Instructions for use Indomethacin Sopharma enteric-coated tablets 25 mg No. 30
Composition
active ingredient: indomethacin;
1 film-coated, enteric-coated tablet contains indomethacin 25 mg;
excipients: lactose monohydrate, wheat starch, povidone K 25, microcrystalline cellulose, magnesium stearate, talc, colloidal anhydrous silicon dioxide;
enteric coating: copolymer methacrylic acid: ethyl acrylate (1:1) 30% dispersion (Eudragit L 30 D-55), copolymer methyl acrylate: methyl methacrylate: methacrylic acid 30% dispersion (Eudragit FS 30 D), sodium hydroxide, triethyl citrate, polysorbate 80, pigment suspension – brown WAS FS (talc, triethyl citrate, titanium dioxide (E 171), iron oxide yellow (E 172), iron oxide red (E 172), propane-1,2 diol alginate, potassium sorbate).
Dosage form
The film-coated tablets are enteric-coated.
Main physicochemical properties: round biconvex tablets, coated with an enteric coating, 7 mm in diameter, orange-brown in color.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related compounds. ATC code M01A B01.
Pharmacological properties
Pharmacodynamics
Indomethacin is a derivative of indoleacetic acid, belongs to the group of nonsteroidal anti-inflammatory drugs (NSAIDs). It has a pronounced anti-inflammatory effect, which significantly exceeds the effect of phenylbutazone and acetylsalicylic acid. Its analgesic activity is comparable to the activity of metamizole. It has an antipyretic effect. Indomethacin has a strong inhibitory effect on prostaglandin synthesis by inhibiting cyclooxygenase. In addition, it reduces platelet aggregation and lipoxygenase activity in the area of inflammation, respectively, and the activity of leukotrienes; it also reduces the release of endogenous pyrogens, inactivates lysosomal enzymes, and inhibits the activity of neutral proteases. Other effects may also be important, such as decoupling of oxidative phosphorylation and inhibition of catecholamine reuptake, increased norepinephrine metabolism, and the known ganglioblocking effect.
Pharmacokinetics
Absorption: When administered orally, 80-90% of the dose is absorbed through the mucosa of the small intestine and to a lesser extent in the stomach. Peak plasma concentrations are reached within 1-2 hours.
Distribution: distributed throughout all tissues and organs. Penetrates through the placental and blood-brain barriers. Penetrates through the synovial membrane into the joints, while its concentration in the synovial fluid is higher than in blood plasma. It binds to plasma proteins by 90-98% and is therefore able to displace other drugs from protein binding and enhance their therapeutic effect when used simultaneously.
Metabolism: metabolized in the liver by oxidation and conjugation.
Elimination: The elimination half-life of indomethacin varies between 2.6 and 11.2 hours, with an average of 5.8 hours. Up to 60-75% is excreted by the kidneys, 10-20% of which is unchanged, and the rest is excreted in bile and feces. Penetrates into breast milk.
Indication
The effectiveness of short-term symptomatic treatment with indomethacin has been established for the following conditions:
acute and chronic pain in inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid arthritis; acute and in the acute stage of chronic ankylosing spondylitis (Bechterew's disease); gout attack and gouty arthritis; osteoarthritis from moderate to severe form; diseases of the periarticular tissues: tendonitis, bursitis (acute painful shoulder), tendobursitis, tendovaginitis, pain syndrome and inflammation after injuries (including in athletes) and surgical interventions; discopathy, plexitis, radiculoneuritis; dysmenorrhea.
The potential benefits and risks of indomethacin and other treatment options should be carefully considered before deciding to prescribe indomethacin. The lowest effective dose should be used for the shortest duration consistent with the individual patient's treatment goals (see section 4.4).
