Instructions for Diclofenac Sodium-KV hard capsules 25 mg blister No. 30
Composition
active ingredient:
1 capsule contains diclofenac sodium 25 mg;
excipient: lactose monohydrate;
capsule shell composition: gelatin, indigo carmine (E 132), titanium dioxide (E 171).
Dosage form
hard capsules.
Main physicochemical properties: hard gelatin capsules with a blue cap and a white body. The contents of the capsules are white crystalline powder.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related compounds. ATC code M01A B05.
Pharmacological properties
Pharmacodynamics
Diclofenac sodium-KV contains diclofenac sodium, a substance with a non-steroidal structure that has a pronounced analgesic and anti-inflammatory effect.
It is an inhibitor of prostaglandin synthetase (cyclooxygenase).
In vitro, diclofenac sodium at concentrations equivalent to those achieved in the treatment of patients does not inhibit the biosynthesis of cartilage proteoglycans.
Pharmacokinetics
Absorption.
Although absorption is complete, the onset of action may be delayed as a result of gastric transit, which may be affected by food, which delays gastric emptying. Mean peak plasma concentrations of 1.48±0.65 μg/ml (1.5 μg/ml = 5 μmol/l) are reached on average 2 hours after administration of the drug at a dose of 50 mg.
Bioavailability: About half of the administered diclofenac is metabolized during the first pass through the liver (first-pass effect); the area under the concentration curve (AUC) after oral administration is approximately half that obtained with an equivalent parenteral dose.
The pharmacokinetic characteristics of the drug do not change with repeated administration. Accumulation does not occur if the recommended dosage is observed.
Plasma concentrations in children receiving equivalent doses (mg/kg body weight) are similar to those observed in adults.
Distribution. The binding of diclofenac to serum proteins is 99.7%, and to albumin - 99.4%.
Diclofenac penetrates into the synovial fluid, where its maximum concentration is reached 2-4 hours later than in the blood plasma. The half-life from the synovial fluid is 3-6 hours. 2 hours after reaching maximum concentrations in the blood plasma, the concentration of diclofenac in the synovial fluid remains higher; this phenomenon is observed for 12 hours.
There is one report of the detection of diclofenac in low concentrations (100 ng/ml) in breast milk. The estimated amount of the drug reaching the infant through breast milk is equivalent to a dose of 0.03 mg/kg/day.
Metabolism: Diclofenac is metabolized partly by glucuronidation of the unchanged molecule, but mainly by single and multiple hydroxylation and methoxylation, leading to the formation of several phenolic metabolites, most of which form conjugates with glucuronic acid. Two of these phenolic metabolites are biologically active, but much less so than diclofenac.
Elimination. The total systemic clearance of diclofenac from plasma is 263±56 ml/min (mean ± SD). The terminal half-life from plasma is 1-2 hours. The half-life from plasma of four metabolites, including two pharmacologically active ones, is also short and is 1-3 hours. About 60% of the administered dose of the drug is excreted in the urine as a glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the administered dose of the drug is excreted as metabolites in the feces.
Pharmacokinetics in certain groups of patients.
Elderly patients: No effect of patient age on absorption, metabolism, or elimination was observed, except that in five elderly patients, a 15-minute intravenous infusion resulted in plasma concentrations that were 50% higher than expected in young healthy volunteers.
Patients with renal impairment. In patients with renal impairment receiving therapeutic doses, no accumulation of unchanged active substance is expected based on the kinetics of the drug after a single dose. In patients with creatinine clearance less than 10 ml/min, the estimated steady-state plasma concentrations of hydroxylated metabolites were approximately 4-fold higher than in healthy volunteers. However, all metabolites were ultimately excreted in the bile.
Patients with liver disease. In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetics and metabolism of diclofenac are similar to those in patients without liver disease.
