MOVICOL Liquid Orange flavour, concentrate for oral solution

For the treatment of chronic constipation.

Posology

A course of treatment for constipation with Movicol Liquid Orange flavour 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 older people: 25 ml diluted in 100 ml of water 1-3 times daily in divided doses, according to individual response.

For extended use, the dose can be adjusted down to 1 or 2 doses per day of 25 ml diluted in 100 ml of water.

Children: Movicol Liquid Orange flavour is not recommended for use in children below the age of 12 years. Alternative Movicol products are available for children.

Patients with renal insufficiency: No dosage change is necessary for the treatment of constipation (see section 4.4 for warning about excipients).

Faecal impaction: Movicol Liquid Orange flavour is not recommended for use for the treatment of faecal impaction (see section 4.4). Alternative Movicol products are available for the treatment of faecal impaction.

Method of administration

The product must not be taken undiluted and may only be diluted in water. For instructions on dilution of the product before administration, see section 6.6.

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 substances or to any of the excipients listed in section 6.1.

The fluid content of Movicol Liquid Orange flavour when re-constituted with water does not replace regular fluid intake and adequate fluid intake must be maintained.

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), Movicol Liquid Orange flavour should be stopped immediately and electrolytes measured and any abnormality should be treated appropriately.

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

This medicinal product contains 8.125 mmol of sodium in each diluted dose of 125 ml. The sodium content of Movicol Liquid Orange flavour should be taken into consideration when administering the product to patients on a controlled sodium diet.

This medicinal product contains 45.6 mg of benzyl alcohol in each 25 ml dose which is equivalent to 1.825 mg/ml. Benzyl alcohol may cause anaphylactoid reactions.

High volumes of benzyl alcohol should be used with caution and only if necessary, especially in subjects with kidney or liver impairment and during pregnancy/breast feeding because of the risk of accumulation and toxicity (metabolic acidosis) of benzyl alcohol.

This medicine contains 74.6 mg of ethanol in 25 mL concentrate for oral solution, which is equivalent to 3.0 mg of ethanol per mL. The amount in 25 mL concentrate for oral solution of this medicine is equivalent to less than 2 mL of beer or 1 mL of wine. The small amount of alcohol in this medicine will not have any noticeable effects.

This product contains ethyl (E214) and methyl (E218) parahydroxybenzoates which may cause allergic reactions, possibly delayed.

This medicinal product contains 186.87mg (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. Movicol Liquid Orange flavour 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.

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 Movicol Liquid Orange flavour (see section 4.4). There have been isolated reports of decreased efficacy with some concomitantly administered medicinal products, e.g. anti-epileptics. Therefore, other medicines should not be taken orally for one hour before, during and for one hour after taking Movicol Liquid Orange flavour.

Movicol Liquid Orange flavour may result in a potential interactive effect if used with starch-based food thickeners. The Macrogol ingredient counteracts the thickening effect of starch, effectively liquefying preparations that need to remain thick for people with swallowing problems.

Pregnancy

There are limited amount of data from the use of Movicol 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.

Movicol can be used during pregnancy.

Breast-feeding

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

Movicol can be used during breast-feeding.

Fertility

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

Movicol Liquid Orange flavour has no influence on the ability to drive and use machines.

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 Movicol Liquid Orange flavour. Mild diarrhoea usually responds to dose reduction.

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

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 Yellow Card Scheme Website www.mhra.gov.uk/yellowcard.

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

Pharmacotherapeutic group: Osmotically acting laxatives. ATC code: A06A D65

Macrogol 3350 acts by virtue of its osmotic action in the gut, which induces a laxative effect. Macrogol 3350 increases the stool volume, which triggers colon motility via neuromuscular pathways. The physiological consequence is an improved propulsive colonic transportation of the softened stools and a facilitation of the defecation.

Electrolytes combined with macrogol 3350 are exchanged across the intestinal barrier (mucosa) with serum electrolytes and excreted in faecal water without net gain or loss of sodium, potassium and water.

Clinical studies in the use of Movicol sachets (parent product) in chronic constipation have shown that the dose needed to produce normal formed stools tends to reduce over time. Many patients respond to between 1 and 2 sachets of powdered Movicol a day (one sachet is equivalent to 25 ml of Movicol Liquid Orange flavour), but this dose should be adjusted depending on individual response.

Macrogol 3350 is unchanged along the gut. It is virtually unabsorbed from the gastro- intestinal tract. Any macrogol 3350 that is absorbed is excreted via the urine.

Preclinical studies provide evidence that macrogol 3350 has no significant systemic toxicity potential, based on conventional studies of pharmacology, repeated dose toxicity and genotoxicity.

There were no direct embryotoxic or teratogenic effects in rats even at maternally toxic levels that are a multiple of 66 x the maximum recommended dose in humans for chronic constipation and 25 x for faecal impaction. Indirect embryofoetal effects, including reduction in foetal and placental weights, reduced foetal viability, increased limb and paw hyperflexion and abortions, were noted in the rabbit at a maternally toxic dose that was 3.3 x the maximum recommended dose in humans for treatment of chronic constipation and 1.3 x for faecal impaction. Rabbits are a sensitive animal test species to the effects of GI-acting substances and the studies were conducted under exaggerated conditions with high dose volumes administered, which are not clinically relevant. The findings may have been a consequence of an indirect effect of MOVICOL related to poor maternal condition as the result of an exaggerated pharmacodynamic response in the rabbit. There was no indication of a teratogenic effect.

There are long-term animal toxicity and carcinogenicity studies involving macrogol 3350. Results from these and other toxicity studies using high levels of orally administered high molecular weight macrogols provide evidence of safety at the recommended therapeutic dose.

Acesulfame potassium E950

Sucralose E955

Benzyl alcohol

Methyl parahydroxybenzoate E218

Ethyl parahydroxybenzoate E214

Orange flavour (contains flavouring substances, flavouring preparations and a small amount of ethanol)

Purified water

Not applicable.

Unopened: 2 years

Opened: 30 days

Diluted solution shelf-life: 6 hours

Bottle: Do not refrigerate or freeze.

Diluted solution: Keep solution covered.

Polyethylene terephthalate bottle with polypropylene – low density polyethylene child- resistant closure with polyethylene liner.

Each carton contains one bottle and a polypropylene measuring cup.

Pack size: 500ml bottle

The product should be diluted as follows:

25 ml should be measured out using the dosing cup provided or five 5 ml teaspoonfuls. This should be diluted in 100 ml (approximately half a glass) of water.

Any unused solution should be discarded within 24 hours. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.