Lactulose Solution BP /Duphalac®.

Lactulose 3.35 g/5 ml.

For excipients, see 6.1

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

1. For the treatment of constipation.

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

Constipation:

All dosages should subsequently be adjusted to the needs of the individual. The starting dose can be adjusted to the individual after reaching adequate treatment effect (maintenance dose). Several days (2-3 days) of treatment may be needed in some patients before treatment effect occurs.

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.

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.

Hepatic encephalopathy:

Adults (including the elderly): Initially 30 - 50 ml (6-10 x 5 ml spoonfuls) three times a day. Subsequently adjust the dose to produce two or three soft stools each day.

Children: no dosage recommendations for this indication.

Contraindicated in patients with galactosaemia and in cases of gastro-intestinal obstruction.

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

The dose normally used in constipation should not pose a problem for diabetics. The dose used in the treatment of (pre)coma hepaticum is usually much higher and may need to be taken into consideration for diabetics.

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

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

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

None known.

Limited data on pregnant patients indicate neither 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.

Lactation

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.

Not known.

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 portosystemic encephalopathy, PSE) 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.

Gastrointestinal disorders

Flatulence, abdominal pain, nausea and vomiting. If dosed too high, diarrhoea.

Investigations

Electrolyte imbalance due to diarrhoea.

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.

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

The active ingredient, lactulose, is metabolised in the colon by the sacchrolytic bacteria, producing low molecular weight organic acids, mainly lactic acid, which lower the pH of the colon contents, promote the retention of water by an osmotic effect, thus increasing peristaltic activity.

In portal systemic encephalopathy (PSE) or (pre)coma hepaticum, 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.

Lactulose is minimally absorbed; therefore, the kinetics of the absorbed material are not relevant to the principal therapeutic action.

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.

None.

None known.

HDPE: 2 years. Other containers: 3 years.

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

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

None.

Abbott Healthcare Products Limited/Abbott Healthcare Products Ltd

Mansbridge Road

West End

Southampton

SO18 3JD

PL 00512/5001R

14.03.88 / 23.07.04

March 2012