Diclofenac

General characteristics. Structure:

Active ingredient - diclofenac of sodium of 25 mg.

Excipients - propylene glycol of 200,0 mg, Mannitolum of 6,0 mg, alcohol of benzylic 40,0 mg, disodium sulfite of 3,0 mg, sodium of hydroxide of 1 M solution to рН 8,0-9,0, water for injections to 1 ml.

Pharmacological properties:

Pharmacodynamics. Diclofenac possesses antiinflammatory, analgeziruyushchy and febrifugal action. Not selectively oppressing cyclooxygenase 1 and 2, breaks metabolism of arachidonic acid, reduces amount of prostaglandins in the inflammation center. At rheumatic diseases protivospalitelny and analgeziruyushchy effect of Diclofenac promotes considerable reduction of expressiveness of pain, morning constraint and a swelling of joints that improves a functional condition of a joint. At injuries, in the postoperative period diclofenac reduces pain and inflammatory hypostasis. Diclofenac eliminates pain at primary dysmenorrhea.

Pharmacokinetics. Absorption. After intramuscular introduction of 75 mg of diclofenac its absorption begins immediately. The maximum concentration in plasma which average value makes about 2.5 mkg/ml (8 µmol/l) is reached approximately in 20 minutes. Right after its achievement bystry decrease in concentration of diclofenac in plasma is observed. The amount of the soaking-up active agent is in linear dependence on drug dose size. Area size under a curve "concentration time" (AUC) after intramuscular administration of medicine is approximately twice more, than after its oral or rectal administration as in prosledny cases about a half of amount of diclofenac is metabolized at "the first passing" through a liver. After repeated use of drug pharmacokinetic indicators do not change. On condition of observance of the recommended intervals between administrations of drug of cumulation it is not noted.

Distribution. Linkng with serum proteins makes 99,7%. The seeming volume of distribution makes 0,12-0,17 l/kg. Diclofenac gets into synovial fluid where its maximum concentration is reached at 2-4 o'clock later, than in a blood plasma. The seeming elimination half-life makes 3-6 hours of synovial fluid. In 2 hours after achievement of the maximum concentration in plasma concentration of a diklofeiak in synovial fluid is higher, than in plasma, and its values remain higher throughout a span till 12 o'clock.

Metabolism. Metabolism of diclofenac is carried out partially by a glyukuronization of not changed molecule, but, mainly, by means of a single and repeated metoksilirovaniye that leads to formation of several phenolic metabolites (Z1-gidroksi-, 4-gidroksi-, 5-gidroksi-, 4,5-digidroksi-and 3-hydroxy-4-metoksidiklofenaka), the majority of which turns into glyukuronidny conjugates. Two of these phenolic a metabolite are biologically active, but in much smaller degree, than diclofenac.

Removal. The general system plasma clearance of diclofenac makes 263±56 ml/min. The final elimination half-life makes 1-2 hours. The elimination half-life of 4 metabolites, including two pharmacological active, is also short and makes 1-3 hours. One of metabolites, 3-hydroxy - 4-метокси-diclofenac, has longer elimination half-life, however this metabolite is completely inactive. About 60% of the applied dose of drug are removed with urine in the form of glucuronic conjugates of not changed active agent, and also in the form of metabolites, the majority of which is represented by glucuronic conjugates. In not changed look less than 1% of diclofenac are removed. The rest of the applied dose of drug is removed in the form of metabolites through intestines.

Pharmacokinetics at separate groups of patients. In usual single doses of accumulation of diclofenac it was not noted. If the clearance of creatinine makes less than 10 ml/min., settlement equilibrium concentration of hydroxymetabolites of diclofenac are about 4 times higher, than at healthy patients. However, eventually metabolites are removed with bile. At patients with chronic hepatitis or the compensated cirrhosis indicators of pharmacokinetics of diclofenac are similar to that at patients without liver diseases.

