Instructions for use of Cigan film-coated tablets No. 4
Composition
active ingredients: 1 tablet contains: 100 mg nimesulide, 20 mg dicycloverine hydrochloride;
excipients: anhydrous lactose, corn starch, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A), croscarmellose sodium, povidone, microcrystalline cellulose, talc, magnesium stearate;
film coating: hypromellose, talc, titanium dioxide (E 171), macrogol 6000, quinoline yellow supra dye (E 104).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, yellow, round, biconvex, smooth on both sides.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs.
ATX code M01A X.
Pharmacological properties
Pharmacodynamics.
Sigan is a combined drug, the effect of which is due to the action of the components that make up its composition. Sigan has anti-inflammatory, analgesic, antipyretic and antispasmodic effects.
Nimesulide is an active substance that has anti-inflammatory, analgesic and antipyretic properties. Nimesulide selectively inhibits cyclooxygenase II and suppresses the synthesis of prostaglandins in the focus of inflammation.
Nimesulide inhibits the release of the enzyme myeloperoxidase, and also inhibits the formation of free oxygen radicals, without affecting the processes of phagocytosis and chemotaxis, and inhibits the formation of tumor necrosis factor and other inflammatory mediators.
Dicycloverine hydrochloride reduces spasms of smooth muscles of the digestive system. It acts as an antagonist of cholinergic (muscarinic) receptors, and also directly on smooth muscles as an antagonist of bradykinin and histamine.
Pharmacokinetics.
After oral administration, nimesulide is rapidly absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma is determined after 2–3 hours. The binding of nimesulide to blood plasma proteins reaches 97.5%.
The drug is metabolized in the liver, the main metabolic product is hydroxynimesulide, a pharmacologically active substance.
About 65% of the administered dose of nimesulide is excreted in the urine, the remaining 35% in the feces.
After oral administration, dicyclomine is rapidly absorbed, with peak plasma concentrations occurring approximately 1.5 hours later. The elimination half-life is 4–6 hours. It is excreted in the urine (79.5%) and feces (8.4%).
Indication
Symptomatic treatment of pain syndrome and spasmodic conditions.
Contraindication
Hypersensitivity to the active substances or to any auxiliary component of the medicinal product.
History of hyperergic reactions (e.g. bronchospasm, rhinitis, urticaria) associated with the use of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs.
History of hepatotoxic reactions to nimesulide.
Concomitant use of other substances with potential hepatotoxicity.
Alcoholism and drug addiction.
History of gastrointestinal bleeding or perforation associated with previous use of NSAIDs.
Peptic ulcer in the acute phase or history of gastrointestinal bleeding, ulceration or perforation, paralytic ileus, pyloric stenosis of the gastrointestinal tract with obstruction, severe ulcerative colitis or toxic megacolon, reflux esophagitis.
Cerebrovascular bleeding or other hemorrhages, as well as diseases accompanied by bleeding.
Severe blood clotting disorders.
Severe heart failure, unstable cardiovascular system with acute bleeding.
Severe renal impairment.
Liver dysfunction.
Obstructive diseases of the gastrointestinal tract, biliary and urinary tracts, prostate adenoma with difficulty urinating, prostatic hypertrophy.
Glaucoma.
Myasthenia gravis.
Thyrotoxicosis.
Fever and/or flu-like symptoms.
Suspicion of acute surgical pathology.
Childhood.
Pregnancy and breast-feeding (see section "Use during pregnancy or breast-feeding").
Interaction with other medicinal products and other types of interactions
Nimesulide
Pharmacodynamic interactions.
Corticosteroids: Corticosteroids increase the risk of gastrointestinal ulceration or bleeding (see section 4.4).
Anticoagulants. NSAIDs may enhance the effects of anticoagulants such as warfarin (see section "Special instructions"). When treating patients with nimesulide who are taking warfarin or similar anticoagulants or acetylsalicylic acid, there is an increased risk of bleeding complications, therefore this combination is not recommended (see also section "Special instructions") and is contraindicated in patients with severe blood clotting disorders (see also section "Contraindications"). If concomitant use cannot be avoided, careful monitoring of blood clotting parameters is necessary.
