MOVIPREP ORANGE POWDER FOR ORAL SOLUTION - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

MOVIPREP Orange, powder for oral solution

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

The ingredients of Moviprep Orange are contained in two separate sachets.

Sachet A contains the following active substances:

Macrogol 3350

Sodium sulfate anhydrous            7.500

Sodium chloride                     ­2.691

Potassium chloride                    1­.015 g

Sachet B contains the following active substances:

Ascorbic acid                        4­.700 g

Sodium ascorbate                    5­.900 g

The concentration of electrolyte ions when both sachets are made up to one litre of solution is as follows:

Sodium                            1­81.6 mmol/L (of which not more than

56.2 mmol is absorbable)

Sulfate                             ­52.8 mmol/L

Chloride                           ­59.8mmol/L

Potassium                         ­14.2 mmol/L

Ascorbate                         ­29.8 mmol/L

Excipient(s) with known effect:

This product contains 0.175 g of aspartame and 0.120 g of dextrose per sachet A.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Powder for oral solution

Free flowing white to off-white powder in Sachet A

Free flowing white to light brown powder in Sachet B

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Moviprep Orange is indicated in adults for bowel cleansing prior to any clinical procedures requiring a clean bowel e.g. bowel endoscopy or radiology.

4.2 Posology and method of administration

Posology

Adults and Older People

A course of treatment consists of two litres of Moviprep Orange. It is strongly recommended that one litre of clear liquid, which may include water, clear soup, fruit juice without pulp, soft drinks, tea and/or coffee without milk, is also taken during the course of treatment.

A litre of Moviprep Orange consists of one ‚sachet A‘ and one ‚sachet B‘ dissolved together in water to make one litre of solution. The reconstituted solution should be drunk over a period of one to two hours. This process should be repeated with a second litre of Moviprep Orange to complete the course.

This course of treatment can be taken either as divided or as single doses and timing is dependent on whether the clinical procedure is conducted with or without general anaesthesia as specified below:

For procedures conducted under general anaesthesia:

1. Divided doses: one litre of Moviprep Orange in the evening before and one litre of Moviprep Orange in the early morning of the day of the clinical procedure. Ensure consumption of Moviprep Orange as well as any other clear fluids has finished at least two hours before the start of the clinical procedure.

2. Single dose: two litres of Moviprep Orange in the evening before the clinical procedure or two litres of Moviprep Orange in the morning of the clinical procedure. Ensure consumption of Moviprep Orange as well as any other clear fluids has finished at least two hours before the start of the clinical procedure.

For procedures conducted without general anaesthesia:

1. Divided doses: one litre of Moviprep Orange in the evening before and one litre of Moviprep Orange in the early morning of the day of the clinical procedure. Ensure consumption of Moviprep Orange as well as any other clear fluids has finished at least one hour before the start of the clinical procedure.

2. Single dose: two litres of Moviprep Orange in the evening before the clinical procedure or two litres of Moviprep Orange in the morning of the clinical procedure. Ensure consumption of Moviprep Orange has finished at least two hours before the start of the clinical procedure. Ensure consumption of any clear fluids has finished at least one hour before the clinical procedure.

Patients should be advised to allow for appropriate time to travel to the colonoscopy unit.

No solid food should be taken from the start of the course of treatment until after the clinical procedure.

Paediatric population

Not recommended for use in children below 18 years of age, as Moviprep Orange has not been studied in the paediatric population.

4.3 Contraindications

Do not use in patients with known or suspected:

– hypersensitivity to the active substances or to any of the excipients listed in section 6.1

– gastrointestinal obstruction or perforation

– disorders of gastric emptying (e.g. gastroparesis)

– ileus

– phenylketonuria (due to presence of aspartame)

– glucose-6-phosphate dehydrogenase deficiency (due to presence of ascorbate)

– toxic megacolon which complicates very severe inflammatory conditions of the intestinal

tract including Crohn’s disease and ulcerative colitis.

Do not use in unconscious patients

4.4 Special warnings and precautions for use

Diarrhoea is an expected effect resulting from the use of Moviprep Orange.

