This information is intended for use by health professionals

1. Name of the medicinal product

Duphalac®

2. Qualitative and quantitative composition

Lactulose 3.335 g/5 ml.

For excipients, see 6.1

3. Pharmaceutical form

Oral solution.

A clear, viscous liquid, colourless to brownish yellow.

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 amounts of fluids (1.5–2 litres, equal to 6-8 glasses) during the day.

For lactulose in bottles the measuring cup may be used.

For lactulose in 15 ml single dose sachets the corner of the sachet should be torn off and contents taken immediately.

Dosing in constipation:

Lactulose may be given as a single daily dose or in two divided doses, for lactulose in bottles the measuring cup may be used.

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.

Lactulose oral solution in bottles or 15 ml single dose sachets:

Starting dose daily

Maintenance dose daily

Adults and adolescents

15-45 ml, corresponding to 1-3 sachets

15-30 ml, corresponding to 1-2 sachets

Children

(7-14 years)

15 ml, corresponding to 1 sachet

10-15 ml, corresponding to 1 sachet*

Children

(1-6 years)

5-10 ml

5-10 ml

Infants under 1 year

up to 5 ml

up to 5 ml

* If the maintenance dose is below 15 ml, lactulose in bottles should be used.

For a precise dosing for infants and children up to 7 years lactulose in bottles should be used.

Dosing in HE (for adults only):

Starting dose: 3 to 4 times daily 30-45 ml (6-9 x 5 ml spoonfuls) or 2-3 sachets. 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 HE 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 excipients listed in section 6.1.

• Galactosaemia.

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

4.4 Special warnings and precautions for use

Painful abdominal symptoms of undetermined cause should be evaluated to exclude undiagnosed perforation or obstruction or undiagnosed disease/condition that predisposes to either before the treatment is started.

In case of insufficient therapeutic effect after several days the dose and/or additional measures should be re-considered.

Lactulose should be administered with care to patients who are intolerant to lactose (see section 6.1).

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.

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

This product contains lactose, galactose and small amounts of fructose. Patients with rare hereditary problems of galactose or fructose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Paediatric population

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

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6 Fertility, pregnancy and lactation

Pregnancy

No effects during pregnancy are anticipated, since systemic exposure to lactulose is negligible.

Duphalac can be used during pregnancy.

Breast-feeding

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

Duphalac 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 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.

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 category

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

4.9 Overdose

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

Symptom: diarrhoea, loss of electrolytes 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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Osmotically acting laxatives, ATC code: A 06A D11

In the colon lactulose is broken down by colonic bacteria into low molecular organic acids. These acids lead to a lowering of pH in the colonic lumen and via an osmotic effect to an increase of the volume of colonic contents. These effects stimulate peristalsis of the colon and return the consistency of the stool. The constipation is cleared and the physiological rhythm of the colon is reinstated.

In hepatic encephalopathy (HE) the effect has been attributed to suppression of proteolytic bacteria by an increase of acidophilic bacteria (e.g. lactobacillus), trapping of ammonia in the ionic form by acidification of the colonic contents, catharsis due to the low pH in the colon as well as an osmotic effect, and alteration of the bacterial nitrogen metabolism by stimulating the bacteria to utilize ammonia for bacterial protein synthesis.

5.2 Pharmacokinetic properties

Lactulose is poorly absorbed after oral administration and 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

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

Duphalac does not contain any excipients, but may contain sugars (e.g. lactose, galactose, fructose) from the route of synthesis.

6.2 Incompatibilities

None known.

6.3 Shelf life

HDPE: 2 years. Other containers: 3 years.

6.4 Special precautions for storage

Do not store above 25°C. Do not refrigerate or freeze.

6.5 Nature and contents of container

Brown glass and white HDPE bottles containing 200, 300, 500 and 1000 ml; polyethylene bottles containing 5 litres; 15 ml foil sachets.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Marketing authorisation holder

Mylan Products Ltd.

20 Station Close

Potters Bar

Herts

EN6 1TL

United Kingdom

8. Marketing authorisation number(s)

PL 46302/0032

9. Date of first authorisation/renewal of the authorisation

Date of first authorisation: 14/03/1988

Date of latest renewal: 23/07/2004

10. Date of revision of the text

April 2018