Diuretics, angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II antagonists (AII). NSAIDs may reduce the effect of diuretics and other antihypertensive drugs. In some patients with reduced renal function (e.g. dehydrated patients or elderly patients with compromised renal function), the concomitant use of ACE inhibitors and cyclooxygenase inhibitors may lead to further deterioration of renal function, including the development of acute renal failure, which is usually reversible. The possibility of such interactions should be considered in patients who need to use nimesulide-containing medicinal products together with ACE inhibitors or AII. Therefore, such a combination should be prescribed with caution, especially in elderly patients. Patients should be adequately hydrated. The need for monitoring renal function after starting concomitant treatment and periodic monitoring after its discontinuation should be considered.
Other non-steroidal anti-inflammatory drugs (NSAIDs): The concomitant use of nimesulide-containing medicinal products (see section 4.1) with other NSAIDs, including acetylsalicylic acid at anti-inflammatory doses (≥ 1 g as a single dose or ≥ 3 g per day), is not recommended.
Pharmacokinetic interactions
The effect of nimesulide on the pharmacokinetics of other drugs.
Furosemide. In healthy volunteers, nimesulide temporarily weakens the effect of furosemide on sodium excretion and, to a lesser extent, potassium excretion and reduces the diuretic effect. Simultaneous use of nimesulide and furosemide leads to a decrease (by approximately 20%) in the area under the concentration-time curve (AUC) and cumulative excretion of furosemide without changing its renal clearance. The combined use of furosemide and nimesulide-containing drugs in patients with impaired renal or cardiac function requires caution (see section "Special instructions").
Lithium: NSAIDs have been reported to reduce lithium clearance, leading to increased plasma levels and toxicity. When nimesulide is prescribed to patients receiving lithium therapy, plasma lithium levels should be carefully monitored.
The effect of other drugs on the pharmacokinetics of nimesulide.
In vitro studies have shown that nimesulide is displaced from its binding sites by tolbutamide, salicylic acid and valproic acid. However, despite the possible effect on its plasma concentration, such interactions are not clinically significant.
Other interactions.
Potential pharmacokinetic interactions with glibenclamide, theophylline, warfarin, digoxin, cimetidine and antacids (namely a combination of aluminium and magnesium hydroxide) have also been investigated in vivo. No clinically significant interactions were observed.
Nimesulide inhibits the activity of the CYP2C9 enzyme. Plasma concentrations of drugs that are substrates of this enzyme may increase when used simultaneously with the drug.
Caution should be exercised when nimesulide is used less than 24 hours before or less than 24 hours after taking methotrexate, as it may increase the serum level of the latter and increase its toxicity.
Due to its effect on renal prostaglandins, nimesulide may increase the nephrotoxicity of cyclosporines.
Dicycloverine.
Amantadine, class I antiarrhythmic drugs (e.g. quinidine), antihistamines, antipsychotics (e.g. phenothiazines), benzodiazepines, monoamine oxidase inhibitors, narcotic analgesics (e.g. meperidine), nitrates and nitrites, sympathomimetics, tricyclic antidepressants, corticosteroids and other drugs with anticholinergic activity may enhance the effects or side effects of dicyclomine.
Anticholinergic drugs can neutralize the effect of antiglaucoma drugs, so the drug should be prescribed with caution in cases of increased intraocular pressure and concomitant use of corticosteroids.
Anticholinergic agents enhance the effects of digoxin, salicylic acid, pyrazolone, codeine, caffeine and other anticholinergic agents (e.g. atropine sulfate), therefore their simultaneous use with the drug is not recommended.
Dicyclomine may neutralize the effects of substances that alter gastrointestinal motility, such as metoclopramide.
Potentiates the effect of antispasmodics.
Since antacids may reduce the absorption of anticholinergic drugs, concomitant use of the drug with antacids should be avoided.
The inhibitory effect of anticholinergic agents on gastric hydrochloric acid secretion may counteract the effects of drugs used to treat achlorhydria and study gastric secretion.
