SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Lactulose Teva 670 mg/ml oral solution

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

100 ml contain: - active ingredient: 67 g lactulose.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral solution. Clear, colourless to slightly brownish to yellow, viscous solution.

4. CLINICAL PARTICULARS

4.1. Therapeutic indications

Short-term treatment of occasional constipation, if high fibre food (bran, vegetables and fruits), plenty of liquid and plenty of physical exercise is not sufficient.

4.2. Posology and method of administration

Posology

The correct dose is the minimum sufficient to produce easy evacuation of soft faeces. The minimum doses indicated should be used initially. Where necessary, the dose can then be increased, but without ever exceeding the maximum one indicated.

Adults and adolescents over 14 years: Usual daily dose: 10 - 20 ml daily in two times. This dose may be doubled or halved depending on individual response.

Children and adolescents between 6 and 14 years (see section 4.4): Usual daily dose: 5 - 15 ml daily also in a single time depending on patient age and seriousness of the case.

Infants and children up to 6 years (see section 4.4): Usual daily dose: An average 2.5 - 5 ml daily (corresponding respectively to ½-1 teaspoon; a teaspoon corresponds to 5 ml).

Thereafter, the dosage can be reduced individually according to the clinical response.

Elderly and patients with renal and hepatic failure: There are no particular dosage indications, since systemic exposure to lactulose is negligible.

Method of administration

For oral use. The lactulose solution should be taken together with an adequate amount of water (a full glass).The dosages given here are only for guidance and must be adapted to the needs of the patient.

As measuring device a cup with a graduation from 5 - 30 ml is added to the package. Take preferably in the evening.

Laxatives should be used as infrequently as possible and for no more than seven days. Use for longer periods requires a medical prescription after a careful evaluation of the individual case.

A diet rich in liquids enhances the effect of the product.

A single dose of lactulose should be swallowed at once and not retained in the mouth for a longer period. Since lactulose exerts its effect only upon entry into the colon, it may take 1 - 2 days for the effect to occur.

4.3. Contraindications - Hypersensitivity to the active ingredient or to any of the excipients listed in section 6.1. - Contraindicated in individuals with galactosaemia. - Laxatives are contraindicated in individuals with acute stomach pain or stomach pain of unknown origin, nausea or vomiting, intestinal obstruction or stenosis, rectal bleeding of unknown origin or severe dehydration. - Acute inflammatory bowel disease (ulcerative colitis, Crohn’s disease), or subocclusive syndromes, digestive perforation or risk of digestive perforation, painful abdominal syndromes of undetermined cause.

4.4. Special warnings and precautions for use

The abuse of laxatives (frequent or prolonged use, or use at excessively high doses) may cause persistent diarrhoea with a consequent loss of water, mineral salts (especially potassium) and other essential nutrients. Therefore, patient’s hydration status must be carefully evaluated. In more serious cases, there is a risk of dehydration or hypokalaemia which may determine cardiac or neuromuscular dysfunctions, especially in case of concomitant treatment with cardiac glycosides, diuretics or corticosteroids. The abuse of laxatives, especially contact laxatives (stimulant laxatives), may cause dependency (and thus the need to gradually increase the dosage), chronic constipation and loss of the normal intestinal functions (intestinal atony). Before starting treatment, any abdominal pain symptoms of unknown cause must be evaluated in order to exclude undiagnosed perforations or obstructions or related undiagnosed predisposing pathologies/conditions. In case of insufficient therapeutic effect after several days consultation of a physician is advised. From the route of synthesis Lactulose Teva 670 mg/ml oral solution may contain traces of sugars (not more than 67 mg/ml lactose, 100 mg/ml galactose, 67 mg/ml epilactose, 27 mg/ml tagatose and 7 mg/ml fructose). Patients with rare hereditary problems of galactose, e.g. galactosaemia, or fructose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. The additive effect of concomitantly administered products containing fructose (or sorbitol) and dietary intake of fructose (or sorbitol) should be taken into account. Lactulose should be administered with care to patients who are intolerant to lactose. The dose normally used should not pose a problem for diabetics. In diabetic patients under treatment with high lactulose dosages, it may be necessary to adjust anti-diabetes dosage. 15 ml of Lactulose Teva 670 mg/ml oral solution contain 42.7 KJ (10.2 kcals) = 0.21 carbohydrate units. 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. Chronic use of unadjusted doses and misuse can lead to diarrhoea and disturbance of the electrolyte balance. During the therapy with laxatives it is recommended to drink sufficient amounts of fluids (1.5 - 2 l / day, equal to 6 - 8 glasses). The treatment of chronic or recurrent constipation always requires a doctor to make a diagnosis, prescribe drugs and supervise the treatment. Consult the doctor if the need for the laxative follows a sudden change in the previous bowel habits (frequency and characteristics of bowel movements) that has lasted for more than two weeks or if the use of laxatives has no effect. Elderly people or individuals in a poor state of health should consult a doctor before using the medicine. Inappropriate long-term use of lactulose in elderly patients or patients that are in bad general condition may alter electrolytes balance.

