Thursday, December 8, 2016


3.3g/5ml Syrup

Drug Category: Stimulant Laxative / Osmotically acting laxatives.

Brand Name: Duphalac

Pharmaceutical Form and Composition
Lactulose is an oral solution. It is a clear, viscous liquid, colorless to brownish yellow. Lactulose oral solution does not contain any excipients, but may contain small amounts of related sugars (e.g. lactose, galactose, epilactose, and fructose) derived from the route of synthesis.

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 the colonic contents. These effects stimulate the peristalsis of the colon and return 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 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 osmotic effect, and alteration of the bacterial nitrogen metabolism by stimulating the bacteria to utilize ammonia for bacterial protein synthesis.

Within this context, however, it should be realized that hyperammonemia alone cannot explain the neuropsychiatric manifestation of HE. The ammonia however might serve as a model compound for other nitrogenous substances.

Lactulose as a prebiotic substance strengthens the growth of health promoting bacteria, like Bifidobacterium and Lactobacillus, whereas potentially pathogenic bacteria, like Clostridium and Escherichia coli may be suppressed. This may lead to a more favorable balance of the intestinal flora.

Pharmacokinetic Properties
Lactulose is poorly absorbed after oral administration and it reaches the colon unchanged. There it is metabolized by the colonic bacterial flora. Metabolism is complete at doses up to 25 – 50g or 40 -75ml; at higher dosages, a proportion may be excreted unchanged.

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.

Therapeutic Indications
For Constipation: regulation of the physiological rhythm of the colon. Indicated where a soft stool is considered of medical benefit (hemorrhoids, post colonic/anal surgery). Hepatic Encephalopathy (HE): treatment and prevention of hepatic coma or precoma.

Administration and Dosage
Lactulose solution may be administered diluted or undiluted.
A single dose of lactulose should be swallowed in one and should not be kept in mouth for an extended period of time. The dose 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 liters, equal to 6 – 8 glasses) during the day. Dosing in constipation or where a soft stool is considered of medical benefit. It may be given as a single daily dose or is two divided doses; 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.

The following dose is given:
Adult and adolescents: Starting daily dose 15 – 45ml. Maintenance daily dose 15 – 30ml.
Children (7 – 14years): Starting daily dose 15ml. Maintenance daily dose 10 - 15ml.
Children (1 – 6years): Starting daily dose 5 – 10ml. Maintenance daily dose 5 - 10ml.
Infants under 1 year: Starting daily dose up to 5ml. Maintenance daily dose up to 5ml.

Dosing in HE (for adults only)
Starting dose: 3 to 4 times daily 20 – 30g or 30 – 45ml. This dose may be adjusted to the maintenance dose to achieve 2 to 3 soft stools per day.

Pediatric population
The safety and efficacy in children (newborn to 18years 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.

-  Hypersensitivity to the active substance or to any of the ingredients.
- Galactosemia
- Gastrointestinal obstruction, digestive perforation or risk of digestive perforation.

Special Warnings and Precautions for use
Consultation of a physician is advised in case of:
- Painful abdominal symptoms of undetermined cause before the treatment are started.
- Insufficient therapeutic effect after several days.

Lactulose should be administered with care to patients who are intolerant to lactose.

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 electrolyte balance.

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

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

Pediatric Population
Use of laxatives in children should be exceptional and under medical supervision. It should be taken into account that the defecation reflex could be disturbed during the treatment.

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

No effects on the breastfed newborn/infant are anticipated, since the systemic exposure of the breast-feeding woman to lactulose is negligible. Lactulose can be used during breast-feeding.

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

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

Undesirable Effects
Flatulence may occur during the first few days of treatment. As a rule it disappears after a few days. Abdominal pain and vomiting may occur, as well as, nausea.

When dosages higher than instructed are used, abdominal pain and diarrhea may occur. In such a case the dosage should be decreased.

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.

Drug Interaction
Do not use with any other gastrokinectic drugs or other laxatives. Concomitant use may lead to severe diarrhea.

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.

Shelf life
3 years

Storage condition

Store at temperatures not exceeding 25oC
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