SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Lactolax / Lactulose Solution BP

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Lactulose 3.35g/5ml in aqueous solution

3    PHARMACEUTICAL FORM

A colourless to brownish yellow, clear or not more than slightly opalescent liquid.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

1.    For the treatment of constipation.

2.    For the treatment of hepatic encephalopathy (HE); hepatic coma.

4.2    Posology and method of administration

The lactulose solution may be administered diluted or undiluted. Each dose may if necessary be taken with water or fruit juices, etc.

Each dose of lactulose should be swallowed in one and should not be kept in the mouth for an extended period of time.

The posology should be adjusted according to the individual needs of the patient.

In case of single daily dose, this should be taken at the same time, e.g. during breakfast.

During the therapy with laxatives it is recommended to drink sufficient amount of fluids (1.5-2 litres, equal to 6-8 glasses) during the day.

Dosing in Constipation:

Lactulose may be given as a single daily dose or in two divided doses, After a few days the starting dosage may be adjusted to the maintenance dose based upon treatment response. Several days (2-3 days) of treatment may be needed before treatment effect occurs.

	Starting dose daily	Maintenance dose daily
Adults and adolescents	15-45 ml,	15-30 ml,
Children (7-14 years)	15 ml,	10-15 ml,
Children (1-6 years)	5-10 ml	5-10 ml
Infants under 1 year	up to 5 ml	up to 5 ml

Dosing in HE (for adults only):

Starting dose: 3 to 4 times daily 30-45 ml (6-9 x 5 ml spoonfuls). This dose may be adjusted to the maintenance dose to achieve two or three soft stools each day.

Paediatric population

The safety and efficacy in children (newborn to 18 years of age) with HW have not been established. No data are available

Elderly patients and patients with renal or hepatic insufficiency No special dosage recommendations exist, since systemic exposure to lactulose is negligible.

4.3    Contraindications

•    Hypersensitivity to the active substance or any of the ingredients.

•    Galactosaemia.

•    Gastro-intestinal obstruction, digestive perforation or risk of digestive perforation.

4.4    Special warnings and precautions for use

Consultation of a physician is advised in case of:

- Painful abdominal symptoms of undetermined cause before the treatment is started.

- Insufficient therapeutic effect after several days.

Lactulose should be administered with care to patients who are intolerant to lactose (see section 'List of excipients').

The dose normally used in constipation should not pose a problem for diabetics.

The dose used in the treatment of HE is usually much higher and may need to be taken into consideration for diabetics.

Chronic use of unadjusted doses and misuse can lead to diarrhoea and disturbance of the electrolyte balance.

Dependence/Tolerance: Lactulose Solution does not lead to dependence, and increased tolerance is not a problem. Prolonged use of this product is not recommended except under medical supervision.

This product contains fructose and a small amount of lactose (0.3g/5ml); therefore patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. It should be used with caution in patients who are lactose intolerant. The product provides 58KJ/ 15ml and is unlikely to adversely affect diabetics.

Paediatric population

Use of laxatives in children should be exceptional and under medical supervision.

It should be taken into account that the defaecation reflex could be disturbed during the treatment.

4.5 Interaction with other medicinal products and other forms of interaction

The elimination of certain colonic bacteria by broad-spectrum anti-infective agents may interfere with the degradation of lactulose and prevent acidification of colon contents.

4.6 Fertility, pregnancy and lactation

The safety of lactulose during pregnancy has not been evaluated, although wide clinical experience together with data from animal reproductive studies has not revealed any increase in embryotoxic hazard to the foetus, if used in the recommended dosage. No effects during pregnancy are anticipated, since systemic exposure to lactulose is negligible.

Lactulose can be used during pregnancy

Lactation

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

Lactulose can be used during breast-feeding.

Fertility

No effects are to be expected, since systemic exposure to lactulose is negligible.

4.7 Effects on ability to drive and use machines

Lactulose Solution has no or negligible influence on the ability to drive and use machines.

