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

Composition:1 ml of the solution contains: active ingredient - diclofenac sodium 25 mg; auxiliary substances - propylene glycol 200.0 mg; mannitol 6.0 mg; benzyl alcohol 40.0 mg; sodium disulfite 3.0 mg; sodium hydroxide 1 M solution to pH 8.0-9.0; water for injection up to 1 ml.

Description:transparent or slightly opalescent, slightly colored solution with a characteristic odor.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug (NSAID).

ATX: & nbsp

S.01.B.C.03 Diclofenac

M.01.A.B.05 Diclofenac

Pharmacodynamics:Diclofenac has anti-inflammatory; analgesic, antipyretic action. By indiscriminately inhibiting cyclooxygenase 1 and 2, it breaks the metabolism of arachidonic acid, reduces the amount of prostaglandins in the inflammatory focus. In rheumatic diseases, the anti-inflammatory and analgesic effect of Diclofefaca contributes to 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. Diclofenac eliminates pain in primary dysmenorrhea.

Pharmacokinetics:

Suction. After intramuscular administration of 75 mg of diclofenac, its absorption begins immediately. The maximum concentration in plasma, the mean value of which is about 2.5 μg / ml (8 μmol / L), is reached after about 20 minutes. Immediately after its achievement, a rapid decrease in the concentration of diclofenac in plasma is observed.

The amount of absorbable active substance is linearly dependent on the dose of diclofenac.

The area under the "concentration-time" curve (AUC) after intramuscular

diclofenac administration 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. After repeated application of diclofenac, the pharmacokinetic parameters do not change. Subject to the recommended intervals between diclofenac administration, no cumulation is noted. Distribution. The binding with the serum proteins of Iphovi is 99.7%, it occurs, mainly with albumin (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. - The apparent half-life of the synovial fluid is. 3-6 hours. Two hours after reaching the maximum concentration in plasma, the concentration of diclofenac in the synovial fluid is higher than in the plasma, and its values remain higher for a period of up to 12 hours.

Metabolism. The metabolism of diclofenac is partly due to the glucuronization of the unmodified molecule, but mainly through single and multiple 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 are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.

Excretion. Total - systemic plasma clearance of diclofenac is (263 ± 56) ml / min. The final half-life is 1-2 hours. The half-life of 4 metabolites, including two pharmacologically active metabolites, is also short-lived and is 1-3 hours. One of the metabolites, 3'-hydroxy-4'-methoxy-diclofenac, has a longer half-life, but this metabolite is completely inactive.

Pharmacokinetics in selected groups of patients

In usual single doses of accumulation of diclofenac was not noted. In patients with impaired renal function, when diclofenac is assigned to creatinine clearance less than 10 ml / min, the calculated equilibrium concentrations of diclofenac hydroxy metabolites are approximately 4 "times higher than in healthy patients, but ultimately, metabolites are excreted In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetics of diclofenac are similar to those in patients without liver disease.

Indications:For intramuscular administration (as an initial stage of treatment or in acute cases): inflammatory and degenerative rheumatic diseases - rheumatoid arthritis, ankylosing spondylitis, osteoarthritis,spondyloarthritis; Pain syndromes from the side of the spine; rheumatic diseases of extraarticular soft tissues; an acute attack of gout; post-traumatic and postoperative pain syndromes, accompanied by inflammation and edema; attacks of migraine of a heavy current.

Contraindications:Hypersensitivity to the active substance, incl. other NSAIDs or ancillary components; complete or incomplete combination of bronchial asthma, recurrent nasal polyposis or paranasal sinuses and intolerance to acetylsalicylic acid and other NSAIDs (including anamnesis); erosive and ulcerative lesions of the gastrointestinal tract or duodenum, active gastrointestinal bleeding, cerebrovascular or other bleeding; inflammatory bowel disease in the stage of exacerbation (Crohn's disease, ulcerative colitis) in the phase of exacerbation; hemophilia and other bleeding disorders; Decompensated heart failure; severe hepatic impairment or, active liver disease; expressed renal failure (creatinine clearance less than 30 ml / min), progressive kidney disease,confirmed hyperkalemia; period after aortocoronary shunting; pregnancy, the period of breastfeeding; children's age till 18 years.

