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

Pharmacodynamics:Diclofenac has anti-inflammatory, analgesic, antiplatelet and antipyretic effect. Indiscriminately inhibiting cyclooxygenase 1 and 2, disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins in the inflammatory focus.In rheumatic diseases, the anti-inflammatory and analgesic effect of diclofenac significantly reduces 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:

Absorption - fast and complete, the food slows the absorption rate for 1 to 4 hours and reduces the maximum concentration by 40%. After oral intake of 50 mg of the drug, the maximum concentration (C max) - 1.4 μg / ml is achieved after 2-3 hours, after taking 25 mg - 1.0 μg / ml. The concentration in the plasma is linear depending on the amount of the administered dose.

Changes in the pharmacokinetics of diclofenac against the background of repeated administration are not noted, do not accumulate.

Bioavailability - 50%. The connection with plasma proteins is more than 99% (most of it is associated with albumins). Penetrates into the synovial fluid; the maximum concentration in the synovial fluid is observed 2 to 4 hours later than in the plasma. The half-life of the synovial fluid is 3-6 hours (the concentration of active substance in the synovial fluid is 4-6 hours after the administration of the drug is higher than in the plasma, and remains higher for another 12 hours).The relationship between the concentration of the drug in the synovial fluid and the clinical efficacy of the drug has not been elucidated. Metabolism: 50% of the active substance 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. The enzyme system P450 CYP2C9 takes part in the metabolism of the drug. The pharmacological activity of metabolites is lower than that of diclofenac. The system clearance is 350 ml / min, the volume of distribution is 550 ml / kg. Half-life from the plasma - 2 hours 65% of the administered dose is excreted as metabolites by 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), the excretion of metabolites with bile is increased, while there is no increase in their concentration in the blood.

In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetic parameters of diclofenac do not change. Diclofenac penetrates into breast milk.

Indications:

Symptomatic treatment of diseases of the musculoskeletal system (rheumatoid arthritis, psoriatic, ankylosing spondylitis, gouty arthritis, rheumatic soft tissue damage, osteoarthritis of peripheral joints and spine, including radicular syndrome, tendovaginitis, bursitis).

Pain syndrome of mild or moderate severity: neuralgia, myalgia, lumboschialgia, posttraumatic pain syndrome, accompanied by inflammation, postoperative pain, headache, migraine, algodismenorea, adnexitis, proctitis, toothache.

In the complex therapy of infectious and inflammatory diseases of the ear, throat, nose with severe pain syndrome (pharyngitis, tonsillitis, otitis). Feverish syndrome.

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 other non-steroidal anti-inflammatory drugs (NSAIDs));

- erosive and ulcerative changes in the gastric mucosa or duodenum, active gastrointestinal bleeding;

- inflammatory bowel disease (ulcerative colitis, Crohn's disease); ....

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses, urticaria or acute rhinitis, triggered by the use of acetylsalicylic acid (ASA) or other NSAIDs (including in the anamnesis);

- uncompensated heart failure;

- period after aortocoronary shunting;

- cerebrovascular bleeding or other bleeding and hemostasis disorders;

- severe renal failure (creatinine clearance less than 30 ml / min), progressive kidney disease, incl. confirmed hyperkalemia;

- severe hepatic impairment or active liver disease;

- hereditary intolerance to galactose, impaired absorption of glucose-galactose, severe lactose deficiency;

- III trimester of pregnancy, lactation period;

- children's age (up to 6 years for tablets of 25 mg, up to 15 years for tablets of 50 mg).

Carefully:

Anemia, bronchial asthma, cerebrovascular diseases, congestive heart failure, ischemic heart disease, arterial hypertension, peripheral arterial disease, edematous syndrome,hepatic or renal insufficiency, dyslipidemia or hyperlipidemia, diabetes mellitus, smoking, inflammatory bowel disease, condition after extensive surgical interventions, induced porphyria, advanced age, diverticulitis, systemic connective tissue diseases, pregnancy I - II trimester, creatinine clearance less than 60 ml / min .

Anamnestic data on the development of gastrointestinal ulcer, presence of Helicobacter pylori infection, old age, prolonged use of NSAIDs, frequent alcohol consumption, severe somatic diseases.

Simultaneous therapy with anticoagulants (for example, warfarin), antiplatelet agents (eg, ASA, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, fluoxetine, paroxetine, sertraline).

Dosing and Administration:Inside, without chewing, during or after a meal, with a small amount of water. Adults and adolescents with 15 years of age - 50 mg 2-3 times a day. When the optimal therapeutic effect is achieved, the dose is gradually reduced and switched to maintenance treatment at a dose of 50 mg / day. The maximum daily dose is 150 mg.For children over 6 years of age, the daily dose to 2 mg / kg of body weight, divided into 2-3 admission. With juvenile rheumatoid arthritis, the daily dose can be increased to 3 mg / kg body weight.

