SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Lactuflave 3.25 g/5 ml oral gel

2    QUALITATIVE AND QUANTITATIVE    COMPOSITION

1 ml oral gel contains 650 mg lactulose as lactulose liquid 66 % (w/v).

1 measuring spoon with 5 ml oral gel contains 3.25 g lactulose.

Contains fructose, galactose and lactose.

For the full list of excipients, see section 6.1.

3    PHARMACEUTICAL FORM

Oral gel

Brownish to dark brown gel

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Symptomatic treatment of constipation

4.2    Posology and method of administration Posology

The posology should be adjusted according to the individual needs of the patient. The starting dose can be adjusted after adequate treatment effect individually (maintenance dose). Several days (2 - 3 days) of treatment may be needed in some patients before adequate treatment effect occurs. In case of single daily dose, this should be taken at the same time each day, e.g. during breakfast.

The quantities indicated can be measured with the accompanying measuring spoon, which has a filling volume of 5 ml. For example, for a quantity of 30 ml of the gel, 6 full measuring spoons should be taken. For the precise dosing and to avoid overfilling, the excess gel should be scraped off the filled measuring spoon e.g. with the back of a knife.

Constipation

	Starting dose		Maintenance dose
Adults and adolescents over 14 years	15 - 45 ml	corresponding to about 10 - 30 g lactulose	15 -30 ml	corresponding to about 10 - 20 g lactulose
Children (7 - 14 years)	15 ml	corresponding to about 10 g lactulose	10 -15 ml	corresponding to about 7 - 10 g lactulose
Children (1 - 6 years)	5 - 10 ml	corresponding to about 3 - 7 g lactulose
Babies	up to 5 ml	corresponding to about up to 3 g lactulose

If diarrhoea occurs, the dosing regimen should be reduced. The dosage can be individually reduced, producing bowel movements with soft stool.

Method of administration

Lactuflave is taken orally. It can be taken any time regardless of meals. The dose should be titrated according to the clinical response. Lactulose may be given as a single daily dose or in two divided doses, using the measuring spoon.

Duration of treatment

The duration of treatment has to be adopted according to the symptoms.

4.3 Contraindications

-    Hypersensitivity to the active substance or to any of the excipients listed in section 6

-    Use in patients with galactosaemia

-    Bowel obstruction

-    Organic inflammatory bowel disorders (ulcerative proctocolitis, Crohn's disease)

-    Abdominal pain syndromes of unknown cause

4.4 Special warnings and precautions for use

Lactuflave should not be used in case of disturbances of water and electrolyte balance.

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

In case of insufficient therapeutic effect after several days consultation of a physician is advised.

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

Lactulose should be administrated with caution in infants and small children, since they may have an undetected autosomal recessive hereditary fructose intolerance. In these patients the incomplete degradation may lead to fructosemia and fructosuria, hypoglycaemia and hypoglycaemic hepatic, renal and cerebral damages.

The defecation reflex may be altered during the treatment with lactulose.

For patients with gastro-cardiac syndrome (Roemheld syndrome) lactulose should only be taken after consultation of a physician. If symptoms like meteorism or bloating occur in such patients after lactulose intake, the dose should be reduced or the treatment should be discontinued.

For elderly patients or patients that are in bad general health and who take lactulose for a more than 6 months period, periodic control of electrolytes is indicated.

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

Important information about some of the ingredients of Lactuflave

Patients with rare hereditary problems of fructose intolerance, galactose intolerance e.g. galacotosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Information for diabetics and patients with other disturbances of carbohydrate metabolism

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

However, from the route of synthesis Lactuflave may contain traces of sugars (not more than 6.5 mg/ml fructose, 65 mg/ml lactose, 97.5 mg/ml galactose, 65 mg/ml epilactose and 26 mg/ml tagatose). This medicinal product contains in 1 measuring spoon, corresponding to 5 ml (about 6.7 g) oral gel, a maximum content of 0.98 g of digestible carbohydrates, e.g. fructose, lactose, galactose, equivalent to about 0.08 bread units.

