregnancy and lactation

Pregnancy

There are limited amount of data (less than 300 pregnancy outcomes) from the use of ispaghula husk in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3 Preclinical safety data).

Breast-feeding

The use of ispaghula husk may be considered during pregnancy and lactation, if necessary and if change of nutrition is not successful. Laxative bulk producers should be used before using other purgatives.

Fertility

No known effects.

4.7 Effects on ability to drive and use machines

None

4.8 Undesirable effects

Special attention should be given to individuals manipulating the powder formulations routinely (see 4.4 Special warnings and precautions for use).

Adverse events which have been associated with ispaghula husk are given below, tabulated by system organ class and frequency. Frequencies are defined as: Very common (≥1/10); Common (≥1/100 and <1/10); Uncommon (≥1/1000 and <1/100); Rare (≥1/10,000 and <1/1000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data). Within each frequency grouping, adverse events are presented in order of decreasing seriousness.

System Organ Class

Frequency

Adverse Events

Immune System Disorders

Not known

Hypersensitivity disorders1,2

Eye Disorders

Not known

Conjunctivitis2

Respiratory, Thoracic and Mediastinal Disorders

Not known

Rhinitis2

Gastrointestinal Disorders

Not known

Flatulence, abdominal distension, intestinal obstruction, oesophageal obstruction, faecal impaction3

Skin and Subcutaneous Tissue Disorders

Not known

Skin Rash2

1 Including rash, anaphylaxis, pruritus, and bronchospasm

2 Ispaghula/psyllium husk contains potent allergens. The exposure to these allergens is possible through oral administration, contact with the skin and, in the case of powder formulations, also by inhalation. As a consequence to this allergic potential, individuals exposed to the product can develop hypersensitivity reactions such as rhinitis, conjunctivitis, bronchospasm and in some cases, anaphylaxia. Cutaneous symptoms as exanthema and/or pruritus have also been reported. Special attention should be given to individuals manipulating the powder formulations routinely (see section 4.4).3 A small amount of flatulence and abdominal distension may sometimes occur during the first few days of treatment, but should diminish during continued treatment. Abdominal distension and risk of intestinal or oesophageal obstruction and faecal impaction may occur, particularly if swallowed with insufficient fluid

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal 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 the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Symptoms

In the event of an overdose, abdominal discomfort flatulence and intestinal obstruction may occur.

Management

Adequate fluid intake maintained, particularly if the granules have been taken without water contrary to administration instructions, and management should be symptomatic

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Bulk producer

ATC Code: A06A C01

The active ingredient ispaghula husk consists of the episperm and collapsed adjacent layers removed from the seeds of Plantago ovata Forssk (Plantago ispaghula Roxb.). Ispaghula husk is particularly rich in alimentary fibres and mucilages, its mucilage content being higher than that of other Plantago species. Ispaghula husk is capable of absorbing up to 40 times its own weight in water. Ispaghula husk consists of 85% water-soluble fibre; 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 ispaghula husk 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. When taken with a sufficient amount of liquid (at least 30 ml per 1 g of herbal substance) ispaghula husk produces an increased volume of intestinal contents due to its highly bulking properties and hence a stretch stimulus, which triggers defecation; at the same time the swollen mass of mucilage forms a lubricating layer, which makes the transit of intestinal contents easier.

Progress of action: ispaghula husk 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

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 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, such fibre 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.

5.3 Preclinical safety data

In a study on fertility, embryo-foetal development and pre- and postnatal development (multigeneration study) ispaghula husk (0, 1, 2.5, or 5% (w/w) of the diet) was administered to rats continuously through two generations. For fertility and foetal development and teratogenesis the no-observed-adverse-effects-limit (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.

The study on embryo-foetal development in rabbits (ispaghula husk as 0, 2.5, 5 or 10% (w/w) of diet) has to be considered as preliminary. Conclusions cannot be drawn.

The non-clinical data on toxicology of ispaghula husk preparations are incomplete, but available data indicate no signals of toxicological concern. Adequate tests on reproductive toxicity, genotoxicity and carcinogenicity have not been performed.

6. Pharmaceutical particulars
6.1 List of excipients

Sodium bicarbonate

Orange flavour 501071 AP0551 (maize maltodextrin, alpha tocopherol and flavouring components)

β-carotene 10%

Aspartame E951

Citric acid anhydrous

Riboflavin 5 sodium phosphate.

6.2 Incompatibilities

None known

6.3 Shelf life

3 years

6.4 Special precautions for storage

Do not store above 25°C. Store in the original package.

6.5 Nature and contents of container

Sachets of 3, 5, 10, 30 or 60 enclosed in a carton

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Ispagel Orange granules are to be dispersed in water forming a drink.

7. Marketing authorisation holder

Bristol Laboratories Limited

Unit 3, Canalside,

Northbridge road,

Berkhamsted, HP4 1EG

United Kingdom

8. Marketing authorisation number(s)

PL 17907/0397

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 17/04/2000

Date of last renewal: 07/12/2005

10. Date of revision of the text

27/10/2017