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

Excipients: lactose monohydrate 46.6000 mg, corn starch 59.2000 mg, povidone-K30 10.0000 mg, sodium lauryl sulfate 10.0000 mg, sodium carboxymethyl starch 20.0000 mg, silicon colloidal dioxide 3.0000 mg , magnesium stearate - 1.2000 mg; shell: methacrylic acid and ethyl acrylate copolymer - 4.1379 mg, macrogol 6000 - 1.0345 mg, talc - 6.7241 mg, titanium dioxide E 171 CI 77891 - 1,0345 mg, dye solar sunset yellow [E110] - 2,0670 mg.

Description:Round biconvex tablets, covered with an enteric orange coating, on a break from white to almost white.

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

ATX: & nbsp

S.01.B.C.03 Diclofenac

M.01.A.B.05 Diclofenac

Pharmacodynamics:Non-steroidal anti-inflammatory drug (NSAID), a derivative of phenylacetic acid. Diclofenac has anti-inflammatory, analgesic, anti-inflammatory and antipyretic effects. By indiscriminately inhibiting cyclooxygenase 1 and 2 (COX1 and COX2), it disrupts the metabolism of arachidonic acid, reduces the amount of prostaglandins in the inflammatory focus. The most effective for inflammatory pain.

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 is fast and complete, the food slows the absorption rate by 1-4 hours and reduces the maximum concentration (C max) by 40%. After oral administration, 50 mg maximum concentration (Cmax) - 1.5 μg / ml is achieved after - 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 respecting the recommended interval between doses.Bioavailability - 50%. The connection with plasma proteins is more than 99% (most of it is associated with albumins). Penetrates into the synovial fluid; Stax in the synovial fluid is observed 2-4 hours later than in the plasma. The half-life (T1 / 2) of the synovial fluid is 3-6 hours (the concentration of active substance in the synovial fluid 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 isozyme CYP2C9 is involved in the metabolism of the drug. The pharmacological activity of metabolites is lower than that of diclofenac.

Systemic clearance is about 260 ± 50 ml / min, the volume of distribution is 550 ml / kg. T'1 / 2 from the plasma averages about 2.5 hours. 65% of the administered dose is excreted as metabolites by the kidneys; less than 1% is unchanged, the rest of the dose is excreted as metabolites with bile.

In patients with severe renal insufficiency (creatinine clearance less than 10 ml / min), the excretion of metabolites with bile is increased, while the increase in their concentration in the blood is not observed.

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 arthritis, juvenile chronic arthritis, ankylosing spondylitis (Bechterew's disease), gouty arthritis, rheumatic soft tissue damage, osteoarthritis of the peripheral joints and spine, including radicular syndrome, tendovaginitis, bursitis) .

The drug removes or reduces pain and inflammation during the treatment period, without affecting the progression of the disease.

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).

Contraindications:

- Hypersensitivity to the active substance (including other NSAIDs) or ancillary components;

- Complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including in the anamnesis);

- Erosive-ulcerous changes in the mucous membrane of the stomach or duodenum, active gastrointestinal hemorrhage:

- Inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the phase of exacerbation;

- Period after aortocoronary bypass surgery;

- III trimester of pregnancy, the period of breastfeeding;

- Confirmed chronic heart failure (II-IV functional class according to NYHA classification);

- Cardiac ischemia;

- Peripheral artery disease or cerebrovascular disorders;

- Violations of hematopoiesis, hemostasis disorders (including hemophilia);

- Severe hepatic impairment or active liver disease;

- Severe renal insufficiency (creatinine clearance less than 30 ml / min); progressive kidney disease;

- Confirmed hyperkalemia;

- Lactose intolerance, lactase deficiency, glucose-galactose malabsorption (the preparation contains lactose).

- Children up to 15 years.

Carefully:

Anemia, bronchial asthma, confirmed chronic heart failure of NYHA functional class I, arterial hypertension, edematous syndrome, hepatic or renal insufficiency (creatinine clearance 30-60 ml / min), dyslipidemia, hyperlipoproteinemia, diabetes mellitus, smoking, inflammatory bowel disease, condition after extensive surgical interventions, induced porphyria, diverticulitis, systemic connective tissue diseases, pregnancy I-II trimester.

