DUPHALAC®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DUFALAC® (DUPHALAC®)

Composition:

Active substance: lactulose;

1 ml of syrup contains 667 mg of lactulose;

Excipient: purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear, viscous liquid, colorless to brownish-yellow.

Pharmacotherapeutic group. Osmotic laxatives. ATC code A06AD11.

Pharmacological properties.

Pharmacodynamics.

In the colon, lactulose is broken down by intestinal bacteria into low-molecular-weight organic acids. These acids reduce the pH within the lumen of the colon and, due to their osmotic effect, increase the volume of intestinal contents. This stimulates colonic peristalsis and normalizes stool consistency. Constipation is corrected, and the physiological rhythm of the intestine is restored.

In hepatic encephalopathy (or hepatic coma and precoma), the drug's action is due to suppression of proteolytic bacterial growth as a result of increased numbers of acidophilic bacteria (e.g., lactobacilli), binding of ammonia in its ionic form due to acidification of intestinal contents, cleansing of the colon due to low pH, as well as the osmotic effect and altered bacterial nitrogen metabolism through stimulation of bacterial utilization of ammonia for synthesis of bacterial proteins. In this context, however, it should be noted that the neuropsychiatric manifestations of hepatic encephalopathy cannot be explained solely by hyperammonemia. Nevertheless, ammonia may be considered representative of other nitrogenous compounds.

As a prebiotic, lactulose enhances the growth of beneficial bacteria such as bifidobacteria and lactobacilli, while growth of potentially pathogenic bacteria such as clostridia and Escherichia coli may be suppressed. This may lead to a more favorable balance of intestinal flora.

Pharmacokinetics.

Lactulose is almost not absorbed after oral administration and reaches the colon unchanged, where it is metabolized by the bacterial flora. When Dufragalac® is administered at doses of 25–50 g or 40–75 mL, lactulose is completely metabolized. When higher doses are used, part of the lactulose may be excreted unchanged.

Clinical characteristics.

Indications.

• Constipation: regulation of the physiological bowel rhythm.
• Conditions requiring facilitation of defecation (hemorrhoids, post-surgery of the colon and anorectal area).
• Hepatic encephalopathy: treatment and prevention of hepatic coma and precoma.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients, galactosemia, gastrointestinal obstruction, gastrointestinal perforation or risk of gastrointestinal perforation.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted.

Lactulose may increase potassium loss induced by other medicinal products (e.g. thiazide diuretics, corticosteroids, and amphotericin B). Potassium deficiency may potentiate the effect of cardiac glycosides.

Special precautions for use.

Consultation with a physician is recommended if:

• abdominal pain of unknown origin is present before starting treatment;
• therapeutic effect is insufficient after several days of treatment.

Lactulose (Duhalac®) should be used with caution in patients with lactose intolerance.

The dose usually used for the treatment of constipation generally does not cause problems in patients with diabetes mellitus. However, the dose used for the treatment of hepatic encephalopathy is usually much higher, and this should be taken into account when treating diabetic patients.

Prolonged use of the drug without proper dose adjustment or incorrect use may lead to the development of diarrhea and electrolyte imbalance.

This medicine contains lactose, galactose, and a small amount of fructose. Therefore, patients with rare hereditary disorders of galactose or fructose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

This medicine contains sulfites due to the manufacturing process. Sulfites may rarely cause severe hypersensitivity reactions, including bronchospasm.

Lactulose should be used in patients with gastroesophageal syndrome (Röhmel's syndrome) only after consultation with a physician. To prevent the occurrence of flatulence, it is recommended to increase the dose gradually. If flatulence occurs, the dose should be reduced or treatment discontinued.

Use during pregnancy or breastfeeding.

Pregnancy

During pregnancy, no adverse effects are expected, as systemic exposure to lactulose in pregnant women is negligible.

Duhalac®, syrup, may be used during pregnancy.

Breastfeeding

During breastfeeding, no adverse effects in the newborn/infant are expected, as systemic exposure to lactulose in breastfeeding women is negligible.

Duhalac®, syrup, may be used during breastfeeding.

Fertility

No effects on fertility are expected, as systemic exposure to lactulose is negligible.

Ability to influence reaction rate while driving or operating machinery.

Duhalac® has no effect or has a negligible effect on the ability to drive or operate machinery.

Method of administration and dosage.

Dufalac® can be taken either diluted or undiluted.