Indications to use:

For intramuscular introduction (as the initial stage of treatment or acute cases):

- inflammatory and degenerative rheumatic diseases - pseudorheumatism ankylosing a spondylitis, an osteoarthrosis, spondylarthrites;

- pain syndromes from a backbone;

- rheumatic diseases of extraarticular soft tissues;

- bad attack of gout;

- the posttraumatic and postoperative pain syndromes which are followed by an inflammation and hypostasis;

- attacks of migraine of a heavy current.

Route of administration and doses:

Drug is used at adult patients. It is necessary to use a minimal effective dose minimum possible short course. Usually enter on 1 ampoule (3 ml = 75 mg of diclofenac of sodium) in day deeply into a verkhnenaruzhny quadrant of a gluteus. In acute cases (for example, at gripes) the day dose can be increased to 150 mg: on 1 ampoule twice a day (on one in each buttock).

It is not necessary to apply diclofenac injections more than 2-3 days in a row. In case of need treatment can be prolonged with purpose of peroral or rectal forms of drugs of diclofenac of sodium. At the same time it is not necessary to exceed the general maximum daily dose of diclofenac of sodium (150 mg), including in day of an injection of drug.

Features of use:

At poyavlenn of signs of damage of a liver it is necessary to stop administration of drug and to see the attending physician. It is not necessary to use drug along with other NPVP.

Drug can change properties of thrombocytes, however does not replace preventive effect of acetylsalicylic acid at cardiovascular diseases. Use of drug can negatively influence female fertility and is not recommended to the women planning pregnancy. At patients with infertility (including undergoing inspection) it is recommended to cancel drug.

Because of an important role of prostaglandins in maintenance of a renal blood-groove patients should show extra care at appointment with a heart or renal failure, and also at therapy of the elderly patients accepting diuretics and patients at whom for any reason decrease in OTsK is observed (including after extensive surgical intervention). If in such cases appoint diclofenac, recommend to control function of kidneys as a precautionary measure.

Side effects:

Often - 1-10%; infrequently - 0.1-1%; seldom - 0.01-0.1%; very seldom - less than 0.001%, including separate cases.

From the alimentary system: often - epigastric pain, nausea, vomiting, diarrhea, dyspepsia, a meteorism, anorexia, increase in activity of aminotransferases; seldom - gastritis, a proctitis, bleeding from a GIT (vomiting with blood, a melena, diarrhea with blood impurity), GIT ulcers (with or without bleeding or perforation), hepatitis, jaundice, an abnormal liver function; very seldom - stomatitis, a glossitis, an esophagitis, nonspecific hemorrhagic colitis, an exacerbation of ulcer colitis or a disease Krone, a lock, pancreatitis, fulminant hepatitis, an exacerbation of hemorrhoids (for rectal suppositories).

From a nervous system: often - a headache, dizziness; seldom - drowsiness; very seldom - sensitivity disturbance (including paresthesia), dysmnesias, a tremor, spasms, alarm, cerebrovascular disturbances, aseptic meningitis, a disorientation, a depression, sleeplessness, night "nightmares", irritability, mental disturbances.

From sense bodys: often - вертиго; very seldom - a vision disorder (an illegibility of visual perception, a diplopia), a hearing disorder, a sonitus, disturbance of flavoring feelings.

From an urinary system: very seldom - an acute renal failure, a hamaturia, a proteinuria, intersticial nephrite, a nephrotic syndrome, a papillary necrosis.

From bodies of a hemopoiesis: very seldom - thrombocytopenia, a leukopenia, hemolitic and aplastic anemia, an agranulocytosis.

Allergic reactions: anaphylactic/anaphylactoid reactions, including the expressed decrease in the ABP and shock; very seldom - a Quincke's disease (including persons).

From CCC: very seldom - heartbeat, a stethalgia, increase in the ABP, a vasculitis, SN, a myocardial infarction.

From respiratory system: seldom - bronchial asthma (including an asthma); very seldom - a pneumonitis.

From integuments: often - skin rash; seldom - a small tortoiseshell; very seldom - violent rashes, an erythema, including multiformny and Stephens-Johnson's syndrome, a Lyell's disease, exfoliative dermatitis, an itch, a hair loss, a photosensitization, a purpura, including allergic.

Others: often - irritation in the place of an injection (for parenteral LF); very seldom - abscess in an injection site (for parenteral LF); seldom - hypostases.

