Lactunorm®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Lactunorm® (Lactunorm)

Composition:

Active substance: lactulose;

1 ml of syrup contains lactulose (in the form of liquid lactulose) 670.0 mg.

Pharmaceutical form. Syrup.

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

Pharmacotherapeutic group. Osmotic laxatives. Lactulose.

ATC code A06AD11.

Pharmacological properties.

Pharmacodynamics.

Lactulose, a synthetic derivative of lactose, is broken down by intestinal flora in the colon into low-molecular-weight organic acids. These acids lower the pH within the lumen of the colon and, through osmotic effects, increase the volume of intestinal contents, thereby stimulating colonic peristalsis. Concurrently, stool volume increases and consistency normalizes, relieving constipation and restoring the physiological rhythm of digestion.

As a prebiotic, lactulose promotes the growth of bifidobacteria and lactobacilli, while suppressing the growth of potentially pathogenic bacteria such as Escherichia coli and clostridia. This facilitates the restoration of normal intestinal microflora balance.

In hepatic encephalopathy or hepatic coma and precoma, the therapeutic effect of lactulose is related to:

• inhibition of proteolytic bacterial growth due to increased numbers of acidophilic bacteria (e.g., lactobacilli);
• transformation of ammonia into its ionized form, facilitated by acidification of intestinal contents;
• laxative effect due to low pH and osmotic action;
• alteration of nitrogen metabolism in bacteria, through stimulation of bacterial utilization of ammonia for protein synthesis.

Pharmacokinetics.

When administered orally, lactulose is virtually not absorbed and not hydrolyzed in the stomach or small intestine, reaching the colon unchanged due to the absence of a specific enzyme in the body.

When administered at doses of 40–75 mL, the drug is completely metabolized by bacterial flora. When doses exceeding these amounts 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, postoperative states following surgery on the large intestine and anorectal region.

Hepatic encephalopathy: treatment and prevention of hepatic coma and precoma.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients;
• acute abdominal pain of unknown origin;
• nausea, vomiting;
• galactosemia;
• gastrointestinal obstruction and/or intestinal stenosis;
• perforation of the gastrointestinal tract or risk of gastrointestinal perforation;
• acute inflammatory bowel diseases (ulcerative colitis, Crohn’s disease);
• rectal bleeding;
• severe dehydration.

Interaction with other medicinal products and other forms of interaction.

If the patient is taking any other medicinal products, this should be reported to the physician.

When administering lactulose with enteric-coated pH-dependent release medicinal products, it should be remembered that lactulose reduces the intestinal pH.

Concomitant use with broad-spectrum antibiotics or antacids may reduce the therapeutic efficacy of lactulose.

Lactulose should not be taken within 2 hours after taking other drugs.

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.

Before starting treatment with lactulose, consult a physician, as the physician should determine the dosage and duration of treatment.

Use with caution in patients with diabetes mellitus. For the treatment of hepatic coma and precoma, significantly higher doses are usually required, which should be taken into account when prescribing the medicinal product to diabetic patients.

Prolonged use of the medicinal product (more than 6 months) without proper dose adjustment or incorrect use may lead to the development of diarrhea and electrolyte imbalance. In severe cases, dehydration or hypokalemia may occur. Hypokalemia may cause cardiac or neuromuscular dysfunction, especially during concomitant treatment with cardiac glycosides, diuretics, or corticosteroids. Plasma electrolyte levels should be monitored regularly, especially in elderly and debilitated patients.

The medicinal product should be used in patients with gastroesophageal syndrome (Röhmel's syndrome) only after consultation with a physician. In gastroesophageal syndrome, the dose should be increased gradually to avoid flatulence.

If symptoms such as flatulence and bloating occur in these patients after taking lactulose, the dose should be reduced or treatment discontinued.

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

If symptoms of the disease do not begin to resolve, or if the patient's condition worsens or adverse reactions occur, the use of the medicinal product should be discontinued and medical advice should be sought regarding further treatment.

