Lactulose

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LACTULOSE (LACTULOSE)

Composition:

Active substance: lactulose;

1 ml of syrup contains 670 mg of lactulose.

Pharmaceutical form. Syrup.

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

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 reduce the pH level within the lumen of the colon and, through osmotic effects, increase the volume of intestinal contents—this stimulates colonic peristalsis. In addition, stool volume increases and consistency normalizes, thereby relieving constipation and restoring the physiological rhythm of digestion.

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

In hepatic encephalopathy or hepatic (pre)coma, the therapeutic effect of lactulose is associated with inhibition of proteolytic bacterial growth due to increased numbers of acidophilic bacteria (e.g., lactobacilli), conversion of ammonia into its ionized form through acidification of intestinal contents, laxative effect due to low pH and osmotic action, and alteration of nitrogen metabolism in bacteria via stimulation of bacterial utilization of ammonia for protein synthesis.

Pharmacokinetics.

When administered orally, lactulose is virtually not absorbed and not hydrolyzed in the stomach and 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 easier defecation (hemorrhoids, after surgery on the large intestine and anorectal area).

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

Contraindications.

• Hypersensitivity to the active substance or to other components of the medicinal product;
• galactosemia;
• gastrointestinal obstruction / intestinal stenosis;
• gastrointestinal tract perforation or risk of gastrointestinal tract perforation;
• acute inflammatory bowel diseases (ulcerative colitis, Crohn's disease);
• acute abdominal pain of unknown origin.

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 taking lactulose with enteric-coated pH-dependent release formulations, 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.

It is not recommended to take lactulose within 2 hours after taking other drugs.

Lactulose may increase potassium loss induced by other drugs (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 (pre)coma, significantly higher doses are usually prescribed, which should be taken into account when administering the drug to diabetic patients.

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.

During prolonged treatment (more than 6 months), plasma electrolyte levels should be monitored regularly, especially in elderly and debilitated patients.

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

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

Use during pregnancy or breastfeeding.

Pregnancy

During pregnancy, no adverse effects on the fetus are expected, as the systemic impact of lactulose on the pregnant woman is negligible.

Lactulose syrup can be used during pregnancy.

Breastfeeding period

During breastfeeding, no effects in the newborn/infant are expected, as the systemic impact of lactulose on the mother is negligible. Lactulose syrup may be used during breastfeeding.

Fertility

No effects on fertility are expected, as the systemic impact of lactulose is negligible.

Ability to influence reaction rate while driving or operating machinery

Lactulose intake 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.

Dosage and Administration.

The dose should be adjusted based on 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 dosing device or measuring cup may be used for measuring the dose.

Dosing for constipation or conditions requiring facilitation of defecation

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

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

Dosage must be individually determined and prescribed only by a physician.

For patients in coma, the drug may be administered via a gastric tube or as an enema.

Children. The safety and efficacy of the drug 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 effect of lactulose is negligible, no special dosage recommendations are required 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 for hepatic encephalopathy.

It should be noted 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 electrolyte imbalance.

If symptoms of overdose do not resolve, immediate medical attention is required.

Adverse reactions.

During the first days of treatment, flatulence may occur, which usually resolves 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. During prolonged use of high therapeutic doses (usually only in patients with portosystemic encephalopathy), electrolyte imbalance due to diarrhea may occur.

During post-marketing use, hypersensitivity reactions have been reported, predominantly limited to skin manifestations, which have been classified as possible adverse reactions. Since these reactions were reported spontaneously from a population of unknown size, the frequency cannot be reliably estimated.

Immune system disorders

Frequency unknown — hypersensitivity reactions.

Skin and subcutaneous tissue disorders

Frequency unknown — rash, pruritus, urticaria.

Gastrointestinal disorders

Flatulence, abdominal pain, nausea and vomiting. Diarrhea (if doses are too high).

Laboratory test abnormalities

Electrolyte imbalance due to diarrhea.

Children

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

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

Reporting of adverse reactions

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

Shelf life.

2 years from the date of manufacturing of the bulk product.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Packaging.

100 ml in polymer bottles with a tamper-evident cap; 1 bottle with a dosing device in a cardboard box.

200 ml in polymer bottles with a tamper-evident cap; 1 bottle with a measuring cup in a cardboard box.

Availability category.

Over-the-counter.

Manufacturer.

Limited Liability Company "Pharmaceutical Company "Vertex".

Manufacturer's location and address of business activity.

33, Astronomichna Street, lit. "V-1", Kharkiv, Kharkiv Oblast, 61085, Ukraine.