Duphalac: Each 5 mL of Duphalac contains lactulose 3.3 g.
Duphalac does not contain any excipients but may contain small amounts of related sugars (eg, lactose, galactose, epilactose, fructose) derived from the route of synthesis.
Duphalac Fruit: Lactulose (Duphalac Fruit) oral solution contains 667 g lactulose per 1000 ml flavored with plum aroma.
Lactulose (Duphalac Fruit) oral solution contains plum aroma and no further excipients.
Lactulose (Duphalac Fruit) may contain small amounts of related sugars (e.g. lactose, galactose, epilactose, fructose) from the route of synthesis.
Pharmacotherapeutic group: Osmotically acting laxatives. ATC code: A 06A D11.
Pharmacology: Pharmacodynamics: 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 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 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.
Within this context, however, it should be realized that hyperammonemia alone cannot explain the neuropsychiatric manifestations 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.
Pharmacokinetics: 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 25-50 g or 40-75 mL; at higher dosages, a proportion may be excreted unchanged.
Toxicology: 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.
Constipation: regulation of the physiological rhythm of the colon.
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.
The lactulose solution may be administered diluted or undiluted.
The posology should be adjusted according to the individual needs of the patient.
A single dose of lactulose should be swallowed in one and should not be kept in the mouth for an extended period of time.
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: Lactulose may be given as a single daily dose or in two divided doses, for lactulose (Duphalac/Duphalac Fruit) 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. See Table 1.
Click on icon to see table/diagram/image
Dosing in HE (for adults only): For oral administration: Starting dose: 3 to 4 times daily 20-30 g or 30-45 mL.
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 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.
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.
Hypersensitivity to the active substance or to any of the ingredients.
Gastrointestinal obstruction, digestive perforation or risk of digestive perforation.
Consultation of a physician is advised in case of: Painful abdominal symptoms of undetermined cause before the treatment is started.
Insufficient therapeutic effect after several days.
Lactulose should be administered with care to patients who are intolerant to lactose (see Description).
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 diarrhea and disturbance of the electrolyte balance.
This product contains lactose, galactose and small amounts of fructose. Therefore, patients with the rare 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.
Effects on ability to drive and use machines: Lactulose has no or negligible influence on the ability to drive and use machines.
Pregnancy: No effects during pregnancy are anticipated, since systemic exposure to lactulose is negligible.
Lactulose (Duphalac/Duphalac Fruit) can be used during pregnancy.
Lactation: No effects on the breastfed newborn/infant are anticipated, since the systemic exposure of the breast-feeding woman to lactulose is negligible.
Lactulose (Duphalac/Duphalac Fruit) can be used during breast-feeding.
Fertility: No effects are to be expected, since systemic exposure to lactulose is negligible.
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.
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)]. See Table 2.
Click on icon to see table/diagram/image
The safety profile in children is expected to be similar as in adults.
No interaction studies has been performed.
Incompatibilities: Not applicable.
Duphalac: Store at temperatures not exceeding 25°C.
Shelf-Life: 3 years.
Duphalac Fruit: Store at temperatures not exceeding 30°C.
Shelf-Life: 2 years.
A06AD11 - lactulose ; Belongs to the class of osmotically acting laxatives.
Duphalac: Syr (plain flavor; clear, viscous liquid, colorless to brownish yellow) 3.3 g/5 mL x 45 mL, 120 mL.
Duphalac Fruit: Syr (plum aroma flavor; clear, viscous liquid, colorless to brownish yellow) 3.3 g/5 mL x 200 mL.