Contraindication
Hypersensitivity to the components of the drug; hypersensitivity to acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs with clinical manifestations of asthmatic attack, angioedema, urticaria or rhinitis; active peptic ulcer of the stomach and duodenum or relapses (two or more cases of proven ulcers and bleeding), ulcerative colitis and/or enterocolitis; history of gastrointestinal bleeding or perforation associated with the use of NSAIDs in history; severe heart failure; severe hepatic and renal failure; pre- and postoperative pain during coronary artery bypass grafting surgery.
Interaction with other medicinal products and other types of interactions
Concomitant use of zalcitabine and indomethacin causes changes in their pharmacodynamics.
Concomitant use of zidovudine and indomethacin increases the risk of hematological toxicity.
Caution should be exercised when used concomitantly with antiepileptic drugs due to increased effects of phenytoin.
Concomitant use with haloperidol increases drowsiness.
When taken simultaneously with benzodiazepines, the risk of dizziness increases.
Indomethacin increases the bioavailability of bisphosphonates when used simultaneously with tiludronic acid.
When taken simultaneously with desmopressin, the effect of the latter is enhanced.
Nonsteroidal anti-inflammatory drugs should be avoided for 8-12 days after mifepristone administration.
Indomethacin is able to reduce the rate of elimination of baclofen and, thus, increase the level of its toxic effect.
Indomethacin may distort the results of laboratory tests:
cause an increase in the level of one or more liver enzymes; cause false negative results in the dexamethasone suppression test.
The simultaneous use of NSAIDs and COX-2 inhibitors increases the risk of developing "analgesic" nephropathy and renal papillary necrosis. Therefore, their simultaneous use should be avoided.
Concomitant use with vasodilators increases the risk of bleeding.
Other NSAIDs, alcohol: simultaneous use of indomethacin with other NSAIDs and alcohol increases the risk of gastrointestinal side effects.
Diflunisal: Increases plasma levels and decreases renal clearance of indomethacin. May cause fatal gastrointestinal bleeding. This combination is not recommended.
Digoxin: indomethacin may increase the concentration of digoxin in the blood plasma (reduces its excretion by the kidneys), which requires dose adjustment and monitoring of digoxin levels.
Lithium salts: indomethacin prolongs and potentiates the effect of lithium salts and increases lithium toxicity, which requires monitoring of lithium levels.
Immunosuppressants: Concomitant use of indomethacin and immunosuppressants such as methotrexate and cyclosporine leads to increased toxicity.
Concomitant use with tacrolimus increases the risk of nephrotoxicity; concomitant use with muromonab-CD3 increases the risk of psychosis and encephalopathy. Caution should be exercised when used concomitantly with cyclophosphamide due to the occurrence of water intoxication.
Diuretics: NSAIDs reduce the therapeutic efficacy of diuretics (due to a decrease in their tubular secretion). There may be an increased risk of hyperkalemia with concomitant use with potassium-sparing diuretics and a decrease in renal function with an increased risk of acute renal failure with combined use with thiazide diuretics (triamterene). Concomitant administration with triamterene should be avoided due to the occurrence of reversible renal failure. Diuretics may enhance the nephrotoxicity of indomethacin.
Antihypertensives: Indomethacin may weaken the antihypertensive effect of ACE inhibitors and beta-blockers when used concomitantly.
Corticosteroids: increased risk of gastrointestinal ulceration and bleeding (see section "Special warnings and precautions for use").
Anticoagulants: increased risk of ulceration and hemorrhage due to inhibition of platelet function and aggressive effect on the gastrointestinal mucosa.
Bleeding time and prothrombin time should be monitored. Indomethacin competes with coumarin anticoagulants for plasma protein binding, resulting in increased plasma concentrations. In case of concomitant use, indomethacin should be administered at the lowest possible dose and the use of protective agents should be considered (see section 4.4).
Antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").
Caution should be exercised when used concomitantly with antidepressants (SSRIs) due to increased risk of bleeding.
Concomitant use with antibacterial agents may increase the risk of seizures; concomitant use of quinolones and indomethacin may increase the risk of seizures in patients with or without a history of epilepsy or seizures; with ciprofloxacin - the risk of skin reactions and neurotoxicity.
