Diclofenac - instructions for use, dose, side effects, contraindications

Pharmacodynamics:Diclofenac has anti-inflammatory, analgesic and antipyretic effects. Indiscriminately inhibiting cyclooxygenase 1 and 2, disrupts the metabolism of arachidonic acid, reduces the number of prostaglandins in the inflammatory focus. In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac promotes a significant reduction in the severity of pain, morning stiffness, swelling of the joints,which improves the functional state of the joint. With injuries. in the postoperative period diclofenac reduces pain and inflammatory swelling.

Pharmacokinetics:

Suction

After intramuscular injection of diclofenac, its absorption begins immediately. The maximum concentration in plasma (C_m_Oh), the mean value of which is about 2.5 μg / ml (8 μmol / L), is reached after about 20 minutes. The amount of absorbing active substance is in linear dependence on the amount of the drug. The area under the "concentration-time" curve (AUC) after intramuscular administration of diclofenac is approximately 2 times greater than after its oral or rectal administration, since in the latter cases about half the amount of diclofenac is metabolized by "first passage" through the liver. With subsequent administration of the drug, pharmacokinetic parameters do not change. Provided that the recommended intervals between injections of the drug cumulation is not noted.

Distribution

The connection with serum proteins is 99.7%, mainly with albumins (99.4%).The apparent volume of distribution is 0.12-0.17 l / kg.

Diclofenac penetrates into the synovial fluid, where its maximum concentration is reached 2-4 hours later than in the blood plasma. Apparent half-life (T_1/2) of the synovial fluid is 3-6 hours. Two hours after reaching the maximum concentration in the blood plasma, the concentration of diclofenac in the synovial fluid is higher than in the plasma, and its values remain higher for a period of time, up to 12 hours. Metabolism

The metabolism of diclofenac is partly due to the glucuronization of the immutable molecule, but, mainly, through single and multiple hydroxylation and methoxylation. which leads to the formation of several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5'-hydroxy-, 4 ', 5-dihydroxy- and 3'-hydroxy-4'-methoxydiclofenac), most of which turn into glucuronide conjugates. Two phenolic metabolites are biologically active, but to a much lesser extent. than diclofenac. In the metabolism of the drug takes part isoenzyme CYP2C9.

Excretion

The total systemic plasma clearance of diclofenac is 263 ± 56 ml / min. Finite TA is 1-2 hours. T_1/2 4 metabolites, including two pharmacologically active, also short-lived and is 1-3 hours. One of the metabolites, 3'-hydroxy-4'-methoxydiclofenac, has a longer T_1/2, but this metabolite is completely inactive.

About 60% of the drug dose is excreted through the kidneys in the form of glucuronic conjugates of a constant active substance, as well as in the form of metabolites, most of which are also glucuronic conjugates. In an unchanged form, less than 1% of diclofenac is excreted. The rest of the dose is excreted as metabolites with bile. Pharmacokinetics in selected patient groups

The pharmacokinetic parameters of diclofenac in elderly patients do not change.

In patients with impaired renal function, cumulation of an unchanged active substance is not observed when the recommended dosage regimen is observed. When creatinine clearance is less than 10 ml / min, the calculated equilibrium concentrations of diclofenac hydroxy metabolites are approximately 4 times higher than in healthy volunteers, with the metabolites being excreted exclusively with bile.

In patients with chronic hepatitis or compensated cirrhosis, pharmacokineticsDiclofenac are similar to those in patients without liver disease.

Diclofenac penetrates into breast milk.

Indications:

For short-term treatment of pain of different genesis, moderate intensity:

- diseases of the musculoskeletal system (rheumatoid arthritis, psoriatic, juvenile chronic arthritis, ankylosing spondylitis, gouty arthritis, rheumatic soft tissue damage, osteoarthrosis of the peripheral joints and spine (including radicular syndrome);

- lumbago, sciatica, neuralgia;

- algodismenorea, inflammatory processes of the pelvic organs, incl. adnexitis;

- post-traumatic pain syndrome, accompanied by inflammation;

- Postoperative pain.

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected.

Contraindications:Hypersensitivity (including to other NSAIDs or ancillary components), erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase), bleeding from the gastrointestinal tract, inflammatory bowel disease, severe hepatic insufficiency,liver disease in the acute period, marked renal failure (creatinine clearance less than 30 ml / min), hyperkalemia, complete or incomplete acetylsalicylic acid intolerance syndrome (rhinosinusitis, urticaria, polyps of the nasal mucosa, bronchial asthma arising from the intake of acetylsalicylic acid or other NSAIDs). disorders of hematopoiesis, hemostasis disorders (including hemophilia), pregnancy, children's age (under 18 years), lactation period, period after coronary artery bypass grafting, at an increased risk of arterial thrombosis and thromboembolism, chronic heart failure, coronary heart disease, diseases of peripheral arteries and cerebrovascular diseases.

Carefully:

Arterial hypertension, edematous syndrome, peripheral arterial diseases, dyslipidemia, diabetes mellitus, anemia, bronchial asthma, hemostatic system defects, risk of cardiovascular thrombosis (including myocardial infarction and strokes), renal failure (creatinine clearance 30-60 ml / min), alcoholism, erosive and ulcerative diseases of the gastrointestinal tract without exacerbation, Helicobacter pylori infection,diverticulitis, condition after extensive surgical interventions, induced porphyria, advanced age, smoking, severe physical illnesses, systemic connective tissue diseases, prolonged use of non-steroidal anti-inflammatory drugs.

Care should be taken when using in patients with seasonal allergic rhinitis, edema of the nasal mucosa (including with nasal polyps), chronic infectious diseases of the respiratory tract (especially associated with allergic rhinitis-like symptoms).

