SUMMARY OF PRODUCT CHARACTERISTICS 1    NAME OF THE MEDICINAL PRODUCT

Molaxole powder for oral solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sachet contains following active substances

Macrogol 3350	13.125 g
Sodium chloride	350.7	mg
Potassium chloride	46.6	mg
Sodium hydrogen carbonate	178.5	mg

The content of electrolyte ions per sachet when made up to 125 ml of solution. Sodium    65    mmol/l

Potassium    5.4    mmol/l

Chloride    53    mmol/l

Hydrogen carbonate    17    mmol/l

For a full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Powder for oral solution A white crystalline powder.

4    CLINICAL PARTICULARS

4.1 Therapeutic indications

For the treatment of chronic constipation. Resolving faecal impaction, defined as refractory constipation with faecal loading of the rectum and/or colon confirmed by physical examination of the abdomen and rectum.

4.2 Posology and method of administration

Chronic constipation:

Adults: 1-3 sachets daily in divided doses. Normal dose for most patients is 12 sachets per day. Depending on the individual response 3 sachets per day might be needed.

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

For extended use, the lowest effective dose should be used.

Children:

Not recommended for children below 12 years old.

Faecal impaction:

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

A course of treatment for faecal impaction does not normally exceed 3 days. Children:

Not recommended for children below 12 years old.

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.

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.

4.3 Contraindications

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

Hypersensitivity to the active substances or to any of the excipients.

4.4 Special warnings and special precautions for use

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

The cause of constipation should be investigated if daily use of laxatives is necessary.

Patients using this preparation should seek medical advice if there is no improvement after two weeks.

Long term use can be necessary in serious chronical or refractory constipation due to i.e multiple sclerosis (MS) or Parkinsons disease, or constipation induced by drugs, especially opioides or antimuscarine products.

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

There is no clinical data on the use of Molaxole in children, therefore it is not recommended.

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

4. 5 Interaction with other medicinal products and other forms of interaction

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

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no experience of the use of Molaxole during pregnancy and it should only be used if considered essential by the physician.

Lactation

There is no experience of the use of Molaxole during lactation. The risk of undesirable effects in nursing infants is considered to be negligible since the systemic exposure of the breast-feeding woman of Macrogol 3350 is negligible.

Fertility

There are no or limited amount of data on the effect of Molaxole on fertility.

4.7 Effects on ability to drive and use machines

There is no effect on the ability to drive and use machines.

4.8 Undesirable effects

The most common undesirable effects are gastrointestinal effects. 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 Molaxole. Mild diarrhoea usually responds to dose reduction.

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: 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).

System Organ Class	Frequency	Adverse Event
Immune system disorders	Common	Pruritus
	Uncommon	Rash
	Very rare	Allergic reactions, including anaphylaxis, angioedema, dyspnoea, erythema, urticaria and rhinitis
Metabolism and nutrition disorders	Very rare	Electrolyte disturbances, particularly hyperkalaemia and hypokalaemia.
Nervous system disorders	Common	Headache
Gastrointestinal disorders	Very common	Stomach ache and cramp, diarrhoea, vomiting, nausea, borborygmi, flatulence
	Uncommon	Dyspepsia, abdominal distension
	Very rare	Anal discomfort
General disorders and administration site conditions	Common	Peripheral oedema

4.9 Overdose

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

5.1 Pharmacodynamic properties

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 consequences are 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 or water.

For the indication of faecal impaction controlled comparative studies have not been performed with other treatments (e.g. enemas). In a non-comparative study in 27 adult patients, macrogol, sodium chloride, potassium chloride and sodium hydrogen carbonate cleared the faecal impaction in 12/27 (44%) after 1 days' treatment; 23/27 (85%) after 2 days' treatment and 24/27 (89%) at the end of 3 days.

Clinical studies in the use of macrogol, sodium chloride, potassium chloride and sodium hydrogen carbonate 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 a day, but this dose should be adjusted depending on individual response.

5.2 Pharmacokinetic properties

Macrogol is unchanged along the gut. It is virtually unabsorbed from the gastrointestinal tract and has no known pharmacological activity. Any macrogol 3350 that is absorbed is excreted via the urine.

5.3 Preclinical safety data

Preclinical studies provide evidence that macrogol 3350 has no significant systemic toxicity potential, although no tests of its effects on reproduction or genotoxicity have been conducted.

There are no long term animal toxicity or carcinogenicity studies involving macrogol 3350, although there are toxicity studies using high levels of orally administered high molecular weight macrogols that provide evidence of safety at the recommended therapeutic dose.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Acesulfam potassium (E950), lemon flavour.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

Store the reconstituted solution in refrigerator (2°C-8°C) and discard any solution not used within 6 hours.

6.4. Special precautions for storage

This medicinal product does not require any special temperature storage conditions.

Store in the original package in order to protect from moisture.

For storage conditions of the reconstituted medicinal product, see section 6.3.

6.5 Nature and content of container

Sachets of Paper/LDPE/Aluminium/LDPE alternatively

Sachets of Paper/PE/Aluminium/ Ethylene Methacrylic Acid Copolymer e.g. Surlyn Package of: 2, 6, 8, 10, 20, 30, 40, 50, 60 and 100 sachets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Meda Pharmaceuticals Ltd Skyway House Parsonage Road Takeley

Bishop’s Stortford CM22 6PU

8    MARKETING AUTHORISATION NUMBER(S)

PL 15142/0108

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

10/04/2013

10 DATE OF REVISION OF THE TEXT

04/07/2013