Probenecid: slows down the excretion and increases the toxicity of indomethacin.
Antidiabetic agents: Indomethacin does not alter the therapeutic efficacy of oral antidiabetic agents and insulin, although there have been reports of hypo- or hyperglycaemic effects with their concomitant use. The effect of sulfonylureas may be potentiated by NSAIDs. In isolated cases, concomitant use with metformin may cause metabolic acidosis.
Application features
General
Side effects can be reduced by using the lowest effective dose of the drug for the shortest period of time to control symptoms (see section "Method of administration and dosage" and gastrointestinal and cardiovascular risk factors below).
Patients with systemic lupus erythematosus and connective tissue diseases may be at increased risk of developing viral meningitis.
In patients with reduced blood flow, in whom renal prostaglandins play an important role in maintaining renal perfusion, NSAIDs can provoke pronounced renal decompensation. Patients at risk for this reaction include patients with renal or hepatic dysfunction, diabetic patients, elderly patients, patients with reduced interstitial fluid volume, congestive heart failure, sepsis, and those taking nephrotoxic drugs. Such patients should have their renal function monitored while taking the drug.
The drug should be used with caution in patients with impaired renal, hepatic or cardiac function or conditions leading to fluid retention in the body, as indomethacin causes impaired renal function and fluid retention.
There is a risk of hyperkalemia when taking NSAIDs, especially in patients over 65 years of age, patients with renal insufficiency, patients treated with beta-blockers, ACE inhibitors and potassium-sparing diuretics. In such patients, serum potassium levels should be monitored.
Patients taking the drug for a long time should have periodic blood, liver or stomach function tests to detect any unwanted effects as early as possible.
Use with extreme caution in patients with hypersensitivity to food and drugs, patients with allergic diseases such as hay fever, bronchial asthma, nasal polyposis. Caution should be exercised when using the drug in patients with bronchial asthma due to the possibility of bronchospasm.
Elderly patients (over 65 years of age)
The use of NSAIDs in patients aged 65 years and over is associated with an increased risk of adverse reactions, mainly gastrointestinal bleeding or perforation, sometimes fatal (see section "Method of administration and dosage").
Gastrointestinal hemorrhages, ulcerations, and perforations
Gastrointestinal bleeding, ulceration and perforation (sometimes fatal) have been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal events.
The risk of gastrointestinal adverse reactions is higher with high doses of NSAIDs in patients with a history of ulcer, especially complicated by hemorrhage or perforation, and in elderly patients. In such patients, NSAID treatment should be started at the lowest possible dose, taking into account the need for protective drugs (e.g. misoprostol or proton pump inhibitors). This approach is also recommended in the case of concomitant use of low doses of acetylsalicylic acid or other drugs that increase the risk of gastrointestinal complications (corticosteroids, anticoagulants, antiplatelet agents, selective serotonin reuptake inhibitors).
Particular caution is required when treating patients with other gastrointestinal diseases (ulcerative colitis, Crohn's disease), which may be exacerbated by the use of NSAIDs, and patients with anomalies of the sigmoid colon.
There is an increased risk of gastrointestinal complications in patients who abuse alcohol or smoke, so their treatment should be carried out with special caution.
Patients with a history of gastrointestinal disorders (elderly patients) should be informed of unusual abdominal symptoms (especially gastrointestinal bleeding), especially at the beginning of treatment.
Particular caution is required when treating patients with medicinal products that may increase the risk of ulceration or bleeding (oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other types of interactions")).
The use of the drug should be discontinued if gastrointestinal lesions and bleeding occur.
Disorders of the cardiovascular system and cerebral circulation
Appropriate supervision and advice should be provided to patients with a history of hypertension and/or mild to moderate congestive heart failure, as oedema and fluid retention have been reported in association with NSAID treatment.
Clinical trials and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term use) may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There are insufficient data to exclude such a risk for indomethacin.