Special care should be taken when using diclofenac in patients receiving drugs that increase the risk of gastrointestinal bleeding: systemic glucocorticosteroids (incl. prednisolone), anticoagulants (incl. warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel) or selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline).

Pregnancy and lactation:The drug is contraindicated during pregnancy (see section "Contraindications"). Information on the use of the drug Diclofenac during pregnancy is absent. Diclofenac should not be taken during breastfeeding (see the section "Contraindications"). Diclofenac penetrates into breast milk.

Dosing and Administration:It is administered intramuscularly. Single dose for adults - 75 mg (1 ampoule). If necessary, repeated administration is possible, but not earlier than 12 hours later. Duration of use no more than 2 days, if necessary, further pass to oral, or rectal administration of diclofenac.

Side effects:

To assess the incidence of adverse reactions of diclofenac (various dosage forms), the following grades are used:

"very often"> 1/10: "often" from> 1/100 to <1/10, "infrequently" from> 1/1000 to <1/100, "rarely" from> 1/10000 to <1/1000 . "very rarely" from <1/10000. including individual messages.

From the digestive tract:

Often - epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia, increased activity of aminotransferases: rarely - gastritis, proctitis, bleeding from the gastrointestinal tract (vomiting with blood, melena, diarrhea with blood impurities), ulcers Gastrointestinal tract (with or without bleeding or perforation), hepatitis, jaundice, impaired liver function; very rarely - stomatitis, glossitis, esophagitis, nonspecific hemorrhagic colitis,exacerbation of ulcerative colitis or Crohn's disease, constipation, pancreatitis, fulminant hepatitis, hepatorenal syndrome. From the nervous system:

Often - headache, dizziness; rarely - drowsiness; very rarely - a violation of sensitivity (including paresthesia), memory disorders, tremors, convulsions, anxiety. cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, "nightmarish" dreams, irritability, mental disorders.

From the sense organs:

Often - vertigo; very rarely - visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, a violation of taste.

From the skin:

Often - skin rash; rarely - hives; very rarely - bullous eruptions, erythema, including multiform and Stevens-Jones syndrome, Lyell's syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, including allergic.

From the genitourinary system:

Very rarely - acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoiesis:

Very rarely - thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis, eosinophilia.

From the respiratory system:

Rarely - bronchial asthma (including dyspnea), cough, laryngeal edema; very rarely - pneumonitis.

From the cardiovascular system:

Very rarely - palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

Allergic manifestations:

Rarely, anaphylactic / anaphylactoid reactions, including marked lowering of blood pressure and shock; very rarely - angioedema (including face). Other:

Often - irritation at the injection site; very rarely - an abscess at the injection site; rarely - swelling.

Overdose:

Symptoms:

Vomiting, dizziness, headache, shortness of breath, confusion, in children - myoclonic cramps, nausea, vomiting, abdominal pain, bleeding, liver and kidney dysfunction, respiratory depression, coma.

Treatment:

Symptomatic therapy, forced diuresis.

Hemodialysis is ineffective.

Interaction:

Increases the concentration in the plasma digoxin, methotrexate, lithium and cyclosporine.

Reduces the effect of diuretics, against the background of potassium-sparing diuretics increases the risk of hyperkalemia; on the background of anticoagulants, thrombolytic agents (alteplase, streptokinase, urokinase) - the risk of bleeding (more often from the gastrointestinal tract). Reduces the effects of hypotensive and hypnotics.

Increases the likelihood of side effects of other non-steroidal anti-inflammatory drugs and glucocorticosteroid agents (bleeding in the gastrointestinal tract), toxicity of methotrexate and nephrotoxicity of cyclosporine. Acetylsalicylic acid reduces the concentration of diclofenac in the blood. Simultaneous use with paracetamol increases the risk of developing nephrotoxic effects of diclofenac. Reduces the effect of hypoglycemic agents.

Cefamandol, cefoperazone, cefotetan. valproic acid and plikamycin increase the incidence of hypoprothrombinemia.

Cyclosporine and gold preparations increase the effect of diclofenac on the synthesis of prostaglandins in the kidneys, which increases nephrotoxicity.

Simultaneous administration with ethanol, colchicine, corticotropin, selective serotonin reuptake inhibitors, and preparations of St. John's wort increases the risk of bleeding in the gastrointestinal tract.

Diclofenac enhances the effect of drugs that cause photosensitivity. Drugs that block tubular secretion, increase the concentration in the plasma of diclofenac, thereby increasing its toxicity.

Diclofenac has antiprostaglandin action, therefore, diclofenac is not recommended for 8-12 days after the use of mifepristone.

Special instructions:To reduce the risk of developing adverse events, a minimally effective dose of diclofenac should be used with the minimum possible short course. Long-term diclofenac therapy and high-dose therapy may lead to an increased risk of developing serious cardiovascular thrombotic complications (including myocardial infarction and stroke).

Effect on the ability to drive transp. cf. and fur:Patients suffering from vertigo and other disorders from the central nervous system during the treatment period should refrain from driving and working with dangerous mechanisms.

Form release / dosage:

Solution for intramuscular injection 25 mg / ml.

Packaging:

3 ml per ampoule of low density polyethylene or polypropylene. For 5 or 10 ampoules together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date!

Terms of leave from pharmacies:On prescription

Registration number:LP-003237

Date of registration:08.10.2015

Date of cancellation:2020-10-08

The owner of the registration certificate:GROTEKS, LLC GROTEKS, LLC Russia

Manufacturer: & nbsp

GROTEKS, LLC Russia

Information update date: & nbsp05.02.2016

Illustrated instructions

Instructions

Diclofenac (Diclofenac)