Duphalac® frut

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

Composition:

Active ingredient: lactulose, liquid;

1 ml of solution contains 667 mg of lactulose, liquid;

Excipients: plum flavoring additive¹.

¹Natural plum flavoring additive ZINS D (with other natural flavoring additives).

Pharmaceutical form. Oral solution.

Main physico-chemical 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. These effects stimulate colonic peristalsis and normalize stool consistency. Constipation is corrected, and the physiological rhythm of the colon is restored.

In hepatic encephalopathy, the drug's action is due to inhibition of proteolytic bacterial growth as a result of increased numbers of acidophilic bacteria (e.g., lactobacilli), transformation of ammonia into its ionized form due to acidification of colonic contents, laxative effect caused by low pH in the colon, as well as osmotic effect, and alteration of bacterial nitrogen metabolism through stimulation of bacterial utilization of ammonia for bacterial protein synthesis. In this context, however, it should be noted that neuropsychiatric manifestations of hepatic encephalopathy cannot be explained solely by hyperammonemia. Nevertheless, ammonia may serve as a model compound for other nitrogenous substances.

As a prebiotic, lactulose enhances the growth of beneficial bacteria such as bifidobacteria and lactobacilli, while the growth of potentially pathogenic bacteria such as clostridia and Escherichia coli may be suppressed. This leads to a more favorable balance of intestinal flora and relief from constipation, thereby positively affecting quality of life and health.

Pharmacokinetics.

Lactulose is poorly absorbed following oral administration and reaches the colon unchanged. There, it is metabolized by the colonic bacterial flora. When 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 rhythm of the large intestine.
• Conditions requiring easier defecation (e.g., hemorrhoids, postoperative states following surgery on the large intestine/ano-rectal region).
• Hepatic encephalopathy: treatment and prevention of hepatic coma or precoma.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Galactosemia.

Gastrointestinal obstruction, gastrointestinal tract perforation, or risk of gastrointestinal tract perforation (e.g., acute inflammatory bowel diseases such as ulcerative colitis, Crohn's disease).

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., thiazides, corticosteroids, and amphotericin B). Concomitant use with cardiac glycosides may enhance the effect of glycosides due to potassium deficiency.

Special precautions for use.

A doctor's consultation is recommended if:

• painful abdominal symptoms of unknown origin are present before the start of treatment;
• the therapeutic effect after several days of treatment is insufficient.

Patients with lactose intolerance should use lactulose with caution.

The dose usually used for constipation does not cause problems in patients with diabetes mellitus.

The dose used for the treatment of hepatic encephalopathy is usually much higher, so its consideration may be necessary when administering the drug to patients with diabetes mellitus.

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 fructose related to the manufacturing process. Therefore, patients with rare hereditary galactose intolerance, fructose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicine. Patients with lactose intolerance should use lactulose with caution.

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

This medicine contains a small amount of propylene glycol (E1520) as part of the excipient "plum flavoring". Concurrent use with any alcohol dehydrogenase substrate, such as ethanol, may cause serious adverse effects in newborns.

Lactulose should be used in patients with gastroesophageal syndrome (Röhmel's syndrome) only after consultation with a physician. If symptoms such as flatulence and bloating occur in these patients after taking lactulose, the dose should be reduced or treatment discontinued.

Use during pregnancy or breastfeeding.

Pregnancy

No adverse effects on the fetus are expected during pregnancy, as the systemic effect of lactulose is negligible.

Dufalac® Frut may be used during pregnancy.

Breastfeeding

No adverse effects on the newborn/infant are expected during breastfeeding, as the systemic effect of lactulose in breastfeeding women is negligible.

Dufalac® Frut may be used during breastfeeding.

Fertility

No adverse effects are expected, as the systemic effect of lactulose is negligible.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration

Lactulose solution can be taken either diluted or undiluted.

The single dose of lactulose should be swallowed immediately and not retained in the mouth.

The dosing regimen should be adjusted according to the individual needs of the patient.

If the drug is prescribed 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, corresponding to 6–8 glasses) per day.

When using the preparation in bottles, a measuring cup may be used.

Dosage for constipation or conditions requiring facilitation of defecation

Lactulose can be administered as a single daily dose or divided into two doses. When using the preparation in bottles, a measuring cup may be used.

After a few days, the initial dose can be adjusted to a maintenance dose based on the response to treatment. A therapeutic effect may require several days of treatment (2–3 days).

For accurate dosing in children under 7 years of age, the medication should be administered in bottles.

Dosing in hepatic encephalopathy (adults only)

Initial dose: 30–45 mL (20–30 g) 3–4 times daily.

This dose may be adjusted until a maintenance dose is achieved that produces soft bowel movements 2–3 times per day.

Children

The safety and efficacy of the medication in children (0–18 years) with hepatic encephalopathy have not been established. Data are lacking.

Geriatric patients and patients with renal or hepatic impairment

Since the systemic effects of lactulose are minimal, no specific dosing 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 the dose is too high, the following symptoms may occur: diarrhea and abdominal pain.

Treatment: discontinue the medication or reduce the dose. Correction of electrolyte imbalances may be required due to excessive fluid loss caused by diarrhea or vomiting.

Side effects

General information on the safety profile

During the first few days of treatment, flatulence may occur. Usually, it resolves within a few days.

When the drug is used at doses exceeding the recommended ones, abdominal pain and diarrhea may occur. In such cases, the dose should be reduced.

With prolonged use of high doses (usually only in hepatic encephalopathy), the patient may develop electrolyte imbalance due to diarrhea.

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

The following adverse reactions occurred at the specified frequencies 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 spontaneously reported during post-marketing use [frequency not known (the exact frequency cannot be determined 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.

Investigations: uncommon – electrolyte imbalance due to diarrhea.

Children

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

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

Additionally, in case of any adverse reactions, lack of efficacy during use of the drug, or quality complaints, please notify the company LLC "Abbott Ukraine" at +38 044-498-60-80 or by 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. 200 ml or 500 ml of solution in a bottle with a measuring cup.

Prescription status. Over-the-counter.

Manufacturer. Abbott Biologicals B.V.

Manufacturer's address and place of business. Veerweg 12, 8121 AA Olst, The Netherlands.