Indication
Inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis);
· pain syndromes in the spine;
· rheumatic diseases of extra-articular soft tissues;
· post-traumatic and postoperative pain syndromes accompanied by inflammation and edema, for example after dental and orthopedic interventions;
· gynecological diseases accompanied by pain and inflammation, such as primary dysmenorrhea or adnexitis;
· as an adjuvant in severe inflammatory diseases of the ENT organs, which are accompanied by severe pain syndrome, for example, in pharyngotonsillitis, otitis. In accordance with general therapeutic principles, the underlying disease should be treated with basic therapy. Fever as a symptom is not an indication for the use of the drug.
Contraindication
Hypersensitivity to the active substance or to any other component of the drug;
· acute stomach or intestinal ulcer; gastrointestinal bleeding or perforation;
· history of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
Active peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (two or more separate episodes of diagnosed ulcer or bleeding);
· Third trimester of pregnancy;
Inflammatory bowel diseases (e.g. Crohn's disease or ulcerative colitis);
· liver failure;
· renal failure;
· congestive heart failure (NYHA II-IV);
· ischemic heart disease in patients with angina pectoris or previous myocardial infarction;
· cerebrovascular diseases in patients who have had a stroke or have episodes of transient ischemic attacks;
· peripheral artery disease;
· treatment of perioperative pain during coronary artery bypass grafting (or use of a cardiopulmonary bypass machine);
· Diclofenac sodium, like other nonsteroidal anti-inflammatory drugs (NSAIDs), is contraindicated in patients who develop attacks of bronchial asthma, angioedema, urticaria or acute rhinitis, nasal polyps and other allergic symptoms in response to the use of ibuprofen, acetylsalicylic acid or other NSAIDs.
Interaction with other medicinal products and other types of interactions
The interactions observed with the use of diclofenac in capsules and/or other dosage forms are listed below.
Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.
Digoxin: Diclofenac may increase the plasma concentration of digoxin when used concomitantly. Monitoring of serum digoxin levels is recommended.
Diuretics and antihypertensives. As with other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensives (e.g. beta-blockers, angiotensin-converting enzyme (ACE) inhibitors) may lead to a reduction in their antihypertensive effect by inhibiting the synthesis of vasodilator prostaglandins. Therefore, such a combination should be used with caution and patients, especially the elderly, should be closely monitored for blood pressure. Patients should be adequately hydrated and monitoring of renal function is recommended after initiation of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity.
Drugs known to cause hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increases in serum potassium, and patients should be monitored more frequently.
Anticoagulants and antithrombotic agents. Concomitant use may increase the risk of bleeding, therefore precautions are recommended. Although clinical studies do not indicate an effect of diclofenac on the activity of anticoagulants, there is some evidence of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly. Therefore, close monitoring of such patients is recommended to ensure that no changes in the dosage of anticoagulants are necessary. As with other non-steroidal anti-inflammatory drugs, diclofenac in high doses may temporarily inhibit platelet aggregation.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors and corticosteroids.
Concomitant use of diclofenac and other NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. The simultaneous use of two or more NSAIDs should be avoided.
Selective serotonin reuptake inhibitors (SSRIs): Concomitant use of NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. Caution should be exercised when NSAIDs, including diclofenac, are administered less than 24 hours before methotrexate, as this may increase the blood concentration of methotrexate and increase its toxicity. Serious toxicity has been reported when the interval between administration of methotrexate and NSAIDs, including diclofenac, was within 24 hours. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
Cyclosporine: The effect of diclofenac, like other NSAIDs, on renal prostaglandin synthesis may potentiate the nephrotoxicity of cyclosporine; therefore, diclofenac should be used at lower doses than in patients not taking cyclosporine.
Tacrolimus: There is a possible increased risk of nephrotoxicity when NSAIDs are used with tacrolimus, which may be mediated through the renal antiprostaglandin effects of the NSAID and the calcineurin inhibitor.
Quinolone antibacterials. Convulsions may occur in patients receiving concomitant quinolones and NSAIDs. This may occur in patients with or without a history of epilepsy and seizures. Therefore, caution should be exercised when considering the use of a quinolone in patients already receiving NSAIDs.
