Indometacin

General characteristics. Structure:

Active agent: indometacin - 25,0 mg

Excipients (kernel): lactoses monohydrate (sugar milk) - 41,6 mg, potato starch - 10,0 mg, cellulose microcrystallic - 16,0 mg, povidone (polyvinylpirrolidone) - 2,50 mg, magnesium stearate - 0,90 mg

Excipients (cover): целлацефат (atsetilftaliltsellyuloza) - 2,20 mg, polysorbate-80 - 0,72 mg, titanium dioxide - 1,08 mg.

Pharmacological properties:

Pharmacodynamics. Indometacin renders antiinflammatory, analgetic, febrifugal and anti-aggregation action. Suppresses activity of pro-inflammatory factors, reduces aggregation of thrombocytes. Oppressing cyclooxygenase I and II, breaks metabolism of arachidonic acid, reduces amount of prostaglandins (Pg) both in the inflammation center, and in healthy fabrics, suppresses exudative and proliferative phases of an inflammation. Eliminates or reduces a pain syndrome of rheumatic and not rheumatic character (including at joint pains at rest and at the movement, reduction of morning constraint and a swelling of joints, promotes increase in volume of movements; at the inflammatory processes arising after operations and injuries; quickly facilitates both spontaneous pain, and an oxycinesia; reduces inflammatory hypostasis on site of a wound).

Pharmacokinetics. Bioavailability at oral administration - 8090%. The maximum plasma concentration is reached during 1-2 h. It is soaked up through a mucous membrane of a small bowel, and in much smaller degree through a mucous membrane of a stomach. It is distributed in all bodies and fabrics. Gets through a placental and blood-brain barrier. Gets through a synovial membrane into joints, and concentration of indometacin in synovial fluid increases. Communication with proteins of plasma - 90-98%, an elimination half-life - 2,6 and 11,2 h. It is metabolized generally in a liver, in an invariable look 10-20% of drug are removed, 70% are removed by kidneys, 30% - through the digestive tract (DT). Is not removed at dialysis. It is allocated with breast milk.

Indications to use:

• Acute and chronic pains at inflammatory diseases of a musculoskeletal system: pseudorheumatism; juvenile chronic arthritis; ankylosing chronic spondylitis (Bekhterev's disease); gouty arthritis; psoriasis arthritis; disease of Reuters;
• Diseases of circumarticular fabrics: tendinites, bursitis, tendobursita, tendovaginitis;
• Injuries at athletes;
• Diskopathies, neuritis, plexites, radiculoneurites. Drug is intended for symptomatic therapy, reduces pain and an inflammation at the time of use, does not influence progressing of a disease.

Route of administration and doses:

Inside, after meal, washing down with enough water. Adults and children are more senior than 14 years: the initial dose makes 25 mg 2-3 times a day. At insufficient therapeutic action the dose is increased to 50 mg by 3 times a day. The maximum daily dose makes 200 mg At long treatment the daily dose should not exceed 75 mg Gouty arthritis
For stopping of a bad gouty attack, the initial dosage makes 100 mg then continue treatment on 50 mg 3 times a day before disappearance of pain.
Side effects can be reduced, using a minimal effective dose for perhaps shorter span.

Features of use:

During treatment control of a picture of peripheral blood and a functional condition of a liver and kidneys is necessary. In need of definition of 17 ketosteroids drug should be cancelled for 48 h prior to a research. For decrease in risk of the undesirable phenomena from digestive tract it is necessary to use minimum effective dose minimum possible short course. Serious skin reactions, inclusive with a lethal outcome, the phenomenon NPVP which are very seldom observed at use, concern cases of exfoliative dermatitis, Stephens-Johnson's syndrome, a toxic epidermal necrolysis. The highest is the risk in an initiation of treatment. Administration of drug should be stopped at emergence of the first skin or other signs of hypersensitivity. Drug can mask symptoms of an acute inflammation that demands an exception of a bacterial infection at its appointment.
At administration of drugs from the NPVP group, there is a risk of development of a hyperpotassemia, especially at patients 65 years are more senior, than patients with a renal failure, patients who accept R-blockers, APF inhibitors and kaliysberegayushchy diuretics. At such patients it is necessary to trace the level of serumal potassium.
Women at reproductive age have a risk of reversible suppression of fertility. Drug contains monohydrate in quality of excipient of lactose that patients need to consider at appointment with insufficiency of lactase, a galactosemia, a glucose/galactose sprue. Patients with a glyuteinovy enteropathy should consider existence in composition of drug of potato starch.

INFLUENCE ON ABILITY TO MANAGE MOTOR TRANSPORT AND TO WORK WITH MECHANISMS
During treatment by indometacin it is necessary to abstain from control of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

