LAXIDO PAEDIATRIC PLAIN 6.9 G POWDER FOR ORAL SOLUTION - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Laxido Paediatric Plain 6.9 g, powder for oral solution

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each sachet contains the following quantitative composition of active ingredients:

Macrogol 3350 6.563 g

Sodium Chloride      175.4 mg

Sodium Hydrogen Carbonate 89.3 mg

Potassium Chloride    25.1 mg

The content of electrolyte ions per sachet following reconstitution in 62.5 ml of water is equivalent to:

Sodium 65 mmol/l

Chloride      53 mmol/l

Hydrogen Carbonate (Bicarbonate) 17 mmol/l

Potassium     5.4 mmol/l

3 PHARMACEUTICAL FORM

Powder for oral solution.

Single-dose sachet containing a white powder.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Laxido Paediatric Plain is indicated for the treatment of chronic constipation in children aged 1 to 11 years.

Laxido Paediatric Plain is indicated for the treatment of faecal impaction in children from the age of 5 years, defined as refractory constipation with faecal loading of the rectum and/or colon.

4.2 Posology and method of administration

Laxido Paediatric Plain is for oral use.

Posology

Chronic constipation:

The usual starting dose is 1 sachet daily for children aged 1 to 6 years, and 2 sachets daily for children aged 7 to 11 years. The dose should be adjusted up or down as required to produce regular soft stools. If the dose needs increasing this is best done every second day. For children below 2 years of age, the maximum recommended dose should not exceed 2 sachets a day. For children aged 2 to 11 years, the maximum recommended dose needed does not normally exceed 4 sachets a day.

Treatment of children with chronic constipation needs to be for a prolonged period (at least 6 to 12 months). However, safety and efficacy have only been proven for a period of up to 3 months. Treatment should be stopped gradually and resumed if constipation recurs.

Faecal impaction:

A course of treatment for faecal impaction with Laxido Paediatric Plain is for up to 7 days as follows:

Daily dosage regimen:

The daily number of sachets should be taken in divided doses, all consumed within a 12 hour period. The above dosage regimen should be stopped once disimpaction has occurred. An indicator of disimpaction is the passage of a large volume of stools. After disimpaction it is recommended that the child follows an appropriate bowel management program to prevent re-impaction (dosing for prevention of re-impaction should be as for patients with chronic constipation; see above.)

Laxido Paediatric Plain is not recommended for children below 5 years of age for the treatment of faecal impaction, or in children below 1 year of age for the treatment of chronic constipation. For patients of 12 years and older it is recommended to use Laxido.

Patients with impaired cardiovascular function: There are no clinical data for this group of patients. Therefore Laxido Paediatric Plain is not recommended for treating faecal impaction in children with impaired cardiovascular function.

Patients with renal insufficiency: There are no clinical data for this group of patients. Therefore Laxido Paediatric Plain is not recommended for treating faecal impaction in children with impaired renal function.

Method of administration

Each sachet should be dissolved in 62.5 ml (quarter of a glass) of water, to make a clear or slightly hazy solution. The correct number of sachets may be reconstituted in advance and kept covered and refrigerated for up to 24 hours. For example, for use in faecal impaction, 12 sachets can be made up into 750 ml of water.

4.3 Contraindications

Hypersensitivity to the active substances.

Laxido Paediatric Plain is contraindicated in intestinal obstruction or perforation caused by functional or structural disorder of the gut wall, ileus and in patients with severe inflammatory conditions of the intestinal tract (e.g. ulcerative colitis, Crohn’s disease and toxic megacolon).

4.4 Special warnings and precautions for use

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

The faecal impaction diagnosis should be confirmed by appropriate physical or radiological examination of the rectum and abdomen.

Mild adverse drug reactions are possible as indicated in Section 4.8. Rarely symptoms indicating shifts of fluid/electrolytes e.g. oedema, shortness of breath, increasing fatigue, dehydration and cardiac failure have been reported in adults when using preparations containing macrogol. If this occurs Laxido Paediatric Plain should be stopped immediately, electrolytes measured, and any abnormality should be treated appropriately.

When used in high doses to treat faecal impaction this medicinal product should be administered with caution to patients with impaired gag reflex, reflux oesophagitis or diminished levels of consciousness.

Laxido Paediatric Plain solution when reconstituted has no calorific value.

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

This medicinal product contains 93 mg of sodium per sachet, equivalent to approximately 4.6% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

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.

4.5 Interaction with other medicinal products and other forms of interaction

Medicinal products in solid dose form taken within one hour of administration of large volumes of macrogol preparations (as used when treating faecal impaction) may be flushed from the gastro-intestinal tract and not absorbed.

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 Laxido Paediatric Plain (see section 4.4).

