LACTECON

The lactulose solution may be administered diluted or undiluted.

A single 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 during the day.

For Lactecon in bottles the measuring cup may be used.

Dosing in constipation

Lactulose may be given as a single daily dose or in two divided doses, using the measuring cup.

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 years)	15-45 ml	15 - 30ml
Children (7-14 years)	15 ml	10 - 15ml
Children (1-6 years)	5-10 ml	5-10 ml
Infants under 1 year	2.5-5 ml	up to 5 ml

Dosing in hepatic encephalopathv - for adults only:

Starting dose: 3 to 4 times daily 30 - 45 ml.

This dose may be adjusted to the maintenance dose to achieve 2 to 3 soft stools per 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

No special dosage recommendations exist, since systemic exposure to lactulose is negligible.

Patients with renal or hepatic insufficiency

No special dosage recommendations exist, since systemic exposure to lactulose is negligible.

The product has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

Flatulence may occur during the first few days of treatment. As a rule it disappears after a few days. When dosages higher than instructed are used, abdominal pain and diarrhea may occur. In such a case the dosage should be decreased (see 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 diarrhea.

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	Diarrhea	Flatulence, abdominal pain, nausea, vomiting
Investigations			Electrolyte imbalance due to diarrhea

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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: http://www.hpra.ie/; e-mail: medsafety@hpra.ie

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

Symptom: diarrhea and abdominal pain.

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

Pharmacotherapeutic group: Osmotically acting laxatives.

ATC code: A 06A D11.

In the colon, lactulose is broken down by colonic bacteria into low molecular weight 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 the colonic contents. These effects stimulate the peristalsis of the colon and return the consistency of the stools. The constipation is cleared and the physiological rhythm of the colon is reinstated.

In hepatic encephalopathy (HE), the effect has been attributed to the 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 the alteration of the bacterial nitrogen metabolism by stimulating the bacteria to utilise ammonia for bacterial protein synthesis. Within this context, however, it should be realised that hyperammonemia alone cannot explain the neuropsychiatric manifestations of HE. The ammonia however might serve as a model compound for other nitrogenous substances.

Lactulose is poorly absorbed after oral administration and reaches the colon unchanged. There it is metabolised by the colonic bacterial flora. Metabolism is complete at doses up to 40 - 75 ml; at higher dosages, a proportion may be excreted unchanged.