Phenytoin: When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentrations is recommended due to the expected increase in phenytoin exposure.
Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4-6 hours after colestipol/cholestyramine.
Cardiac glycosides: Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate (GFR), and increase plasma glycoside levels.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.
Potent CYP2C9 inhibitors: Caution is advised when co-administering diclofenac with potent CYP2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in maximum plasma concentrations and exposure to diclofenac due to inhibition of diclofenac metabolism.
Application features
General
The patient's need for diclofenac to relieve symptoms and response to therapy should be reviewed periodically.
To minimize undesirable effects, treatment should be initiated at the lowest effective dose for the shortest period of time necessary to control symptoms.
The concomitant use of Diclofenac Sodium with systemic NSAIDs such as cyclooxygenase-2 selective inhibitors should be avoided due to the lack of any evidence of a synergistic effect and due to potential additive side effects. Caution is required in elderly patients. Use with caution in patients over 65 years of age. In particular, it is recommended to use the lowest effective dose in frail elderly patients or patients with low body weight.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac.
Due to its pharmacodynamic properties, diclofenac sodium, like other NSAIDs, may mask the signs and symptoms of infection.
Diclofenac Sodium-KV contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Diclofenac Sodium-KV.
Effects on the digestive tract
Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and can occur at any time during treatment with or without warning symptoms or a previous history of serious gastrointestinal events, have been reported with all NSAIDs, including diclofenac. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
As with other NSAIDs, including diclofenac, medical supervision and special caution are required in patients presenting with symptoms suggestive of gastrointestinal (GI) disorders. The risk of GI bleeding, ulceration or perforation increases with increasing dose of NSAIDs, including diclofenac.
To reduce the risk of such gastrointestinal toxicity, treatment should be initiated and maintained at the lowest effective dose. For such patients, as well as for those requiring concomitant use of medicinal products containing low doses of acetylsalicylic acid (ASA/aspirin) or other medicinal products likely to increase the risk of gastrointestinal adverse effects, combination therapy including proton pump inhibitors or misoprostol should be considered. Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant medicinal products that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agents (e.g. ASA) or selective serotonin reuptake inhibitors.
Effect on the liver
Close medical supervision is required when prescribing Diclofenac Sodium-KV to patients with impaired liver function, as their condition may worsen. As with other NSAIDs, including diclofenac, the level of one or more liver enzymes may increase.
During long-term treatment with Diclofenac Sodium-KV, regular monitoring of liver function and liver enzyme levels should be prescribed as a precautionary measure.
If liver function abnormalities persist or worsen, if clinical signs or symptoms are consistent with progressive liver disease, or if other manifestations (e.g. eosinophilia, rash) occur, diclofenac sodium should be discontinued. Diseases such as hepatitis may occur without prodromal symptoms. Caution is required when diclofenac sodium is used in patients with hepatic porphyria (due to the possibility of triggering an attack).
Effects on the kidneys
Since cases of fluid retention and edema have been reported with NSAIDs, including diclofenac, special attention should be paid to patients with impaired cardiac or renal function, a history of hypertension, elderly patients, patients receiving concomitant therapy with diuretics or drugs that significantly affect renal function, and patients with a significant decrease in extracellular fluid volume for any reason, such as before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually leads to a return to the state that existed before treatment.
Effects on the skin
Serious skin reactions (some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported very rarely in association with the use of NSAIDs, including diclofenac sodium. Patients are at greatest risk of developing these reactions at the beginning of therapy: the onset of the reaction is noted in most cases within the first month of treatment. Diclofenac sodium should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Systemic lupus erythematosus (SLE) and mixed connective tissue diseases
Patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.
Cardiovascular and cerebrovascular effects
Diclofenac should only be prescribed to patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) after careful clinical evaluation. Since the cardiovascular risks of diclofenac may increase with increasing dose and duration of treatment, it should be used for the shortest possible period and at the lowest effective dose.
