Diclofenac ретард

General characteristics. Structure:

Active ingredient: 100 mg of diclofenac of sodium.

Excipients: [gipromelloz (gidroksipropilmetiltsellyuloz), gietelloza (hydroxyethylcellulose), коллидон SR [polyvinyl acetate of 80%, povidone of 19%, sodium lauryl sulfate of 0,8%, silicon dioxide of 0,2%], sodium алгинат, cellulose microcrystallic, magnesium stearate].

Has antiinflammatory, analgeziruyushchy and febrifugal effect.

Pharmacological properties:

Pharmacodynamics. Non-steroidal anti-inflammatory drug (NPVP), derivative phenylacetic acid; has antiinflammatory, analgeziruyushchy and febrifugal effect.

Not selectively oppressing cyclooxygenase 1 and 2 (TsOG1 and TsOG2), breaks metabolism of arachidonic acid, reduces amount of prostaglandins in the inflammation center. It is most effective at pains of inflammatory character. As all NPVP, drug has antiagregantny effect. 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 on 1-4 h and reduces the maximum concentration (Cmax) by 40%.

As a result of the slowed-down release of the drug Cmax in plasma is lower than that which is created at administration of the medicines (M) of short action; however it remains high after reception for a long time. Cmax – 0,5-1,0 mkg/ml, time of achievement of the maximum concentration in a blood plasma (TCmax) – 5 h after reception of 100 mg of tablets of the prolonged action.

Change of pharmacokinetics of diclofenac against the background of repeated introduction is not noted. Does not kumulirut at observance of the recommended interval between meals.

Bioavailability – 50%. Communication with proteins of plasma – more than 99% (the most part contacts albumine). Gets into breast milk, synovial fluid; Cmax in synovial fluid is observed on 2-4 h later, than in plasma. An elimination half-life (T1/2) from synovial fluid – 3-6 h (concentration of drug in synovial fluid in 4-6 h after its introduction are higher, than in plasma, and remain higher during 12 h).

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 system of CYP2C9 P 450 cytochrome takes part in metabolism of drug. Pharmacological activity of metabolites is less, than diclofenac.

The system clearance makes 206 ml/min. of T1/2 of plasma – 1-2 h 60% of the entered dose are brought in the form of metabolites through 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 (the clearance of creatinine (CC) 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 do not change.

Diclofenac gets into breast milk.

Indications to use:

Musculoskeletal system diseases (a pseudorheumatism, the psoriasis, juvenile chronic arthritis ankylosing a spondylarthritis (Bekhterev's disease); gouty arthritis; rheumatic defeat of soft tissues; an osteoarthrosis of peripheral joints and a backbone, including with a radicular syndrome; tendovaginitis; 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).

Drug is intended for symptomatic therapy, reducing pains and inflammations at the time of use, does not influence progressing of a disease.

Route of administration and doses:

Inside, without chewing, washing down with a small amount of water, as a rule, in time and after food.
Diclofenac of the prolonged action is appointed on 100 mg of 1 times a day (at a dysmenorrhea and attacks of migraine - to 200 mg/days).

At reception of 100 mg of tablets of the prolonged action in need of increase in a daily dose up to 150 mg it is possible to accept in addition on 1 usual tablet (50 mg) of diclofenac.

Features of use:

Use at pregnancy and during breastfeeding. The drug Diclofenac ретард is contraindicated to use in ΙΙΙ a trimester of pregnancy and during breastfeeding. Use in Ι-ΙΙ a trimester of pregnancy is possible with care, is proved if the advantage for mother exceeds possible risk for a fruit.

For the purpose of bystry achievement of desirable therapeutic effect accept in 30 min. prior to meal. In other cases accept to, in time or after food without chewing, washing down with enough water.

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 (for example, after extensive surgical intervention). If in such cases appoint diclofenac, recommend to control function of kidneys as a precautionary measure.

At patients with a renal failure at KK less than 10 ml/min. equilibrium concentration of metabolites in plasma has to be theoretically much higher, than at patients with normal function of kidneys, however it really is not observed as in this situation removal of metabolites with bile amplifies.

At patients with a liver failure (chronic hepatitis, the compensated cirrhosis) the kinetics and metabolism do not differ from similar processes at patients with normal function of a liver. When performing long therapy it is necessary to control function of a liver, a picture of peripheral blood, the analysis a calla on the occult blood.

Due to the negative effect on fertility, the women wishing to become pregnant are not recommended to use drug. At patients with infertility (including undergoing inspection) it is recommended to cancel drug.

For decrease in risk of development of the undesirable phenomena from a GIT it is necessary to use a minimal effective dose minimum possible short course.

