Normase

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NORMASE® (NORMASE®)

Composition:

Active substance: lactulose;

1 ml of syrup contains 0.667 g of lactulose (10 g/15 ml);

Excipients: citric acid monohydrate; cream flavoring; purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: a clear, colorless or slightly brownish-yellow syrupy liquid, sweet to taste, with a characteristic odor (candy-like).

Pharmacotherapeutic group. Osmotic laxatives. ATC code A06AD11.

Pharmacological properties.

Pharmacodynamics.

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

In portal-systemic encephalopathy or hepatic (pre)coma, the drug's action is manifested by inhibition of proteolytic bacterial growth due to an increase in the number of acidophilic bacteria (e.g., lactobacilli), transformation of ammonia into its ionized form due to acidification of intestinal contents, intestinal cleansing facilitated by the 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. However, in this context, it should be noted that neuropsychiatric manifestations of portal-systemic encephalopathy cannot be explained solely by hyperammonemia. Nevertheless, the described mechanism of ammonia reduction by lactulose may be analogous for other nitrogen 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 lead to a more favorable balance of intestinal flora.

Pharmacokinetics.

Lactulose is poorly absorbed after oral administration and reaches the intestine unchanged. The effect may be achieved within 48 hours after administration. Daily excretion of lactulose components in urine is approximately 3%.

Clinical characteristics.

Indications.

• Constipation: restoration of the physiological rhythm of intestinal defecation.
• Conditions requiring facilitation of defecation (hemorrhoids, after surgery on the large intestine and anorectal area).
• Portosystemic hepatic encephalopathy: treatment and prevention of hepatic precoma and coma.

Contraindications.

Hypersensitivity to lactulose or to any component of the medicinal product. Galactosemia. Lactose intolerance. Acute abdominal pain of unknown origin, nausea, vomiting, gastrointestinal obstruction or stenoses, rectal bleeding of unknown origin, severe dehydration, gastrointestinal tract perforation or risk of gastrointestinal tract perforation.

Interaction with other medicinal products and other forms of interaction.

A broad spectrum of antibacterial agents used concomitantly with lactulose may impair its degradation, reduce the acidifying effect on intestinal contents, and overall efficacy. Antibiotics (neomycin) and non-absorbable antacids reduce the effect of lactulose.

Laxatives may reduce intestinal load, and thus absorption of other medicinal products administered concomitantly by the oral route.

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

Lactulose may increase potassium loss induced by other medicinal products (e.g., thiazide diuretics, corticosteroids, and amphotericin B). Potassium deficiency may potentiate the effect of cardiac glycosides.

Concomitant use of laxatives with other medicinal products should be avoided: after administration of any medicinal product, it is recommended to wait at least two hours before taking a laxative.

Special precautions for use.

Abuse of laxatives (frequent or prolonged use, or use in excessive doses) may lead to chronic diarrhea, followed by loss of water, mineral salts (especially potassium), and other essential nutrients. In severe cases, dehydration or hypokalemia may develop. Hypokalemia may cause cardiac or neuromuscular dysfunction, particularly when concomitant therapy with cardiac glycosides, diuretics, or corticosteroids is administered.

Prior to prolonged use, a physician should be consulted.

Use with caution in patients with diabetes mellitus. For elderly and debilitated patients receiving Normase for more than 6 months, monitoring of serum electrolyte levels is recommended. Normase should be administered to children under 12 years of age only after consultation with a physician.

In patients with gastroesophageal reflux, doses should be gradually increased to avoid flatulence; flatulence usually resolves spontaneously within 2–3 days of treatment.

Do not use the drug in case of abdominal pain, nausea, or vomiting. If diarrhea develops, discontinue treatment.

Lactulose is poorly absorbed and metabolized. The preparation also contains other sugars such as fructose, galactose, and lactose. Therefore, patients with diagnosed sugar intolerance should consult a physician before taking this medicinal product. The preparation may also be harmful to teeth.

Elderly patients or patients with other underlying diseases should consult a physician before starting treatment.

Use during pregnancy or breastfeeding.

Pregnancy.

Limited data on use in pregnant women indicate no fetotoxic or neonatal toxicity of lactulose and no potential to cause malformations.

Normase may be used during pregnancy if needed.

Breastfeeding period.

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

Normase may be used during breastfeeding.

Ability to influence reaction rate while driving or operating machinery.

Effect not established.

Method of administration and dosage.

Normase can be taken either undiluted or diluted. The dose should be adjusted according to the clinical response.

A single dose of lactulose should be swallowed immediately without holding it in the mouth.

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

If the patient is prescribed the drug 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.

Dosage for constipation or conditions requiring facilitation of defecation.

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 apparent.

Dosage in hepatic coma and precoma (adults only).

Initial dose: 30–45 mL three to four times daily.

This dose may be adjusted to achieve a maintenance dose that allows for soft bowel movements two to three times per day.

The safety and efficacy of using the drug in children (0–18 years) with portosystemic 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 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 noted that the defecation reflex may be impaired during treatment.

Overdose.

Abuse of laxatives (frequent or prolonged use, or use in excessive doses) may lead to persistent diarrhea with subsequent loss of water, mineral salts (especially potassium), and other essential nutrients. In severe cases, dehydration or hypokalemia may develop. Hypokalemia may cause cardiac or neuromuscular dysfunction, particularly if the patient is concurrently receiving cardiac glycosides, diuretics, or corticosteroids.

In case of overdose, mild abdominal pain, bloating, 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. After discontinuation of Normase, these symptoms resolve.

Adverse Reactions.

Symptoms.

During the first days of treatment, flatulence may occur, which usually resolves after several days. When the drug is used at doses exceeding the recommended ones, abdominal pain and cramps may occur, more frequently in severe cases of constipation and flatulence. High doses may also cause nausea in some patients. In such cases, the dose should be reduced. These symptoms usually disappear after several days of treatment.

Diarrhea may occur, especially when higher doses are used, for example during treatment of portosystemic encephalopathy. Dosage adjustment or discontinuation of treatment may be necessary. Diarrhea may persist after dose reduction or discontinuation of the drug.

With prolonged use, electrolyte imbalance is possible.

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 determined from available data).

Gastrointestinal disorders: very common – diarrhea; common – flatulence, abdominal pain or cramps, nausea and vomiting.

Immune system disorders: not known – hypersensitivity reactions.

Skin and subcutaneous tissue disorders: not known – rash, pruritus, urticaria.

Laboratory test abnormalities: uncommon – electrolyte imbalance due to diarrhea.

Children

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

Shelf life.

3 years.

Storage conditions.

No special storage conditions required. Store in the original packaging, in a place inaccessible to children.

Packaging.

200 ml in a bottle; 1 bottle with a measuring cup in a cardboard box.

Prescription status.

Over-the-counter.

Manufacturer.

L. Molteni & C. dei F.lli Alitti Societa di Esercizio S.p.A. /
L.Molteni & C.dei F.lli Alitti Societa di Esercizio S.p.A.

Manufacturer's address and place of business.

S.S.67 (Tosco Romagnola) Localita Granatieri, 50018 Scandicci (Fi), Italy /
S.S.67 (Tosco Romagnola) Localita Granatieri-50018 Scandicci, Italy.