SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

MACROGOL APPLE FLAVOUR 4g powder for oral solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sachet contains 4g of macrogol 4000.

Excipients with known effect:

Apple flavour 4g sachet: Sucrose 50.4mg per sachet Wheat starch 3.9mg per sachet

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for an oral solution in a sachet.

Apple flavour: Almost white to slightly yellowish powder with an odour and taste of apple.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Symptomatic treatment of constipation in adults and children aged 6 months and above.

An organic disorder should have been ruled out before initiation of treatment, especially in the age group under 2 years.

MACROGOL should remain a temporary adjuvant treatment to appropriate lifestyle and dietary management of constipation, and with a maximum 3-month treatment course in children. If symptoms persist despite associated dietary measures, an underlying cause should be suspected and treated.

4.2 Posology and method of administration

Oral use

There are two strengths available for use, 4 g sachets for use in children from 6 months to 8 years and 10 g sachets for children from 8 years and adults.

Children from 6 months to 8 years - 4g sachets

Children from 6 months to 1 year: 1 sachet (4g) per day.

Children from 1 to 4 years: 1-2 sachets (4-8g) per day.

Children from 4 to 8 years: 2-4 sachets (8-16g) per day.

If the dosage is 1 sachet per day, the dose should be preferably taken as a single dose in the morning. If a dose is higher, the dose should be divided into morning and evening dose.

Each sachet should be dissolved in at least 50 ml water just before use.

The effect of macrogol becomes apparent within 24 to 48 hours after its administration.

In children, treatment should not exceed 3 months due to a lack of clinical data for treatment lasting longer than 3 months. Treatment-induced restoration of bowel movements will be maintained by lifestyle and dietary measures.

The daily dose should be adapted according to the clinical effects and may range from one sachet every other day (especially in children) up to 4 sachets a day. The recommended dosage for every age group shouldn’t be exceeded.

Appearance of the product after reconstitution: Almost white to lightly yellowish opalescent solution.

4.3 Contraindications

-    severe inflammatory bowel disease (such as ulcerative colitis, Crohn's disease) or toxic megacolon, associated with symptomatic stenosis,

-    digestive tract perforation or risk of digestive tract perforation,

-    ileus or suspicion of intestinal obstruction,

-    painful abdominal syndromes of indeterminate cause,

hypersensitivity to macrogol (polyethylene glycol) or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Warnings

Data on efficacy in children under 2 years are limited.

The treatment of constipation with any medicinal product is only an adjuvant to a healthy lifestyle and diet, for example:

-    increased intake of liquids and dietary fibre,

-    appropriate physical activity and rehabilitation of the bowel reflex.

Before treatment initiation it is necessary to exclude organic disorder.

After 3 months of treatment in children a complete clinical examination of constipation should be carried out.

In case of diarrhoea, caution should be exercised in patients who are prone to a disturbance of water electrolyte balance (e.g. the elderly, patients with impaired hepatic or renal function or patients taking diuretics) and electrolyte control should be considered.

Precautions for use

Very rare cases of hypersensitivity reactions (rash, urticaria, oedema) have been reported with drugs containing macrogol (polyethylene glycol). Exceptional cases of anaphylactic shock have been reported.

Apple flavour: This product contains small amount of sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

MACROGOL APPLE FLAVOUR contains 50.4mg of sucrose in 4g sachets

This product does not contain a significant quantity of sugar and can be prescribed to diabetic patients.

MACROGOL APPLE FLAVOUR contains 3.9mg of wheat starch in 4g sachets. Wheat starch may contain gluten, but only in trace amounts, and is therefore considered safe for people with celiac disease.

4.5 Interaction with other medicinal products and other forms of interaction

Not applicable.

4.6 Fertility, pregnancy and lactation

Pregnancy

Macrogol 4000 was not teratogenic in rats or rabbits.

No effects during pregnancy are anticipated, since systemic exposure to MACROGOL is negligible. MACROGOL can be used during pregnancy.

Lactation

No effects on the breast-feeding newborn/infant are anticipated since the systemic exposure of the breast-feeding woman to macrogol 4000 is negligible. MACROGOL can be used during breast-feeding.

Fertility

There are no fertility data available.

4.7 Effects on ability to drive and use machines

Not applicable.