Moviprep Orange should be administered with caution to fragile patients in poor health or patients with serious clinical impairment such as:

– impaired gag reflex, or with a tendency to aspiration or regurgitation

– impaired consciousness

– severe renal insufficiency (creatinine clearance <30 mL/min)

– cardiac impairment (NYHA grade III or IV)

– those at risk of arrhythmia, for example those on treatment for cardiovascular

disease or who have thyroid disease

– dehydration

– severe acute inflammatory bowel disease

The presence of dehydration should be corrected before the use of Moviprep Orange.

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

Semi-conscious patients or patients prone to aspiration or regurgitation should be closely observed during administration, especially if this is via a nasogastric route.

If patients develop any symptoms indicating arrhythmia or shifts of fluid/electrolytes (e.g. oedema, shortness of breath, increasing fatigue, cardiac failure), plasma electrolytes should be measured, ECG monitored and any abnormality treated appropriately.

In debilitated fragile patients, patients with poor health, those with clinically significant renal impairment, arrhythmia and those at risk of electrolyte imbalance, the physician should consider performing a baseline and posttreatment electrolyte, renal function test and ECG as appropriate.

There have been rare reports of serious arrhythmias including atrial fibrillation associated with the use of ionic osmotic laxatives for bowel preparation. These occur predominantly in patients with underlying cardiac risk factors and electrolyte disturbance.

If patients experience symptoms such as severe bloating, abdominal distention, abdominal pain or any other reaction which makes it difficult to continue the preparation, they may slow down or temporarily stop consuming Moviprep Orange and should consult their doctor.

Ischaemic colitis

Post-marketing cases of ischaemic colitis, including serious, have been reported in patients treated with macrogol for bowel preparation. Macrogol should be used with caution in patients with known risk factors for ischaemic colitis or in case of concomitant use of stimulant laxatives (such as bisacodyl or sodium picosulfate). Patients presenting with sudden abdominal pain, rectal bleeding or other symptoms of ischaemic colitis should be evaluated promptly.

This medicinal product contains 363.2 mmol (8.4 g) sodium per course of treatment, equivalent to 420% of the WHO recommended maximum daily intake of 2 g sodium for an adult. (A course of treatment consists of two litres of Moviprep Orange.) To be taken into consideration by patients on a controlled sodium diet. Only a proportion (up to 112.4 mmol (2.6 g) per course treatment) of sodium is absorbed.

This medicinal product contains 28.4 mmol (1.1 g) potassium per course of treatment. (A course of treatment consists of two litres of Moviprep Orange). To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

The medicinal product contains aspartame, which is a source of phenylalanine. This may be harmful for people with phenylketonuria.

Patients with rare glucose-galactose malabsorption should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

Oral medication should not be taken within one hour of administration of Moviprep Orange as it may be flushed from the gastro-intestinal tract and not absorbed. The therapeutic effect of drugs with a narrow therapeutic index or short half-life may be particularly affected.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data on the use of Moviprep Orange during pregnancy.

The preparation should only be used during pregnancy if considered essential by the physician.

Breastfeeding

There are no data on the use of Moviprep Orange during lactation.

The preparation should only be used during lactation if considered essential by the physician.

Fertility

There are no data on the effects of Moviprep Orange on fertility.

4.7 Effects on ability to drive and use machines

Moviprep Orange has no influence on the ability to drive and use machines.

4.8 Undesirable effects

Diarrhoea is an expected outcome of bowel preparation. Due to the nature of the intervention, undesirable effects occur in the majority of patients during the process of bowel preparation. Whilst these vary between preparations, nausea, vomiting, bloating, abdominal pain, anal irritation and sleep disturbance commonly occur in patients undergoing bowel preparation. Dehydration may occur as a result of diarrhoea and/or vomiting.

As with other macrogol containing products, allergic reactions including rash, urticaria, pruritus, dyspnoea, angioedema and anaphylaxis are a possibility.

Data from clinical studies are available in a population of 825 patients treated with Moviprep in which undesirable effect data were actively elicited.

Additionally, adverse events reported in post marketing are included.