Such an assessment is also necessary before starting long-term treatment in patients with risk factors for cardiovascular events (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).
Skin effects
Serious skin reactions, including fatal ones, have been reported very rarely with NSAIDs and include exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The risk of these reactions is greatest at the beginning of treatment (in the first month). The drug should be discontinued at the first appearance of skin or other signs of hypersensitivity.
Renal effects
Indomethacin should be used with caution in patients with kidney disease (creatinine clearance < 30 ml) due to possible kidney damage.
Hematological effects
It should be prescribed with caution to patients with a history of impaired coagulation, as the drug inhibits prostaglandin biosynthesis and affects platelet function.
Hepatic effects
Treatment with indomethacin, as with other NSAIDs, with prolonged use may cause changes in liver function, which requires periodic monitoring of liver enzymes.
Infections and vaccines
Due to the existing anti-inflammatory effect of the drug, in rare cases, it may mask the symptoms of acute inflammation, therefore it is necessary to exclude the presence of a bacterial infection when prescribing it. Caution should also be exercised when using live vaccines.
Impact on fertility
In women of reproductive age, there is a risk of reversible inhibition of fertility when using the drug.
Mental effects
Use with caution in patients with mental disorders, depression, epilepsy, and parkinsonism, as this may lead to worsening of the underlying disease.
Excipients
The tablets contain lactose as an excipient. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
The tablets contain wheat starch as an excipient. It can be used by patients with celiac disease. Patients with wheat allergy (different from celiac disease) should not use this medicine.
Ability to influence reaction speed when driving vehicles or other mechanisms
Indomethacin Sopharma may cause side effects (tinnitus, dizziness, drowsiness, hearing and vision impairment) that may impair active attention and reflexes and affect the ability to drive vehicles and operate other mechanisms.
Use during pregnancy or breastfeeding
Pregnancy
The drug is contraindicated during pregnancy.
Breast-feeding
Breastfeeding should be discontinued during treatment, as indomethacin passes into breast milk in small amounts.
Method of administration and doses
Method of application
The drug should be taken orally after meals. The tablet should be swallowed whole with sufficient liquid.
Dosage
Adults and children aged 14 and over
The initial dose is 25-50 mg (1-2 tablets) 2-4 times a day.
If the therapeutic effect is insufficient, the dose should be increased to 150 mg (6 tablets) per day, divided into 3 doses. The maximum daily dose is 200 mg (8 tablets). With long-term treatment, the daily dose should not exceed 75 mg (3 tablets).
Gout
To relieve an acute gout attack, prescribe an initial dose of 100 mg (4 tablets), then continue treatment with a dose of 50 mg (2 tablets) 3 times a day until the pain subsides.
Elderly patients (65 years and older)
There is an increased risk of adverse reactions. The lowest effective dose for the shortest duration is recommended. The patient should be monitored for possible gastrointestinal bleeding.
Duration of treatment
Treatment should be carried out for the shortest possible time at the lowest possible effective dose to reduce the likelihood of side effects (see section "Special instructions").
Children
The use of indomethacin is contraindicated in children under 14 years of age.
Overdose
Symptoms: nausea, vomiting, abdominal pain, severe headache, dizziness, memory impairment, confusion, disorientation or lethargy. There are reports of paresthesia, stiffness and convulsions.
Treatment: symptomatic and supportive.
Gastric lavage should be performed as soon as possible if the drug has been taken recently. If there is no spontaneous vomiting, vomiting should be induced by administering ipecacuanha to the patient. After gastric emptying, 25 g or 50 g of activated charcoal may be administered. Continuous medical and nursing care may be necessary depending on the patient's condition. The patient should be observed for several days, as gastrointestinal ulceration and bleeding have been reported as side effects of indomethacin. Antacids may be useful. Indomethacin cannot be removed from the body by hemodialysis.