Application features
Adverse reactions can be minimized by using the lowest effective dose for the shortest time necessary to control symptoms (see section "Method of administration and dosage").
If treatment is ineffective, therapy should be discontinued.
The drug should be prescribed only after a careful assessment of the risk/benefit ratio. If the patient's condition does not improve, treatment should be discontinued. With prolonged use of the drug, liver function tests should be monitored every 2 weeks.
If liver enzyme levels increase or signs of liver damage occur (e.g. anorexia, nausea, vomiting, abdominal pain, fatigue, dark urine), the drug should be discontinued. Further use of Cigan is contraindicated in such patients.
During treatment with the drug, it is recommended to avoid the simultaneous use of hepatotoxic drugs, analgesics, other non-steroidal anti-inflammatory drugs, and to refrain from drinking alcohol.
Gastrointestinal bleeding or ulceration/perforation may occur at any time during treatment with or without warning symptoms, with or without a history of gastrointestinal complications. If gastrointestinal bleeding or ulceration occurs, the drug should be discontinued.
Ulceration, bleeding or perforation in the digestive tract can be life-threatening, especially if there is a history of similar events in the patient when using any other NSAIDs (without a prescription). The risk of such events increases with increasing NSAID dose in patients with a history of gastrointestinal ulcer, especially complicated by bleeding or perforation, and in elderly patients. In such patients, treatment should be started with the lowest possible effective dose. For such patients, as well as for those taking concomitant low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications, the possibility of using combination therapy with protective agents, for example, misoprostol or proton pump inhibitors, should be considered.
Patients with toxic lesions of the digestive tract, especially the elderly, should be informed of any unusual symptoms that occur in the digestive tract, especially bleeding. This is especially important in the initial stages of treatment. Patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as corticosteroids, anticoagulants, selective serotonin reuptake inhibitors, antiplatelet agents (acetylsalicylic acid), should be informed of the need to exercise caution when using nimesulide.
If a patient receiving nimesulide experiences bleeding or ulcers in the digestive tract, treatment with the drug should be discontinued.
Patients with a history of hypertension, as well as patients with fluid retention and edema due to the use of NSAIDs, require appropriate monitoring of their condition and consultation with a doctor.
Clinical trials and epidemiological data suggest that some NSAIDs, especially at high doses and in long-term use, slightly increase the risk of arterial thrombotic events, such as myocardial infarction and stroke. There is insufficient data to exclude a risk of such events with nimesulide.
Patients with uncontrolled hypertension, established coronary artery disease, peripheral arterial disease and/or cerebrovascular disease should be prescribed nimesulide after careful assessment. Patients with risk factors for cardiovascular disease, such as hypertension, hyperlipidemia, diabetes mellitus, and smoking, should also be carefully assessed before prescribing the drug.
The drug should be prescribed with caution to patients with a history of gastrointestinal disorders, ulcerative colitis, or Crohn's disease.
The drug should be prescribed with caution to patients with renal insufficiency, as its use may lead to impaired renal function. In case of deterioration of the patient's condition, treatment should be discontinued.
There have been rare reports of severe skin reactions with NSAIDs, some of which may be life-threatening, such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. Patients are at very high risk of such reactions if they have previously experienced severe skin reactions during the first month of treatment with NSAIDs. Nimesulide should be discontinued at the first signs of skin rash, mucosal lesions or other allergic manifestations.
Nimesulide may impair female fertility and is not recommended for use in women attempting to conceive. Nimesulide is not recommended for women who have difficulty conceiving or are undergoing investigation for infertility.
Since nimesulide may impair platelet function in patients with hemorrhagic diathesis, it should be used with caution under constant monitoring.
The use of nonsteroidal anti-inflammatory drugs may mask fever associated with an underlying bacterial infection. In the event of fever or flu-like symptoms, the drug should be discontinued. During treatment with nimesulide, the patient should refrain from taking other analgesics. Concomitant use of other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.
