Zelmac (Tablets) Instructions for Use

Marketing Authorization Holder

Novartis Pharma AG (Switzerland)

ATC Code

A06AX06 (Tegaserod)

Active Substance

Tegaserod (Rec.INN registered by WHO)

Dosage Form

Zelmac

Tablets 6 mg: 20, 30, 50, 60, 100, or 300 pcs.

Dosage Form, Packaging, and Composition

Tablets are round, flat, with beveled edges, whitish to slightly yellowish in color, with marbling, marked with “EH” on one side and “NVR” on the other.

Excipients: crospovidone, glyceryl monostearate, hypromellose, lactose monohydrate, macrogol 4000, poloxamer 188.

10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (3) – cardboard packs.
10 pcs. – blister packs (5) – cardboard packs.
10 pcs. – blister packs (6) – cardboard packs.
10 pcs. – blister packs (10) – cardboard packs.
10 pcs. – blister packs (30) – cardboard packs.

Clinical-Pharmacological Group

Selective serotonin 5-HT₄ receptor agonist

Pharmacotherapeutic Group

Serotonin receptor stimulant

Pharmacological Action

An agent that regulates the motor function of the gastrointestinal tract, a partial agonist of serotonin 5-HT₄ receptors.

It has a selective effect on the gastrointestinal tract. It stimulates serotonin 5-HT₄ receptors on the endings of sensory (afferent) neurons of the gastrointestinal tract and causes the release of a number of mediators (in particular, calcitonin gene-related peptide). It enhances peristalsis, increases basal motor activity, and normalizes impaired propulsive activity throughout the gastrointestinal tract.

Due to the increase in cyclic AMP production under the action of tegaserod, the secretion of chloride ions and water by the intestinal crypts is increased. Under the influence of tegaserod, the number of impulses generated by afferent neurons in response to rectal distension is reduced.

Tegaserod has a high affinity for human serotonin 5-HT₄ receptors, while it has no significant affinity for 5-HT₃ and dopamine receptors.

In patients with irritable bowel syndrome with constipation predominance, Tegaserod accelerates the passage of intestinal contents through the small and large intestine. It helps to normalize stool consistency and increases the number of bowel movements; reduces the severity of the symptom complex (abdominal discomfort/pain, constipation) characteristic of irritable bowel syndrome.

Pharmacokinetics

After oral administration, Tegaserod is rapidly absorbed from the gastrointestinal tract. The time to reach C_max is about 1 hour. When taken on an empty stomach, the bioavailability is about 10%. Food reduces the bioavailability of tegaserod by 40-65% and C_max by approximately 20-40%.

Plasma protein binding is 98%. It penetrates the blood-brain barrier to a small extent.

It is metabolized mainly by presystemic hydrolysis in the stomach with the participation of acid catalase and by direct glucuronidation.

In vitro studies have shown that Tegaserod does not inhibit the CYP2C8, CYP2C9, CYP2C19, CYP2E1, and CYP3A4 isoenzymes. However, inhibition of the CYP1A2 and CYP2D6 isoenzymes cannot be ruled out. In studies of human metabolism, it was shown that Tegaserod does not suppress the activity of any of the aforementioned cytochrome P₄₅₀ system isoenzymes.

About two-thirds of the orally administered dose is excreted unchanged in the feces; the remaining part of the dose is excreted in the urine, mainly as the main metabolite.

No significant accumulation of tegaserod in plasma is observed.

In individuals with mild or moderate hepatic impairment, an increase in the mean AUC by 43% and C_max by 18% was noted compared to healthy individuals.

Indications

Irritable bowel syndrome.

ICD codes

Dosage Regimen

Administer Zelmac orally twice daily at the recommended dose of 6 mg.

Take each dose immediately before meals to ensure consistent absorption.

Do not exceed the prescribed daily dose of 12 mg.

Swallow the tablet whole with a sufficient amount of water; do not crush or chew.

Continue therapy only as directed by a physician, based on symptom assessment and treatment response.

Discontinue use and contact a physician immediately if severe diarrhea or new, persistent abdominal pain occurs.

This medication is contraindicated in patients with a history of cardiovascular disease, severe hepatic impairment, or known hypersensitivity to Tegaserod.

Use with caution in patients with mild to moderate hepatic impairment due to potential increases in drug exposure.

Adverse Reactions

Possible diarrhea, abdominal pain, nausea, flatulence, headache, dizziness, back pain, flu-like symptoms.

Placebo-controlled safety studies have established that patients receiving Tegaserod have an increased risk of developing an attack of angina, stroke, and increased chest pain, which may lead to an anginal attack. In this regard, the drug is not currently used on the market.

Contraindications

Severe hepatic failure, childhood, pregnancy, lactation period, hypersensitivity to tegaserod.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure. Use with caution in patients with mild or moderate hepatic impairment.

Pediatric Use

Contraindicated in children.

Special Precautions

Use with caution in patients with mild or moderate hepatic impairment.

Due to the risk of developing serious side effects, Tegaserod has been withdrawn from the market in the USA.!!!!

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.