Molaxole powder for oral solution

Each sachet contains following active substances

The content of electrolyte ions per sachet when made up to 125 ml of solution.

For the full list of excipients, see section 6.1.

Powder for oral solution

A white crystalline powder.

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.

Posology

Chronic constipation:

Adults: 1-3 sachets daily in divided doses. Normal dose for most patients is 1-2 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.

Faecal impaction:

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

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

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.

Paediatric population:

Not recommended for children below 12 years old.

Method of administration

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.

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 listed in section 6.1.

The fluid content of Moxalole, when reconstituted with water, cannot substitute normal fluid intake, and a suitable level of fluid intake should therefore be maintained.

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).

This medicinal product contains 187 mg sodium in each sachet equivalent to 9.5 % of the WHO maximum recommended daily intake of 2 g sodium for an adult.

Paediatric population

Not recommended for children below 12 years old.

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.

Pregnancy

There is limited data on the use of macrogol 3350 in pregnant women. Studies in animals have shown indirect reproduction toxicity (see section 5.3). No effects during pregnancy are anticipated, since systemic exposure to macrogol 3350 is negligible. Molaxole can be used during pregnancy.

Breast-feeding

No effects on a breast-feeding child are anticipated since the systemic exposure of the breast-feeding woman to macrogol 3350 is negligible. Molaxole can be used when breast-feeding.

Fertility

There are no clinical data on the effect of Molaxole on fertility. A non-clinical study indicates that there is no effect of macrogol 3350 on the fertility of rats (see section 5.3).

Molaxole has no effect on the ability to drive and use machines.

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).

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.

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

Pharmacotherapeutic group: Drugs for constipation, 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.

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

Preclinical studies provide evidence that macrogol 3350 has no significant systemic toxic effect. This has been determined based on conventional studies of pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development (in rats).

No direct embryotoxic or teratogenic effects were seen in rats even at levels that were toxic to the mother, which were 66 times higher than the maximum human recommended dose for chronic constipation and 25 times higher than that for faecaloma. Indirect embryofoetal effects including reduction in foetal and placental weight, reduced foetal survival, increased hyperflexion in extremities and paws as well as miscarriage were observed in rabbits at doses toxic to the mother, equivalent to 3.3 times the maximum recommended human dose for the treatment of chronic constipation, and 1.3 times the maximum recommended dose for faecaloma. Rabbits are exceptionally sensitive to the effect of substances that act on the gastrointestinal tract, and the studies were performed under exaggerated conditions with the administration of high doses which are not clinically relevant. The findings may be a consequence of an indirect effect of macrogol 3350 combined with the mother being in poor general condition, caused by an exaggerated pharmacodynamic response in the rabbit. There were no signs of teratogenic effects.

Long-term studies on the toxicity and carcinogenicity of use of macrogol 3350 have been performed in animals. Results from these and other toxicity studies, in which high doses of orally-administered macrogols were used with high molecular weight, support the safety of the product at the recommended therapeutic doses.

Acesulfam potassium (E950), lemon flavour.

Not applicable.

3 years.

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

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 after reconstitution of the medicinal product, see section 6.3.

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 or 2x50 sachets.

Not all pack sizes may be marketed.

No special requirements for disposal.

Mylan Products Ltd,

Station Close,

Potters Bar,

Hertfordshire

EN6 1TL, UK

PL 46302/0180

27/01/2009

11^th October 2019