Диклонат® P

General characteristics. Structure:

Active agent - diclofenac of sodium of 75 mg and excipients: benzyl alcohol, attracts, sodium hydroxide, sodium metabisulphite, propylene glycol, water for injections.

Description: Transparent, from colourless till slightly yellowish color solution, with a slight smell of benzyl alcohol.

Pharmacological properties:

Pharmacodynamics. Is derivative phenylacetic acid; has antiinflammatory, analgetic and febrifugal effect.

Not selectively oppressing cyclooxygenase 1 and cyclooxygenase 2, diclofenac breaks metabolism of arachidonic acid, suppresses biosynthesis of prostaglandins which are mediators of an inflammation, pain and rise in temperature.

Diclofenac leads to decrease in expressiveness of a pain syndrome (at rest and the movement), to reduction of puffiness in joints and morning constraint at rheumatic diseases. As well as all NPVP drug has antiagregantny activity.

Pharmacokinetics. After introduction of 75 mg in oil of diclofenac of sodium the maximum concentration in plasma - 2.5 mkg/ml (8 µmol/l) are noted in 20 min. and is in linear dependence on size of the entered dose.

Later in/in drop introductions of 75 mg within over 2 hours the maximum concentration of diclofenac in plasma makes 1.9 mkg/ml (5.9 µmol/l) and is in inverse relation from drug infusion time.

Communication with proteins of a blood plasma high (to 99%) and the most part contacts albumine. Plasma elimination half-life of blood makes 1-2 hours.

Cumulation at observance of the recommended dosing interval is not observed. It is well distributed on fabrics and liquids of an organism. Gets into synovial fluid and reaches the maximum concentration in 3-6 hours after introduction.

Drug is metabolized in a liver: 50% of active agent are exposed to metabolism during "the first passing" through a liver; the area under a curve "concentration time" (AUC) is twice less after oral administration of drug, than after parenteral administration of the same dose. Metabolism results from a repeated or single hydroxylation and a konjyugirovaniye. The fermental P450 CYP2C9 system takes part in metabolism. Pharmacological activity of metabolites is lower, than diclofenac.

Drug is removed generally through kidneys. The system clearance makes 260 ml/min. The elimination half-life makes 1-2 hours. 60% of the entered dose are removed through kidneys in the form of metabolites and less than 1% - in not changed look. Other part of drug is removed in the form of metabolites with bile.

It is noted that the pharmacokinetics of drug does not change depending on age of the patient.

Against the background of repeated administration of diclofenac there is no change of pharmacokinetics.

At patients with the expressed renal failures (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 same, as well as at patients without liver diseases.

Indications to use:

Intramuscular injections at:

• Inflammatory diseases of a musculoskeletal system (a pseudorheumatism, the psoriasis, juvenile chronic arthritis ankylosing a spondylarthritis; acute gouty arthritis).
• Inflammatory processes in a small basin, an adnexitis, primary альгодисменорея, renal or bilious to colic, a proctitis.
• Degenerative diseases of a musculoskeletal system (the deforming osteoarthrosis, osteochondrosis).
• Pain syndrome (lumbago, sciatica, neuralgia, mialgiya, tendovaginitis, bursitis, rheumatic defeat of soft tissues, tooth and headache, migraine and pains of moderate expressiveness of other genesis).
• The posttraumatic pain syndrome which is followed by an inflammation.
• Postoperative pain.
• 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).
• Feverish syndrome.

Intravenous drop infusions
Prevention and treatment of postoperative pains.

Route of administration and doses:

The drug is administered intramusculary or intravenously kapelno in the form of infusion. No more than 2 days are entered. In case of need treatment extensions to patients appoint drug in the form of tablets or suppository.
Intramuscular injections:
to patients at acute pains appoint 75 mg daily intramusculary. In case of need (bilious or renal colic) the daily dose can be increased to 150 mg (on 1 ampoule 2 times a day)

Intravenous infusions: The drug is administered kapelno in the form of infusions. Just before introduction contents of 1 ampoule (75 mg) should be parted in 100-500 ml 0.9% of NaCl solution or 5% of solution of a dextrose (previously having added to infusion solutions bicarbonate sodium solution - 0.5 ml of 8.4%). The prepared solutions for infusion have to be transparent.

At treatment of a post-operational pain syndrome of average and strong degree of manifestation the drug is administered in a dose 75 mg within 30 - 120 min. If necessary, the drug can be administered repeatedly in several hours. However the dose of drug should not exceed 150 mg in 24 hours.

For the purpose of prevention of postoperative pains carry out infusion by a "shock" dose of drug of 25-50 mg within 15-60 min. Further infusion continue with a speed of 5 mg/h before achievement of the maximum daily dose 150 mg.

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 requiring special attention and bystry mental and motor reactions, alcohol intake.

Side effects:

From the alimentary system

• often (> 1 case on 100 appointments): The NPVP-gastropathy (a gastralgia and discomfort in epigastric area, nausea, vomiting, feeling of overflow of a stomach, an eructation, heartburn, diarrhea, abdominal pain, a meteorism), GIT erosive cankers (including damage of a gullet, stomach, a round ulcer, multiple damages of a GIT); perforation of a wall of intestines (the intensive cutting pain, burning in epigastric area, a bloody chair, a melena, a hematemesis), GIT bleeding (a hematemesis, a melena), nonspecific colitis with bleeding, dryness in a mouth, locks, pancreatitis, toxic hepatitis.