Anamnestic data on the development of gastrointestinal ulcer, presence of Helicobacter pylori infection, old age, prolonged use of NSAIDs, frequent alcohol consumption, severe physical illnesses. Simultaneous therapy with anticoagulants (for example, warfarin), antiplatelet agents (for example, acetylsalicylic acid, clopidogrel), oral glucocorticosteroids (for example, prednisolone), selective serotonin reuptake inhibitors (eg, citalopram, fluoxetine, paroxetine, sertraline).

In patients with seasonal allergic rhinitis, edema of the nasal mucosa (including with nasal polyps), chronic obstructive pulmonary disease, chronic respiratory infections (especially associated with allergic rhinitis-like symptoms), allergy to other drugs, in patients with a significant decrease in the volume of circulating blood diclofenac with caution.

Pregnancy and lactation:There is insufficient data on the safety of diclofenac in pregnant women. Therefore, appoint diclofenac in the I and II trimesters of pregnancy should only be in cases where the expected benefit to the mother exceeds the potential risk to the fetus.

Diclofenac, like other inhibitors of prostaglandin synthesis, is contraindicated in the last 3 months of pregnancy (possibly suppressing the contractility of the uterus and premature closure of the arterial duct in the fetus). Diclofenac gets into small amounts in breast milk.To prevent undesirable effects on the child, the drug should not be prescribed to nursing women. If it is necessary to use the drug, breastfeeding should be discontinued.

Dosing and Administration:

In all patients receiving diclofenac, it should be used at the lowest effective dose for the shortest time required to reduce the severity of the symptoms.

Inside, without chewing, during or after a meal, with enough 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.

Side effects:

Criteria for assessing the incidence of adverse reactions: very often (> 1/10), often (>1/100, <1/10), infrequently (>1/1000, <1/100), rarely (>1/10 000, <1/1000), very rarely (<1/10 000); the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

Disorders from the side of the gastrointestinal tract: often - epigastric pain, nausea, vomiting, diarrhea, dyspepsia, flatulence, anorexia; rarely - gastritis, proctitis, bleeding from the gastrointestinal tract (GIT) (vomiting with blood, melena,diarrhea with an admixture of blood), gastrointestinal ulcers (with or without bleeding or perforation); very rarely - stomatitis, glossitis, esophagitis, nonspecific hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn's disease, the appearance of diaphragm-like strictures in the intestine, constipation, pancreatitis.

Disturbances from the liver and bile ducts: often - increased activity aminotransferase; rarely - hepatitis, jaundice, a violation of liver function; rarely - fulminant hepatitis, liver necrosis, hepatic insufficiency.

Impaired nervous system: often - headache, dizziness; rarely - drowsiness; very rarely - a violation of sensitivity, incl. paresthesia, disorders memory, tremor, convulsions, anxiety, cerebrovascular disorders, aseptic meningitis.

Disorders of the psyche: very rarely - disorientation, depression, insomnia, night "nightmares", irritability, mental disorders.

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

Disorders from the kidneys and urinary tract: very rarely - acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, papillary necrosis.

Violations from the blood and lymphatic system: very rarely thrombocytopenia, leukopenia, hemolytic and aplastic anemia, agranulocytosis, eosinophilia.

Immune system disorders: anaphylactic / anaphylactoid reactions, including a marked decrease in blood pressure (BP) and shock; very rarely - angioedema (including face).

Disorders from the cardiovascular system: very rarely - a feeling of palpitation, chest pain, increased blood pressure, vasculitis, heart failure, myocardial infarction.

Disturbances from the respiratory system, chest and mediastinal organs: rarely - exacerbation of bronchial asthma, cough, laryngeal edema; very rarely - pneumonitis.

Disturbances from the skin and subcutaneous tissues: 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.

General disorders and disorders at the site of administration: rarely - swelling.

Overdose:

Symptoms: vomiting, bleeding from the gastrointestinal tract, diarrhea, dizziness, tinnitus, seizures, increased blood pressure, respiratory depression, with a significant overdose - acute renal failure, hepatotoxic effect.

Treatment: gastric lavage, Activated carbon, symptomatic therapy aimed at eliminating the increase in blood pressure, impaired renal function, seizures, gastrointestinal tract damage, respiratory depression. Forced diuresis, hemodialysis are ineffective (due to the significant connection with proteins and intensive metabolism).

