Diclofenac

General characteristics. Structure:

Active agent: diclofenac of sodium of 75 mg.
Excipients: propylene glycol - 600,0 mg, Mannitolum - 18,0 mg, sodium disulphite - 9 mg, benzyl alcohol - 120 mg, sodium hydroxide solution 1M - to pH 8,0-9,0, water for injections - to 3 ml.

Description: colourless or with a yellowish shade transparent liquid.

Pharmacological properties:

Pharmacodynamics. Diclofenac - non-steroidal anti-inflammatory drug (NPVP). Possesses expressed analgeziruyushchy, febrifugal and antiinflammatory actions. Non-selective inhibitor of cyclooxygenases 1 and 2 of type. Breaks metabolism of arachidonic acid and synthesis of prostaglandins which are the main link in development of an inflammation.
 At rheumatic diseases drug promotes considerable reduction of pain, morning constraint, a swelling of joints that promotes improvement of a functional condition of a joint. At injuries, in the postoperative period diclofenac reduces pain and inflammatory hypostasis.

Pharmacokinetics. The maximum concentration is reached after single intramuscular introduction of 75 mg – in 15-30 min. and averages 2,7 mkg/ml. Later 3 h after introduction plasma concentration makes about 10% from maksimalnoy.99 the % of diclofenac contacts plasma proteins, namely albumine).

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 at diclofenac.

The system clearance of active agent makes about 260 ml/min. An elimination half-life – 1-2 h. About 60% are removed by kidneys in the form of metabolites; less than 1% in not changed look are excreted with urine, other part 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:

For short-term treatment of pains of various genesis of moderate intensity:
inflammatory and degenerative diseases of a musculoskeletal system: a pseudorheumatism, the psoriasis, juvenile chronic arthritis ankylosing a spondylitis (Bekhterev's disease), gouty arthritis, rheumatic defeat of soft tissues, an osteoarthrosis of peripheral joints and a backbone (including with a radicular syndrome);
lumbago, sciatica, neuralgia;
альгодисменорея, inflammatory processes of bodies of a small pelvis, century of h adnexitis;
the posttraumatic pain syndrome which is followed by an inflammation;
postoperative pain.

Route of administration and doses:

Solution is entered deeply intramusculary. A single dose for adults - 75 mg (1 ampoule). If necessary perhaps repeated introduction, but not earlier than in 12 hours.

Use duration no more than 2 days, if necessary further is passed to peroral, or rectal use of diclofenac.

Features of use:

With extra care appoint drug to patients with a heart or renal failure, and also to the elderly people accepting diuretics and to patients at whom for any reason decrease in volume of the circulating blood nablizdatsya. In these cases it is recommended to control function of kidneys as a precautionary measure.

At patients with a liver failure (chronic hepatitis, the compensated cirrhosis) the kinetics and metabolism of diclofenac do not differ from those 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, a research a calla on availability of blood.

Due to the negative influence on fertility, the women planning to become pregnant are not recommended to apply diclofenac. At patients with infertility (including undergoing inspection) it is recommended to cancel drug.

During treatment by diclofenac 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:

Digestive Tract (DT):
more often than 1% - abdominal pains, feeling of abdominal distention, diarrhea, digestion disturbance, 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 in a mouth, hepatitis (perhaps fulminantny current), a liver necrosis, cirrhosis, a gepatorenalny syndrome, anorexia, pancreatitis, holetsistopankreatit, colitis, gastritis, a proctitis, an abnormal liver function, a glossitis, nonspecific hemorrhagic colitis, an exacerbation of ulcer colitis or a disease Krone.
 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, feelings of fear, sensitivity disturbance, including, paresthesias, dysmnesias, a tremor, alarm, cerebrovascular disturbances, mental disturbances.
 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, toxic epidermapny некропиз (Lyell's disease), the increased photosensitivity, mapkotochechny hemorrhages.
 Urinogenital system:
more often than 1% - a liquid delay;
more rare than 1% - a nephrotic syndrome, a proteinuria, an oliguria, a hamaturia, interstitsiapny nephrite, a papillary necrosis, an acute renal failure, an azotemia.
 Bodies of a hemopoiesis:
more rare than 1% - anemia (including hemolitic and aplastmchesky anemias), a leukopenia, thrombocytopenia, an eosinophilia, an agranulocytosis, a Werlhof's disease.
 Respiratory system:
more rare than 1% - cough, a bronchospasm, throat hypostasis, pneumonia.
Cardiovascular system:
more rare than 1% - increase in arterial pressure; congestive heart failure, premature ventricular contraction, thorax pain, heartbeat, myocardial infarction.
 Allergic reactions:
more rare than 1% - anaphylactoid reactions, an acute anaphylaxis (usually develops promptly), hypostasis of lips and language, an allergic vasculitis.
 