Carefully:Anemia, bronchial asthma, coronary heart disease, congestive heart failure, dyslipidemia / hyperlipidemia, diabetes mellitus, cerebrovascular disease, hypertension, peripheral arterial disease, smoking, hepatic or renal insufficiency (creatinine clearance less than 30-60 ml / min); frequent alcohol use, alcoholism, inflammatory bowel disease without exacerbation (Crohn's disease, ulcerative colitis), anamnestic data on the development of ulcerative lesions of the gastrointestinal tract, the presence of Helicobacter pilori infection, a significant decrease in the volume of circulating blood (including after extensive surgery ), induced porphyria, elderly age, diverticulitis, systemic connective tissue diseases, severe somatic diseases, concomitant therapy with the following drugs: anticoagulants ( For example, warfarin), antiplatelet agents (e.g., acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (for example, citalopram, fluoxetine, paroxetine, sertraline), prolonged use of NSAIDs.

Dosing and Administration:

The drug is used in adult patients. A minimum effective dose should be used with the minimum possible short course. Do not inject Diclofenac more than 2-3 consecutive days. If necessary, treatment can be continued with Diclofenac in tablets or rectal suppositories.

The drug is injected intramuscularly by deep injection into the gluteal region. When carrying out intramuscular injection in order to avoid damage to nerves or other tissues at the injection site, it is recommended that the following rules be adhered to. The drug should be injected deeply intramuscularly into the upper outer quadrant of the gluteal region. The dose is usually 75 mg (the contents of 1 ampoule) 1 time per day. In severe cases, as an exception, 2 injections of 75 mg can be given, with an interval of several hours (the second injection should be performed in the opposite gluteal region).Alternatively, one injection of the drug per day (75 mg) can be combined with the administration of other dosage forms of Diclofenac (tablets, rectal suppositories), with a maximum daily dose of 150 mg.

Side effects:

Often - (1-10)%; sometimes - (0,1-1)%; rarely - (0,01-0,1)%; very rarely - (less than 0.001%, including individual cases.

From the digestive system: often - epigastric pain, nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, flatulence, anorexia, increased activity of aminotransferases; rarely - gastritis, proctitis, bleeding from the gastrointestinal tract (vomiting with blood, melena, 'diarrhea with blood impurity), gastrointestinal ulcers, accompanied or not accompanied by 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.

From the nervous system: often - headache, dizziness; rarely - drowsiness; very rarely - disorders of sensitivity (including paresthesia), memory disorders, tremor,convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, night "nightmares", irritability, mental disorders.

From the sense organs: often - vertigo; very rarely - visual impairment (blurred vision, diplopia), hearing impairment, tinnitus, taste disorders.

From the urinary 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.

Allergic reactions: rarely - anaphylactic / anaphylactoid reactions, including a marked decrease in blood pressure and shock; very rarely - angioedema (including facial).

From the side of the cardiovascular system: very rarely - palpitations, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

From the respiratory system: rarely bronchial asthma (including dyspnea); very rarely - pneumonitis.

From the skin: often - skin rash; rarely - hives; very rarely - bullous eruptions, erythema, including multiform and Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, incl. allergic.

Other: often - irritation at the injection site; rarely - swelling; very rarely - an abscess at the injection site.

If any of the side effects indicated in the manual are aggravated, or if you notice other side effects not listed in the instructions, tell your doctor.

Overdose:

Vomiting, bleeding from the gastrointestinal tract, epigastric pain, diarrhea, dizziness, tinnitus, lethargy, convulsions, rarely - increased blood pressure, acute renal failure, hepatoxic effect, respiratory depression, coma.