Use during pregnancy or breastfeeding.

Pregnancy

No adverse effects on the fetus are expected during pregnancy, as systemic exposure of lactulose to the pregnant woman is negligible.

Lactunorm**®** may be used during pregnancy.

Period of breastfeeding

No effects in the newborn/infant are expected during breastfeeding, as systemic exposure of lactulose to the mother is negligible. Lactunorm**®** may be used during breastfeeding.

Fertility

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

Ability to influence reaction speed when driving vehicles or operating machinery.

Lactulose does not affect the ability to drive vehicles or operate machinery, or to engage in other potentially hazardous activities requiring increased attention and visual acuity.

Administration and Dosage

The dosage should be adjusted according to the clinical response. Lactulose may be taken orally either undiluted or diluted.

The single dose of lactulose should be swallowed immediately (do not retain in the oral cavity for prolonged periods).

The dosing regimen should be individualized according to the patient's needs.

If the medicinal product 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 per day, equivalent to 6–8 glasses).

The syrup may be mixed with fruit or vegetable juices or food mixtures. A measuring cup may be used when administering the medicinal product.

Dosage for constipation or conditions requiring facilitation of defecation

After a few days of treatment, the initial dose may be adjusted to a maintenance dose based on the response to therapy.

The entire daily dose is better taken as a single dose (without holding in the oral cavity for a prolonged period) in the morning with breakfast, or divided into 2 doses. The effect may be observed within 1–2 days, due to the action of lactulose.

For hepatic encephalopathy, hepatic coma, and precoma

Adults. The medicinal product is prescribed at an initial dose of 30–45 mL 3–4 times daily. The maintenance dose is established according to individual response (aim to achieve 2–3 soft bowel movements per day). The dose is individually determined and prescribed only by a physician.

For patients in coma, the medicinal product can be administered via a nasogastric tube or as an enema.

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

Elderly patients and patients with renal or hepatic impairment

Since the systemic effect of lactulose is negligible, there are no special dosage recommendations for these patient groups.

Children.

Laxatives should be used in children only in exceptional cases and under medical supervision.

There are no data on the use of the medicinal product in children with hepatic encephalopathy.

It should be borne in mind that the intestinal defecation reflex may be impaired during treatment.

Lactulose should be used with caution in infants and children with hereditary fructose intolerance inherited in an autosomal recessive manner.

Overdose.

Symptoms: abdominal pain, bloating, vomiting, diarrhea.

Treatment: dose reduction or discontinuation of the medicinal product is recommended. Excessive fluid loss due to vomiting and diarrhea may require correction of the electrolyte balance.

If symptoms of overdose do not resolve, seek immediate medical assistance.

Adverse Reactions

During the first days of treatment, flatulence may occur, which usually resolves spontaneously within a few days. When the medicinal product 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 therapeutic doses (usually only in patients with portosystemic encephalopathy), electrolyte imbalance due to diarrhea may be observed.

Gastrointestinal disorders: flatulence, abdominal pain, nausea and vomiting. Diarrhea (with excessively high doses).

Immune system disorders: frequency unknown – hypersensitivity reactions.

Skin and subcutaneous tissue disorders: frequency unknown – rash, pruritus, urticaria.

Laboratory findings: electrolyte imbalance due to diarrhea.

If any adverse reactions occur, consult a physician regarding further use of the medicinal product.

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

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after registration of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Medical and pharmaceutical personnel, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and/or lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging. 100 ml, 200 ml, or 500 ml in a bottle; 1 bottle with a measuring cup in a carton.

Availability. Over-the-counter (without prescription).

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturing from bulk product supplied by:

Fresenius Kabi Austria GmbH.

Manufacturer's address and location of its business activity.

Ukraine, 02093, Kyiv, 13 Boryspylska Street.

Manufacturing from bulk product supplied by:

Fresenius Kabi Austria GmbH,

Austria, 4020, Linz, Estermannstrasse 17.