Local reactions:
burning, infiltrate, aseptic necrosis, necrosis of fatty tissue.
Other:
more rare than 1% - deterioration in a course of infectious processes (development of a necrotizing fasciitis, pneumonia).

Interaction with other medicines:

Increases concentration in plasma of digoxin, a methotrexate, ions of lithium and cyclosporine.

Reduces effect of diuretics, against the background of kaliysberegayushchy diuretics the risk of development of a giperkapiyemiya 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 glucocorticosteroids (bleeding from digestive tract), toxicity of a methotrexate and nephrotoxicity of cyclosporine. Reduces effect of hypoglycemic medicines.

Acetylsalicylic acid reduces concentration of diclofenac in blood. Simultaneous use with paracetamol increases risk of development of nefrotoksichny effects of diclofenac. 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, selective serotonin reuptake inhibitors and drugs of the St. John's Wort which is made a hole: increases risk of development of bleedings in digestive tract. Diclofenac strengthens effect of the drugs causing a photosensitization.

The drugs blocking kanaptsevy secretion increase concentration in diclofenac plasma, thereby increasing its toxicity. Antibacterial medicines from group of a hinolon - risk of development of spasms.

Contraindications:

hypersensitivity (including to other non-steroidal anti-inflammatory drugs or auxiliary components);
digestive tract erosive cankers (in an aggravation phase);
bleedings from digestive tract, inflammatory diseases of intestines in an aggravation phase (nonspecific ulcer colitis, a disease Krone);
heavy liver failure or diseases of a liver during the acute period;
heavy renal failure (clearance of creatinine less than 30 ml/min.);
the progressing diseases of kidneys;
hyperpotassemia;
the bronkhoobstruktion, rhinitis, urticaria provoked by reception of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including in the anamnesis);
disturbance of a hemopoiesis, disturbance of a hemostasis (including hemophilia);
pregnancy (III trimester);
lactation period;
children's age (up to 18 years);
the period after performing aortocoronary shunting.

With care

Anemia, bronchial asthma, cerebrovascular diseases, coronary heart disease, congestive heart failure, arterial hypertension, diseases of peripheral arteries, edematous syndrome, liver or renal failure (clearance of creatinine of 30 - 60 ml/min.), dislipidemiya/giperpipidemiya, diabetes mellitus, smoking, inflammatory diseases of intestines, state after extensive surgical interventions, the induced porphyria, advanced age, a diverticulitis, general diseases of connecting fabric, erosive and ulcer diseases of digestive tract out of an aggravation.

Anamnestic 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 (for example, acetylsalicylic acid, клопидогреп), perorapny glucocorticoids (for example, Prednisolonum), selective serotonin reuptake inhibitors (for example, to tsitalopra, fluoxetine, пароксетин, сертрапин).

Use at pregnancy and during breastfeeding

Drug cannot be used in the III trimester of pregnancy and during breastfeeding.

Overdose:

Symptoms: nausea, vomiting, severe pains in a stomach, bleeding from digestive tract, diarrhea, dizziness, a headache, a sonitus, spasms, short wind, consciousness opacification. At considerable overdose - an acute renal failure, a hepatotoxic action.

Treatment: the specific antidote does not exist. Treatment - symptomatic, directed to elimination of renal failures, irritations of a GIT, respiratory depression, spasms. Constant observation of a condition of the patient within several days as there is a danger of later manifestation of some gastrointestinal defeats - an ulceration or bleedings is necessary. The artificial diuresis and a hemodialysis are ineffective (owing to considerable linkng with proteins of a blood plasma and intensive metabolism).

Storage conditions:

Period of validity: 5 years. Not to use after the period of validity specified on packaging. In the 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:

Solution for intramuscular introduction of 25 mg/ml. On 3 ml in ampoules of colourless glass. On 5 ampoules in a blister strip packaging. On 1 or 2 blister strip packagings together with the application instruction in a pack from a cardboard.