SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Co-Danthramer 75mg/1000mg per 5ml Oral Suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml of suspension contains:    Dantron    75 mg

Poloxamer 188    1000 mg

3 PHARMACEUTICAL FORM

Oral Suspension.

Peach flavoured, yellow suspension.

4 CLINICAL PARTICULARS

4.1    Therapeutic indications

A lubricant, faecal softener and laxative for the prophylaxis and treatment of constipation in terminally ill patients of all ages.

4.2    Posology and Method of administration

Adults:    One 5 ml spoonful at bedtime.

Children:    Not recommended in children under the age of 12.

4.3 Contraindications

1.    Co-Danthramer 75mg/1000mg per 5ml Oral Suspension is contraindicated in pregnant and nursing mothers.

2.    Co-Danthramer 75mg/1000mg per 5ml Oral Suspension should not be used in intestinal obstruction.

3.    It should not be used if signs of appendicitis or inflamed bowel are apparent.

4. Hypersensitivity to dantron, poloxamer 188 and/or any of the excipients.

4.3 Special Warnings and Precautions for Use

Urine may be coloured red; avoid prolonged contact with skin (as in incontinent patients) since irritation and excoriation may occur.

The oral administration of Dantron has been reported to cause intestinal tumours in rats and mice.

The substance is hepatocarcinogenic in both species.

No evidence exists for a ‘no-effect’ dose. As such there may be a risk of such effects in humans. In the presence of renal failure/insufficiency hypermagnesemia may occur.

Not to be used in patients who are incontinent or in children wearing napkins as superficial sloughing of discoloured skin may occur, (see Section 4.8, Undesirable effects).

Glycerol may cause headache, stomach upset and diarrhea.

This product contains 1.3 g of sorbitol per 5 ml. When taken according to the dosage recommendations each dose supplies up to 2.6 g of sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine. Propylene glycol may cause alcohollike symptoms.

Ethlyhydroxybenzoate (E214), propylhydroxybenzoate (E216) and methylpropylbenzoate (E218) may cause allergic reactions (possibly delayed).

This medicinal product contains 3.71% v/v of ethanol. Each dose contains up to 0.15 g of alcohol. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high-risk groups such as patients with liver disease, or epilepsy.

4.5 Interactions with other Medicaments and other forms of Interaction

Concurrent use with a stool softener laxative may enhance the systemic absorption of Dantron.

4.6 Fertility, pregnancy and lactation

Co-danthramer 75mg/1000mg per 5ml Oral Suspension is contraindicated in pregnant and nursing mothers. Dantron is excreted in breast milk. Some rodent studies suggest that Dantron may be associated with a potential carcinogenic risk.

4.7 Effects on ability to drive and use machines

Co-Danthramer 75mg/1000mg per 5ml Oral Suspension may cause unusual tiredness or weakness, therefore, if affected, the patient should not drive or operate machinery while taking this medicine.

4.4 Undesirable Effect

1.    As a stimulant laxative it increased motility and may cause abdominal cramp.

2.    Dantron may colour the perianal skin pink or red as well as colour the urine.

3.    Superficial sloughing of discoloured skin may occur in incontinent patients or children wearing napkins; Dantron should not be used with such patients.

4.    The mucosa of the large intestine may be discoloured with prolonged use or high dosage.

5.    Unusual tiredness or weakness.

6.    Rash

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

Laxatives can cause diarrhoea if taken in overdose and constipation if over used. Chronic overuse of laxatives may lead to the development of a ‘cathartic colon’, with accompanying metabolic disturbances such as hypokalaemia and metabolic acidosis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Dantron is an anthraquinone stimulant laxative, which acts on nerve endings in the colonic mucosa. Poloxamer 188 is a wetting agent, which acts as a stool softener.

Pharmacokinetic Properties

Like other anthraquinone compounds, Dantron is partially absorbed from the small intestine, where it has no action, and is carried via the circulation to the large intestine where it acts on the nerve endings of the myenteric plexus to stimulate the muscles of the large intestine. Dantron begins to act between 6 and 12 hours after administration.

Poloxamer 188, a non-ionic surfactant is not absorbed and is fully recovered in the faeces.

5.3 Preclinical Safety Data

The oral administration of Dantron has been reported to cause intestinal tumours in rats and mice.

The substance is hepatocarcinogenic in both species.

No evidence exists for a ‘no-effect’ dose. As such there may be a risk of such effects in humans.

In the presence of renal failure/insufficiency hypermagnesemia may occur. Rodents treated for 16 months with doses approximately 300 times those used in humans associate Dantron with the development of intestinal and liver tumours. However, two major studies did not show any association between ingestion of anthraquinones and cancer in humans. Because of the concern over rodent carcinogenicity use of Dantron tends to be restricted to the elderly and terminally ill patients.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Aluminium Magnesium Silicate Xanthan Gum Glycerol Sorbitol 70%

Saccharin Sodium Propylene Glycol Ethanol 96%

Methylhydroxybenzoate (E218) Ethylhydroxybenzoate (E214) Propylhydroxybenzoate (E216) Citric Acid Monohydrate Sodium Citrate Purified Water Peach Flavour Liquid

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 container.

6.1    Nature and Contents of Container

Pharmaceutical Grade Type III amber glass bottles with pilfer proof screw cap and high density polyethylene bottles with tamper evident seal.

Pack sizes: 100 ml, 150 ml, 200 ml, 300 ml, 500 ml, and 1 litre

6.2    Special precautions for disposal and other handling

Shake the bottle before use. Avoid contact with the skin to avoid staining.

7.    MARKETING AUTHORISATION HOLDER

Pinewood Laboratories Limited

Ballymacarbry

Clonmel

Co. Tipperary

Ireland

8.    MARKETING AUTHORISATION NUMBER

PL 04917/0026

9    DATE OF FIRST AUTHORISATION/RENEWAL OF    THE

AUTHORISATION 16/03/2007

10 DATE OF REVISION OF THE TEXT

17/05/2016