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

Composition:active substance: diclofenac sodium - 25.0 mg; Excipients: propylene glycol, 200.0 mg, mannitol (mannitol) 6.0 mg, benzyl alcohol 40 mg, sodium disulphite (sodium sulphurous pyro) 3.0 mg, sodium hydroxide solution 1 M-up to pH 8.4, water for injections up to 1 ml.

Description:Transparent slightly yellowish liquid with a faint odor.

Pharmacotherapeutic group:Non-steroidal anti-inflammatory drug.

ATX: & nbsp

S.01.B.C.03 Diclofenac

M.01.A.B.05 Diclofenac

Pharmacodynamics:NSAIDs, a phenylacetic acid derivative; has anti-inflammatory, analgesic and antipyretic effect. Indiscriminately inhibiting cyclooxygenase 1 and cyclooxygenase 2, disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandin in the inflammatory focus. The most effective for inflammatory pain. Like all NSAIDs, the drug has antiplatelet activity.

Pharmacokinetics:Absorption is fast and complete, food slows down the absorption rate. After intramuscular injection, the maximum plasma concentration in the plasma (FROM_m_Oh ) - 2.5 μg / ml (8 μmol / L), time to reach the maximum concentration in the plasma of the TC_m_Oh -20 minutes.

The concentration in the plasma is linear depending on the amount of the administered dose. Changes, pharmacokinetics of diclofenac against a background of repeated administration are not noted: Do not cumulate when observing the recommended interval between meals. Bioavailability - 50%. The connection with plasma proteins is more than 99% (most of it is associated with albumins). Penetrates into breast milk, synovial fluid; FROM_m_Oh in the synovial fluid is observed 2-4 hours later than in the plasma. The period of drug clearance (T_1/2) from the synovial fluid - 3-6 hours (the concentration of the drug in the synovial fluid 4-6 hours after its administration is higher than in the plasma, and remain higher for another 12 hours). 50% of the drug is metabolized during the "first pass" through the liver. Metabolism occurs as a result of multiple or one-time hydroxylation and conjugation with glucuronic acid. In the metabolism of the drug is also involved isoenzyme CYP2C9. Pharmacological activity of metabolites is less than diclofenac.

Systemic clearance is 260 ml / min. T_1/2of plasma - 1-2 hours 60% of the administered dose is excreted as metabolites through the kidneys; less than 1% is excreted unchanged, the rest of the dose is excreted as metabolites with bile. In patients with severe renal failure (creatinine clearance less than -10 ml / min), excretion of metabolites with zhelwhose, in this case, an increase in their concentration in the blood is not observed.

In patients with chronic hepatitis or compensated cirrhosis of the liver, the pharmacokinetic parameters do not change.

Indications:Inflammatory and degenerative diseases of the musculoskeletal system: rheumatoid, psoriatic, juvenile chronic arthritis, ankylosing spondylitis (Bechterew's disease), osteoarthritis, gouty arthritis, arthritis with Reiter's disease. The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, the progression of the disease is not affected. Pain syndrome: headache (including migraine) and toothache, bursitis, tendonitis, lumbago, sciatica, ossalgia, neuralgia, myalgia; arthralgia,radiculitis, with oncological diseases, post-traumatic and postoperative pain syndrome, accompanied by inflammation.

Algodismenorea; inflammatory processes in the small pelvis, including adnexitis.

Infectious and inflammatory diseases of the ENT organs with severe pain syndrome (as part of complex therapy): pharyngitis, tonsillitis, otitis media.

Contraindications:Hypersensitivity (including other NSAIDs), a complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to creatinine clearance or other NSAIDs (including history), erosive and ulcerative lesions of the gastrointestinal tract and 12-finger intestines, active gastrointestinal bleeding, inflammatory bowel disease, severe renal / hepatic and cardiac failure; severe lactose insufficiency; period after aortocoronary shunting; severe renal failure (creatinine clearance less than 30 ml / min), progressive kidney disease, active liver disease, confirmed hyperkalemia, pregnancy (III trimester), lactation period,childhood; period of aortocoronal bypass surgery; violation of hematopoiesis; disturbances of homeostasis; bronhoobstruktsiya, rhinitis, urticaria, provoked by the reception of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including in the anamnesis).

Carefully:Stomach ulcer and duodenal ulcer (in the anamnesis), ulcerative colitis, Crohn's disease, liver disease in history, hepatic porphyria, chronic renal failure, chronic heart failure, arterial hypertension, a significant decrease in the volume of circulating blood (including after a massive surgical interventions), elderly patients (including those receiving diuretics, weakened patients and low body weight), bronchial asthma (for parenteral administration - risk of exacerbation), simultaneous administration glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), ischemic heart disease,cerebrovascular diseases, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, creatinine clearance less than -60 ml / min, presence of Helicobacter pylori infection, prolonged use of NSAIDs, alcoholism, severe physical illness; during pregnancy I - II trimester.

