This information is intended for use by health professionals

1. Name of the medicinal product

Co-Danthramer 25 mg/200mg per 5ml Oral Suspension

2. Qualitative and quantitative composition

Each 5 ml of suspension contains:

Dantron

Poloxamer 188

25 mg

200 mg

Excipients with known effect:

Sorbitol

Propylene glycol

Ethanol

Ethyl parahydroxybenzoate

Methyl parahydroxybenzoate

Propyl parahydroxybenzoate

1300 mg

260 mg

150 mg

2.4 mg

11.0 mg

1.6 mg

For the full list of excipients, see section 6.1.

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:

Children:

One to two 5 ml spoonfuls at bedtime.

Should be avoided in children, but if recommended, a suitable dose is half to one 5 ml spoonful at bedtime.

4.3 Contraindications

1. Co-Danthramer 25 mg/200mg per 5ml Oral Suspension is contraindicated in pregnant and nursing mothers.

2. Co-Danthramer 25 mg/200mg 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 listed in section 6.1 .

4.4 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 medicine contains 1300 mg of sorbitol per 5 ml which is equivalent to 260 mg per ml. When taken according to the dosage recommendations each dose supplies up to 2600 mg of sorbitol per 10 ml. Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to some sugars or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which a person cannot break down fructose, talk to your doctor before you (or your child) take or receive this medicine.

Sorbitol may cause gastrointestinal discomfort and mild laxative effect.

This medicine contains 260 mg propylene glycol in each 5 ml which is equivalent to 52 mg/ml. If your baby is less than 4 weeks old, talk to your doctor or pharmacist before giving them this medicine, in particular if the baby is given other medicines that contain propylene glycol or alcohol.

This medicine contains 150 mg of alcohol (ethanol) in each 5 ml which is equivalent to 30 mg per ml. The amount in 5 ml of this medicine is equivalent to 3.6 ml beer, 1.5 ml wine per dose. The amount of alcohol in this medicine is not likely to have an effect in adults and adolescents, and its effects in children are not likely to be noticeable. It may have some effects in younger children, for example feeling sleepy. The alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines. If you are pregnant or breast-feeding, talk to your doctor or pharmacist before taking this medicine. If you are addicted to alcohol, talk to your doctor or pharmacist before taking this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per 5 ml, that is to say essentially 'sodium-free'.

Ethyl parahydroxybenzoate (E214), propyl parahydroxybenzoate (E216), methyl parahydroxybenzoate (E218): may cause allergic reactions, which may be delayed.

4.5 Interaction with other medicinal products and other forms of interaction

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

4.6 Pregnancy and lactation

Co-Danthramer 25 mg/200mg 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 25 mg/200mg 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.

4.8 Undesirable effects

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 or search for MHRA Yellow Card in the Google Play or Apple App Store

4.9 Overdose

Laxatives can cause diarrhea 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

Pharmacotherapeutic group: Contact laxatives

ATC code: A06AB53

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.

5.2 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 to 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 ( E422)

Sorbitol 70% (E420)

Saccharin Sodium

Propylene Glycol

Ethanol 96%

Methyl parahydroxybenzoate (E218)

Ethyl parahydroxybenzoate (E214)

Propyl parahydroxybenzoate (E216)

Citric Acid Monohydrate

Sodium Citrate

Purified Water

Peach Flavour Liquid (contains propylene glycol)

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.

6.5 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

6.6 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

8. Marketing authorisation number(s)

PL 04917/0025

9. Date of first authorisation/renewal of the authorisation

15/03/2007

10. Date of revision of the text

15/05/2020