4.8 Undesirable effects

Adverse Drug Reactions are listed under headings of frequency using the following categories:

Very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Adult population:

The undesirable effects listed in the table below have been reported during clinical trials (including 600 adult patients) and post-marketing use. Generally, adverse reactions have been minor and transitory and have mainly concerned the gastrointestinal system:

System Organ Class	Adverse Reactions
Gastrointestinal Disorders
Common	Abdominal pain and/or distension Diarrhoea Nausea
Uncommon	Vomiting Urgency to defecate Faecal incontinence
Metabolism and Nutrition Disorders
Unknown	Electrolytes disorders (hyponatremia, hypokalaemia) and or dehydration, especially in elderly patients
Immune System Disorders
Very rare	Hypersensitivity reactions (pruritus, rash, face oedema, Quincke oedema, urticaria, anaphylactic shock)

Excessive doses can cause diarrhoea, which usually disappear after dose reduction or temporary discontinuation of treatment.

Paediatric population:

The undesirable effects listed in the table below have been reported during clinical trials including 147 children aged from 6 months to 15 years and post-marketing use. As in adult population, adverse reactions have generally been minor and transitory and have mainly concerned the gastrointestinal system:

System Organ Class	Adverse Reactions
Gastrointestinal Disorders
Common	Abdominal pain
	Diarrhoea*
Uncommon	Vomiting
	Bloating
	Nausea

Immune System Disorders

Unknown    Hypersensitivity reactions

* Diarrhoea may cause perianal soreness

Excessive doses can cause diarrhoea, which usually disappear after dose reduction or temporary discontinuation of treatment. Diarrhoea can cause perianal pain.

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: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Overdose leads to diarrhoea which disappears when treatment is temporarily interrupted or the dosage is reduced.

Excessive fluid loss by diarrhoea or vomiting may require correction of electrolyte disturbances.

Cases of aspiration have been reported when extensive volumes of polyethylene glycol and electrolytes were administered with nasogastric tube. Neurologically impaired children who have oromotor dysfunction are particularly at risk of aspiration.

Perianal inflammation and pain have been reported when extensive volumes of macrogol solution (4-11 l) were administered prior to colonoscopy or before the defecation in case of encopresis.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Osmotically acting laxatives ATC code: A06AD15

High molecular weight (4000) macrogols are long linear polymers which retain water molecules by means of hydrogen bonds. When administered by the oral route, they lead to an increase in volume of intestinal fluids.

The volume of unabsorbed intestinal fluid accounts for the laxative properties of the solution.

5.2    Pharmacokinetic properties

The pharmacokinetic data confirm that macrogol 4000 undergoes neither gastrointestinal resorption nor biotransformation following oral ingestion.

5.3 Preclinical safety data

Toxicological studies in different species of animals did not reveal any signs of systemic or local gastrointestinal toxicity of macrogol 4000. Macrogol 4000 had no teratogenic, mutagenic, nor carcinogenic effect. Potential drug interaction studies performed in rats on some NSAIDs, anticoagulants, gastric antisecretory agents, or on a hypoglycaemic sulfamide showed that MACROGOL did not interfere with gastrointestinal absorption of these compounds.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Saccharin sodium dehydrate (E 954)

Silica, colloidal anhydrous

MACROGOL APPLE FLAVOUR contains also Apple flavour powder:

Sucrose

Wheat starch

Aroma

Silica, colloidal hydrated

6.2 Incompatibilities

Not applicable.

6.3    Shelf life

24 months

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of container

Size of packing

(Paper / PE / Aluminium / PE) sachet.

Single dose 4g sachets presented in pack sizes of 12 sachets.

Single dose 10g sachets presented in pack sizes of 12 and 24 sachets. Not all pack sizes may be marketed

6.6 Special precautions for disposal

Description of the appearance of the product after reconstitution: Almost white to lightly yellowish opalescent solution.

Instructions for preparation: The powder from the sachet(s) is dissolved in a glass of water, and then the whole contents of the glass should be used up.

7 MARKETING AUTHORISATION HOLDER

Winthrop Pharmaceuticals UK Limited

One Onslow Street

Guildford

Surrey

GU1 4YS

United Kingdom

Trading as: Zentiva, One Onslow Street, Guildford, Surrey, GU1 4YS, UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 17780/0554

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

08/10/2012

10    DATE OF REVISION OF THE TEXT

05/06/2015