4.1. Therapeutic indications

For the treatment of chronic constipation in adults and children above 12 years. Compound Macrogol is also effective in resolving faecal impaction, defined as refractory constipation with faecal loading of the rectum and/or colon in adults and children above 12 years.

4.2. Posology and method of administration

Posology

Chronic constipation

A course of treatment for constipation with Compound Macrogol does not normally exceed 2 weeks, although this can be repeated if required.

As for all laxatives, prolonged use is not usually recommended. Extended use may be necessary in the care of patients with severe chronic or resistant constipation, secondary to multiple sclerosis or Parkinson's disease, or induced by regular constipating medication in particular opioids and antimuscarinics.

Adults, adolescents and the elderly: 1 –3 sachets daily in divided doses, according to individual response.

For extended use, the dose can be adjusted down to 1 or 2 sachets daily.

Paediatric population

Children (below 12 years old): Not recommended. Alternative Compound Macrogol Paediatric powder for oral solution 6.86 g product is available for children.

Faecal impaction

A course of treatment for faecal impaction with Macrogol does not normally exceed 3 days.

Adults, adolescents and the elderly: 8 sachets daily, all of which should be consumed within a 6 hour period.

Paediatric population

Children (below 12 years old): Not recommended. Alternative Compound Macrogol Paediatric powder for oral solution 6.86 g product is available for children.

Patients with impaired cardiovascular function: For the treatment of faecal impaction the dose should be divided so that no more than two sachets are taken in any one hour.

Patients with renal insufficiency: No dosage change is necessary for treatment of either constipation or faecal impaction.

Method of administration

Each sachet should be dissolved in 125 ml water. For use in faecal impaction 8 sachets may be dissolved in 1 litre of water.

4.3. Contraindications

Intestinal perforation or obstruction due to structural or functional disorder of the gut wall, ileus, severe inflammatory conditions of the intestinal tract, such as Crohn's disease and ulcerative colitis and toxic megacolon.

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

4.4. Special warnings and precautions for use

The fluid content of Compound Macrogol when re-constituted with water does not replace regular fluid intake and adequate fluid intake must be maintained.

Diagnosis of impaction/faecal loading of the rectum should be confirmed by physical or radiological examination of the abdomen and rectum.

Mild adverse drug reactions are possible as indicated in Section 4.8. If patients develop any symptoms indicating shifts of fluids/electrolytes (e.g. oedema, shortness of breath, increasing fatigue, dehydration, cardiac failure) Compound Macrogol should be stopped immediately and electrolytes measured, and any abnormality should be treated appropriately.

In case of diarrhoea, caution should be exercised, particularly in patients who are at higher risk for water -electrolyte balance disorders (e.g. the elderly, patients with impaired hepatic or renal function or patients taking diuretics) and electrolyte control should be considered.

If patients develop any symptoms indicating shifts of fluid/ electrolytes (e.g. oedema, shortness of breath, increasing fatigue, dehydration, cardiac failure) Macrogol should be stopped immediately, electrolytes measured, and any abnormality treated appropriately.

The absorption of other medicinal products could transiently be reduced due to an increase in gastro-intestinal transit rate induced by Compound Macrogol (see section 4.5).

Compound Macrogol contains 0.6213 mmol (24.230) of potassium per sachet. This should be taken into consideration if the patient takes more than one sachet daily and has reduced kidney function or is on a controlled potassium diet.

This medicinal product contains 186.87 mg (8.125 mmol) sodium per dose, equivalent to 9.3% of the WHO recommended maximum daily intake for sodium. When used long term for constipation the maximum daily dose of this product is equivalent to 28% of the WHO recommended maximum daily intake for sodium. Compound Macrogol is considered high in sodium. This should be particularly taken into account for those on a low salt diet.

In patients with swallowing problems, who need the addition of a thickener to solutions to enhance an appropriate intake, interactions should be considered, see section 4.5.

Avoid mixing PEG laxatives and starch-based thickeners in patients with dysphagia, considered at risk of aspiration

Paediatric population

There is no clinical data on the use of Compound Macrogol 13.72 g, powder for oral solution in children, therefore it should not be used in children below 12 years of age.

4.5. Interaction with other medicinal products and other forms of interaction

Macrogol raises the solubility of medicinal products that are soluble in alcohol and relatively insoluble in water.

There is a possibility that the absorption of other medicinal products could be transiently reduced during use with Compound Macrogol (see section 4.4). There have been isolated reports of decreased efficacy with some concomitantly administered medicinal products, e.g. anti-epileptics.

Compound Macrogol may result in a potential interactive effect when used with starch-based food thickeners. The polyethylene glycol (PEG) ingredient counteracts the thickening effect of starch, effectively liquefying preparations that need to remain thick for people with swallowing problems.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are limited amount of data from the use of Compound Macrogol in pregnant women. Studies in animals have shown indirect reproductive toxicity (see section 5.3). Clinically, no effects during pregnancy are anticipated, since systemic exposure to macrogol 3350 is negligible.

Compound Macrogol can be used during pregnancy.

Breastfeeding

No effects on the breastfed newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to Macrogol 3350 is negligible.

Compound Macrogol can be used during breast-feeding.

Fertility

There are no data on the effects of Compound Macrogol on fertility in humans. There were no effects on fertility in studies in male and female rats (see section 5.3).

4.7. Effects on ability to drive and use machines

Compound Macrogol has no or negligible influence on the ability to drive and use machines.

4.8. Undesirable effects

Reactions related to the gastrointestinal tract occur most commonly.

These reactions may occur as a consequence of expansion of the contents of the gastrointestinal tract, and an increase in motility due to the pharmacologic effects of Compound Macrogol. Mild diarrhoea usually responds to dose reduction.

The frequency of the adverse effects is not known as it cannot be estimated from the available data.

System Organ Class

Adverse Event

Immune system disorders

Allergic reactions, including anaphylactic reactions, dyspnoea and skin reactions (see below)

Skin and subcutaneous tissue disorders

Allergic skin reactions including angioedema, urticaria, pruritus, rash, erythema.

Metabolism and nutrition disorders

Electrolyte disturbances, particularly hyperkalaemia and hypokalaemia.

Nervous system disorders

Headache

Gastrointestinal disorders

Abdominal pain, diarrhoea, vomiting, nausea, dyspepsia, abdominal distension, borborygmi, flatulence and anorectal discomfort.

General disorders and administration site conditions

Peripheral oedema.

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 Website: www.mhra.gov.uk/yellowcard.

4.9. Overdose

Severe abdominal pain or distension can be treated by nasogastric aspiration. Extensive fluid loss by diarrhoea or vomiting may require correction of electrolyte disturbances.