In the absence of treatment effectiveness (reduction of symptoms of the disease), therapy with the drug should be discontinued. Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially possible bleeding and perforation in the digestive tract, which can be life-threatening.
There have been reports of serious liver reactions, including fatal ones, with the use of nimesulide. Regarding liver damage: re-administration of nimesulide in such patients is contraindicated.
Use with caution at high ambient temperatures during treatment with the drug, as overheating of the body is possible (increased body temperature and heat stroke due to decreased sweating). If appropriate symptoms appear, discontinue use of the drug and consult a doctor.
In individuals with individual hypersensitivity to anticholinergics, the drug may cause such effects on the central nervous system as confusion, disorientation, ataxia, increased fatigue, or vice versa - euphoria, excitement, insomnia, affective state. Usually these symptoms disappear within 12-24 hours after discontinuation of the drug.
The drug should be used with caution in patients with autonomic neuropathy, liver or kidney disease, ulcerative colitis (taking high doses can cause paralytic intestinal obstruction and the development or exacerbation of such a serious complication as toxic megacolon), arterial hypertension, ischemic heart disease, tachyarrhythmias, tachycardia, hiatal hernia.
Excipients.
This medicinal product contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
The medicine contains quinoline yellow dye (E 104), which may cause allergic reactions.
Use during pregnancy or breastfeeding
The use of nimesulide may impair female fertility and is not recommended for women planning to become pregnant. Like other non-steroidal anti-inflammatory drugs that inhibit prostaglandin synthesis, nimesulide may cause premature closure of the botal duct, pulmonary hypertension, oliguria, oligohydramnios. The risk of bleeding, uterine atony and peripheral edema increases. Also taking into account the lack of data on the use of the drug in pregnant women, Sigan is contraindicated during pregnancy. Since it is not known whether nimesulide penetrates into breast milk, the use of the drug is contraindicated during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.
Method of administration and doses
The drug is prescribed to adults after a careful assessment of the benefit/risk ratio.
It is taken orally after meals, washed down with sufficient liquid.
For adults – 1 tablet (100 mg of nimesulide) 1–2 times a day – morning and evening. Daily dose: 200 mg of nimesulide.
The maximum duration of treatment is 5 days.
For elderly patients, this regimen does not require dose adjustment.
Renal impairment. Given the pharmacokinetics of the drug, patients with mild and moderate renal insufficiency (creatinine clearance - 30-80 ml/min) do not need to change the dose. In severe renal insufficiency (creatinine clearance less than 30 ml/min), the drug is contraindicated.
Liver dysfunction. The use of tablets containing 100 mg of nimesulide for the treatment of patients with liver failure is contraindicated.
Children
The use of the drug is contraindicated in children.
Overdose
Dicyclomine overdose is characterized by a two-phase nature: first, central nervous system excitation occurs, which is manifested by restlessness, the appearance of illusions, hallucinations, persistent mydriasis, tachycardia, and arterial hypertension. Then, central nervous system depression occurs, up to a comatose state.
Symptoms: headache, nausea, vomiting and abdominal pain, decreased appetite, pale skin, increased intraocular pressure, dizziness, blurred vision, dilated pupils, hot and dry skin, dry mouth, difficulty swallowing, central nervous system excitation, tachycardia, change in respiratory rate.
Curare-like effects (neuromuscular blockade, feeling of muscle weakness and paralysis) may occur.
Treatment: symptomatic therapy. In the first hours of acute poisoning, it is necessary to wash the stomach through a probe, use activated charcoal and/or an osmotic laxative. Kidney and liver functions should be monitored. Diazepam (0.5% solution, 2 ml) is used to relieve psychomotor agitation.
Adverse reactions
The following side effects may occur when using the medicine, mainly within the first week of starting treatment.
Side effect of dicycloverine hydrochloride.
Cardiovascular system: tachycardia, palpitations, fainting, hot flushes.
From the nervous system: dizziness, headache, paresthesia, sensory disturbances, drowsiness, nervousness, dyskinesia, gait disturbance, lethargy, insomnia, general weakness, increased fatigue, syncope (loss of consciousness), numbness of the upper and lower extremities, coldness of the extremities.