The approximate mode of application is shown in the table:

Age (body weight, kg)	Single dose (number of tablets, mg)	The daily dose (number of tablets, mg)
6-7 years (20-24)	1 (25)	1 (25)
8-11 years old (25-37)	1 (25)	2-3 (50-75)
12-14 years old (38-50)	1-2 (25-50)	3-4 (75-100)
Older than 15 and adults	1-2 (25-50)	2-6 (50-150)

Side effects:

Often - 1 -10%; sometimes - 0,1 - 1%; rarely - 0,01 - 0,1%; very rarely - less than 0.01%, including individual cases.

From the digestive system:

often - epigastric pain, flatulence, diarrhea, nausea, vomiting, flatulence, dyspepsia, anorexia, increased activity of aminotransferases; rarely - gastritis, proctitis, gastrointestinal ulcers (with or without bleeding or perforation), bleeding from the digestive tract (vomiting with blood, melena, diarrhea with a trace of blood), hepatitis, jaundice, impaired liver function;

very rarely - stomatitis, glossitis, dry mouth, esophagitis, diaphragm-like intestinal strictures (nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease), constipation, pancreatitis, fulminant hepatitis.

From the nervous system: often - headache, dizziness; rarely - sleep disturbance, drowsiness;

very rarely - a violation of sensitivity, incl. paresthesia, memory disorders, tremor, convulsions, anxiety, cerebrovascular. violations, depression! irritability, aseptic meningitis (usually in patients with systemic lupus erythematosus and other systemic connective tissue diseases), general weakness, disorientation, nightmares, insomnia, a sense of fear, mental disorders.

Co side of the senses: often - vertigo;

very rarely - visual impairment (blurred vision, diplopia, scotoma), violation taste, hearing impairment, tinnitus, small-to-large hemorrhages.

Co skin:

often - skin rash;

rarely - hives;

very rarely - hair loss, bullous eruptions, eczema, incl. multiform and Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, itching, photosensitivity, purpura, incl. allergic.

Co side of the urinary system: often - peripheral edema;

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

Co side of the organs of hematopoiesis and the immune system:

Very rarely - anemia (including hemolytic and aplastic anemia), leukopenia, thrombocytopenia, agranulocytosis.

Co the respiratory system:

rarely - bronchial asthma (including dyspnea);

very rarely - pneumonitis.

Co cardiovascular system:

very rarely - palpitations, increased blood pressure; congestive heart failure, zkstrasistoliya, chest pain, myocardial infarction, vasculitis.

Allergic reactions:

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

Overdose:

Symptoms: vomiting, dizziness, headache, dyspnea, confusion, in children - myoclonic cramps, nausea, abdominal pain, bleeding, impaired liver and kidney function.

Treatment: gastric lavage, Activated carbon, symptomatic therapy aimed at eliminating the increase in blood pressure, impaired renal function, seizures, irritation of 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, methotrexate, lithium and cyclosporine.

Reduces the effect of diuretics, against the background of potassium-sparing diuretics increases the risk of hyperkalemia; against 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 NSAIDs and glucocorticosteroids (bleeding in the gastrointestinal tract), toxicity of methotrexate and nephrotoxicity of cyclosporine.

ASA 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 St. John's Wort preparations increases the risk of developing bleeding in the digestive 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.

Antibacterial drugs from the quinolone group increase the risk of seizures.

Special instructions:

In order to quickly achieve the desired therapeutic effect take 30 minutes before meals. In other cases, take before, during or after eating, without chewing, squeezed with enough water.

Because of the important role of prostaglandins in maintaining renal blood flow, special care should be taken in patients with cardiac or renal insufficiency, as well as in the treatment of elderly patients taking diuretics and patients who for any reason have a decrease in circulating blood volume (for example, after extensive surgical intervention). If in such cases appoint diclofenac, recommend as a precautionary measure to monitor kidney function.

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 monitor liver function, 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 those 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, alcohol consumption. To reduce the risk of developing adverse events from the gastrointestinal tract, a minimum effective dose of the drug should be used with the minimum possible short course.

Form release / dosage:

Intestine-soluble film coated tablets, 25 mg and 50 mg.

Packaging:

10 tablets per blister AL / PVC

For 2, 3, 5 blisters in a cardboard box together with instructions for use.

Storage conditions:

List B. Store in a dry, the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014940 / 01

Date of registration:24.11.2008

The owner of the registration certificate:M. J. Biofarm Pvt. Ltd.M. J. Biofarm Pvt. Ltd. India

Manufacturer: & nbsp

M.J. BIOPHARM, Pvt. Ltd. India

Representation: & nbspM.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group M.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group India

Information update date: & nbsp26.02.2016

Illustrated instructions

Instructions

Diclofenac (Diclofenac)