Duphalac

Lactulose.

Duphalac oral solution contains 667 g lactulose per 1000 ml.
One 15 ml sachet contains 10 g lactulose.
Excipients/Inactive Ingredients: Duphalac oral solution does not contain any excipients, but 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 lower the pH in the colonic lumen and increase the volume of the colonic contents via an osmotic effect. These effects stimulate the peristalsis of the colon and return consistency to the stool. Constipation is corrected 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 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 might, however, serve as a model compound for other nitrogenous substances.
Lactulose as a prebiotic substance promotes the growth of normal flora, like Bifidobacterium and lactobacillus.
Pharmacokinetics: 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 dose 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.
When a soft stool is considered of medical benefit (haemorrhoids, post colonic/anal surgery).
Hepatic encephalopathy (HE): Treatment and prevention of hepatic coma or precoma.

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 is prescribed, 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 Duphalac in bottles the measuring cup may be used.
For Duphalac in 15 ml single dose sachets the corner of the sachet should be torn off and contents taken immediately.
Dosing in constipation or where soft stool is considered of medical benefit: Lactulose may be taken as a single daily dose or in two divided doses; for Duphalac 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 (2-3 sachets) or 30-45 ml (2-3 sachets).
This dose may be adjusted to the maintenance dose to achieve 2 to 3 soft stools per day.
For rectal administration: In acute cases (impending coma or coma stage) Duphalac may be administered as a retention enema (300 ml Duphalac/700 ml water). The enema is to be retained for 30-60 minutes; the procedure is to be repeated every 4-6 hrs until oral medication can be administered.
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.

If the dose is too high, the following symptoms may occur: diarrhea and abdominal pain.
Recommended treatments include the cessation of treatment or dose reduction and correction of electrolyte disturbances when extensive fluid loss secondary to diarrhea or vomiting has occurred.

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

Consultation with a physician is advised in case of: Painful abdominal symptoms of undetermined cause before the treatment is started; Insufficient therapeutic effect after several days.
With regard to sugar content, the dose normally used to treat constipation should not pose a problem for diabetics. However, the dose used to treat HE is usually much higher and may cause problem in diabetic patients. Sugar content of the medicine should 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 fructose from the route of production. Therefore, patients with rare hereditary problems of galactose or fructose intolerance, the total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Lactulose should be administered with care to patients who are intolerant to lactose (see Description).
When administered as a retention enema, due to the strong cathartic effect, fecal incontinence, bedsoiling, and peri-anal irritation due to the acidic stool can be expected. The hydration status of the patient should be observed carefully.
Effects on ability to drive and use machine: Based on its pharmacological properties, lactulose is likely to have no or negligible influence on the ability to drive and use machines.
Use in Children: Use of laxatives in children should be exceptional and under medical supervision.
It should be taken into account that the defaecation reflex could be disturbed during the treatment.

Pregnancy: No effect during pregnancy are anticipated, since systemic exposure to lactulose is negligible.
Duphalac oral solution can be used during pregnancy.
Lactation: No effects on the breastfed newborn/infant are anticipated since systemic exposure of lactulose to the breast-feeding woman is negligible.
Duphalac oral solution can be used during breastfeeding.
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 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.
Hypersensitivity reactions mainly limited to the skin have been observed and identified as potential adverse reactions during post-approval use. Because these reactions were reported spontaneously from a population of uncertain size, it is not possible to reliably estimate their frequency.*
Tabulated list of adverse reactions: The following undesirable effects have been experienced with the following 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)] or have been reported spontaneously during post-approval use [frequency not known (a precise frequency cannot be estimated from the available data)]. (See Table 2.)

Click on icon to see table/diagram/image

Paediatric population: The safety profile in children is expected to be similar as in adults.

No interaction studies have been performed.

Incompatibilities: Not applicable.

Do not store above 30°C. Store in the original package.
Shelf-life: 2 years.

Laxatives, Purgatives / Cholagogues, Cholelitholytics & Hepatic Protectors

A06AD11 - lactulose ; Belongs to the class of osmotically acting laxatives.

NDD