Diclofenac

General characteristics. Structure:

Active agent: sodium diclofenac - 100 mg; Excipients: Metotsel of K4M, cellulose microcrystallic, magnesium stearate, aerosil (silicon dioxide colloid). Cover: Опадрай yellow OY 7915: Gidroksipropil marked cellulose, milk sanst yellow (Е 110), polyethylene glycol 4000, talc, sugar (lactose).

Pharmacological properties:

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

Pharmacokinetics. Absorption - bystry and full, food slows down absorption speed for 1-2 hours and reduces the maximum concentration twice. In case of administration of drug with food the maximum concentration are observed on average in 5-6 hours. Change of pharmacokinetics of diclofenac against the background of repeated introduction is not noted, does not kumulirut. Bioavailability - 50%. Communication with proteins of plasma - more than 99% (the most part contacts albumine). Gets into synovial fluid; The Maximum concentration in synovial fluid is observed on 2-4 h later, than in plasma. The popuvyvedeniye period from synovial fluid of 3-6 h (concentration of active agent in synovial fluid in 4-6 h after administration of drug is higher, than in plasma, and remains higher during 12 h). The interrelation of concentration of drug in synovial fluid with clinical performance of drug is not found out.

Metabolism: 50% of active agent are exposed to metabolism during "the first passing" through a liver. Metabolism    results  from a repeated or single hydroxylation  and a konjyugirovaniye with glucuronic  acid.            The fermental      P450 CYP2C9 system takes part in metabolism of drug. Pharmacological activity of metabolites is lower, than diclofenac. The system clearance makes 350 ml/min., distribution volume - 550 ml/kg. Plasma elimination half-life - 2 h 65% of the entered dose is removed in the form of metabolites by kidneys; less than 1% are removed in not changed look, other part of a dose is removed in the form of metabolites with bile. At patients with the expressed renal failure (clearance of creatinine less than 10 ml/min.) removal of metabolites with bile increases, at the same time increase in their concentration in blood is not observed. At patients with chronic hepatitis  or the compensated    cirrhosis  pharmacokinetic parameters of diclofenac do not change. Diclofenac gets into breast milk.

Indications to use:

Musculoskeletal system diseases (a pseudorheumatism, the psoriasis, juvenile chronic arthritis ankylosing  a spondylarthritis;  gouty  arthritis,  rheumatic  defeat  of soft  tissues,  an osteoarthrosis of peripheral joints and a backbone, including with a radicular syndrome, a tendovaginitis, a bursitis). Pain syndrome of weak or moderate expressiveness: neuralgia, a mialgiya, a lumbar ishialgia, the posttraumatic pain syndrome which is followed by an inflammation, postoperative pain, a headache, migraine, альгодисменорея, an adnexitis, a proctitis, a dentagra. As a part of complex therapy of infectious and inflammatory diseases of an ear, a throat, a nose with the expressed pain syndrome (pharyngitis, tonsillitis, otitis).

Route of administration and doses:

Inside, without chewing, washing down with a small amount of water, as a rule, in time or after food. On 1 tablet of 1 times a day.

Features of use:

During treatment it is necessary to carry out by drug systematic control of a picture of peripheral blood, function of a liver, kidneys, a research a calla on availability of blood. The patients  accepting  drug  need to abstain from  the types of activity demanding the increased concentration of attention and bystry mental and motor reactions, alcohol intake.

Side effects:

Digestive tract: more often than 1% - abdominal pains, feeling of abdominal distention, diarrhea, nausea, a lock, a meteorism, increase in activity of "hepatic" enzymes, a round ulcer with possible complications (bleeding, perforation), gastrointestinal bleeding; more rare than 1% - vomiting, jaundice, a melena, emergence of blood to Calais, damage of a gullet, aphthous stomatitis, dryness of a mouth and mucous membranes, hepatitis (perhaps fulminantny current), a liver necrosis, cirrhosis, a gepatorenalny syndrome, appetite change, pancreatitis, holetsistopankreatit, colitis.

Nervous system: more often than 1% -  a headache,  dizziness; more rare  than 1% -  a sleep disorder, drowsiness, a depression, irritability, aseptic meningitis (is more often at patients with a system  lupus erythematosus and other general diseases of connecting fabric), spasms, weakness, a disorientation, dreadful dreams, feeling of fear.

