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

Pharmacodynamics:Non-steroidal anti-inflammatory drug, a derivative of phenylacetic acid; has anti-inflammatory, analgesic and antipyretic effect. Indiscriminately inhibiting cycloxygenase 1 and cycloxygenase 2, disrupts the metabolism of arachidic acid,reduces the amount of prostaglandins in the focus of inflammation. The most effective for inflammatory pain. Like all non-steroidal anti-inflammatory drugs, the drug has antiplatelet activity.

Pharmacokinetics:

Absorption is fast and complete, food slows down the absorption rate. After oral administration of 50 mg the maximum concentration of the drug in the plasma is 1.5 μg / ml, the time to reach the maximum concentration of the drug in the plasma is 2-3 hours.

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 cumulate while 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; Stax in the synovial fluid is observed 2-4 hours later than in the plasma. The half-life of the drug from the synovial fluid is 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; the area under the concentration-time curve is 2 times lower after oral administration of the drug than after parenteral administration of the same dose. Metabolism occurs as a result of multiple or one-time hydroxylation and conjugation with glucuronic acid. The isozyme CYP2C9 also participates in the metabolism of the drug. Pharmacological activity of metabolites is less than diclofenac. Systemic clearance is 260 ml / min. Half-life from the plasma - 1-2 hours 60% of the administered dose is excreted as metabolites through the kidneys; less than 1% is 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 liver cirrhosis, the pharmaco-kinetic parameters do not change.

Indications:

Inflammatory and degenerative diseases of the musculoskeletal system, including: rheumatoid,psoriatic, juvenile chronic arthritis, ankiloziruyushy spondylitis (Bechterew's disease), osteoarthritis, gouty arthritis, Reiter's disease arthritis, bursitis, tenosynovitis. 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: headache (including migraine headache) and dental pain, lumbago, sciatica, ossalgiya, neuralgia, myalgia, arthralgia, lumbago, in oncology, posttraumatic and postoperative pain, accompanied by inflammation. Algodismenorea; inflammatory processes in the small pelvis, incl. adnexitis. Infectious and inflammatory diseases of ENT organs with severe pain syndrome (as part of complex therapy); pharyngitis, tonsillitis, otitis media.

Contraindications:

- hypersensitivity to the active substance or ancillary components (including other non-steroidal anti-inflammatory drugs);

- complete or partial combination of asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (including history);

- erosive and ulcerative lesions of the gastrointestinal tract in the acute stage, active gastrointestinal bleeding;

- inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the acute stage;

- severe hepatic impairment;

- period after aortocoronary shunting;

- severe renal failure (creatinine clearance less than 30 ml / min);

- Decompensated heart failure;

- cerebrovascular bleeding or other bleeding and hemostasis disorders;

- active liver disease;

- progressive kidney disease,

- confirmed hyperkalemia;

- III trimester of pregnancy;

- 25 mg tablets are contraindicated in children under 6 years of age.

- since the drug contains lactose, additional contraindications: hereditary lactose intolerance, impaired absorption of glucose-galactose, deficiency of lactase.

Carefully:

Anemia, bronchial asthma, cerebrovascular diseases, ischemic heart disease, congestive heart failure, arterial hypertension, peripheral arterial disease, edematous syndrome, hepatic insufficiency, dyslipidemia / hyperlipidemia,diabetes, smoking, erosive and ulcerative lesions of the gastrointestinal tract without exacerbation, inflammatory bowel disease without exacerbation, condition after extensive surgical interventions, induced porphyria, elderly patients (including those receiving diuretics, weakened patients and low body weight), diverticulitis , systemic connective tissue diseases, moderate chronic renal failure (CRF) (creatinine clearance 30-60 ml / min). Anamnestic data on the development of gastrointestinal ulcer, presence of Helicobacter pylori infection, advanced age, long-term use of non-steroidal anti-inflammatory drugs, frequent use of alcohol, smoking, severe physical illnesses.

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

Pregnancy and lactation:

If during the long-term use of diclofenac was indicated the onset of pregnancy, you should inform your doctor about it.

In the first and second trimester of pregnancy, diclofenac can be taken only after consultation with the attending physician. In the last 3 months of pregnancy, you can not take diclofenac in connection with the presence of a high risk of complications in the mother and child. Diclofenac and the products of its decomposition in minor amounts pass into the mother's milk. Since till now it is not known about inflicting harm to an infant during short-term use of diclofenac, as a rule, breast feeding for this period should not be abolished. If it is necessary to use the drug in high doses and for a long time, consideration should be given to the abolition of breastfeeding.

Dosing and Administration:Inside, not liquid, during or after a meal, adults - 25-50 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 and adolescents, 25 mg tablets are used; daily dose of -2 mg / kg of a child.

With juvenile rheumatoid arthritis, the daily dose can be increased to 3 mg / kg.

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, dyspepsia, flatulence, anorexia, increased activity of aminotransferases; 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, impaired liver function; very rarely - stomatitis, glossitis, oesophageal damage, diaphragm-like intestinal strictures (nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease), constipation, pancreatitis, fulminant hepatitis, exacerbation of hemorrhoids (for rectal suppositories).

From the nervous system, often - headache, dizziness; rarely - drowsiness; very rarely - a violation of sensitivity, incl. paresthesia, memory disorders, tremors, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis, disorientation, depression, insomnia, nightmares, irritability, mental disorders.

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

From the urinary system: very rarely - acute renal failure, hematuria, proteinuria, interstitial nephritis, nephritic syndrome, papillary necrosis.

On the part of the organs of 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 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, eczema, incl. multiform and Stevens-Johnson syndrome, Lyell's syndrome, exfoliative dermatitis, itching, hair loss, photosensitivity, purpura, incl. allergic.

Overdose:

Symptoms: dizziness, headache, hyperventilation of the lungs, confusion, diarrhea, tinnitus, in children - myoclonic cramps, nausea, vomiting, 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.

Interaction:

Increases the concentration of dengoxin, methotrexate, lithium and cyclosporine in the plasma.

Reduces the effect of diuretics, against the background of potassium-sparing diuretics, the risk of hyperkalemia increases; 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, serotonin reuptake inhibitors and 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.

Antibacterial drugs from the quinolone group - the risk of seizures. Effect on the results of laboratory tests: diclofenac may affect serum transaminase levels (if this effect is long-lasting or if complications occur, treatment should be discontinued), and may cause an increase in potassium concentration.

Special instructions:

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.

In order to quickly achieve the desired therapeutic effect take 30 minutes before meals. In other cases, take before, during or after a meal in undiluted form, with plenty of water.

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

If the increase in the activity of "liver" transaminases persists or increases during the administration of the drug, if clinical symptoms of hepatotoxicity (including nausea, fatigue, drowsiness, diarrhea, pruritus, jaundice) are noted, treatment should be discontinued.

Diclofenac (as well as other non-steroidal anti-inflammatory drugs) can cause hyperkalemia.

In patients with renal insufficiency, when creatinine clearance is less than 10 ml / min, metabolites in plasma should theoretically be significantly higher than in patients with normal renal function, but 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 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 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 hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets coated with enteric coating, 25 mg.

Packaging:

10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil or paper with polyethylene coating.

30 tablets in a can of orange glass of the BTS type, sealed with a lid of a stretchable with sealing element or in a can of polymer type BP.

Each bank or 1,2,3 contour mesh packs together with the instruction for use is placed in a pack of cardboard.

Storage conditions:In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002266

Date of registration:19.12.2011

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp09.02.2016

Illustrated instructions

Instructions

Diclofenac (Diclofenac)