Adverse reactions
The most common adverse reactions are gastrointestinal disorders. Peptic ulcer, perforation or gastrointestinal bleeding (sometimes fatal) may occur, mainly in elderly patients (see section "Special warnings and precautions for use").
From the blood and lymphatic system: leukopenia, neutropenia, thrombocytopenia, agranulocytosis, anemia (including hemolytic and aplastic), disseminated intravascular coagulation.
On the part of the immune system: very rarely - bronchospasm, asthmatic attacks, anaphylactic or anaphylactoid reactions in allergic patients, fever, vasculitis, anaphylaxis, pulmonary edema, brain edema.
Metabolism and nutrition: increased urea levels, weight gain, increased liver enzymes, increased sweating, accelerated cartilage degeneration, fluid retention, hyperglycemia, glycosuria, hyperkalemia.
Nervous system: agitation, convulsions, muscle weakness, involuntary muscle movements, mental disorders, exacerbation of epilepsy and parkinsonism, impaired consciousness, coma, dysarthria, aseptic meningitis, hallucinations, fear, dizziness, headache, somnolence, depression, fatigue, anxiety, weakness, impaired concentration; sensory disturbances, including paresthesia; disorientation, insomnia, irritability, peripheral neuropathy, memory disorders, psychotic reactions.
Respiratory system: epistaxis, pulmonary subtropical eosinophilia, dyspnea, acute respiratory distress.
On the part of the organs of vision: optic neuritis, corneal deposits and retinal damage, conjunctivitis, pain in the periorbital area, diplopia, blurred vision.
From the side of the organs of hearing and labyrinth: deafness, very rarely - hearing impairment, tinnitus.
Cardiac: tachycardia, angina pectoris, palpitations, arrhythmias, edema, very rarely - worsening of heart failure associated with the use of NSAIDs.
Clinical trials and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term use) may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) (see section "Special warnings and precautions for use").
Vascular disorders: arterial hypertension, hypotension, thrombotic microangiopathy.
On the part of the digestive tract: anorexia, taste disturbance, gastroenteritis, erosive-ulcerative lesions, bleeding and perforation of the digestive tract, proctitis, intestinal strictures, gastritis, bleeding from the sigmoid colon or from diverticulum, regional ileitis, cholestasis, nausea, vomiting, diarrhea, dyspepsia, constipation, abdominal pain, flatulence, melena, hematemesis, ulcerative stomatitis, exacerbation of ulcerative colitis, Crohn's disease, exacerbation of an existing ulcer.
Hepatobiliary disorders: toxic hepatitis with or without jaundice, very rarely - fulminant hepatitis.
Skin and subcutaneous tissue disorders: hair loss, exacerbation of psoriasis, eczema, pruritus with or without rash, urticaria, petechiae, ecchymoses, very rarely - angioedema, exfoliative dermatitis, purpura, erythema nodosum, erythema multiforme, bullous eruptions, including Stevens-Johnson syndrome and toxic epidermal necrosis.
On the part of the kidneys and genitourinary system: renal dysfunction, edema, vaginal bleeding, enlargement and tenderness of the mammary glands, gynecomastia, proteinuria, hematuria, nephrotic syndrome, interstitial nephritis, acute renal failure, papillary necrosis.
Impact on laboratory and instrumental test results: increased serum aminotransferase levels (ALT, AST), transient increase in bilirubin.
Expiration date
5 years.
Storage conditions
Keep out of reach of children.
Store in the original packaging at a temperature not exceeding 25 °C.
Packaging
30 tablets in a blister of PVC film and aluminum foil. 1 blister in a cardboard pack.
Vacation category
According to the recipe.
Producer
JSC "Sopharma", Bulgaria.
JSC "VITAMINS", Ukraine.
Location of the manufacturer and its business address
JSC "Sopharma"
16 Ilienskoe Shose St., Sofia, 1220, Bulgaria.
JSC "VITAMINS"
Ukraine, 20300, Cherkasy region, Uman city, Uspenska st., 31.