4.8 Undesirable effects

Flatulence may occur during the first few days of treatment. As a rule it disappears after a couple of days. When dosages higher than instructed are used, abdominal pain and diarrhoea may occur. In such a case the dosage should be decreased. See also overdose section 4.9.

If high doses (normally only associated with hepatic encephalopathy, HE) are used for an extended period of time, the patient may experience an electrolyte imbalance due to diarrhoea. Dosage should then be adjusted to obtain two or three formed stools per day. In the event of diarrhoea, adequate fluid intake should be maintained during treatment and the dosage reduced to prevent loss of fluid and potassium, and exacerbation of encephalopathy.

Tabulated list of adverse reactions

The following undesirable effects have been experienced with the below indicated frequencies in lactulose-treated patients in placebo-controlled clinical trials:

•    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)].

MedDRA SOC	Frequency cate	gory
	Very common	Common	Uncommon	Rare
Gastrointestinal Disorders	Diarrhoea	Flatulence, Abdominal

		pain, nausea, vomiting
Investigations			Electrolyte imbalance due to diarrhoea

Paediatric population

The safety profile in children is expected to be similar as in adults.

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

4.9 Overdose

If the dose is too high, the following may occur:

Symptom: diarrhoea and abdominal pain.

Treatment: cessation of treatment or dose reduction. Extensive fluid loss by diarrhoea or vomiting may require correction of electrolyte disturbances.

No specific antidote. Symptomatic treatment should be given.

There have been no reports of accidental overdose. It is expected that diarrhoea and abdominal cramps would be major symptoms. Symptomatic treatment should be given. Adverse effects have been reported in 5-14% of patients receiving ciprofloxacin. Most frequent adverse effects of the drug involve the gastro-intestinal tract and the central nervous system.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Lactulose is a synthetic disaccharide analogue of lactose. There is no enzyme in the gastro intestinal area capable of hydrolysing this disaccharide. In the colon lactulose is broken down by the colonic bacteria to low molecular weight acids that produce an increased osmotic pressure and slightly acidify the colon contents, resulting in increase in stool water and stool softening. Furthermore, since the colonic contents are them more acidic than blood, ammonia can be expected to migrate from the blood into the colon. In the acidic environment NH₃ is converted to (NH₄)+, trapping it and preventing its absorption. This is what makes lactulose useful in hepatic encephalopathy.

5.2 Pharmacokinetic properties

Given orally, only small amounts reach the blood. Urinary excretion has been determined to be 3% or less, and this is virtually complete within 24 hours. Lactulose does not exert its effect until it reaches the colon. Therefore 24 to 48 hours may be required to produce a normal bowel movement.

5.3    Preclinical safety data

The results of acute, sub-chronic and chronic toxicity studies in various species indicate that the compound has very low toxicity. The effects observed, appear to be more related to the effect of bulk in the gastrointestinal tract than to a more specific toxic activity. In reproduction and teratology experiments in rabbits, rats or mice no adverse effects were found.

6    PHARMACEUTICAL    PARTICULARS

6.1    List of excipients

No other excipients.

6.2 Incompatibilities

None known.

6.3 Shelf life

The product has a shelf life of 3 years when packed in either the glass or plastic bottles.

6.4 Special precautions for storage

Do not store above 20°C. Protect from light.

6.5 Nature and contents of container

Amber glass bottles with screwcaps of 200 ml, 300 ml, and 500 ml.

Plastic bottles with screwcaps of 200 ml, 300 ml, 500 ml, 1000 ml and 5000 ml.

6.6 Special precautions for disposal

No special instructions.

7 MARKETING AUTHORISATION HOLDER

Fannin (UK) Limited 42-46 Booth Drive Park Farm South Wellingborough Northamptonshire NN8 6GT UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 20417/0095

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

01/08/2008

10 DATE OF REVISION OF THE TEXT

05/11/2014