Bioflorax

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

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. 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, through an 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 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 bacterial flora. When administered at doses of 25–50 g or 40–75 mL, lactulose is completely metabolized. Following administration of higher doses, part of the lactulose may be excreted unchanged.

Clinical characteristics.

Indications.

• Constipation: regulation of the physiological intestinal rhythm.
• Conditions requiring facilitation of defecation (hemorrhoids, postoperative period after surgery on the colon 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, gastrointestinal tract perforation or risk of gastrointestinal tract 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 enhance the effect of cardiac glycosides.

Special precautions for use

Consult a physician if:

• there are abdominal pain symptoms of unknown origin prior to starting treatment;
• the therapeutic effect is insufficient within a few days of treatment.

The medicinal product should be used with caution in patients with lactose intolerance.

The dose of the drug 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 diarrhea and electrolyte imbalance.

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

Lactulose should be used in patients with gastroesophageal syndrome (Röhmheld 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.

No adverse effects are expected during pregnancy, as the systemic effects of lactulose on the pregnant woman are negligible. The syrup can be used during pregnancy.

Breastfeeding period.

No adverse effects are expected in the newborn/infant, as the systemic effects of lactulose on the breastfeeding woman are negligible. The medicinal product can be used during breastfeeding.

Fertility.

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

Ability to affect reaction speed when driving or operating machinery.

The medicinal product has no effect or has a negligible effect on the ability to drive a vehicle or operate machinery.

Administration and Dosage

The medicinal product can be taken either diluted or undiluted.

The dose should be adjusted according to individual patient needs.

The single dose of lactulose should be swallowed immediately and should not be held 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, corresponding to 6–8 glasses) throughout the day.

Dosage for constipation or for medical softening of stools

Lactulose may be taken as a single daily dose or divided into two doses.

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

Dosage in hepatic encephalopathy (adults only)

Initial dose: 30–45 mL three to four times daily. This dose may be adjusted to a 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.

Geriatric patients and patients with renal or hepatic impairment

Since the systemic effect of lactulose is negligible, 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 considered 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 treatment 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

General safety profile

During the first few 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. Prolonged use of high therapeutic doses may lead to electrolyte imbalance due to diarrhea (usually only in patients with hepatic encephalopathy).

During post-marketing use, hypersensitivity reactions have been observed, predominantly limited to skin manifestations, which have been identified as possible adverse reactions. Since these reactions were 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 were 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 adverse reactions

Reporting adverse reactions after medicinal product authorization is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at: 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 of children. Bioflorax can be used throughout the shelf life of the product after opening the bottle, provided it is stored in the original packaging.

Packaging. 100 ml or 200 ml in a bottle with a dosing pipette in a carton.

Prescription status. Over-the-counter.

Manufacturer

Limited liability company "Kharkiv Pharmaceutical Enterprise "Zdorov'ya Narodu".

Manufacturer's address and location of its business activities

Ukraine, 61002, Kharkiv region, Kharkiv, Kulikovska St., 41.

(Packaging from "in bulk" supplied by Fresenius Kabi Austria GmbH, Austria).