Interaction:

Lithium preparations, digoxin: diclofenac can increase the concentration of lithium and digoxin in the blood plasma. It is recommended to monitor the concentration of lithium and digoxin in the plasma with simultaneous application with diclofenac.

Methotrexate: caution should be exercised in appointing diclofenac less than 24 hours before or 24 hours after taking methotrexate, tk. in such cases, the concentration of methotrexate in the blood may increase and its toxic effect may be increased.

Cyclosporine: the effect of diclofenac on the synthesis of prostaglandins in the kidneys can enhance the nephrotoxicity of cyclosporine. Therefore, diclofenac doses used should be lower than in patients not using ciclosporin.

Diuretic and antihypertensive drugs: diclofenac can reduce the hypotensive effect of diuretic and antihypertensive drugs (eg, beta-blockers, angiotensin converting enzyme inhibitors - AG1F). Patients, especially the elderly, these combinations should be administered with caution and regularly monitor blood pressure. Patients should be adequately hydrated. After the onset and periodically during treatment, especially with the simultaneous administration of diuretics and ACE inhibitors, renal function should be monitored because of the increased risk of nephrotoxicity. Drugs that can cause hyperkalemia: simultaneous use of diclofenac with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may lead to an increase in potassium concentration in the blood serum (if this combination of drugs is used, this indicator should be regularly monitored).

Antibacterial agents - derivatives of quinolone: there are some reports of the development of seizures in patients receiving both quinolone derivatives and diclofenac.

Anticoagulants and antiplatelet agents: it is necessary to combine with care diclofenac with the drugs of these groups because of the risk of bleeding. Although clinical studies have not established the effect of diclofenac on the effects of anticoagulants, there are some reports of an increased risk of bleeding in patients taking this combination of drugs. Therefore, in the case of such a combination of drugs, regular and careful monitoring of patients is recommended.

Acetylsalicylic acid reduces the concentration of diclofenac in the blood.

NSAIDs and corticosteroids: simultaneous systemic use of diclofenac and other systemic NSAIDs or corticosteroids may increase the incidence of side effects (in particular, from the gastrointestinal tract).

Selective serotonin reuptake inhibitors (SSRIs): simultaneous use of diclofenac and drugs from the SSRI group increases the risk of developing gastrointestinal bleeding.

Hypoglycemic drugs: in clinical studies it was found that when combined diclofenac does not affect the effectiveness of hypoglycemic drugs. However, some reports of development in such cases as hypoglycemia and hyperglycemia are known, which required a change in the dose of hypoglycemic drugs during diclofenac therapy. Therefore, during the combined use of diclofenac and hypoglycemic drugs, it is recommended to monitor blood glucose concentrations.

Phenytoin: with the simultaneous use of phenytoin and diclofenac, it is necessary to monitor the concentration of phenytoin in the blood plasma because of the possible increase in its systemic effect.

Tacrolimus: it is possible to increase nephrotoxicity with simultaneous use with diclofenac.

Cefamaidole, cefoperazone, cefotetan, valproic acid and plikamycin increase the frequency of hypoprothrombinemia.

The influence of diclofenac on the synthesis of prostaglandins in the kidneys can increase the toxic effect preparations of gold. Simultaneous application with -ethanol, colchicine, corticotropin and preparations of St. John's wort perfumed increases the risk of bleeding in the gastrointestinal tract.

Powerful inhibitors of isoenzyme CYP2C9: caution should be exercised when co-prescribing diclofenac and potent inhibitors of isoenzyme CYP2C9 (such as voriconazole) because of a possible increase in diclofenac concentration in the blood serum and an increase in systemic action.

Special instructions:

In order to reduce the risk of adverse events, the drug should be used at the lowest effective dose for the shortest period necessary to alleviate the symptoms.

Therapy of NSAIDs, including diclofenac, especially long-term therapy and high-dose therapy, may be associated with a slight increase in the risk of developing serious cardiovascular thrombotic complications (including myocardial infarction and stroke).

In patients with significant risk factors for cardiovascular events (eg, hypertension, giperlipoprotenemia, diabetes mellitus and smoking), treatment with drugs containing diclofenac, should be started only after a thorough examination and analysis.