Paediatric population: This medicinal product should not be administered to children aged under 12 years without consulting a doctor beforehand. Lactulose should be administrated with caution in infants and small children with autosomal recessive hereditary fructose intolerance. The defecation reflex may be altered during the treatment with lactulose.

4.5. Interaction with other medicinal products and other forms of interaction

Laxatives may reduce the time for which other drugs administered orally at the same time remain in the intestine and thus affect their absorption. Avoid taking laxatives and other drugs at the same time: having taken a medicine, wait for at least 2 hours before taking the laxative. Lactulose may increase the loss of potassium induced by other drugs (e.g. diuretics, corticosteroids and amphothericin B) and the onset of dehydration and hypokalaemia can occur which can lead to cardiac or neuromuscular dysfunction (see section 4.4). Concomitant use of cardiac glycosides can increase the effect of the glycosides through potassium deficiency. The intestine pH reduction, specific of the lactulose mechanism of action, can cause the inactivation of drugs with a release profile dependent on the intestine pH (for example, 5-ASA drugs). Broad-spectrum antibiotics can reduce the bacterial flora responsible of lactulose degradation, with a possible therapeutic efficacy reduction.

4.6. Fertility, pregnancy and lactation

There are no adequate, controlled studies on the use of the medicine during pregnancy or lactation. This medicinal product should therefore only be used in case of need, under the doctor’s direct supervision, having assessed the expected benefit for the mother in relation to the risk for the newborn/infant.

Animal studies have shown no direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, birth, or postnatal development (see section 5.3).

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

4.7. Effects on ability to drive and use machines

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

4.8. Undesirable effects

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

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 Frequency cannot be estimated from the available data

System organ class Frequency Gastrointestinal disorders Very common: mild abdominal pain*, flatulence*. Common: diarrhoea* with electrolyte disturbances, vomiting*, nausea*. Not known: isolated stomach cramp or colic, more frequent in cases of severe constipation**. Metabolism and nutrition Rare: hypernatremia. disorders Not known: electrolyte imbalance due to diarrhoea. *mainly following excessive dosages. ** occasionally they appear during the first few days of treatment and normally disappear after some days.

When taking a higher dose than prescribed, abdominal pain and diarrhea may appear. In this case the dosage must be reduced. If excessive doses are taken for long periods, the patient may experience electrolyte failure due to diarrhoea.

Pediatric population The safety profile in children is expected to be similar to that of 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 national reporting system listed in the national reporting system listed in Appendix V.

4.9. Overdose

An overdose may cause stomach pain, diarrhoea, nausea, vomiting and loss of electrolytes; liquid and electrolytes lost should be replaced. In this case the dose should be reduced or lactulose should be discontinued. See also the indications given in the “Special warnings and precautions for use” section on the abuse of laxatives.

5. PHARMACOLOGICAL PROPERTIES

5.1. Pharmacodynamic properties

Pharmacotherapeutic group: osmotically acting laxatives, ATC code: A06A D11

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 (non-absorbable). The nitrogen excretion in the stool is accelerated.

By acting as a prebiotic substance, lactulose promotes the growth of bacteria useful to humans, such as Bifidobacterium and Lactobacillus, and can inhibit potentially pathogenic bacteria, such as Clostridium and Escherichia Coli. In this way a more favorable balance of the intestinal flora can be obtained.

5.2. Pharmacokinetic properties

Lactulose is practically not absorbed, because in man there is no corresponding disaccharidase available in the upper intestinal tract. Metabolism is complete at doses up to 40-75 ml; at higher dosages, a portion is excreted unchanged. 5.3. Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of toxicity, carcinogenity and reproductive toxicity. The LD50 values determined in various animal species (rattle, adult rat, mouse, hamster) were always higher than 28 ml/kg of body weight. Studies on mutagenicity are not available.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Purified water.

6.2. Incompatibilities

None.

6.3. Shelf life

3 years. After first opening: 12 months.

6.4. Special precautions for storage

Store below 25°C.

6.5. Nature and contents of container

Brown PET bottles with a screw-on cap and drop stop system with a capacity of 100 ml and 200 ml. As measuring device a measuring cup (polypropylene) with a graduation from 5 - 30 ml is added. Not all pack sizes may be marketed.

6.6. Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER

Teva Italia S.r.l.,Piazzale Luigi Cadorna, 4 – 20123 Milano

8. MARKETING AUTHORISATION NUMBER(S)

AIC no. 037052053 – 670 mg/ml oral solution PET-bottle containing 100 ml AIC no. 037052065 – 670 mg/ml oral solution PET-bottle containing 200 ml

9. DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION

Date of first authorisation: Date of latest renewal:

10. DATE OF REVISION OF THE TEXT