Diclofenac ретард

General characteristics. Structure:

Active agent: sodium diclofenac - 100,0 mg.

Excipients (kernel): lactoses monohydrate (sugar milk) 50,0 mg, gipromelloza of 95,0 mg, cellulose of microcrystallic 53,0 mg, povidone (поливинлпирролидон) 7,0 mg, talc of 2,0 mg, magnesium stearate of 3,0 mg.

Excipients (cover): целлацефат 8,0 mg, polysorbate-80 of 3,0 mg, titanium dioxide of 4,0 mg.

Pharmacological properties:

Non-steroidal anti-inflammatory drug, derivative phenylacetic acid; renders antiinflammatory, analgeziruyushchy, antiagregantny and febrifugal action. Not selectively oppressing a tsikloksigenaza 1 and to a tsikloksigenaz 2, metabolism of arachidonic acid breaks, reduces amount of prostaglandins in the inflammation center. It is most effective at pains of inflammatory character.

Pharmacokinetics. As a result of the slowed-down drug Omax release (the maximum concentration) in plasma below that which is created at administration of medicine of short action; however it remains high after reception for a long time. Omax - 0.5-1 mkg/ml, TCmax (time of achievement of the maximum concentration) - 5 h after reception of 100 mg of tablets of the prolonged action.
Concentration in plasma is in linear dependence on size of the entered dose. Change of pharmacokinetics of diclofenac against the background of repeated introduction is not noted. Does not kumuli-rut 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. T1/2 (elimination half-life) 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 drug are exposed to metabolism during "the first passing" through a liver; AUC (the area under a curve "concentration time") is twice less after peroral administration of drug, than after parenteral administration of the same dose. Metabolism results from a repeated or single hydroxylation and a konjyugirovaniye with glucuronic acid. CYP2C9 isoenzyme also participates in drug metabolism. Pharmacological activity of metabolites is less, than diclofenac.
The system clearance makes 260 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 (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 do not change.

Indications to use:

Inflammatory and degenerative diseases of a musculoskeletal system (a pseudorheumatism, the psoriasis arthritis ankylosing a spondylitis (Bekhterev's disease); gouty arthritis, the osteochondrosis deforming an osteoarthrosis of peripheral joints and a backbone including with a radicular syndrome, a tendovaginitis, a bursitis).
Drug is intended for symptomatic therapy, reduction of pain and an inflammation at the time of use, does not influence progressing of a disease.
• Pain syndrome: head (including migraine) and a dentagra, a lumbago, an ischialgia, an ossalgiya, neuralgia, a mialgiya, an arthralgia, radiculitis, at oncological diseases, the posttraumatic and postoperative pain syndrome which is followed by an inflammation.
• Algodismenorey; inflammatory processes in a small basin, including an adnexitis.
• 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. Accept in time or after food, without chewing, washing down with enough water. Diclofenac of the prolonged action is appointed on 100 mg of 1 times a day.
At achievement of optimum therapeutic effect the dose is gradually reduced and pass to the supporting treatment in a dose 50 mg/days. Maximum daily dose of-150 mg.
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:

For decrease in risk of development of the undesirable phenomena from digestive tract it is necessary to use a minimal effective dose minimum possible short course. 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 volume of the circulating blood is observed (including, extensive surgical intervention). If in such cases appoint diclofenac, recommend to control function of kidneys as a precautionary measure. 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.
Influence on results of laboratory analyses: diclofenac can influence indicators of serumal transaminases (if this influence has long character or if complications take place, treatment needs to be stopped), and also can cause increase in potassium concentration. 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. At a bad attack of gout high-speed dosage forms are preferable.

INFLUENCE ON ABILITY TO MANAGE MOTOR TRANSPORT AND TO WORK WITH 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:

Often - 1-10%; sometimes - 0.1-1%; seldom - 0.01-0.1%; very seldom - less than 0.01%, 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 digestive tract (vomiting with blood, a melena, diarrhea with blood impurity), digestive tract 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 - 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 (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 lowering of arterial pressure and shock; very seldom - a Quincke's disease (including persons).
- From cardiovascular system: very seldom - heartbeat, a stethalgia, increase in arterial pressure, a vasculitis, heart failure, a myocardial infarction.
- From respiratory system: seldom - bronchial asthma (including an asthma); very seldom - a pneumonitis.
- Co of the party of integuments: often - skin rash; seldom - a small tortoiseshell; very seldom - violent 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.
- Other: 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) the risk of development of bleedings increases (more often from digestive tract).
Reduces effects of hypotensive and somnolent medicines.
Increases probability of emergence of side effects of other non-steroidal anti-inflammatory drugs and glucocorticosteroid means (bleeding 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 medicines.
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, inhibitors of the return serotonin reuptake 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 medicines blocking canalicular secretion increase concentration in diclofenac plasma, thereby, increasing its toxicity. Antibacterial medicines from group of a hinolon - risk of development of spasms.

Contraindications:

• Hypersensitivity to active agent, auxiliary components and other non-steroidal anti-inflammatory drugs.
• A full or incomplete combination of bronchial asthma, the nose recuring a polypose and okolonosovy bosoms and intolerance of acetylsalicylic acid or other non-steroidal anti-inflammatory drug (including in the anamnesis).
• Erosive cankers of digestive tract and 12-perstny gut.
• Active gastrointestinal bleeding.
• Inflammatory diseases of intestines (nonspecific ulcer colitis, disease Krone).
• Heavy liver failure; active disease of a liver.
• Heavy heart failure.
• States after performing aortocoronary shunting.
• Heavy renal failure (clearance of creatinine less than 30 ml/min.); the progressing diseases of kidneys.
• The confirmed hyperpotassemia.
• Third trimester of pregnancy.
• Children's age (up to 18 years).
• Hereditary lactose intolerance, glucose galactose absorption disturbance, insufficiency of lactase.

WITH CARE
Bronchial asthma, cerebrovascular diseases, coronary heart disease, chronic heart failure, arterial hypertension, diseases of peripheral arteries, chronic renal failure (clearance of creatinine of 30-60 ml/min.), liver diseases in the anamnesis, a hepatic porphyria, dislipidemiya/a lipidemia, a diabetes mellitus, considerable decrease in volume of the circulating blood (including after extensive surgical intervention). Anamnestic data on development of an ulcer disease of digestive tract, existence of an infection of Helicobacter pylori, long use of non-steroidal anti-inflammatory drugs, alcoholism, smoking, heavy somatopathies.
Elderly patients (including the receiving diuretics weakened patients and with low body weight). Simultaneous therapy by anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogret), peroral glucocorticosteroids (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, sertraline). In the I-II trimesters of pregnancy drug is used with care.

USE AT PREGNANCY AND IN THE PERIOD OF THE LACTATION
At use of medicine in the I-II trimesters of pregnancy it is necessary to be careful.
Use of drug in the third trimester of pregnancy is contraindicated.
In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Symptoms: vomiting, bleeding from digestive tract, epigastric pain, diarrhea, dizziness, a sonitus, a lethargy, spasms, it is rare - increase in arterial pressure, 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 arterial pressure, a renal failure, spasms, irritations of digestive tract, 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 dry, protected from light place at a temperature not above 25 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

The tablets of the prolonged action covered with a kishechnorastvorimy cover of 100 mg. On 10, 20 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 10, 20, 30, 40, 50 or 100 tablets in a container polymeric for medicines. One container or 1, 2, 3, 4, 5, 6, 8 or 10 blister strip packagings together with the application instruction place in a pack from a cardboard.