Because of the important role of prostaglandins in maintaining renal blood flow, care should be taken when administering the drug to patients with cardiac or renal insufficiency, hypertensive disease, elderly patients, patients taking diuretics or other drugs that affect renal function, and patients who, for some reason, there is a decrease in the volume of circulating blood (for example, after extensive surgical intervention). If in such cases appoint diclofenac, recommend as a precautionary measure to monitor kidney function. After discontinuation of therapy with the drug, normalization of renal function to normal values is usually noted.

With the use of diclofenac, there have been phenomena such as bleeding or ulceration / perforation of the gastrointestinal tract, in some cases fatal. These phenomena can occur at any time when the drug is used in patients with or without previous symptoms and with serious gastrointestinal illnesses in or without anamnesis.In elderly patients, such complications can have serious consequences. When developing in patients receiving diclofenac, bleeding or ulceration of the gastrointestinal tract, the drug should be discontinued. To reduce the risk of toxic effects on the gastrointestinal tract, the drug should be used at the lowest effective dose for the shortest possible time, especially for patients with peptic ulcer disease, especially complicated bleeding or perforating history, and elderly patients.

Patients with an increased risk of developing gastrointestinal complications, as well as receiving low-dose acetylsalicylic acid therapy or other drugs that can increase the risk of gastrointestinal tract damage, should take gastroprotectors.

Patients with a history of gastrointestinal disease, especially the elderly, should be informed of all symptoms from the digestive system.

When performing long-term therapy, it is necessary to monitor liver function, the picture of peripheral blood, the analysis of feces for latent blood.

With prolonged use of diclofenac, an increase in the activity of one or more "hepatic" enzymes may be noted. With the preservation and progression of violations of the liver function or the appearance of signs of liver disease or other symptoms (eg, eosinophilia, rash, etc.), the drug should be withdrawn. It should be borne in mind that hepatitis against the background of diclofenac can develop without prodromal phenomena.

Caution should be observed when using diclofenac in patients with hepatic porphyria, because the drug can provoke attacks of porphyria. Diclofenac can reversibly inhibit the aggregation of platelets, therefore, in patients with hemostasis disorders with prolonged use, careful monitoring of the relevant laboratory parameters is necessary. Patients with bronchial asthma, seasonal allergic rhinitis, edema of the nasal mucosa (including those with nasal polyps), chronic obstructive pulmonary disease, chronic respiratory infections (especially associated with allergic rhinitis-like symptoms), as well as in patients with allergy to other medications (rash,itching, urticaria) with the appointment of diclofenac should be very careful (readiness for resuscitation).

When diclofenac is very rare reports of severe, in some cases fatal, skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis. The greatest risk and frequency of severe dermatological reactions were observed in the first month of treatment with diclofenac. With the development in patients receiving the drug, the first signs of skin rash, mucosal lesions or other symptoms of hypersensitivity diclofenac should be canceled.

Anti-inflammatory effects of NSAIDs, including diclofenac, can complicate diagnosis of infectious processes.

In connection with the negative effect on fertility, women planning pregnancy, the drug is not recommended. In patients with infertility (including those undergoing examination) it is recommended to cancel the drug.

Effect on the ability to drive transp. cf. and fur:Patients who, with diclofenac, experience visual disturbances, dizziness,drowsiness or other disorders from the central nervous system, do not drive vehicles and work with mechanisms.

Form release / dosage:

Tablets, coated with enteric coating, 50 mg.

Packaging:

10 tablets in a contour mesh package (blister) made of polyvinylchloride film and aluminum foil printed lacquered.

2 contour squares (blisters) together with instructions for use in a pack of cardboard.

Storage conditions:In a dry, dark place at a temperature of 15 to 25 ° C. Keep out of the reach of children!

Shelf life:3 of the year. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011648 / 01

Date of registration:08.09.2009

The owner of the registration certificate:Nizhny Novgorod Chemical and Pharmaceutical Plant, OJSCNizhny Novgorod Chemical and Pharmaceutical Plant, OJSC

Manufacturer: & nbsp

HEMOFARM, A.D. Serbia

HEMOFARM, LLC Russia

Information update date: & nbsp23.02.2016

Illustrated instructions

Instructions

Diclofenac (Diclofenac)