Trigan-d

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRIGAN-D (TRIGAN-D)

Composition:

Active substances: paracetamol, dicyclomine hydrochloride;

One tablet contains: paracetamol 500 mg, dicyclomine hydrochloride 20 mg;

Excipients: sodium starch glycolate, polyvinylpyrrolidone, microcrystalline cellulose, colloidal anhydrous silicon dioxide, corn starch, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: white or almost white, round tablets with a score line on one side, beveled edges and a flat surface.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol, combinations without psychotropic agents.

ATC code N02BE51.

Pharmacological properties.

A combination drug with analgesic and spasmolytic effects.

Paracetamol acts as an analgesic and antipyretic agent. The analgesic and antipyretic effects of paracetamol (a non-opioid, non-salicylate analgesic) are associated with the drug's action on the thermoregulatory center in the hypothalamus and its ability to inhibit prostaglandin synthesis.

Hydrochloride dicyclomine – a tertiary amine. It has anticholinergic activity, reduces smooth muscle tone, relieves pain, and blocks antagonistic activity. Hydrochloride dicyclomine selectively paralyzes M-cholinoreactive structures by blocking impulse transmission from postganglionic cholinergic nerves to the effector organs they innervate. It causes relaxation of smooth muscles, producing a spasmolytic effect in spasms of the smooth muscles of the stomach, intestines, biliary tract, urogenital and vascular systems.

Clinical characteristics.

Indications.

Pain syndromes with a spastic component of various origins:

• headache;
• toothache;
• muscular pain, neuralgia;
• rheumatic pain, radiculitis;
• renal colic;
• menstrual pain.

Contraindications.

Hypersensitivity to the components of the drug. Glaucoma, tachycardia, urinary tract obstruction, benign prostatic hyperplasia with tendency to urinary retention, myasthenia, severe renal and/or hepatic dysfunction, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood disorders, severe anemia (including hemolytic anemia), leukopenia; dynamic intestinal obstruction, paralytic ileus, pyloric stenosis with obstruction, severe ulcerative colitis, obstructive gastrointestinal and biliary tract diseases with impaired patency, peptic ulcer of the stomach or duodenum, reflux esophagitis; acute bleeding; congenital hyperbilirubinemias (Gilbert, Dubin–Johnson, and Rotor syndromes), myasthenia gravis, thyrotoxicosis, heart failure.

Interaction with other medicinal products and other forms of interactions.

Features of drug interactions are determined by the properties of its components.

Paracetamol, included in the drug formulation, reduces the effectiveness of diuretics and increases the risk of hepatotoxic reactions when used concomitantly with anticonvulsants (barbiturates, phenytoin, carbamazepine), rifampicin, which stimulate the activity of hepatic microsomal enzymes, potentially enhancing the toxic effect of paracetamol on the liver due to increased conversion of the drug into hepatotoxic metabolites. Concurrent use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. Simultaneous use of paracetamol with hepatotoxic agents increases the toxic effects of drugs on the liver. Do not use concurrently with alcohol.

Barbiturates reduce the antipyretic effect. The absorption rate of paracetamol may increase when used concomitantly with metoclopramide and domperidone, and decrease when used concomitantly with cholestyramine. The effect of paracetamol is enhanced when combined with codeine, ascorbic acid, scopolamine, chlorphenamine, propyphenazone, and caffeine. Concurrent use of paracetamol with azidothymidine may lead to the development of neutropenia. The anticoagulant effect of warfarin and other coumarins is enhanced during prolonged regular use of paracetamol, increasing the risk of bleeding. Occasional use does not show such an effect. Concurrent use of paracetamol with nonsteroidal anti-inflammatory drugs increases the risk of renal complications.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as such concurrent use is associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions").

Dicyclomine hydrochloride may enhance the effects of monoamine oxidase inhibitors (imipramine, amitriptyline), sedatives (sodium bromide, valerian tincture), and ethyl alcohol.

The effect of dicyclomine hydrochloride may be enhanced by medicinal products with anticholinergic activity, such as amantadine, antiarrhythmic agents (e.g., quinidine), neuroleptic antihistamines (phenothiazines), benzodiazepines, monoamine oxidase inhibitors (MAO), narcotic analgesics (meperidine), nitrates and nitrites, sympathomimetics, tricyclic antidepressants.

