Tribudat Forte Tablet

Tribudat Forte is a medication containing trimebutine maleate, primarily used for gastrointestinal disorders. This tablet formulation helps regulate intestinal motility and is particularly effective in managing symptoms associated with irritable bowel syndrome. The following comprehensive overview provides detailed information about this medication’s composition, mechanism of action, therapeutic uses, and important considerations for safe usage.

Composition and Formulation

Tribudat Forte contains 200 mg of trimebutine maleate as its active ingredient. The tablet also contains several excipients including bovine lactose monohydrate (180 mg), corn starch, microcrystalline cellulose, bovine gelatin, magnesium stearate, and talc. These inactive ingredients help in the formulation of the tablet and its stability. The tablet is described as white in color, biconvex, with a break line on one side, marked with “TM” above and “20” below the break line.

Mechanism of Action

Pharmacodynamic Properties

Trimebutine maleate functions as a spasmolytic agent that directly acts on the smooth muscle of the gastrointestinal tract to modulate gastric motility. Its action is particularly interesting as it exhibits a dual regulatory effect-it can either stimulate digestive muscle contractions when motility is decreased or resolve spasms when there is increased motility. This regulatory activity occurs throughout the digestive tract, helping to restore physiological motility in functional digestive disorders.

Molecular Mechanisms

At the molecular level, trimebutine exhibits several mechanisms. At high concentrations, it inhibits extracellular Ca²⁺ influx in smooth muscle cells through voltage-dependent L-type Ca²⁺ channels and further prevents Ca²⁺ release from intracellular stores. The medication appears to bind to the inactivated state of the calcium channel with high affinity. Additionally, it inhibits outward K⁺ currents in response to membrane depolarization of gastrointestinal smooth muscle cells through inhibition of delayed rectifier K⁺ channels and Ca²⁺-dependent K⁺ channels.

Receptor Activity

Trimebutine has notable affinity for opioid receptors, particularly binding to mu opioid receptors with greater selectivity compared to delta or kappa receptors, though with lower affinity than their natural ligands. Its metabolite, N-monodesmethyl-trimebutine (nor-trimebutine), also demonstrates binding to opioid receptors on brain membranes and myenteric synaptosomes. Furthermore, trimebutine facilitates the release of gastrointestinal peptides such as motilin and modulates the release of other peptides including vasoactive intestinal peptide, gastrin, and glucagon.

Therapeutic Indications

Irritable Bowel Syndrome

Tribudat Forte is primarily indicated for the symptomatic treatment of irritable bowel syndrome (IBS), also known as spastic colon. This condition is characterized by abdominal pain, gas, cramping, bloating, and alterations in bowel habits such as diarrhea and/or constipation. The medication helps alleviate these symptoms by regulating intestinal motility and reducing hypersensitivity of the digestive tract.

Functional Digestive Disorders

Another indication for Tribudat Forte is the treatment of functional digestive disorders. These are conditions where the digestive system doesn’t function properly without any identifiable underlying disease. The medication helps normalize bowel movements and reduce associated symptoms such as abdominal discomfort and bloating.

Gastrointestinal Pain Management

Tribudat Forte is effective in the symptomatic treatment of gastrointestinal pain. Its action on opioid receptors and ability to regulate intestinal motility make it particularly useful for managing abdominal pain associated with various gastrointestinal conditions. Recent research has also suggested that trimebutine may decrease reflexes induced by distension of the gut lumen, thereby modulating visceral sensitivity.

Postoperative Use

The medication is also indicated for use in postoperative paralytic ileus to accelerate the resumption of intestinal transit following abdominal surgery. Clinical studies have demonstrated that trimebutine maleate helps improve postoperative conditions by decreasing abdominal and colonic discomfort, abdominal pain, and nausea, with resumption of gases appearing within 48 hours in 66.4% of cases and within 72 hours in 85.4% of cases.

Pharmacokinetics

Absorption and Distribution

Trimebutine is rapidly absorbed following oral administration, with peak plasma concentration reached approximately 0.80 hours after ingestion of a 200 mg dose. The medication is believed to accumulate predominantly in the stomach and intestinal walls, with minimal protein binding (approximately 5% to serum albumin). Placental transfer is reported to be low.

