Duphalac/Duphalac Mom

Lactulose.

Duphalac: Each 5mL syrup contains: Lactulose, EP 3.3 g.
A clear, viscous liquid, colorless to brownish yellow oral solution.
Excipients/Inactive Ingredients: Lactulose 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.
Duphalac Mom: Lactulose (Duphalac Mom) oral solution contains 667 g lactulose per 1000 ml flavored with plum aroma.
Oral solution flavored with fruit aroma.
A clear, viscous liquid, colorless to brownish yellow.
Excipients/Inactive Ingredients: Lactulose (Duphalac Mom) oral solution with aroma contains Fruit Aroma and no further excipients.
Fruit aroma contains a substance with known effect: Propylene glycol (E1520).

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.
As a prebiotic substance, lactulose intensifies the growth of Bifidobacterium and Lactobacillus, while Clostridium and Escherichia coli may be suppressed. This may lead to alleviation of the constipation and, in this way, have a favorable effect on the patient's state of health.
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.
Duphalac: For bowel cleansing in preparation for colonoscopy, a regimen is proposed of bisacodyl (10mg) the evening before the colonoscopy and on the day of colonoscopy a 12.5% lactulose solution (m/m). Bisacodyl is a stimulant laxative and lactulose is an osmotic laxative. The pharmacodynamic effect consists of a strong cathartic effect and initiation of diarrhea. The bowel is subsequently emptied and cleansed.
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 (adults).
As a prebiotic, which helps create and maintain a healthy intestinal balance and stimulates the intestinal absorption of minerals like calcium and magnesium (adults).
Duphalac: For bowel cleansing in preparation for colonoscopy (adults).

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 (1.5-2 liters, equal to 6-8 glasses) during the day.
The lactulose (Duphalac) solution may be administered diluted or undiluted.
Lactulose (Duphalac/Duphalac Mom) in bottles the measuring cup may be used.
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. 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.
Dosing in Hepatic Encephalopathy (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.
Dosing in Prebiotic Indication (for adults only): Daily dose of 7.5 mL-15 mL lactulose (corresponding to 5 g to 10 g/day) exerts the prebioric effects.
Special populations: 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.
Duphalac: see Table 1.

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Method of Lactulose administration for bowel cleansing in preparation for colonoscopy (for adults only): A course of treatment consists of taking 10 mg of bisacodyl in the evening before the examination and 1 liter of Lactulose (Duphalac) solution for six hours before colonoscopy (e.g. one hour after a light breakfast on the day of the examination). Patients are allowed to drink water or tea up to three hours before the colonoscopy.
Preparation of the solution: Lactulose (Duphalac) should be diluted in order to obtain a 12.5% lactulose solution. This can be achieved by diluting 200 mL in 800 mL of water or lemon juice (the addition of lemon juice is to make the solution less sweet, should the sweetness impair palatability). (1 liter Lactulose (Duphalac) lactulose = 1334 grams, lactulose content = 667g/L, lactulose percentage = 667/1334 = 50% m/m). The density of the mixture of 200mL lactulose and 800mL water = 1067g/L. The content of lactulose of the mixture = 133g/L and the percentage of the mixture is therefore 12.5% (m/m).
When using lactulose and bisacodyl for bowel cleansing in preparation for colonoscopy, respective warnings, precautions and safety information from corresponding bisacodyl label needs to be taken into consideration. Safety in the pediatric population for bowel cleansing has not been extensively established.
Duphalac Mom: See Table 2.

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Missed Dose: No information available.

Signs and Symptoms: 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.
Galactosemia.
Gastrointestinal obstruction, digestive perforation or risk of digestive perforation.
Duphalac: Lactulose (Duphalac) solution for bowel cleansing should not be administered to unconscious patients or those with impaired consciousness and patients prone to aspiration or regurgitation, general weakness, with severe dehydration or impaired swallowing reflex.

Chronic use of unadjusted doses and misuse can lead to diarrhea and disturbance of the electrolyte balance.
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.
This product contains lactose, galactose and small amounts of fructose from the route of production. Therefore, patients with rare hereditary problems of galactose or fructose intolerance, 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.
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.
Effects on Ability to Drive and Use Machines: Lactulose has 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 defecation reflex could be disturbed during the treatment.
Duphalac: Diarrhea is an expected effect resulting from the use of lactulose for bowel cleansing in preparation for colonoscopy, esp. also in combination with bisacodyl. Should nausea, vomiting, abdominal distension or abdominal pain arise, the rate of administration should be slowed down or temporarily stopped until symptoms subside.
In certain patients at risk, e.g. elderly or debilitated patients, patients with clinically significant renal impairment, careful monitoring of the electrolyte and fluid balance is required.

Pregnancy: No effects during pregnancy are anticipated, since systemic exposure to lactulose is negligible.
Lactulose (Duphalac/Duphalac Mom) 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 Mom) 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.
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.*
Pediatric population: The safety profile in children is expected to be similar as in adults.
Tabulated list of adverse reactions: The following undesirable effects have been experienced with the frequencies indicated as follows 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 3.)

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Duphalac: For bowel cleansing in preparation for colonoscopy (adults): Diarrhea is an expected outcome of bowel preparation. Due to the nature of the intervention, undesirable effects occur during the process of bowel preparation. Nausea, vomiting, abdominal distension, abdominal pain has been observed in patients undergoing bowel preparation, and these undesirable effects were also observed in the clinical studies with lactulose for bowel preparation. Undesirable effect data were actively elicited in clinical studies regarding lactulose for bowel preparation. The mainly observed undesirable effects are gastrointestinal in nature.

No interaction studies have been performed.
Duphalac: Up to several hours before, during or up to one hour after taking Lactulose (Duphalac) solution for bowel cleansing, as with other bowel cleansing regimens, orally administered medicines may possibly be washed out of the gastrointestinal tract or may not, or only partially, be absorbed. If administration of a medicine is absolutely necessary for a life-threatening indication shortly before or whilst taking the treatment regimen for bowel cleansing, oral administration may have to be withheld and a switch made to an alternative.
The concomitant use of other laxatives (bisacodyl) may enhance the gastrointestinal side effects of lactulose.

Incompatibilities: Not applicable.

Duphalac: Store at temperatures not exceeding 25°C.
Shelf life: 36 months.
Duphalac Mom: Store at temperatures not exceeding 30°C. Protect from light.
Shelf-Life: 24 months.

Cholagogues, Cholelitholytics & Hepatic Protectors / Laxatives, Purgatives

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

Non-Rx