Measures to help with overdose

Symptomatic therapy aimed at eliminating the increase in blood pressure, impaired renal function, seizures, respiratory depression. Forced diuresis, hemodialysis are ineffective (due to the significant connection with proteins and intensive metabolism).

Interaction:

Increases the concentration in the plasma digoxin, lithium preparations, methotrexate. Reduces the effect of diuretics, against the background of potassium-sparing diuretics increases the risk of hyperkalemia; on the background of anticoagulants, antiplatelet agents and thrombolytic agents (alteplase, streptokinase, urokinase) increases the risk of bleeding (more often the gastrointestinal tract). Reduces the effect of hypotensive and hypnotic drugs. 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 due to an increase in their concentration in the plasma. Acetylsalicylic acid reduces the concentration of diclofenac in the blood. Reduces the effect of hypoglycemic drugs! Paracetamol increases the risk of developing nephrotoxic effects of diclofenac. Cefamandol, cefoperazone, cefotetan, valproic acid and plikamycin increase the incidence of hypoprothrombinemia. Cyclosporin and gold preparations increase the effect of diclofenac on the synthesis of prostaglandin in the kidneys, which is manifested by increased nephrotoxicity.Selective serotonin reuptake inhibitors increase the risk of bleeding from the gastrointestinal tract. Simultaneous assignment with. ethanol, colchicine, corticotropin, preparations of St. John's wort, increases the risk of bleeding in the gastrointestinal tract. Medicines that cause photosensitivity, increase the sensitizing effect of diclofenac to UV irradiation. Drugs that block tubular secretion increase the concentration in the plasma of diclofenac, thereby increasing its effectiveness and toxicity. Antibacterial drugs from the quinolone group - the risk of seizures.

Do not mix Diclofenac solution with solutions of other drugs for injection.

When taking other medications, you should consult your doctor.

Special instructions:

If there are signs of liver damage (skin itching, yellowing of the skin, nausea, vomiting, abdominal pain, darkening of urine, increased level of "liver" transaminases), stop taking the drug and consult a doctor. Do not use the drug simultaneously with other NSAIDs.

The drug can change the properties of platelets, but does not replace the preventive effect of acetylsalicylic acid in cardiovascular diseases. The use of the drug may adversely affect female fertility and is not recommended for women planning pregnancy. In patients with infertility (including those undergoing examination) it is recommended to cancel the drug.

Because of the important role of prostaglandins in maintaining renal blood flow, care should be taken when assigning to patients with cardiac or renal insufficiency, as well as for the treatment of elderly patients taking diuretics, and patients who for any reason have a decrease in BCC (incl. h after extensive surgery).

When using diclofenac in all of the above cases, it is recommended as a precaution to monitor kidney function.

Effect on the ability to drive transp. cf. and fur:During the treatment period, it is possible to reduce the speed of mental and motor reactions, so it is necessary to refrain from driving transport and other activities.potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intramuscular injection in ampoules of 3 ml (75 mg).

Packaging:

5 ampoules per contour cell packaging from a film of polyvinylchloride (PVC). One or two contoured cell packs of PVC together with instructions for use and a scarifier ampoule or a knife ampullum in a pack of cardboard.

5 or 10 ampoules with the preparation together with instructions for use and a scarifier ampoule or a knife ampullum in a pack of cardboard with corrugated insertion.

When packing ampoules with a dot or a ring of fracture, a scarifier or an ampoule knife is not inserted.

Storage conditions:In the dark place 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 printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001709

Date of registration:18.05.2012

Date of cancellation:2017-05-18

The owner of the registration certificate:ELLARA, LTD. ELLARA, LTD. Russia

Manufacturer: & nbsp

MC ELLARA, LLC Russia

Information update date: & nbsp05.02.2016

Illustrated instructions

Instructions

Diclofenac (Diclofenac)