PREOLICA® FORTE

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PREOLIKA® forte (PREOLIKA® forte)

Composition:

Active substance: trimebutine maleate;

One tablet contains trimebutine maleate 200 mg;

Excipients: microcrystalline cellulose; lactose monohydrate; povidone; crospovidone; magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: elongated, biconvex tablets, white to cream-colored, with a score line on one side.

Pharmacotherapeutic group. Agents used in functional gastrointestinal disorders. Synthetic anticholinergic agents, esters of tertiary amino group. Trimebutine.

ATC code A03A A05.

Pharmacological Properties

Pharmacodynamics

Trimebutine is a synthetic agonist of peripheral μ, δ, and κ opioid receptors. Its mechanism of action involves direct effects on the smooth muscle of the gastrointestinal tract and regulation of motility disorders without affecting the central nervous system. Unlike other opioids, trimebutine does not exhibit selectivity for any of the three receptor types, which allows it to either enhance or inhibit peristalsis. The normalization of motility begins within 30 minutes after administration.

Pharmacokinetics

Absorption

After oral administration, trimebutine is almost completely absorbed from the gastrointestinal tract. Trimebutine maleate reaches maximum plasma concentration within 30 minutes after intake.

Distribution

Plasma protein binding is approximately 5%. After oral administration, it crosses the placental barrier in an amount of about 0.05%, and approximately 0.04% is excreted into breast milk.

Metabolism

Following oral administration, trimebutine is metabolized in the liver.

Elimination

It is excreted in urine in the form of metabolites.

Clinical characteristics

Indications.

Irritable bowel syndrome.

Symptomatic treatment of functional gastrointestinal disorders: constipation, diarrhea, abdominal pain, intestinal spasms.

Contraindications.

Hypersensitivity to trimebutine or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction

Zotepine may enhance the anticholinergic effect of trimebutine.

Trimebutine prolongs and enhances the effect of d-tubocurarine.

Trimebutine reduces the effect of cisapride.

Concomitant use of trimebutine with drugs affecting calcium channels (e.g., calcium channel blockers, captopril, reserpine, midazolam) reduces calcium ion influx into the cell, which may inhibit intestinal smooth muscle contraction.

Usage Notes

The medicinal product contains lactose and therefore should not be used in patients with rare hereditary disorders such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption. If a patient has been diagnosed with intolerance to certain sugars, a physician should be consulted before taking this medicinal product.

Trimetobutine may cause drowsiness; therefore, it should be used with caution in patients with central nervous system depression.

The medicinal product may enhance the sedative effect of drugs that depress the central nervous system and of ethanol.

Use during pregnancy or breastfeeding

Since data on the use of trimetobutine during pregnancy or breastfeeding are lacking, the drug is contraindicated in women during these periods. If the medicinal product is used, breastfeeding should be discontinued.

Ability to affect reaction speed while driving or operating machinery.
If dizziness or drowsiness occurs, driving or operating machinery should be avoided.

Dosage and Administration

Take tablets orally 3 times a day, swallowing with a glass of water.

Adults

Irritable bowel syndrome

100 mg of trimebutine maleate (½ tablet) 3 times a day before meals.

In exceptional cases, the daily dose may be increased to 600 mg, i.e. 1 tablet 3 times a day.

Functional gastrointestinal disorders:

• diarrhea, constipation: 200 mg of trimebutine maleate (1 tablet) 1–2 times a day before meals;
• abdominal pain, intestinal spasms: 100 mg of trimebutine maleate (½ tablet) 3 times a day before meals.

In exceptional cases, the daily dose may be increased to 600 mg per day, i.e. 1 tablet 3 times a day.

The duration of treatment is determined individually. The usual course of therapy is 2–6 weeks, depending on the severity and course of the disease.

Children. Experience with the use of trimebutine in children is limited; therefore, the drug should not be prescribed to this age group.

Overdose

There are no data regarding cases of trimebutine overdose. An overdose may enhance the manifestations of adverse reactions. Treatment is symptomatic.

Adverse Reactions

Adverse effects associated with trimebutine have been classified according to MedDRA [Medical Dictionary for Regulatory Activities].

The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (≤1/10,000); frequency not known (cannot be estimated from available data).

Immune system disorders:

Frequency not known: hypersensitivity reactions (pruritus, urticaria, angioneurotic edema, and in exceptional cases—anaphylactic shock).

Psychiatric disorders:

Very rare: anxiety.

Nervous system disorders:

Common: somnolence, drowsiness, fatigue, dizziness, sensation of heat or cold, headache, apathy.

Ear and labyrinth disorders:

Very rare: hearing loss.

Cardiac disorders:

Rare: cardiac rhythm disturbances.

Gastrointestinal disorders:

Common: dry mouth, dysgeusia, diarrhea, indigestion, upper abdominal pain, numbness of the oral cavity, nausea, vomiting, constipation, thirst.

Hepatobiliary disorders:

Rare: liver function abnormalities.

Very rare: hepatitis.

Skin and subcutaneous tissue disorders:

Uncommon: rash.

Frequency not known: generalized maculopapular rash, erythema, eczematous reactions, and exceptionally severe skin reactions, including cases of acute generalized exanthematous pustulosis (AGEP), erythema multiforme, and febrile toxidermia.

Renal and urinary disorders:

Very rare: urinary retention.

Reproductive system and breast disorders:

Very rare: menstrual cycle disturbances, breast enlargement accompanied by pain in women, gynecomastia in men, breast pain.

Laboratory abnormalities:

Rare: increased levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST]).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is important. It allows continued 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 via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua

Shelf life. 3 years.

Storage conditions. Store at a temperature not exceeding 30 °C. Keep in the original packaging to protect from moisture.

Packaging. 10 tablets per blister pack, 3 blisters per carton.

Prescription category. Prescription only.

Manufacturer. Biofarm Sp. z o.o. / Biofarm Sp. z o.o.

Manufacturer's address

ul. Walbrzyska 13, Poznan, 60-198, Poland / ul. Walbrzyska 13, Poznan, 60-198, Poland.