Since antacid agents may reduce the absorption of dicyclomine hydrochloride, their concomitant use should be avoided.

Dicyclomine hydrochloride reduces the effect of metoclopramide when used simultaneously.

The inhibitory effect of dicyclomine on gastric hydrochloric acid secretion may neutralize agents used for the treatment of achlorhydria and for studying gastric secretion.

Dicyclomine hydrochloride enhances the effect of digoxin and cholinergic blocking agents. Concurrent use of dicyclomine with other cholinergic blocking agents is not recommended.

Dicyclomine hydrochloride may affect gastrointestinal absorption of various extended-release formulations, such as digoxin, potentially leading to increased urinary concentration of the latter.

The drug enhances the effect of salicylic acid, pyrazolone, codeine, caffeine. It potentiates the effect of spasmolytics.

Dicyclomine hydrochloride reduces the effect of anti-glaucoma agents; therefore, the drug should be prescribed with caution in cases of elevated intraocular pressure and concomitant use of corticosteroids.

Special precautions for use

Since the medicinal product contains paracetamol, monitoring of peripheral blood picture and liver function is required during treatment. For the same reason, the medicinal product should not be used concomitantly with other medications containing paracetamol, such as those used for fever reduction, pain relief, flu and cold symptoms, or insomnia. Simultaneous use with other paracetamol-containing products may result in overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or may be fatal.

Do not exceed the recommended doses.

If symptoms of illness do not resolve, consult a physician.

Patients who are regularly taking analgesics for mild forms of arthritis should consult their doctor before using this medicinal product.

Use of the drug for longer than 3 days requires mandatory medical supervision.

If persistent headache develops, consult a physician.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe underlying conditions such as severe renal insufficiency and sepsis, or in patients with malnutrition or other causes of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses over a prolonged period or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with careful patient monitoring. Measurement of urinary 5-oxoproline levels may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

It should be noted that patients with liver disease have an increased risk of hepatotoxic effects of paracetamol; the drug may also affect laboratory test results for blood glucose and uric acid levels.

Use with caution in elderly patients. Dose adjustment is not required when prescribing to elderly individuals. Exercise caution in patients with urinary hesitancy, benign prostatic hyperplasia without urinary retention, mild to moderate ulcerative colitis, or mild to moderate kidney or liver disease. Patients with these conditions should consult their doctor before using the medicinal product.

Cases of liver function impairment / liver failure have been reported in patients with reduced glutathione levels, such as those with severe malnutrition, anorexia, low body mass index, or chronic alcoholism.

In patients with reduced glutathione levels, e.g., in severe infections such as sepsis, the use of paracetamol increases the risk of developing metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention should be sought if these symptoms occur.

Dicyclomine hydrochloride may exacerbate gastroesophageal reflux.

The drug should be prescribed with caution to patients with autonomic neuropathy, arterial hypertension, ischemic heart disease with tachyarrhythmias, tachycardia, predisposition to bronchospasm, and in individuals with increased sensitivity to nonsteroidal anti-inflammatory drugs.

It should be noted that in patients taking anticholinergic drugs, including dicyclomine, symptoms such as psychosis, confusion, disorientation, ataxia, coma, euphoria, weakness, insomnia, agitation, inappropriate emotional responses, and affective disturbances may occur (these symptoms usually resolve within 12–24 hours after dose reduction).

Dicyclomine should be prescribed with caution in patients with hiatal hernia associated with reflux esophagitis.

In high environmental temperatures, dicyclomine hydrochloride, by reducing sweating, may cause an increase in body temperature and increase the risk of heat stroke. If such symptoms occur, the drug should be discontinued and medical advice sought.

Medical advice should be sought before using the medicinal product if the patient is taking warfarin or similar anticoagulant agents.

Use during pregnancy or breastfeeding

The medicinal product should not be used in women during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Given that the drug may reduce psychomotor reaction speed in sensitive patients, it is advisable to refrain from driving vehicles, operating complex machinery, or performing other tasks requiring concentration during treatment.

Method of Administration and Dosage.

The drug is taken orally, swallowed with a small amount of liquid (200 ml).