For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and advice is necessary, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.
Clinical trial data and epidemiological data suggest that a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) may be associated with the use of diclofenac, especially at high doses (150 mg/day) and with long-term treatment.
Patients should be informed about the possibility of serious adverse reactions (chest pain, shortness of breath, weakness, speech disorders) that may occur at any time. In this case, a doctor should be consulted immediately.
Effect on hematological parameters
With prolonged use of this drug, as with other NSAIDs, monitoring of complete blood counts is recommended.
Diclofenac sodium may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis, or hematological disorders should be carefully monitored.
History of asthma
Patients with asthma, seasonal allergic rhinitis, swelling of the nasal mucosa (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic respiratory infections (especially those associated with allergic rhinitis-like symptoms) are more likely to experience reactions to NSAIDs, such as exacerbation of asthma (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Therefore, special precautions (emergency medical attention) are recommended for such patients. This also applies to patients with allergic reactions to other substances.
Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can provoke the development of bronchospasm when used in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.
Fertility in women
The use of Diclofenac Sodium-KV may impair female fertility and is not recommended in women attempting to conceive. In women who may have difficulty conceiving or who are undergoing investigation of infertility, discontinuation of Diclofenac Sodium-KV should be considered.
Use during pregnancy or breastfeeding
Pregnancy. In the I and II trimesters of pregnancy, the drug Sodium diclofenac-KV can be prescribed only when the expected benefit to the mother outweighs the potential risk to the fetus and only in the minimum effective dose, and the duration of treatment should be as short as possible. As with other NSAIDs, the drug is contraindicated in the last 3 months of pregnancy (possible suppression of uterine contractility and premature closure of the ductus arteriosus in the fetus).
Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryo/foetal development. Epidemiological data suggest an increased risk of miscarriage and/or cardiac malformations and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations was increased from less than 1% to approximately 1.5%.
It is possible that the risk increases with dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo/fetal lethality.
In addition, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various malformations, including those of the cardiovascular system, was recorded. If Diclofenac Sodium-KV is used by a woman attempting to conceive, or during the first trimester of pregnancy, the dose of the drug should be as low as possible and the duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect:
on the fruit
-cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- impaired renal function, which may progress to renal failure with oligohydramnios;
on the mother and newborn, as well as on the condition of the woman at the end of pregnancy
- possible prolongation of bleeding time, antiplatelet effect, which can be observed even at very low doses;
-inhibition of uterine contractions, which leads to delayed or prolonged labor.
Therefore, Diclofenac Sodium-KV is contraindicated during the third trimester of pregnancy.
Breastfeeding. Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, Diclofenac Sodium-KV should not be used by women during breastfeeding to avoid undesirable effects on the infant.
Female fertility. Like other NSAIDs, diclofenac sodium may impair female fertility and is therefore not recommended for use in women attempting to conceive. In women who have difficulty conceiving or are undergoing investigation of infertility, discontinuation of diclofenac sodium should be considered.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience visual disturbances, dizziness, vertigo, drowsiness, central nervous system disorders, lethargy or fatigue during therapy with Diclofenac Sodium-KV should not drive or operate machinery.
Method of administration and doses
The drug should be used in the lowest effective doses for the shortest period of time, taking into account the treatment objectives of each individual patient.
The initial dose of the drug is usually 100-150 mg per day. With mild symptoms, as well as with long-term therapy, a dose of 75-100 mg/day is sufficient. The daily dose should be divided into 2-3 doses. The daily dose of the drug should not exceed 150 mg.
In primary dysmenorrhea, the daily dose should be selected individually, usually it is 50-150 mg. The initial dose may be 50-100 mg per day, but if necessary it can be increased over several menstrual cycles to the maximum, but not higher than 200 mg/day. The drug should be started after the first pain symptoms appear and continued for several days, depending on the dynamics of symptom regression.
