This information is intended for use by health professionals

1. Name of the medicinal product

PICOLAX powder for oral solution

2. Qualitative and quantitative composition

Each sachet contains the following active ingredients:

Sodium picosulfate

10.0mg

Magnesium oxide, light

3.5g

Citric acid, anhydrous

12.0g

-

Each sachet also contains:

Potassium hydrogen carbonate 0.5g [equivalent to 5 mmol (195 mg) potassium]

Lactose (as a component of the flavour)

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Powder for oral solution.

White crystalline powder.

4. Clinical particulars
4.1 Therapeutic indications

PICOLAX is indicated in adults, adolescents and children from the age of 1 year:

- To clean the bowel prior to X-ray examination or endoscopy.

- To clean the bowel prior to surgery when judged clinically necessary (see section 4.4 regarding open colorectal surgery).

4.2 Posology and method of administration

Posology

Adults (including the elderly):

The two PICOLAX sachets are taken dependent on the planned time of the procedure:

• The first reconstituted sachet is taken 10 to 18 hours before the procedure, followed by at least five 250 ml drinks of clear liquids, spread over several hours

• The second reconstituted sachet is taken 4 to 6 hours before the procedure, followed by at least three 250 ml drinks of clear liquids, spread over several hours

• Clear liquids may be consumed until 2 hours before the time of the procedure

Special populations

Limited data is available for treatment of patients with low body weight (BMI less than 18). The rehydration regimen above has not been tested in such individuals and therefore monitoring of their hydration status is required and the regimen may need to be altered appropriately (see section 4.4).

Paediatric population:

A measuring spoon is provided with the product. It is recommended that a narrow flat edge, for example the back of a knife blade, is drawn across the top of a heaped measuring spoon to obtain a flat surface of the measure. This will give ¼ of a sachet (4 g powder) per spoonful.

For the timing of dosing in children, refer to the instructions given for adults

1 - 2 years: first dose is 1 spoonful, second dose is 1 spoonful

2 - 4 years: first dose is 2 spoonfuls, second dose is 2 spoonfuls

4 - 9 years: first dose is 1 sachet, second dose is 2 spoonfuls

9 years and above: adult dose

Method of administration

Route of administration: Oral

Directions for reconstitution (Adults):

Reconstitute the contents of one sachet in a cup of water (approximately 150 ml). Stir for 2-3 minutes, the solution should now become an off-white, cloudy liquid with a faint odour of orange. Drink the solution. If it becomes hot, wait until it cools sufficiently to drink.

Directions for reconstitution (Paediatric population):

Reconstitute the required amount of powder in a cup containing approximately 50 ml water per spoonful. Stir for 2-3 minutes, the solution should now become an off-white, cloudy liquid with a faint odour of orange. Drink the solution. If it has become warm, wait until it cools sufficiently to drink.

Discard the remaining contents of the sachet.

For directions on reconstitution of the full sachet for children of 4-9 years, refer to the instructions given for adults.

A low residue diet is recommended on the day prior to the procedure. A clear liquid diet is recommended on the day of the procedure. To avoid dehydration it is important to follow the liquid intake recommendation as advocated together with the PICOLAX dosing whilst the effects of PICOLAX persist (see section 4.2, Posology). Apart from the liquid intake together with the treatment regimen (PICOLAX + additional liquids), a normal, thirst driven intake of clear liquids is recommended.

Clear liquids should include a variety of fruit juice without pulp, soft drinks, clear soup, tea, coffee (without milk, soy or cream) and water. Do not drink only water.

4.3 Contraindications

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1

- Congestive cardiac failure

- Gastric retention

- Gastro-intestinal ulceration

- Toxic colitis

- Toxic megacolon

- Ileus

- Nausea and vomiting

- Acute surgical abdominal conditions such as acute appendicitis

- Known or suspected gastro-intestinal obstruction or perforation.

- Severe dehydration

- Rhabdomyolysis

- Hypermagnesemia

- Active inflammatory bowel disease

- In patients with severely reduced renal function, accumulation of magnesium in plasma may occur. Another preparation should be used in such cases.

4.4 Special warnings and precautions for use

Because a clinically relevant benefit of bowel cleansing prior to elective, open colorectal surgery could not be proven, bowel cleansers should only be administered before bowel surgery if clearly needed. The risks of the treatment should be carefully weighed against possible benefits and needs depending on surgical procedures performed.