Metabolism

The drug undergoes extensive hepatic first-pass metabolism. The primary metabolite is nortrimebutine (N-monodesmethyltrimebutine), which maintains pharmacological activity on the colon. This metabolite can further undergo second N-demethylation to form N-didesmethyltrimebutine. Additional metabolites can be formed through hydrolysis of the ester bond. Trimebutine is also subject to sulfate and/or glucuronic acid conjugation.

Elimination

Renal elimination is the predominant route of excretion, with 94% of an oral dose eliminated by the kidneys in the form of various metabolites. Less than 2.4% of the total ingested drug is recovered as unchanged parent drug in the urine. A small percentage (5-12%) is also excreted into feces. The elimination half-life is approximately 2.77 hours following a single oral dose of 200 mg.

Dosage and Administration

The recommended adult dosage of Tribudat Forte is up to 600 mg daily in divided doses. This is typically administered as one 200 mg tablet three times daily before meals. Alternatively, some sources suggest a regimen of 1-2 tablets three times daily. The tablets should be swallowed whole with sufficient liquid (e.g., a glass of water) and should not be chewed.

The duration of treatment should be determined by the healthcare provider based on the individual’s response and condition. For optimal results, it is essential to follow the prescribed dosage regimen and not to adjust the dose without consulting a healthcare professional.

Side Effects and Adverse Reactions

Gastrointestinal Effects

Common gastrointestinal side effects include dry mouth, foul taste, nausea, diarrhea, constipation, dyspepsia, and epigastric pain. These effects are generally mild to moderate in nature and occur in a small percentage of patients.

Central Nervous System Effects

Central nervous system effects may include drowsiness, fatigue, dizziness, hot or cold sensations, and headaches. These symptoms typically resolve with continued use or dose adjustment.

Dermatological Reactions

Allergic skin reactions such as rash have been reported in approximately 0.4% of patients.

Miscellaneous Effects

Less frequently reported effects include menstrual problems, painful enlargement of breast, anxiety, urine retention, and slight deafness. If any of these effects become severe or persistent, medical attention should be sought.

Contraindications

Tribudat Forte is contraindicated in patients with known hypersensitivity to trimebutine maleate or any of the excipients in the formulation. Given that the tablet contains bovine lactose monohydrate and bovine gelatin, individuals with allergies to these components should avoid this medication.

Special Warnings and Precautions

Pediatric Use

Tribudat Forte is not recommended for use in children under 12 years of age. For pediatric patients, other formulations such as oral suspension may be more appropriate.

Pregnancy and Lactation

Although teratological studies have not shown any drug-related adverse effects on pregnancy outcomes in laboratory animals, the use of Tribudat Forte in pregnant women is not recommended. Limited information is available regarding the excretion of trimebutine in breast milk, therefore caution is advised during breastfeeding.

Hepatic Impairment

The medication should be used with caution in patients with liver disease, as the drug undergoes significant hepatic metabolism.

Operation of Machinery

Due to potential side effects such as drowsiness and dizziness, caution should be exercised when operating machinery or driving vehicles while taking this medication.

Drug Interactions

Animal studies have shown that trimebutine maleate increases the duration of d-tubocurarine-induced curarization. Interactions with other medications including nitrates, beta-blockers, diuretics, tricyclic antidepressants, fentanyl, and alcohol may increase hypotensive effects. Additionally, cimetidine and ranitidine may increase the plasma level of trimebutine, while diltiazem may slow its metabolism.

Patients should inform their healthcare provider about all medications, supplements, and herbal products they are taking before starting Tribudat Forte.

Storage and Handling

Tribudat Forte tablets should be stored at room temperature, away from heat and light. The medication should not be stored in the bathroom or any area with high humidity. It should be kept out of reach of children, and any expired medication should be properly disposed of according to local regulations.

Key Information

Conclusion

Tribudat Forte is an effective medication for managing gastrointestinal motility disorders, particularly irritable bowel syndrome and functional digestive disorders. Its unique mechanism of action, which regulates intestinal motility in both directions (increasing it when too low and decreasing it when too high), makes it particularly valuable in the treatment of functional gastrointestinal disorders.

As with any medication, it should be used under the supervision of a healthcare provider, and patients should be informed about potential side effects and precautions. The beneficial effects on gastrointestinal symptoms must be weighed against potential risks in each individual case.