Sense bodys: more often than 1% - a sonitus; more rare than 1% - a sight illegibility, a diplopia, taste disturbance, reversible or irreversible decrease in hearing, scotoma.

Integuments: more often than 1% -  a skin itch, skin rash; more rare than 1% - an alopecia, urticaria, eczema, toxic dermatitis, a mnogoformny exudative erythema, including Stephens-Johnson's syndrome, toxic epidermal некропиз (Lyell's disease), the increased photosensitivity, punctulate hemorrhages.

Urinogenital system: more often than 1% - a liquid delay; more rare than 1% - a nephrotic syndrome, a proteinuria, an oliguria, a hamaturia, intersticial nephrite, a papillary necrosis, an acute renal failure, an azotemia.

Bodies of a hemopoiesis and immune system: more rare than 1% - anemia (including hemolitic and aplastic anemias), a leukopenia,  thrombocytopenia,  an eosinophilia, an agranulocytosis,  a Werlhof's  disease,  deterioration  in a course of infectious processes (development of a necrotizing fasciitis).

Respiratory system: more rare than 1% - cough, a bronchospasm, throat hypostasis, a pneumonitis.

Cardiovascular system: more rare than 1% - increase in arterial pressure; congestive heart failure, premature ventricular contraction, thorax pain.

Allergic reactions: more rare than 1% - anaphylactoid reactions, an acute anaphylaxis (usually develops promptly), hypostasis of lips and language, an allergic vasculitis.

Interaction with other medicines:

Increases concentration in plasma of digoxin, a methotrexate, drugs of lithium and cyclosporine. Reduces effect of diuretics, against the background of kaliysberegayushchy diuretics the risk of a hyperpotassemia amplifies; against the background of anticoagulants, thrombolytic means (an alteplaza, Streptokinasa, an urokinase) - risk of bleedings (is more often from digestive tract). Reduces effects hypotensive and hypnagogues. Increases  probability  of emergence  of side  effects  of other  NPVP  and  glucocorticosteroid  means (bleedings in  digestive tract), toxicity of a methotrexate and nephrotoxicity of cyclosporine. Acetylsalicylic acid reduces concentration of diclofenac in blood. Simultaneous use with paracetamol increases risk of development of nephrotoxic effects of diclofenac. Reduces effect of hypoglycemic means. Tsefamandol, цефоперазон, цефотетан, vapproyevy acid and пликамицин increase the frequency of development of a prothrombinopenia. Cyclosporine and drugs of gold increase influence of diclofenac on synthesis of prostatandin in kidneys that increases nephrotoxicity. Co-administration with ethanol, colchicine, corticotropin and drugs of a St. John's Wort increases risk of development of bleedings in digestive tract. Diclofenac strengthens effect of the drugs causing a photosensitization. The drugs blocking canalicular secretion increase concentration in diclofenac plasma, thereby, increasing its toxicity.

Contraindications:

Hypersensitivity (including to other NPVP), digestive tract eroeivno-cankers (in an aggravation phase), bleedings from digestive tract, "aspirinovy" asthma, disturbances of a hemopoiesis, disturbance of a hemostasis (including hemophilia), pregnancy, children's age (up to 18 years), the lactation period.

Overdose:

Symptoms: vomiting, dizziness, a headache, short wind, consciousness opacification, children have myoclonic spasms, nausea, abdominal pain, bleedings, an abnormal liver function and kidneys. Treatment: gastric lavage, administration of absorbent carbon, symptomatic therapy, artificial diuresis. The hemodialysis is ineffective.

Storage conditions:

List B. To store in the dry 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:

On 10 tablets in  a blister strip packaging from the polyvinyl chloride film and   printing aluminum foil varnished. On the 2nd blister strip packagings together with the application instruction place in a cardboard pack. Packaging for hospitals. On 100, 200, 300, 400 or 500 blister strip packagings with application instructions place in boxes from a cardboard. On 500,1000 or 2000 tablets pack into banks polymeric with covers from polymeric materials. On 1, 2, 3, 4, 5 or 6 cans with application instructions put in boxes from a cardboard.