Interaction with other medicines:

Increases concentration in plasma of digoxin, drugs of lithium, a methotrexate. Reduces effect of diuretics, against the background of kaliysberegayushchy diuretics the risk of development of a hyperpotassemia amplifies; against the background of anticoagulants, antiagregantny and thrombolytic means (an alteplaza, Streptokinasa, an urokinase) the risk of development of bleedings increases (more often than digestive tract).

Reduces effect of hypotensive and somnolent medicinal stredstvo. Increases probability of emergence of side effects of other non-steroidal anti-inflammatory drugs. Uvelichiavet toxicity of a methotrexate and nephrotoxicity of cyclosporine due to increase in their concentration in plasma. Acetylsalicylic acid reduces concentration of diclofenac in blood. Reduces effect of hypoglycemic medicines. Paracetamol increases risk of development of nefrotoksichny effects of diclofenac. Tsefamandol, цефоперазон, цефотетан, valproic acid and пликамицин increase the frequency of development of a prothrombinopenia. Cyclosporine and drugs of gold increase influence of diclofenac on synthesis of prostaglandin in kidneys that is shown by increase in nephrotoxicity. Selective serotonin reuptake inhibitors increase risk of development of bleedings from digestive tract. Co-administration with ethanol, colchicine, corticotropin and drugs of the St. John's Wort which is made a hole increases risk of development of bleedings in digestive tract. The medicines causing a photosensitization increase the sensibilizing effect of diclofenac to UF-radiation. The drugs blocking canalicular secretion increase concentration in diclofenac plasma, thereby increasing its efficiency and toxicity. Antibacterial medicinal stredstvo from group of a hinolon - risk of development of spasms. It is not necessary to mix Diclofenac solution with solutions of other medicines for injections.

Contraindications:

- hypersensitivity to active agent, including to other NPVP or auxiliary components;

- a full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of acetylsalicylic acid or other NPVP (including in the anamnesis);

- erosive cankers of a GIT and 12-perstny gut, active gastrointestinal bleeding, cerebrovascular or other bleeding;

- inflammatory diseases of intestines in an aggravation stage;

- hemophilia and other disturbances of coagulability of blood;

- heavy liver failure;

- the progressing diseases of kidneys;

- the period after performing aortocoronary shunting;

- the confirmed hyperpotassemia;

- pregnancy, lactation period;

- children's age up to 18 years.

With care. Bronchial asthma, coronary heart disease, diabetes mellitus; cerebrovascular diseases, arterial hypertension, diseases of peripheral arteries, smoking, a pechenony or renal failure, alcoholism, considerable decrease in volume of the circulating blood (including after extensive surgical intervention), advanced age, a diverticulitis, general diseases of connecting fabric, heavy somatopathies, anticoagulants (for example, warfarin), selective serotonin reuptake inhibitors (a naprmer, to tsitalopra, fluoxetine, пароксетин, sertraline), long use of NPVP.

Overdose:

Symptoms: vomiting, bleeding from a GIT, epigastric pain, diarrhea, dizziness, a sonitus, a lethargy, spasms, it is rare - increase in the ABP, an acute renal failure, a hepatotoxic action, respiratory depression, a coma.

Treatment: a gastric lavage, absorbent carbon, the symptomatic therapy directed to elimination of increase in the ABP, a renal failure, spasms, irritations of a GIT, respiratory depression. The artificial diuresis, a hemodialysis are ineffective (in connection with considerable communication with proteins and intensive metabolism).

Storage conditions:

To store 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:

Solution for intramuscular introduction in ampoules on 3 ml (75 mg).

On 5 ampoules in a blister strip packaging from a film polyvinyl chloride (PVC). One or two planimetric cell packagings from PVC together with the application instruction and a skarirfikator ampoule or a knife ampoule in a pack from a cardboard.

5 or 10 ampoules with drug together with the instruction for use and the scarificator ampoule or a knife ampoule in a pack from a cardboard with a corrugated insert.

When packaging ampoules with a point or a ring of a break the scarificator or a knife ampoule do not put.