Adults and children aged 15 years and older: 1–2 tablets, depending on the severity of pain, 1 to 4 times daily. For adult therapy, treatment should preferably start with 4 tablets per day. The maximum daily dose may be increased to 8 tablets, provided the drug is well tolerated and no adverse effects occur.

Children: aged 7 to 13 years: ½ tablet 1–2 times daily;
aged 13 to 15 years: 1 tablet 1–3 times daily.

The duration of treatment is determined individually by a physician, depending on the patient's condition and response. If therapeutic efficacy is not achieved within 2 weeks or if signs of adverse effects occur at a dose of less than 4 tablets per day, the medication should be discontinued.

Children.

The drug is not recommended for children under 7 years of age.

Overdose.

Signs and symptoms of overdose are related to the properties of individual components of the drug.

Paracetamol. Liver damage is possible in adults after ingestion of 10 g of paracetamol and in children who have ingested more than 150 mg/kg body weight. The risk of paracetamol overdose is higher in patients with non-cirrhotic alcoholic liver disease.

In patients with risk factors [long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs that induce liver enzymes; regular consumption of excessive amounts of ethanol; glutathione depletion (due to malnutrition, cystic fibrosis, HIV infection, fasting, or cachexia)], ingestion of 5 g or more of paracetamol may cause severe liver damage. Symptoms within the first 24 hours: pallor, anorexia, nausea, vomiting, diarrhea, epigastric discomfort (lasting up to 1 day), abdominal pain. Liver damage may become evident 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may occur.

The following symptoms may be observed: increased activity of liver transaminases, lactate dehydrogenase, bilirubin levels, and decreased prothrombin levels (lasting 1–2 days); hepatotoxic effect characterized by general symptoms (pain, weakness, asthenia) and specific symptoms (hepatomegaly, jaundice, elevated liver enzymes).

In severe poisoning, liver failure may progress to hepatic encephalopathy (impaired thinking, depression of higher nervous activity, agitation, and stupor), disseminated intravascular coagulation (DIC) syndrome, hypoglycemia, hemorrhages, arrhythmias, seizures, respiratory depression, coma, cerebral edema, hypocoagulation, collapse, and may result in death. Rarely, liver dysfunction develops rapidly and may be complicated by renal failure. Acute renal failure with acute tubular necrosis may present as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and acute pancreatitis have been reported, usually accompanied by liver dysfunction and hepatotoxicity.

With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop from the hematopoietic system. When large doses are taken, effects on the central nervous system may include dizziness, psychomotor agitation, and disorientation; effects on the urinary system may include nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

Hydrochloride of dicyclomine. Tachycardia, bradycardia, arrhythmia, changes in respiratory rate, dry mouth, excitation, drowsiness, loss of accommodation, photophobia, seizures, dryness of skin and mucous membranes, increased intraocular pressure, headache, dizziness, central nervous system excitation, urinary retention, psychomotor agitation, disorientation.

Overdose develops in two stages: initially, central nervous system excitation is observed, manifested by restlessness, hallucinations, persistent mydriasis, tachycardia, and arterial hypertension. This is then replaced by a phase of central nervous system depression, progressing to coma.

In the first hours (up to 1 day), pallor of the skin, nausea, anorexia, vomiting, and abdominal pain may occur. During the second to third day, kidney and liver damage may develop, leading to liver failure (increased activity of liver transaminases, dehydrogenase, increased bilirubin and prothrombin concentrations), as well as tachycardia, arrhythmias, changes in respiratory rate, and pancreatitis.

Treatment. In case of paracetamol overdose, immediate medical assistance is required. Treatment should be initiated as soon as possible. The patient must be taken to a hospital immediately, even if early symptoms of overdose are absent. Symptoms may be limited to nausea and vomiting or may not reflect the severity of the overdose or risk of organ damage. Gastric lavage is indicated, and activated charcoal should be administered (if the excessive dose of paracetamol was taken within 1 hour). Paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). If necessary, N-acetylcysteine should be administered intravenously within 24 hours after ingestion, but the maximum protective effect is achieved when administered within 8 hours after ingestion, with monitoring of respiratory and circulatory systems (adrenaline must not be used). The efficacy of the antidote decreases sharply after this time. In case of seizures, diazepam is prescribed. In the absence of vomiting, methionine may be administered orally as an alternative in remote areas outside the hospital.