- From the alimentary system: The NPVP-gastropathy, abdominal pains, nausea, vomiting, heartburn, anorexia, diarrhea, bleedings, an abnormal liver function (increase in blood of bilirubin, "hepatic" transaminases (ALAT, ASAT)). At prolonged use in high doses - an ulceration of a mucous membrane of digestive tract, a stomacace Toxic hepatitis with jaundice or without jaundice, fulminantny hepatitis
- From the central nervous system: headache, dizziness, excitement, drowsiness, fatigue, peripheral neuropathy. The sensitivity disturbances including paresthesia; feeling of a disorientation, sleeplessness, irritability, depression, uneasiness, dysmnesia, psychotic reactions.
- From cardiovascular system: development (aggravation) of the phenomena of chronic heart failure, a tachyarrhythmia, is messages on an edematous syndrome, increase in arterial pressure.
- From sense bodys: decrease in hearing, a sonitus, taste disturbance, a diplopia, a sight illegibility, opacification of a cornea, conjunctivitis from an urinary system: hypostases, proteinuria, hamaturia, intersticial nephrite, nephrotic syndrome, necrosis of nipples. From system of a hemopoiesis and system of a hemostasis: bleedings (gastrointestinal, from gums, uterine, hemorrhoidal), thrombocytopenia, an eosinophilia,  an agranulocytosis,  a Werlhof's disease.
- Allergic reactions: skin rash, itch; small tortoiseshell, Quincke's disease, bronchospasm; photosensitization, Lyell's disease, knotty erythema, Stephens-Johnson's syndrome, acute anaphylaxis.
- Laboratory indicators: agranulocytosis, leukopenia, thrombocytopenia, hyperglycemia, glucosuria, hyperpotassemia.

Interaction with other medicines:

Simultaneous use of indometacin with other drugs from the NPVP group, acetylsalicylic acid, glucocorticosteroids, alcohol, colchicine and corticotropin increases risk of development of bleedings in digestive tract. Indometacin reduces efficiency of diuretics, against the background of use of kaliysberegayushchy diuretics the risk of a hyperpotassemia increases; reduces efficiency of uricosuric and hypotensive drugs; strengthens effect of indirect anticoagulants, antiagre-gant, trombolitik (an alteplaza, Streptokinasa and an urokinase); strengthens side effects of glucocorticosteroids, NPVP, estrogen, acetylsalicylic acid; strengthens hypoglycemic effect of derivatives of sulphonylurea.
Sharing with paracetamol increases risk of development of nephrotoxic effects. Cyclosporine and drugs of gold increase nefro-toxicity (obviously due to suppression of synthesis of prostaglandins (Pg) in kidneys). Increases concentration in plasma of drugs of lithium, a methotrexate and digoxin that can lead to strengthening of their toxicity. Tsefamandol, цефаперазон, цефотетан, valproic acid, пликамицин increase risk of development of a prothrombinopenia and danger of bleedings. Exponentiates toxic action zi-
dovudina. Antacids and Colestyraminum reduce indometacin absorption. Myelotoxic medicines strengthen manifestation of a gematotoksichnost of drug. Combined use from hinolona can increase threat of development of spasms in patients with or without anamnestic data on epilepsy or spasms.
Strengthens hypoglycemic effect of insulin and peroral hypoglycemic medicines.

Contraindications:

Hypersensitivity to indometacin or any of drug excipients; anamnestic data on an attack of a bronkhoobstruktion, rhinitis, small tortoiseshell after reception of acetylsalicylic acid or other NPVP (the full or incomplete syndrome of intolerance of acetylsalicylic acid - rinosinusit, a small tortoiseshell, polyps mucous a nose, asthma);
erosive and ulcer changes mucous stomach or 12-perstny gut, active gastrointestinal bleeding;
inflammatory diseases of intestines (nonspecific ulcer colitis, disease Krone); inborn heart diseases (heavy coarctation of an aorta, atresia of a pulmonary artery, heavy tetrad of Fallo);
the period after aortocoronary shunting; dekompensirovanny heart failure; a renal failure (the clearance of creatinine (CC) less than 30 ml/min.), the progressing diseases of kidneys;
liver failure or active disease of a liver;
disturbances of coagulability of blood (including hemophilia, lengthening of a bleeding time, tendency to bleedings);
hemopoiesis disturbance (leukopenia and anemia);
the confirmed hyperpotassemia; hereditary lactose intolerance, lactose intolerance and glyukozo-galaktozny malabsorption.
pregnancy and breastfeeding; children's age (up to 14 years).

WITH CARE
Coronary heart disease, cerebrovascular diseases, congestive heart failure, dislipidemiya, lipidemia, diabetes mellitus, thrombocytopenia, diseases of peripheral arteries, arterial hypertension, smoking, clearance of creatinine of 30-60 ml/min., cirrhosis with portal hypertensia, a hyperbilirubinemia, a digestive tract canker in the anamnesis, existence of an infection of Helicobacter pylori, long use of NPVP, frequent alcohol intake, heavy somatopathies. The accompanying therapy by the following drugs: anticoagulants (including warfarin), antiagregant (including acetylsalicylic acid, klopidogret), peroral glucocorticosteroids (including Prednisolonum), selective serotonin reuptake inhibitors (including to tsitalopa, fluoxetine, пароксетин, sertraline); mental disorders, epilepsy, parkinsonism, depression, advanced age

USE DURING PREGNANCY AND DURING BREASTFEEDING
Drug is contraindicated to use during pregnancy and during breastfeeding. Indometacin is emitted with breast milk. In need of use of drug in the period of a lactation for the period of treatment it is necessary to stop breastfeeding.

Overdose:

Symptoms: nausea, vomiting, severe headache, dizziness, memory disturbance, disorientation. In hard cases of paresthesia, numbness of extremities, spasms.
Treatment: symptomatic therapy. The hemodialysis is inefficient.

Storage conditions:

In the place protected from light at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

The tablets covered with a kishechnorastvorimy cover of 25,0 mg.
On 10, 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 10, 20, 30, 40, 50, 60 or 100 tablets in banks polymeric for medicines. To one bank or 1, 2, 3, 4, 5, 6, 8 or 10 blister strip packagings together with the application instruction place in cardboard packaging (pack) from a cardboard.