The frequency of adverse reactions to Moviprep Orange is defined using the following convention:

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 Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for the MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

5   PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Osmotically acting laxative.

ATC code: A06A D

The oral administration of macrogol-based electrolyte solutions causes moderate diarrhoea and results in rapid emptying of the colon.

Macrogol 3350, sodium sulfate and high doses of ascorbic acid exert an osmotic action in the gut, which induce a laxative effect.

Macrogol 3350 increases the stool volume, which triggers colon motility via neuromuscular pathways.

The physiological consequence is a propulsive colonic transportation of the softened stools. The electrolytes present in the formulation and the supplementary clear liquid intake are included to prevent clinically significant variations of sodium, potassium or water, and thus reduce dehydration risk.

5.2 Pharmacokinetic properties

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.

Ascorbic acid is absorbed mainly at the small intestine level by a mechanism of active transport, which is sodium dependant and saturable. There is an inverse relationship between the ingested dose and the percentage of the absorbed dose. For oral doses between 30 and 180 mg an amount of about 70–85% of the dose is absorbed. Following oral intake of up to 12 g ascorbic acid, it is known that only 2 g is absorbed.

After high oral doses of ascorbic acid and when plasma concentrations exceed 14 mg/litre, the absorbed ascorbic acid is mainly eliminated unchanged in the urine.

Osmotically-acting bowel preparations lead to a copious diarrhoea, resulting in extensive elimination of most of the product via the faeces. They can also lead to changes in electrolyte balance in the body, often with depletion of sodium and potassium. The additional sodium and potassium included in the MOVIPREP Orange formulation help to balance the electrolytes. While some absorption of sodium takes place, the bulk of sodium is expected to be excreted in the faeces as the sodium salts of sulfate and ascorbate, the osmotic active ingredients included in the MOVIPREP Orange composition.

5.3 Preclinical safety data

Preclinical studies provide evidence that macrogol 3350, ascorbic acid and sodium sulfate have no significant systemic toxicity potential, based on conventional studies of pharmacology, repeated dose toxicity, genotoxicity and carcinogenicity.

No studies have been carried out on the genotoxicity, carcinogenicity or toxic effect on reproduction with this product.

In reproductive toxicity studies with macrogol 3350 + electrolytes there were no direct embryotoxic or teratogenic effects in rats even at maternally toxic levels that are a multiple of 14× the maximum recommended dose of Moviprep Orange in humans. 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 are 0.7 fold of the maximum recommended dose of Moviprep Orange in humans.

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 + electrolytes related to poor maternal condition as the result of an exaggerated pharmacodynamic response in the rabbit. There was no indication of a teratogenic effect.

6.1 List of excipients

Aspartame (E951)

Acesulfame Potassium (E950)

Orange flavour (containing natural flavouring substances and preparations, maltodextrin, dextrose)

6.2 Incompatibilities

Not applicable

6.3

Sachets

Reconstituted solution

3 years

24 hours

6.4. Special precautions for storage

Sachets: Store below 25°C.

Reconstituted solution: Store below 25°C. The solution may be refrigerated.

Keep the solution covered

6.5 Nature and contents of container

A paper / low density polyethylene / aluminium / low density polyethylene sachet containing 112 g of powder (‘sachet A’) and a paper / low density polyethylene / aluminium / low density polyethylene sachet containing 11 g of powder (‘sachet B’). Both sachets are contained in a transparent bag. One pack of Moviprep Orange contains a single treatment of two bags.

Pack sizes of 1, 10, 40, 80, 160 and 320 packs of a single treatment.

Hospital packs of 40 single treatments. Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Reconstitution of Moviprep Orange in water may take up to 5 minutes and is best performed by adding the powder to the mixing vessel first followed by the water. The patient should wait until all the powder has dissolved before drinking the solution.

After reconstitution in water Moviprep Orange consumption may begin immediately or if preferred it may be cooled before use.

7 MARKETING AUTHORISATION HOLDER

Norgine Pharmaceuticals Limited

Widewater Place, Moorhall Road

Harefield, UB9 6NS UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 20011/0006

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

06/08/2010