Pregnancy and lactation:I-II semester in case of emergency (according to strict doctor's testimony). In the first 6 months should be used in the smallest dosage. It is forbidden to apply the drug in the third semester of pregnancy. Do not use the drug while breastfeeding (enters breast milk).

Dosing and Administration:

Solution for intramuscular injection 25 mg / ml. An individual dose is established taking into account the severity of the disease. Adults are usually prescribed for 1 ampoule (75 ml 1-2 times a day). The maximum daily dose is 150 mg (2 ampoules). The injection solution is injected deep into the gluteus muscle. Duration of use no more than two days, if necessary, then switch to oral and rectal administration of diclofenac.

Side effects:

Often - 1-10%, sometimes - 0.1-1%, rarely - 0.01-1.1%, very rarely - less than 0.001%, including individual cases.

From the digestive system: often - epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence; anorexia, increased activity aminotransferase; rarely - gastritis, proctitis, bleeding from the gastrointestinal tract (vomiting with blood, melena, diarrhea with a trace of blood), ulcers of the gastrointestinal tract (with or without bleeding or perforation); hepatitis, jaundice, dysfunction of the liver; 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; rarely -. disorders of sensitivity, including paresthesia, memory disorders, tremors, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares; irritability, mental disorders.

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

From the side of the urinary system: very rarely - acuterenal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

From the hematopoiesis: very rarely - thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis.

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

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

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

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

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

Overdose:

Symptoms: vomiting, bleeding from the gastrointestinal tract, diarrhea; dizziness, noise in the ears, convulsions, with a significant overdose - acute renal failure, hepatotoxic effect.

Treatment: symptomatic therapy aimed at eliminating the increase in blood pressure, impaired renal function, seizures, irritation from the gastrointestinal tract, 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.

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 drugs (alteplase, streptokinase, urokinase) increases the risk of bleeding (more often in the gastrointestinal tract).

Reduces the effect of hypotensive and hypnotic drugs. Increases the likelihood of side effects of other NSAIDs and glycocorticosteroids (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. Simultaneous use with paracetamol increases the risk of developing nephrotoxic effects of diclofenac.

Reduces the effect of hypoglycemic drugs. Cefamandol, cefoperazone, cefotetan, valproic acid and plikamycin increase the frequency of developed 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 administration with ethanol, colchicine, corticotropin and 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.

Special instructions:Because of the important role of prostaglandin in maintaining renal blood flow, caution should be exercised in appointing patients with cardiac or renal insufficiency, as well as in the therapy of elderly patients taking diuretics and patients who for any reason have a decrease in circulating blood volume (in including after extensive surgical intervention). If in such cases appoint diclofenac, recommend as a precautionary measure to monitor kidney function. In patients with renal failure with creatinine clearance less than 10 ml / min Css metabolites in plasma should theoretically be significantly higher than in patients with normal renal function, however this is not really observed, since in this situation the excretion of metabolites with bile is enhanced.

In patients with hepatic insufficiency (chronic hepatitis, compensated cirrhosis), the kinetics and metabolism do not differ from similar processes in patients with normal liver function.When performing long-term therapy, it is necessary to control the function of the liver, the picture of peripheral blood, the analysis of feces for latent blood. In connection with the negative effect on fertility, women who want to become pregnant, the drug is not recommended. In patients with infertility (including undergoing examination) it is recommended to cancel the drug. During the treatment period, it is possible to reduce the speed of mental and motor reactions, so it is necessary to refrain from driving motor vehicles and practicing other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

To reduce the risk of developing adverse events from the gastrointestinal tract, a minimum effective dose should be used with the minimum possible short course.

Form release / dosage:

Solution for intramuscular injection 25 mg / ml.

Packaging:

3 ml of the drug in ampoules with a capacity of 5 ml of neutral glass.

5 ampoules are placed in a contoured cell pack without coating from a polyvinyl chloride film.

1 or 2 contour squares are placed in a pack of cardboard.

5,10 ampoules are placed in a pack of cardboard for consumer containers with partitions or lattices, or a separator of cardboard.

10 ampoules are placed in a box of cardboard.

Each instruction pack or box is supplied with instructions for use, an ampoule knife or ampoule scarifier.

When using ampoules with incisions, white breaking rings or white breaking points, the ampoule opener or ampoule ampoule opener is not inserted.

Storage conditions:In a place protected from light and inaccessible to children at a temperature of no higher than 25 ° C.

Shelf life:2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-001402

Date of registration:25.08.2011

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Information update date: & nbsp13.02.2016

Illustrated instructions

Instructions

Diclofenac (Diclofenac)