Medulac

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

Composition:

Active substance: lactulose;

1 ml of the medicinal product contains lactulose 667 mg;

Excipients: sodium benzoate (E 211), purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear, viscous liquid, colorless or pale brownish-white, sweet to taste.

Pharmacotherapeutic group.

Osmotic laxatives. ATC code A06AD11.

Pharmacological properties.

Pharmacodynamics.

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

In portosystemic encephalopathy or hepatic (pre)coma, 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 intestinal contents, intestinal cleansing due to low pH, as well as the 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 portosystemic encephalopathy cannot be explained solely by hyperammonemia. Nevertheless, the described mechanism of ammonia reduction by lactulose may be analogous for other nitrogenous compounds.

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

Pharmacokinetics.

Lactulose is poorly absorbed after oral administration and reaches the intestine unchanged. When administered at doses of 25–50 g, or 40–75 mL, lactulose is completely metabolized by bacterial flora. When higher doses are used, part of the lactulose may be excreted unchanged.

Clinical characteristics.

Indications.

• Constipation: regulation of the physiological intestinal rhythm.
• Conditions requiring easier defecation (hemorrhoids, after surgery on the large intestine and anorectal region).
• Hepatic encephalopathy: treatment and prevention of hepatic coma and precoma.

Contraindications.

• Hypersensitivity to the active substance and/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 interactions.

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.

The possibility of inactivation of medicinal products whose release depends on intestinal pH should be considered.

Antibiotics (neomycin) and non-absorbable antacids reduce the effect of lactulose.

Special precautions for use.

Consult a physician if:

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

The drug 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 administering the drug to patients with diabetes mellitus.

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

The drug contains lactose, galactose, and a small amount of fructose; therefore, it should not be administered to patients with rare hereditary disorders of galactose or fructose intolerance, lactase deficiency, or glucose-galactose malabsorption.

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

Use during pregnancy or breastfeeding.

Pregnancy.

No adverse effects are expected during pregnancy, as the systemic effect of lactulose on the pregnant woman is negligible. The drug may be used during pregnancy.

Breastfeeding.

No adverse effects are expected in the newborn/infant, as the systemic effect of lactulose on the breastfeeding woman is negligible. The drug may be used during breastfeeding.

Fertility.

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

Ability to influence reaction rate when driving or operating machinery.

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

Dosage and Administration.

Administration.

The medicinal product is intended for oral administration. The syrup can be taken either diluted or undiluted.

The dose should be adjusted according to individual patient needs.

The single dose of the medicinal product should be swallowed immediately and not held in the mouth for a prolonged period.

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, equivalent to 6–8 glasses, per day).

For dosing the medicinal product, a tablespoon (15 ml) or teaspoon (5 ml) may be used.

Dosage.

Use for constipation or for medical softening of stools.

The medicinal product can 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 apparent.

Use in hepatic encephalopathy (adults only).

The initial dose of the medicinal product is 30–45 mL 3–4 times daily.

This dose may be adjusted to achieve a maintenance dose allowing soft bowel movements 2 to 3 times daily.

The safety and efficacy of the medicinal product in children (from birth to 18 years of age) with portosystemic 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, no special 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 excessively high doses are administered, abdominal pain and diarrhea may occur.

Recommended treatment includes discontinuation of the medicinal product or dose reduction; in case of excessive fluid loss due to diarrhea or vomiting, correction of electrolyte imbalance is required.

Side effects.

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 are possible. In such cases, the dose of the medicinal product should be reduced. With prolonged use of high therapeutic doses of the medicinal product (usually only in patients with portosystemic encephalopathy), electrolyte imbalance due to diarrhea may occur.

During post-marketing use, hypersensitivity reactions have been observed, mostly limited to skin manifestations, which have been considered as possible adverse reactions. Since these reactions were reported spontaneously and the size of the patient population is unknown, the frequency of these reactions cannot be reliably estimated.

Criteria for assessing the frequency of adverse reactions: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); not known (frequency cannot be estimated from the available data).

Immune system disorders:

Not known — hypersensitivity reactions.

Gastrointestinal disorders:

Very common — diarrhea; common — flatulence, abdominal pain, nausea and vomiting.

Skin and subcutaneous tissue disorders:

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.

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

Shelf life.

3 years.

After opening the bottle, the medicinal product should be used within 12 months.

Storage conditions.

Store at temperatures not exceeding 25 ºC in the original packaging and in a place inaccessible to children.

Packaging.

180 ml in a bottle; 1 bottle in a cardboard box.

Availability category.

Over-the-counter.

Manufacturer.

ABC Farmaceutici S.p.A. /
ABC Farmaceutici S.p.A.

Manufacturer's address and location of operations.

Via Cantone Moretti, 29 (Localita San Bernardo) – 10015 Ivrea (TO), Italy /
Via Cantone Moretti, 29 (Localita San Bernardo) – 10015 Ivrea (TO), Italy.

Marketing Authorization Holder.

WORLD MEDICINE, LLC, Ukraine /
WORLD MEDICINE, LLC, Ukraine.