4.5 Interaction with other medicinal products and other forms of interaction

Lactulose may increase the loss of potassium induced by other drugs (e.g. thiazides, steroids and amphothericin B). Concomitant use of cardiac glycosides can increase the effect of the glycosides through potassium deficiency.

With increasing dosage a decrease of pH-value in the colon is found. Therefore drugs which are released in the colon pH-dependently (e.g. 5-ASA) can be inactivated.

4.6 Fertility, pregnancy and lactation

Limited data on pregnant patients indicate no malformative nor foeto/neonatal toxicity. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3).

The use of lactulose may be considered during pregnancy if necessary.

Lactuflave can be used during breastfeeding.

4.7 Effects on ability to drive and use machines

Lactuflave 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.

Gastrointestinal disorders

Very common (> 1/10): Flatulence, abdominal pain

Common (>1/100 to <1/10): Nausea, vomiting; if dosed too high, diarrhoea

The usual disturbances in water and electrolyte balance associated with laxatives and their sequelae have to be taken into account if dosages regularly producing thin stools are administered over a prolonged period of time.

4.9 Overdose

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

Symptom: Nausea, vomiting, diarrhoea, abdominal pain and loss of electrolytes.

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

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Osmotically acting laxatives ATC-Code: A06AD11

Lactulose is a synthetic disaccharide formed from D-galactose and fructose. In the colon lactulose is metabolised by bacterial enzymes to short chained fatty acids mainly lactic and acetic acid as well as methane and hydrogen. This effect leads to a decrease of the pH-value and an increase of the osmotic pressure in the colon. This causes stimulation of peristalsis and an increase of the water content of the faeces.

In higher dosage lactulose causes a reduction of the pH-value, which results in an increased H+-concentration and a shift from NH₃ (absorbable) to NH₄+ (nonabsorbable). The nitrogen excretion in the stool is accelerated. This effect may be used in the treatment of hyperammonaemia.

Lower pH in the colon leads to suppression of proteolytic bacteria, which are involved in the formation of ammonia. Decrease in pH is caused by increasing the content of acidophilic bacteria (e.g. Lactobacillus). Reduced pH and the osmotic effect cleanse the colon; this stimulates the bacteria to use ammonia for bacterial protein synthesis.

5.2 Pharmacokinetic properties

Lactulose is practically not absorbed, because in man there is no corresponding disaccharidase available in the upper intestinal tract. Not being absorbed as such, it reaches the colon unchanged. There it is metabolised by the colonic bacterial flora. Metabolism is complete at doses up to 25 - 50 g or 40 - 75 ml; at higher dosages, a proportion may be excreted unchanged.

5.3 Preclinical safety data

Preclinical data based on studies of single and repeated dose toxicity reveal no special hazards for humans. A long-term animal study does not give reference to tumorigenic potential. Lactulose was not teratogenic in mice, rats and rabbits. After oral administration systemic toxicity is not to be expected due to the pharmacological and pharmacokinetic properties of lactulose.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Agar

Cola flavour (flavouring substance(s), flavouring preparation(s), natural flavouring substance(s), glyceryl triacetate (E1518))

Sulphite ammonia caramel (E150d)

Water, purified

Citric acid, anhydrous

Lactuflave also contains fructose, galactose and lactose due to the manufacturing process.

6.2    Incompatibilities

Not applicable.

6.3    Shelf life

3 years

The shelf-life after first opening of the jar is 6 weeks.

6.4    Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5    Nature and contents of container

Polyethylene terephthalate (PET) jar with polypropylene screw cap and polypropylene measuring spoon

Jars of 100 ml, 200 ml, 500 ml

The included measuring spoon has a volume of 5 ml.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

7    MARKETING AUTHORISATION HOLDER

MIP Pharma GmbH Kirkeler StraBe 41 66440 Blieskastel Germany

8    MARKETING AUTHORISATION NUMBER(S)

PL 26928/0003

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

29/06/2012

10    DATE OF REVISION OF THE TEXT

29/06/2012