An insufficient or excessive oral intake of water and electrolytes could create clinically significant, deficiencies, particularly in less fit patients. In this regard patients with low body weight, children, the elderly, debilitated individuals and patients at risk of hypokalaemia or hyponatremia may need particular attention. Prompt corrective action should be taken to restore fluid/electrolyte balance in patients with signs or symptoms of hypokalaemia or hyponatremia.

Drinking only water to replace the fluid losses may lead to electrolyte imbalance.

Care should also be taken in patients with recent gastro-intestinal surgery, renal impairment, heart disease or inflammatory bowel disease.

Use with caution in patients on drugs that might affect water and/or electrolyte balance e.g. diuretics, corticosteroids, lithium (see 4.5).

PICOLAX may modify the absorption of regularly prescribed oral medication and should be used with caution e.g. there have been isolated reports of seizures in patients on antiepileptics, with previously controlled epilepsy (see 4.5 and 4.8).

The period of bowel cleansing should not exceed 24 hours because longer preparation may increase the risk of water and electrolyte imbalance.

For an early time of the day procedure it may be required to take the second dose during the night and possible sleep disturbance may occur.

This medicine contains 5 mmol (or 195 mg) potassium per sachet. This should be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

This medicine contains lactose as a component of the flavour. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Picolax should not be used as a routine laxative.

4.5 Interaction with other medicinal products and other forms of interaction

As a purgative, PICOLAX increases the gastrointestinal transit rate. The absorption of other orally administered medicines (e.g. anti-epileptics, contraceptives, anti-diabetics, antibiotics) may therefore be modified during the treatment period (see 4.4). Tetracycline and fluoroquinolone antibiotics, iron, digoxin, chlorpromazine and penicillamine, should be taken at least 2 hours before and not less than 6 hours after administration of PICOLAX to avoid chelation with magnesium.

The efficacy of PICOLAX is lowered by bulk-forming laxatives.

Care should be taken with patients already receiving drugs which may be associated with hypokalaemia (such as diuretics or corticosteroids, or drugs where hypokalaemia is a particular risk i.e. cardiac glycosides). Caution is also advised when PICOLAX is used in patients on NSAIDs or drugs known to induce SIADH e.g. tricyclic antidepressants, selective serotonin re-uptake inhibitors, antipsychotic drugs and carbamazepine as these drugs may increase the risk of water retention and/or electrolyte imbalance.

4.6 Fertility, pregnancy and lactation

Pregnancy

For PICOLAX no clinical data on exposed pregnancy are available.

Studies in animals have shown reproductive toxicity (see section 5.3). As picosulfate is a stimulant laxative, for safety measure, it is preferable to avoid the use of PICOLAX during pregnancy.

Fertility

There are no data on the effect of PICOLAX on fertility in humans.

Male and female rat fertility was not affected by oral doses of sodium picosulfate up to 100 mg/kg (see section 5.3).

Breastfeeding

There is no experience with the use of PICOLAX in nursing mothers. However, due to the pharmacokinetic properties of the active ingredients, treatment with PICOLAX may be considered for females who are breastfeeding.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

The most frequent adverse reactions seen in clinical trials are nausea, headache and vomiting.

MedDRA Organ Class

Common

(≥1/100 to <1/10)

Uncommon

(≥1/1000 to <1/100)

Not known (cannot be estimated from the available data)

Immune system disorder

Anaphylactic reaction, hypersensitivity

Metabolism and nutrition disorders

Hyponatraemia and hypokalaemia

Nervous system disorders

Headache

Epilepsy, grand mal convulsion, convulsions, confusional state

Gastrointestinal disorders

Nausea and proctalgia

Vomiting, abdominal pain, aphthoid ileal ulcers*

Diarrhoea, faecal incontinence

Skin and subcutaneous tissue disorders

Rash (including erythematous and maculo-papular rash, urticaria, purpura)

*Isolated cases of mild reversible aphthoid ileal ulcers have been reported.

¤ The frequencies of the side effects are based on post-marketing experience.

Diarrhoea and faecal incontinence are the primary clinical effect of PICOLAX. Isolated cases of severe diarrhoea have been reported post-marketing.

Hyponatraemia has been reported with or without associated convulsions. In epileptic patients, there have been isolated reports of seizure/grand mal convulsion without associated hyponatraemia. There have been isolated reports of anaphylactoid reaction.

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.

