It contains
1. Duphalac enema 300 ml
2. 1 Empty pouch with extended tube for enema administration

For the Use of a Registered Medical Practitioner Only

1. GENERIC NAME AND BRAND NAME
Lactulose Solution USP
Duphalac®
Duphalac® Enema

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 5ml contains:
Lactulose Solution USP
equivalent to Lactulose … 3.335 g

3. DOSAGE FORM AND STRENGTH
Refer section 1 & 2

4. CLINICAL PARTICULARS
4.1 THERAPEUTIC INDICATION

• Constipation: regulation of the physiological rhythm of the colon.
• Where a soft stool is considered of medical benefit (haemorrhoids, post colonic/anal surgery)
• Hepatic encephalopathy (HE): treatment and prevention of hepatic coma or precoma (adults)

4.2 POSOLOGY AND METHOD OF ADMINISTRATION
Duphalac®

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 litres, 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 which 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.

Dosing in HE (for adults only)
For oral administration:
Starting dose: 3 to 4 times daily 30-45 ml.
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) Trademark may be administered as a retention enema (300ml Trademark/700ml 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.

Duphalac® Enema
The administration of Duphalac as a retention enema is an alternative technique. This can be done by diluting Duphalac and is of considerable value especially in unconscious patient. In such cases 300 ml of Duphalac may be mixed with 700ml of potable water to be used as retention enema; the enema is to be retained for 30 – 60 minutes and repeated every 4 – 6 hours until the patient is able to take oral medication.

Paediatric population
The safety and efficacy in children (newborn to 18 years of age) has 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

4.3 CONTRAINDICATIONS

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

4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE

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.
The dose normally used in constipation should not pose a problem for diabetics.

Paediatric population
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.
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 rare hereditary problems of galactose or fructose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
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.
This product contains sulphite from the route of production.

4.5 DRUG INTERACTIONS
No interaction studies have been performed.

4.6 USE IN SPECIAL POPULATIONS (SUCH AS PREGNANT WOMEN, LACTATING WOMEN, PAEDIATRIC PATIENTS, GERIATRIC PATIENTS ETC.)

PREGNANCY AND LACTATION
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.

4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Lactulose has no or negligible influence on the ability to drive and use of machines.

4.8 UNDESIRABLE EFFECTS
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 diarrhoea 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. *
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)] or have been reported spontaneously during postapproval use [frequency not known (a precise frequency cannot be estimated from the available data)].

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

4.9 OVERDOSE
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 diarrhoea or vomiting may require correction of electrolyte disturbances.

5. PHARMACOLOGICAL PROPERTIES
5.1 Mechanism of action and Pharmacodynamic properties 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.

5.3 PHARMACOKINETIC PROPERTIES
Lactulose is poorly absorbed after oral administration and it reaches the colon unchanged. There it is metabolised 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.

6. NONCLINICAL PROPERTIES
6.1 ANIMAL TOXICOLOGY OR PHARMACOLOGY
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.

7.DESCRIPTION
DUPHALAC/ DUPHALAC ENEMA is supplied for oral administration, as a solution of Lactulose. Each 5ml solution of DUPHALAC/ DUPHALAC ENEMA contains Lactulose solution equivalent to Lactulose 3.335g.

8. PHARMACEUTICAL PARTICULARS
8.1 INCOMPATIBILITIES
Not applicable

8.2 SHELF-LIFE
Refer Pack

8.3 PACKAGING INFORMATION
Refer Pack

8.4 STORAGE CONDITION AND HANDING INSTRUCTIONS
Refer Pack

9. PATIENT COUNSELLING INFORMATION
a) Appropriate treatment
Each 5 ml lactulose solution equivalent to 3.335 grams.
Indicated in constipation: regulation of the physiological rhythm of the colon, where a soft stool is considered of medical benefit (hemorrhoids, post colonic/anal surgery)
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 litres, equal to 6-8 glasses) during the day.

b) Interactions
No interaction studies have been performed.
c) Warning and precautions
Consultation of a physician is advised in case of insufficient therapeutic effect after several days.
Lactulose should be administered with care to patients who are intolerant to lactose.
Persistent Loose Stools
Advise patients to stop Duphalac and contact their healthcare provider if they experience persistent
loose stools

10. DETAILS OF MANUFACTURER
Refer Pack for manufacturer details.

11. DETAILS OF PERMISSION OR LICENCE NUMBER
Refer Pack for Permission/License details

12. DATE OF REVISION
Version 11, Dated 19th Oct 2023

Source: Company Core Data Sheet version 9 dated 17 Jan 2023,

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