There have been isolated reports of decreased efficacy with some concomitantly administered medicinal products, e.g. anti-epileptics.

Laxido Paediatric Plain 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is a limited amount of data from the use of the Laxido formulation 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.

Laxido Paediatric Plain can be used during pregnancy.

Breast-feeding

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

Laxido Paediatric Plain can be used during breast-feeding.

Fertility

There are no data on the effects of the Laxido formulation 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

Laxido Paediatric Plain has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Reactions related to the gastro-intestinal tract occur most commonly.

These reactions may occur as a consequence of expansion of the contents of the gastro-intestinal tract, and an increase in motility due to the pharmacological effects of Laxido Paediatric Plain.

In the treatment of chronic constipation, diarrhoea or loose stools normally respond to a reduction in dose.

Diarrhoea, abdominal distension, anorectal discomfort and mild vomiting are more often observed during the treatment for faecal impaction. Vomiting may be resolved if the dose is reduced or delayed.

The frequency of the adverse reactions listed below is defined using the following convention: very common (> 1/10); common (> 1/100, < 1/10); uncommon (> 1/1000, <1/100); rare (> 1/10,000, < 1/1000); and 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 website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Severe distension or pain can be treated using nasogastric aspiration. Vomiting or diarrhoea may induce extensive fluid loss, possibly leading to electrolyte disturbances that should be treated appropriately.

5 PHARMACOLOGICAL PROPERTIES

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 consequence is an improved propulsive colonic transportation of the softened stools and a facilitation of the defaecation. 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.

In an open study of macrogol with electrolytes in chronic constipation, weekly defaecation frequency was increased from 1.3 at baseline to 6.7, 7.2 and 7.1 at weeks 2, 4 and 12 respectively. In a study comparing macrogol with electrolytes and lactulose as maintenance therapy after disimpaction, weekly stool frequency at the last visit was 9.4 (SD 4.46) in the macrogol with electrolytes group compared with 5.9 (SD 4.29). In the lactulose group 7 children re-impacted (23%) compared with no children in the macrogol with electrolytes group.

In one retrospective-prospective study, 35 patients <24 months age were treated with macrogol with electrolytes for functional constipation for a mean duration of 4.6 ± 3.67 months (from 3 weeks to 18 months). Mean stool frequency before treatment was 2.34 ± 0.98 per week. Following treatment, the frequency of bowel movements was 7.31 ± 1.60 per week, which was a significant difference from baseline (p < 0.001). There was also a significant difference in improvement from baseline in the stool consistency score after treatment (1.57 ± 0.54 vs. 3.34 ± 0.58; p < 0.001).

In an observational, prospective, longitudinal, parallel group study 62 children aged 1–17 years were treated for chronic constipation with macrogol / macrogol with electrolytes for 12 weeks. Of these 62 patients 30 were aged 1 – 3 years. The number of bowel movements per week was similar in both groups at weeks 6 and 12: mean (SD) 6.1 (2.5) and 6.0 (2.7) at 6 weeks, and 4.6 (2.2) and 5.4 (1.8) at 12 weeks for macrogol and macrogol with electrolytes. Similar improved efficacy results were observed in 2 further trials where patients 6 months – 15 years were treated with macrogol with electrolytes.

For the indication of faecal impaction comparative studies have not been performed with other treatments (e.g. enemas). In a non-comparative study in 63 children, macrogol with electrolytes (paediatric formulation) cleared the faecal impaction in the majority of patients within 3 to 7 days of treatment. For the 5 to 11 years age group the average total number of sachets of macrogol with electrolytes (paediatric formulation) required was 47.2.

5.2 Pharmacokinetic properties

Macrogol 3350 is virtually unabsorbed from the gastro-intestinal tract and is excreted, unaltered, in faeces. Any macrogol 3350 that enters the systemic circulation is excreted in urine.

5.3 Preclinical safety data

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 embryofetal effects, including reduction in fetal and placental weights, reduced fetal 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 macrogol 3350 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.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

None.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Sachet: 2 years.

Reconstituted solution: 24 hours.

6.4 Special precautions for storage

Sachet: Store below 25 °C.

Reconstituted solution: Store covered in a refrigerator (2 °C to 8 °C).

6.5 Nature and contents of container

6.9 g sachet.

The sachet is composed of paper, low density polyethylene and aluminium. Sachets are packed in cartons of 2, 6, 8, 10, 20, 30, 50 or 100 sachets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused solution should be discarded after 24 hours.

7 MARKETING AUTHORISATION HOLDER

Galen Limited

Seagoe Industrial Estate

Craigavon

BT63 5UA

UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 27827/0028

9 DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE

Date of first authorisation: 02/06/2015

Date of latest renewal: 28/04/2020