Indovis EC (Tablets) Instructions for Use

Marketing Authorization Holder

CTS Chemical Industries Ltd. (Israel)

ATC Code

M01AB01 (Indometacin)

Active Substance

Indometacin (Rec.INN registered by WHO)

Dosage Form

Indovis EC

Enteric-coated tablets, 25 mg: 50 or 1000 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (5) – cardboard boxes.
1000 pcs. – polyethylene containers.

Clinical-Pharmacological Group

NSAID

Pharmacotherapeutic Group

NSAID

Pharmacological Action

NSAID, an indoleacetic acid derivative. It has anti-inflammatory, analgesic, and antipyretic effects. The mechanism of action is associated with the inhibition of the COX enzyme, which leads to the suppression of prostaglandin synthesis from arachidonic acid.

It suppresses platelet aggregation.

It helps to alleviate pain, especially joint pain at rest and during movement, reduce morning stiffness and joint swelling, and increase the range of motion.

Pharmacokinetics

After oral administration, Indometacin is rapidly absorbed from the gastrointestinal tract. C_max in plasma is reached after 2 hours. It is metabolized in the liver. Undergoes enterohepatic recirculation. Indometacin is determined in blood plasma as an unchanged substance and unconjugated metabolites – desmethyl, desbenzoyl, desmethyl-desbenzoyl.

T_1/2 is about 4.5 hours. It is excreted in the urine – 60% as unchanged substance and metabolites, and in the feces – 33% mainly as metabolites.

Indications

Joint syndrome (including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, gout), spinal pain, neuralgia, myalgia, traumatic inflammation of soft tissues and joints, rheumatism, diffuse connective tissue diseases, dysmenorrhea. As an auxiliary agent in infectious and inflammatory diseases of the ENT organs, adnexitis, prostatitis, cystitis.

It is intended for symptomatic therapy, to reduce pain and inflammation at the time of use, it does not affect the progression of the disease.

ICD codes

Dosage Regimen

The dosage is set individually, taking into account the severity of the disease and the dosage form used. For adults, when taken orally, the initial dose is 25 mg 2-3 times/day. If the clinical effect is insufficient, the dose is increased to 50 mg 3 times/day. Prolonged-release dosage forms are used 1-2 times/day. The maximum daily dose when combining any dosage forms of indometacin is 200 mg.

When the effect is achieved, treatment is continued for 4 weeks at the same or a reduced dose. With long-term use, the daily dose should not exceed 75 mg.

Adverse Reactions

From the digestive system nausea, anorexia, vomiting, abdominal pain and discomfort, constipation or diarrhea, erosive and ulcerative lesions, bleeding and perforations of the gastrointestinal tract; rarely – intestinal strictures, stomatitis, gastritis, flatulence, bleeding from the sigmoid colon or from a diverticulum, jaundice, hepatitis.

From the nervous system dizziness, headache, depression, feeling of fatigue; rarely – anxiety, fainting, drowsiness, convulsions, peripheral neuropathy, muscle weakness, involuntary muscle movements, sleep disorders, mental disorders (depersonalization, psychotic episodes), paresthesia, dysarthria, parkinsonism.

From the cardiovascular system edema, increased blood pressure, tachycardia, chest pain, arrhythmia, palpitation, arterial hypotension, congestive heart failure, hematuria.

Allergic reactions rarely – itching, urticaria, angiitis, erythema nodosum, skin rash, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, hair loss, acute respiratory distress, sharp drop in blood pressure, anaphylactic reactions, angioneurotic edema, dyspnea, bronchial asthma, pulmonary edema.

From the hematopoietic system rarely – leukopenia, petechiae or ecchymoses, purpura, aplastic and hemolytic anemia, thrombocytopenia, DIC syndrome.

From the sensory organs rarely – impaired visual acuity, diplopia, orbital and periorbital pain, tinnitus, hearing impairment, deafness.

From the urinary system rarely – proteinuria, nephrotic syndrome, interstitial nephritis, renal function disorders, renal failure.

From the metabolism rarely – hyperglycemia, glucosuria, hyperkalemia.