Influence on ability to driving of vehicles and to control of mechanisms. During treatment reduction of speed of mental and motor reactions therefore it is necessary to abstain from driving of motor transport and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions is possible.

Side effects:

Frequency of the side effects developing at reception of a karvedilol is classified according to recommendations of World Health Organization: very often – not less than 10%; often – not less than 1%, but less than 10%; infrequently – not less than 0,1%, but less than 1%; seldom – not less than 0,01%, but less than 0,1%; very seldom – less than 0,01%, including separate messages.

From digestive organs: 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.

From a nervous system: often – a headache, dizziness; seldom – a sleep disorder, drowsiness; very seldom – sensitivity disturbance, including paresthesias, 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 (sight misting, a diplopia), a hearing disorder, a sonitus, disturbance of flavoring feelings.

From an urinary system: often – a liquid delay; very seldom – an acute renal failure, a hamaturia, intersticial nephrite, a nephrotic syndrome, a papillary necrosis.

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

Allergic reactions: seldom – anaphylactic/anaphylactoid reactions, including the expressed lowering of arterial pressure (ABP) and shock; very seldom – a Quincke's disease (including persons).

From cardiovascular system: very seldom – heartbeat, a stethalgia, increase in the ABP, a vasculitis, heart failure, 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 – painful rashes, eczema, 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: seldom – hypostases.

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 a GIT).

Reduces effects hypotensive and HP hypnotic drugs.

Increases probability of emergence of side effects of other NPVP and glucocorticosteroid means (GIT bleedings), 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, valproic acid and пликамицин increase the frequency of development of a prothrombinopenia.

Cyclosporine and drugs of gold increase influence of diclofenac on synthesis of prostaglandins 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 of a GIT.

Diclofenac strengthens effect of the drugs causing a photosensitization.

The drugs blocking canalicular secretion increase concentration in diclofenac plasma, thereby increasing its toxicity.

Antibacterial HP from group of a hinolon increase risk of development of spasms.

Selective serotonin reuptake inhibitors increase risk of development of bleedings from a GIT.

The HP causing a photosensitization increase the sensibilizing effect of diclofenac to ultra-violet radiation.

The HP blocking canalicular secretion increase concentration in diclofenac plasma, thereby increasing its efficiency and toxicity.

Contraindications:

· Hypersensitivity to active or to auxiliary components (including to other NPVP);
· 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 mucous stomach or 12-perstny gut, active bleeding of the digestive tract (DT);
· Inflammatory diseases of intestines (nonspecific ulcer colitis, disease Krone);
· The period after performing aortocoronary shunting;
· III trimester of pregnancy, lactation period;
· Heavy heart failure;
· Cerebrovascular bleeding or other bleedings and disturbances of a hemostasis;
· The expressed liver failure or an active disease of a liver;
· The expressed renal failure (KK less than 30 ml/min.), the progressing diseases of kidneys, including the confirmed hyperpotassemia;
· Children's age up to 18 years.
· Hereditary intolerance of a galactose, glucose galactose absorption disturbance, heavy lactose intolerance

With care: Anemia, bronchial asthma, cerebrovascular diseases, the coronary heart disease (CHD), congestive heart failure, the arterial hypertension (AH), diseases of peripheral arteries, an edematous syndrome, a liver or renal failure, liver diseases in the anamnesis, дислипидемия / a lipidemia, a diabetes mellitus, smoking, inflammatory diseases of intestines, considerable decrease in the volume of the circulating blood (VCB), including after extensive surgical interventions, a porphyria, advanced age, including the patients receiving diuretics, weakened patients and with low body weight, a diverticulitis, general diseases of connecting fabric, pregnancy the I-II trimester, KK less than 60 ml/min.

Peptic ulcer of a stomach and 12 perstny guts, ulcer colitis, disease Krone, ΙΙанамнестические data on development of an ulcer disease of digestive tract, existence of an infection of Helicobacter pylori, long use of NPVP, frequent alcohol intake, heavy somatopathies.

Simultaneous therapy by anticoagulants (for example, warfarin), antiagregant (including acetylsalicylic acid, клопидогреля), peroral glucocorticosteroids (for example, dexamethazone), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline).

Overdose:

Symptoms: dizziness, a headache, a hyperventilation of lungs, consciousness opacification, vomiting, bleeding from a GIT, diarrhea, a sonitus, spasms, at considerable overdose - an acute renal failure, a hepatotoxic action.

Treatment: gastric lavage, reception of absorbent carbon. Symptomatic therapy is 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:

In the dry, protected from light place at a temperature not over 25 ºС. To store in the place, unavailable to children. Period of validity: 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

The tablets of the prolonged action covered with a kishechnorastvorimy cover, 100 mg. On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3, 5 or 10 blister strip packagings with the application instruction place in a pack from a cardboard.