• not often (<1 case on 100 appointments, but not> 1 case on 1000 appointments) - vomiting, colitis or its aggravation, a loss of appetite or anorexia, dryness, morbidity of a mucous membrane of an oral cavity, spasms, aphthous stomatitis (erosion, ulcers, a white plaque on a mucous membrane of an oral cavity)

From a nervous system

• often (> 1 case on 100 appointments): headache, dizziness

• not often (<1 case on 100 appointments, but not> 1 case on 1000 appointments): spasms, aseptic meningitis, decrease in memory, a depression, psychotic reactions, peripheral polyneuropathy (a giposteziya, a tremor, pain or weakness in muscles of hands and legs), drowsiness, irritability and nervousness, sensation of fear, sleeplessness, increased fatigue.

From sense bodys:

• often (> 1 case on 100 appointments): a toxic amblyopia, decrease in visual acuity, a diplopia, scotoma, decrease in hearing, etc. hearing disorder, a ring in ears.

From integuments:

• often (> 1 case on 100 appointments): skin itch, skin rash (preferential erythematic and urtikarny), dermahemia;

• not often (<1 case on 100 appointments, but not> 1 case on 1000 appointments): mnogoformny exudative erythema, including Stephens-Johnson's syndrome, toxic epidermal necrolysis (Lyell's disease), photodermatitis (heavy sunblisters, skin rash, pigmentation disturbance);

• seldom (<0,001% of cases): in the place in oil introductions are possible: burning; infiltrate, aseptic necrosis, necrosis of fatty tissue. In some cases in the place of an injection the necrosis can develop.

From urinogenital system:

• often (> 1 case on 100 appointments): liquid delay;

• not often (<1 case on 100 appointments, but not> 1 case on 1000 appointments): the repeating vaginal pains of not clear genesis, a dysmenorrhea, a hamaturia, cystitis, a pollakiuria, a proteinuria, intersticial nephrite, a nephrotic syndrome, an oliguria or an anury, depression of function of kidneys or its aggravation peripheral hypostases.

From bodies of a hemopoiesis

• not often (<1 case on 100 appointments, but not> 1 case on 1000 appointments): an agranulocytosis, hemolitic anemia, aplastic anemia, the anemia connected with internal bleedings, ecchymomas, a leukopenia, neutropenia thrombocytopenia with a purpura or without it.

From respiratory system

• not often (<1 case on 100 appointments, but not> 1 case on 1000 appointments): asthma.

From cardiovascular system

• often (> 1 case on 100 appointments): increase in the ABP;

• not often (<1 case on 100 appointments, but not> 1 case on 1000 appointments): arrhythmias, cardialgia, collapse;

• seldom (<0,001% of cases): pain behind a breast, aggravation of congestive heart failure.

Endocrine disturbances

• seldom (<0,001% of cases): decrease in body weight.

Allergic reactions

• seldom (<0,001% of cases): an anaphylaxis and anaphylactoid reactions (a focal hyperemia, a small tortoiseshell, a skin itch, an asthma, a Quincke's edema in the field of a century or paraorbital fabrics, lips, language, the glottis pressing pains behind a breast, rattles, an acute anaphylaxis (usually develops promptly), bronkhospastichesky allergic reactions.

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 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 hypoglycemic effect of hypoglycemic means.

Tsefamandol, цефаперазон, 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 is shown by increase in nephrotoxicity.

Co-administration with ethanol, colchicine, corticotropin and drugs of a St. John's Wort increases risk of development of bleedings in digestive tract.

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

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

Contraindications:

• Hypersensitivity to NPVP (including acetylsalicylic acid), "aspirinovy" asthma,
• GIT erosive cankers (in an aggravation phase), bleedings from a GIT,
• oppression of a marrowy hemopoiesis,
• various disturbances of a hemostasis (including hemophilia),
• at the states associated with high risk of bleedings (including in the anamnesis),
• children's age up to 15 years,
• pregnancy,
• lactation period

With care: anemia, bronchial asthma, congestive heart failure, arterial hypertension, an edematous syndrome, a liver or renal failure, alcoholism, a diverticulitis, erosive and ulcer diseases of digestive tract out of an aggravation, a diabetes mellitus, the postoperative period, the induced acute hepatic porphyria, advanced age.

Overdose:

Symptoms: symptomatology from a GIT, hypotension, nephrotoxicity (up to an acute renal failure), disturbances from TsNS (from slackness and drowsiness to spasms and a coma).

Treatment: symptomatic and supporting, directed to elimination of symptomatology. The artificial diuresis, a hemodialysis are ineffective.

Storage conditions:

Period of validity of 5 years. Not to use upon termination of a period of validity. Storage conditions List B. At a temperature of 15-25 °C, in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

5 ampoules on 3 ml place in the transparent pallet and together with the application instruction put in a cardboard pack.