4.9 Overdose

Overdose would lead to profuse diarrhoea. Treatment is by general supportive measures and correction of fluid and electrolyte balance.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Contact Laxatives

ATC code: A06A B58

The active components of PICOLAX are sodium picosulfate and magnesium citrate. Sodium picosulfate is a locally acting stimulant cathartic, which after bacterial cleavage in the colon forms the active laxative compound, bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM), which has a dual-action with stimulation of the mucosa of both the large intestine and of the rectum. Magnesium citrate acts as an osmotic laxative by retaining moisture in the colon. The combined action of the two substances is of a 'washing out' effect combined with peristaltic stimulation to clear the bowel.

The product is not intended for use as a routine laxative.

Clinical efficacy and safety

The dosing regimen as described in section 4.2 Posology, and herein further referred to as the tailored dosing regimen, was investigated and evaluated in trial 000121 (OPTIMA) that compared the efficacy, safety and tolerability of PICOLAX administered according to the tailored dosing regimen versus the fixed schedule of dosing (i.e. first dose is taken before 8am and second dose is taken 6-8 hours later on the day before procedure), called day before dosing regimen (204 patients were randomized, 131 received tailored dosing, 73 received day before dosing).

Superiority of the tailored dosing regimen was demonstrated compared to the day before dosing regimen in overall colon cleansing and responder status for ascending colon cleansing. For overall colon cleansing, the tailored dosing regimen was compared to the day before dosing regimen, based on the treatment difference in mean total Ottawa Scale score (4.26 versus 8.19 in mean total Ottawa scale score for tailored dosing regimen and day before dosing regimen respectively, with a corresponding p-value <0.0001, for the Intend to Treat (ITT) analysis set). For the responder status of the ascending colon, the proportion of patients with an Ottawa Scale score of either 0 (excellent) or 1 (good), was compared between the tailored dosing regimen and the day before dosing regimen. Patients randomized to the tailored dosing regimen were observed to have a 4.05 greater chance of being a responder with respect to ascending colon cleansing compared to patients randomized to the day before dosing regimen.

Endpoint

Study Population

(n=204)

PICOLAX day before dosing regimen

Estimate

(n=73)

PICOLAX tailored dosing regimen

Estimate (95%CI)

(n=131)

Mean Total Ottawa Scale Score

(Adjusted estimate)

ITT

8.19

4.26

-3.93(-4.99,-2.87)

p-value < 0.0001

Proportion of patients with an Ottawa Scale score of either 0 (excellent) or 1 (good) for Ascending Colon Cleansing (Crude estimate)

ITT

15.1%

61.1%

RD* 0.46 (0.34; 0.58)

RR** 4.05 (2.31; 7.11)

* Absolute Risk Difference (Crude)

** Relative Risk (Crude)

5.2 Pharmacokinetic properties

Both active components are locally active in the colon, and neither are absorbed in any detectable amounts.

5.3 Preclinical safety data

Prenatal developmental studies in rats and rabbits did not reveal any teratogenic potential after oral dosing of sodium picosulfate, but embryotoxicity has been observed in rats at 1000 and 10000 mg/kg/day and in rabbits at 1000 mg/kg/day. The corresponding safety margins were 3000 to 30000 times the anticipated human dose. In rats, daily doses of 10 mg/kg during late gestation (fetal development) and lactation reduced body weights and survival of the offspring. Male and female rat fertility was not affected by oral doses of sodium picosulfate up to 100 mg/kg.

6. Pharmaceutical particulars
6.1 List of excipients

Potassium hydrogen carbonate

Sodium saccharin

Natural, spray dried orange flavour which contains acacia gum, lactose, ascorbic acid, butylated hydroxyanisole.

6.2 Incompatibilities

Not applicable

6.3 Shelf life

3 years

Once the sachet has been opened, use immediately and discard any unused powder or solution.

6.4 Special precautions for storage

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

6.5 Nature and contents of container

Sachet:

4 layers: paper-low density polyethylene-aluminium-thermofusible resin

Pairs of sachets can be separated by tearing apart the perforated strip.

Weight of sachet contents: 16.1g

A measuring spoon for paediatric dosing is included in the pack.

PICOLAX is supplied in packages of 2 sachets, 100 sachets (50 packs of 2 sachets), or 300 sachets (150 packs of 2 sachets).

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. Marketing authorisation holder

Ferring Pharmaceuticals Ltd.

Drayton Hall

Church Road

West Drayton

UB7 7PS

United Kingdom

8. Marketing authorisation number(s)

PL 03194/0014

9. Date of first authorisation/renewal of the authorisation

1st September 2013

10. Date of revision of the text

June 2016