The dose should be adjusted according to individual patient needs.

A single dose of lactulose should be swallowed immediately and should not be retained in the mouth for a prolonged period.

If the patient is prescribed the medication once daily, the dose should always be taken at the same time of day, for example, during breakfast. During therapy with laxatives, it is recommended to consume an adequate amount of fluid (1.5–2 liters, equivalent to 6–8 glasses) throughout the day.

When using the medication in bottles, the measuring cap can be used.

When using the medication in 15 ml single-dose sachets, tear off the corner of the sachet and immediately consume the contents.

Dosing for constipation or for medical softening of stools

Lactulose can be taken as a single daily dose or divided into two doses. When using Dufalac® in bottles, the measuring cap can be used.

After a few days, the initial dose may be adjusted to a maintenance dose based on the response to treatment. Several days of therapy (2–3 days) may be required before the therapeutic effect becomes apparent.

* If the maintenance dose is less than 15 mL, and for accurate dosing in infants and children under 7 years of age, it is necessary to use DUFA-LAC® in bottles.

Dosing in hepatic encephalopathy (adults only)

Initial dose: 30–45 mL (2–3 sachets) 3–4 times daily.

This dose may be adjusted to the maintenance dose to achieve soft bowel movements 2 to 3 times per day.

Children

The safety and efficacy of the drug in children (from birth to 18 years of age) with hepatic encephalopathy have not been established. Data are lacking.

Older patients and patients with renal or hepatic impairment

Since the systemic effects of lactulose are minimal, no specific dosage recommendations are required for these patient groups.

Children

The use of laxatives in children should occur only in exceptional cases and requires medical supervision.

It should be noted that the defecation reflex may be impaired during treatment.

Overdose.

If doses are too high, symptoms such as abdominal pain and diarrhea may occur. Recommended management includes discontinuation of the drug or dose reduction, and correction of electrolyte imbalances caused by excessive fluid loss due to diarrhea or vomiting.

Adverse reactions.

Overall safety profile

During the first few days of treatment, flatulence may occur, which usually resolves within a few days. When the drug is used in doses exceeding the recommended ones, abdominal pain and diarrhea may occur. In such cases, the dose should be reduced. During prolonged use of high therapeutic doses (usually only in patients with hepatic encephalopathy), electrolyte imbalance due to diarrhea may occur.

During post-marketing use, hypersensitivity reactions have been observed, predominantly limited to skin manifestations, which have been considered as possible adverse reactions. Since these reactions have been reported spontaneously from a population of unknown size, it is not possible to reliably estimate their frequency.

List of adverse reactions

The adverse reactions listed below occurred with the specified frequency in patients treated with lactulose in placebo-controlled clinical trials [very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000)], or have been reported spontaneously during post-marketing use [frequency not known (cannot be estimated from available data)].

Immune system disorders: frequency not known – hypersensitivity.

Gastrointestinal disorders: very common – diarrhea; common – flatulence, abdominal pain, nausea, vomiting.

Skin and subcutaneous tissue disorders: frequency not known – rash, pruritus, urticaria, erythema.

Laboratory test abnormalities: uncommon – electrolyte imbalance due to diarrhea.

Children

The safety profile in children is expected to be the same as in adults.

Reporting of suspected adverse reactions and lack of efficacy after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Information System of Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Additionally, in case of any adverse reactions, lack of efficacy during use of the product, or quality complaints, please report to the company LLC "Abbott Ukraine" by phone: +38 044-498-60-80 or e-mail: [email protected].

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 25 °C. Keep out of reach of children!

Packaging. Bottles of 200 ml, 300 ml, 500 ml, or 1000 ml made of high-density polyethylene, with a cap and a measuring cup made of polypropylene. Graduations on the measuring cup are at 2.5 ml, 5 ml, 10 ml, 15 ml, 20 ml, 25 ml, and 30 ml.

Sachets made of polyester-aluminum-polyester-polyethylene laminate, containing 15 ml of syrup, packed in cardboard boxes of 10, 20, and 50 pieces.

Dispensing category. Over-the-counter.

Manufacturer. Abbott Biologicals B.V., the Netherlands / Abbott Biologicals B.V., The Netherlands.

Manufacturer's address and location of operations. Veerweg 12, 8121 AA Olst, the Netherlands / Veerweg 12, 8121 AA Olst, The Netherlands.