Diklofenak-FPO

General characteristics. Structure:

Active ingredient: 25 mg or 50 mg of diclofenac of sodium in 1 tablet.

Excipients: silicon dioxide colloid (aerosil), potato starch, кросповидон, calcium stearate, cellulose microcrystallic.

Excipients for a cover: methacrylic acid and ethyl acrylate copolymer (Kollikut MAY of P100), povidone (Kollidon 30), iron oxide brown, propylene glycol, talc, titanium dioxide, gidroksipropilmetiltsellyuloz (gipromelloz).

Drug has antiinflammatory, analgeziruyushchy and febrifugal effect. 

Pharmacological properties:

Pharmacodynamics. Non-steroidal anti-inflammatory drug, derivative phenylacetic acid; has antiinflammatory, analgeziruyushchy and febrifugal effect. 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. As all non-steroidal anti-inflammatory drugs, 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%. After oral administration of 25 mg of Cmax – 1,0 mkg/ml; 50 mg of Cmax – 1,5 mkg/ml, TCmax – 2-3 h.

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 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).

Metabolism – 50% of active agent is 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 CYP2C9 P 450 system takes part in metabolism of drug. 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.

Diclofenac gets into breast milk.

Indications to use:

Symptomatic treatment of diseases of a musculoskeletal system (a pseudorheumatism, a psoriasis, ankylosing 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).

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, in time or after food, washing down with a small amount of water. To adults and teenagers since 15 years – on 25-50 mg 2-3 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.

The maximum daily dose – 150 mg.

For children over 6 years and teenagers tablets on 25 mg are applied; a daily dose – 2 mg/kg of body weight of the child, divided into 2-3 receptions. At a juvenile pseudorheumatism the daily dose can be increased to 3 mg/kg of body weight. A pill should be taken entirely, without chewing, on an empty stomach, with a small amount of liquid.

Features of use:

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 volume of the circulating blood 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 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.

Influence on ability to driving of motor transport 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:

Often – 1-10%; sometimes – 0,1-1%; seldom – 0,01-0,1%; very seldom – less than 0,001%, including separate cases.

From digestive organs: 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, diafragmopodobny stiktura of intestines (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 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.

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.

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 development of a hyperpotassemia amplifies; against the background of anticoagulants, antiagregantny and thrombolytic medicines (an alteplaza, Streptokinasa, an urokinase) the risk of development of bleedings increases (more often from digestive tract).

Reduces effect 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 nefrotoksichny 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, inhibitors of the return serotonin reuptake 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.

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

Contraindications:

– Hypersensitivity to active agent or auxiliary components;

– 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);

– The period after performing aortocoronary shunting;

– III trimester of pregnancy, breastfeeding period;

– Noncompensated 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 (clearance of creatinine less than 30 ml/min.), the progressing diseases of kidneys, including the confirmed hyperpotassemia;

– Children's age up to 6 years for tablets on 25 mg, tablets on 50 mg are contraindicated to children up to 15 years.
 
With care: Anemia, bronchial asthma, cerebrovascular diseases, coronary heart disease, congestive heart failure, arterial hypertension, diseases of peripheral arteries, an edematous syndrome, a liver or renal failure, дислипидемия / a lipidemia, a diabetes mellitus, smoking, inflammatory diseases of intestines, a state after extensive surgical interventions, the induced porphyria, advanced age, a diverticulitis, general diseases of connecting fabric, pregnancy the I-II trimester, clearance of creatinine less than 60 ml/min.

Anamnestic data on development of an ulcer disease of digestive tract, existence of an infection of Helicobacter pylori, advanced age, long use of NPVP, frequent alcohol intake, heavy somatopathies.

Simultaneous therapy by anticoagulants (for example, warfarin), antiagregant (for example, acetylsalicylic acid, klopidogret), 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, children have myoclonic spasms, nausea, vomiting, an abdominal pain, bleedings, an abnormal liver function and kidneys.

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, hemodialysis are ineffective.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

The tablets covered with a kishechnorastvorimy cover on 25 mg and 50 mg. On 10 or 20 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2, 3, 10 (for a dosage of 25 mg) or on 2, 3, 5, 10 (for a dosage of 50 mg) blister strip packagings with the application instruction in a pack from a cardboard.