There is no specific antidote for dicyclomine hydrochloride.

If necessary, symptomatic therapy and peritoneal dialysis should be performed.

General supportive measures should also be taken.

Adverse reactions.

The medicinal product is usually well tolerated. Adverse effects related to active substances contained in the product generally occur with prolonged use of the drug in high doses.

Paracetamol

Gastrointestinal disorders: nausea, vomiting, loss of appetite, constipation, diarrhoea or flatulence. With prolonged use of high doses – epigastric pain.

Hepatobiliary disorders: increased liver enzyme activity, usually without development of jaundice, hepatic dysfunction, hepatonecrosis (dose-dependent effect), hepatotoxic effect.

Metabolism and nutrition disorders: metabolic acidosis with high anion gap – frequency "unknown" (cannot be estimated from available data).

Endocrine system disorders: hypoglycaemia (up to hypoglycaemic coma).

Blood and lymphatic system disorders: haemolytic anaemia, thrombocytopenia; aplastic anaemia, pancytopenia, sulfhaemoglobinaemia and methaemoglobinaemia (cyanosis, dyspnoea, chest pain), neutropenia, agranulocytosis, leucopenia, bruising, bleeding.

Renal and urinary disorders: dysuria, renal colic, aseptic pyuria, interstitial glomerulonephritis; nephrotoxic effect, papillary necrosis.

Immune system disorders: hypersensitivity reactions, allergic reactions including skin rash, mucosal rash, pruritus, urticaria, hyperaemia; bronchial obstruction, erythema multiforme exudativum (Stevens–Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome); anaphylaxis, generalized rash, angioneurotic oedema, angioedema, erythematous rash.

Respiratory, thoracic and mediastinal disorders: bronchospasm in patients sensitive to aspirin and other nonsteroidal anti-inflammatory drugs.

Central nervous system disorders (usually after high-dose intake): dizziness, psychomotor agitation and disorientation, tinnitus, psychosis, coma.

Other: general weakness.

Description of individual adverse reactions

Metabolic acidosis with high anion gap

Cases of metabolic acidosis with high anion gap as a result of pyroglutamic acidosis have been observed in patients with risk factors who used paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Dicyclomine hydrochloride

Skin and subcutaneous tissue disorders: rash, pruritus, urticaria, severe allergic reactions or drug idiosyncrasy, including anaphylaxis.

Gastrointestinal disorders: dry mouth, thirst, taste disturbances, digestive disturbances, anorexia, nausea, vomiting, flatulence, constipation, abdominal pain.

Eye disorders: blurred vision, diplopia, mydriasis, cycloplegia (paralysis of accommodation), increased intraocular pressure.

Central nervous system and psychiatric disorders: dizziness, fatigue, sensory disturbances, impaired gait stability, dyskinesia, tingling sensation, numbness in extremities, tinnitus, headache, dysphasia, dysarthria, ataxia, euphoria, inappropriate emotional responses (symptoms decrease within 12–24 hours after dose reduction), insomnia, somnolence, hallucinations, general weakness, mood changes, nervousness, disorientation, transient memory loss, psychosis, confusion and/or agitation, dyskinesia, lethargy, loss of consciousness, coma.

Cardiovascular disorders: tachycardia, arrhythmia, rapid heartbeat.

Renal and urinary disorders: urinary disorders, urinary incontinence, urinary retention.

Musculoskeletal and connective tissue disorders: muscle weakness.

Respiratory, thoracic and mediastinal disorders: dyspnoea, apnoea, asphyxia, nasal congestion, sneezing, pharyngeal hyperaemia.

Endocrine disorders: inhibition of lactation, impotence.

Other: sensation of warmth, decreased sweating.

Shelf life. 3 years.

Storage conditions.

Store in a place protected from light and moisture, at a temperature not exceeding 30°C. Keep out of reach of children.

Packaging.

10 tablets per strip; 1 or 10 strips per cardboard pack.

Prescription category.

№ 10 — over-the-counter.

№ 100 — prescription only.

Manufacturer.

Cadila Pharmaceuticals Limited, India.

Manufacturer's address and location of operations.

1389, Trasad Road, Dholka - 382 225, Ahmedabad, Gujarat, India.