Other rarely – vaginal bleeding, hot flashes, increased sweating, nosebleed, enlargement and tension of the mammary glands, gynecomastia.

Contraindications

Hypersensitivity to indometacin, erosive and ulcerative lesions of the gastrointestinal tract in the acute phase, “aspirin triad”, hematopoiesis disorders, blood clotting disorders, severe liver and/or kidney dysfunction, confirmed hyperkalemia, severe forms of chronic heart failure, congenital heart defects, period after coronary artery bypass surgery, severe arterial hypertension, pancreatitis, pregnancy, breastfeeding; children under 14 years of age.

With caution

Coronary artery disease, cerebrovascular diseases, congestive heart failure, dyslipidemia, hyperlipidemia, diabetes mellitus, thrombocytopenia, peripheral arterial diseases, arterial hypertension, smoking, creatinine clearance 30-60 ml/min, liver cirrhosis with portal hypertension, hyperbilirubinemia, history of ulcerative gastrointestinal tract lesions, presence of Helicobacter pylori infection, long-term use of NSAIDs, frequent alcohol consumption, severe somatic diseases. Concomitant therapy with the following drugs: anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (including prednisolone), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline); mental disorders, epilepsy, parkinsonism, depression, elderly age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Indometacin is excreted in small amounts in breast milk.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction. Use with caution in liver diseases.

Use in Renal Impairment

Contraindicated in severe kidney dysfunction. Use with caution in kidney diseases.

Pediatric Use

Contraindicated for use in children and adolescents under 14 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Use with caution in elderly patients, as well as in patients with a history of liver, kidney, gastrointestinal tract diseases, with dyspeptic symptoms at the time of use, arterial hypertension, heart failure, immediately after major surgical interventions, with parkinsonism, epilepsy.

In case of a history of allergic reactions to NSAIDs, use only in emergency cases.

During treatment, systematic monitoring of liver and kidney function, peripheral blood picture is necessary.

Effect on ability to drive vehicles and mechanisms

During treatment, one should refrain from potentially hazardous activities that require concentration and increased speed of psychomotor reactions.

Drug Interactions

Simultaneous use of indometacin with other drugs from the NSAID group, acetylsalicylic acid, glucocorticosteroids, alcohol, colchicine and corticotropin increases the risk of gastrointestinal bleeding.

Indometacin reduces the effectiveness of diuretics; against the background of potassium-sparing diuretics, the risk of hyperkalemia increases; reduces the effectiveness of uricosuric and antihypertensive drugs; enhances the effect of indirect anticoagulants, antiplatelet agents, thrombolytics (alteplase, streptokinase and urokinase); enhances the side effects of glucocorticosteroids, NSAIDs, estrogens, acetylsalicylic acid; enhances the hypoglycemic effect of sulfonylurea derivatives.

Concomitant use with paracetamol increases the risk of nephrotoxic effects.

Cyclosporine and gold preparations increase nephrotoxicity (apparently due to suppression of prostaglandin synthesis in the kidneys).

It increases the plasma concentration of methotrexate, which can lead to increased toxicity of the latter.

With simultaneous use of indometacin with digoxin, an increase in the plasma concentration of digoxin and an increase in the T_1/2 of digoxin are possible.

Indometacin at a dose of 50 mg 3 times/day increases the plasma concentration of lithium and reduces the clearance of lithium from the body in patients with mental illnesses. When using indometacin concomitantly with lithium preparations, the possibility of symptoms of lithium toxic action should be considered.

Cefamandole, cefoperazone, cefotetan, valproic acid, plicamycin increase the risk of hypoprothrombinemia and the danger of bleeding.

It potentiates the toxic effect of zidovudine.

Antacids and cholestyramine reduce the absorption of indometacin.

Myelotoxic drugs enhance the manifestation of hematotoxicity of indometacin.

Concomitant use with quinolones may increase the threat of seizures in patients with or without a history of epilepsy or seizures.

It enhances the hypoglycemic effect of insulin and oral hypoglycemic drugs.

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.