Psychiatric disorders: hallucinations, confusion and/or agitation, speech disorders, mood swings, tinnitus, psychosis, coma, disorientation, short-term memory loss, hallucinations, dysarthria, ataxia, euphoria, inappropriate emotional reactions (symptoms subside 12–24 hours after dose reduction).
Skin and subcutaneous tissue disorders: skin rashes, rarely – red, spotted papular rashes, urticaria, itching, dry skin and other dermatological manifestations.
On the part of the digestive system: dry mouth, thirst, nausea, vomiting, constipation, flatulence (feeling of bloating), abdominal pain, taste disturbances, indigestion, anorexia.
Musculoskeletal and connective tissue disorders: muscle weakness.
From the genitourinary system: urination disorders, urinary retention, difficulty urinating, in men - erectile dysfunction.
On the part of the organs of vision: blurred vision, darkening in the eyes, diplopia, mydriasis, cycloplegia of vision (paralysis of accommodation), increased intraocular pressure.
On the part of the respiratory system and chest organs: dyspnea, apnea, asphyxia, nasal congestion, sneezing, throat hyperemia.
Immune system: severe allergic reactions or drug idiosyncrasy, including anaphylaxis.
On the part of the endocrine system: suppression of lactation.
Side effects of nimesulide.
Skin and subcutaneous tissue: most often hyperemia, rash, itching, increased sweating, decreased sweating, erythema, dermatitis; in rare cases - angioedema, facial edema, hyperemia and edema of the oral mucosa, tongue edema, lip edema, eyelid edema, facial swelling, erythema multiforme, rarely - vesicular rashes, in rare cases - punctate rashes, skin redness, urticaria, Stevens-Johnson syndrome and toxic epidermal necrolysis.
On the part of the digestive system: nausea, heartburn, gastritis, abdominal pain, diarrhea, constipation, flatulence; in rare cases - stomatitis, melena, peptic ulcer of the stomach or duodenum, ulcer perforation or gastrointestinal bleeding.
Liver: jaundice, cholestasis, increased levels of hepatic transaminases, sometimes cases of acute hepatitis, even fatal, are possible.
From the side of the central nervous system: drowsiness, headache, dizziness, encephalopathy (Reye's syndrome).
Mental disorders: feeling of anxiety, nervousness, nightmares.
Renal: edema, dysuria, hematuria, urinary retention, isolated cases of oliguria, interstitial nephritis and renal failure.
On the part of the blood system: anemia, eosinophilia, isolated cases of pancytopenia, purpura and thrombocytopenia.
Immune system disorders: hypersensitivity reactions, anaphylaxis, angioedema.
Respiratory system: dyspnea, in rare cases - asthma, bronchospasm, especially in patients with hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.
From the cardiovascular system: tachycardia, arterial hypertension, rarely - bleeding, hot flashes, feeling of heat, palpitations, fluctuations in blood pressure, rarely - collapse.
The most common adverse reactions are from the digestive tract. Peptic ulcers, perforation or bleeding in the digestive tract may occur, sometimes life-threatening, especially in elderly patients. Nausea, vomiting, diarrhea, bloating, constipation, dyspepsia, abdominal pain, melena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported after the use of nimesulide-containing drugs. Gastritis has been observed less frequently. There have been reports of edema, hypertension and heart failure in connection with NSAID treatment. Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely. Clinical and epidemiological studies suggest that the use of some NSAIDs, especially at high doses and during long-term treatment, slightly increases the risk of arterial thrombotic complications, such as myocardial infarction or stroke (see section "Special warnings and precautions for use").
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions after the registration of a medicinal product plays an important role. This allows for continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС, out of the reach of children.
Packaging
4 tablets in a strip, 1 strip in a cardboard envelope.
Vacation category
According to the recipe.
Producer
Genom Biotech Pvt. Ltd.
Location of the manufacturer and address of its place of business.
Plot No. D-121, 122, 123, M.I.D.C. Malegaon, Tal. Sinnar, Nashik 422103, Maharashtra, India.