Children aged 5-14 years
Capsules in a dose of 25 mg can be used in children from 5 years of age as prescribed by a doctor in a daily dose of 0.5-2 mg/kg of body weight depending on the severity of symptoms; this dose should be divided into 2-3 doses. In the treatment of juvenile rheumatoid arthritis, the daily dose may be increased to 3 mg/kg per day in several doses.
For example, for a child weighing 30 kg, the daily dose may be from 15 to 60 mg. Based on this range, the child can be prescribed 1 capsule (25 mg) 2 times a day.
For children aged 14 and over, the drug should be used in a dosage of 75 to 150 mg per day in 2 or 3 doses.
Elderly patients. Although the pharmacokinetics of diclofenac sodium are not altered to any clinically significant extent in elderly patients, NSAIDs should be used with caution in elderly patients, who are generally more susceptible to adverse reactions. In particular, the lowest effective dose is recommended for frail elderly patients or patients with low body mass; patients should also be monitored for gastrointestinal bleeding during NSAID therapy.
Children
The drug should be used in children over 5 years of age.
Overdose
Symptoms.
There is no typical clinical picture of diclofenac overdose. Overdose may cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, agitation, coma, drowsiness, tinnitus, or convulsions. Acute renal failure and liver damage are possible in severe intoxication.
Treatment. Treatment of acute poisoning with NSAIDs, including diclofenac, consists of supportive and symptomatic therapy. This includes the treatment of manifestations such as arterial hypotension, renal failure, convulsions, gastrointestinal disorders, respiratory depression. It is unlikely that such specific therapeutic measures as forced diuresis, dialysis or hemoperfusion will be effective in removing NSAIDs, including diclofenac, since the active substances of these drugs are largely bound to plasma proteins and undergo extensive metabolism. Activated charcoal can be used after taking potentially toxic doses, and gastric decontamination (e.g., induction of vomiting, gastric lavage) after taking potentially life-threatening doses.
Adverse reactions
The following undesirable effects include those reported with short-term or long-term use of the drug.
Blood and lymphatic system disorders: thrombocytopenia, leukopenia, anemia (including hemolytic anemia and aplastic anemia), agranulocytosis.
Immune system disorders: hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock), angioedema (including facial edema).
Psychiatric: disorientation, depression, insomnia, nightmares, irritability, psychotic disorders.
From the nervous system: headache, dizziness, drowsiness, fatigue, paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disorders, stroke, confusion, hallucinations, sensory disturbances, general malaise.
From the organs of vision: visual disturbances, blurred vision, diplopia, optic neuritis.
From the side of the organs of hearing and labyrinth: vertigo, tinnitus, hearing disorders.
Cardiovascular system: palpitations, chest pain, heart failure, hypertension, hypotension, vasculitis; increased risk of thrombotic complications (e.g. myocardial infarction or stroke) associated with the use of diclofenac, particularly at high therapeutic doses (150 mg per day) and with prolonged use.
Respiratory, thoracic and mediastinal disorders: asthma (including dyspnea), pneumonitis.
Gastrointestinal: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia, gastritis, gastrointestinal bleeding (hemorrhage, melena, diarrhea with blood), gastric and intestinal ulcers, accompanied or not accompanied by bleeding or perforation (sometimes fatal, especially in elderly patients), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal dysfunction, diaphragmatic stenosis of the intestine, pancreatitis.
Skin and subcutaneous tissue disorders: rash, urticaria, blistering rash, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), exfoliative dermatitis, hair loss, photosensitivity reactions, purpura (including allergic), itching.
Renal and urinary disorders: acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.
From the reproductive system: impotence.
Clinical studies and epidemiological data suggest that diclofenac, especially at high doses (150 mg/day) and with long-term use, may slightly increase the risk of arterial thromboembolism (e.g. myocardial infarction or stroke).
Expiration date
3 years.
Storage conditions
In the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 capsules in a blister; 3 blisters in a pack.
Vacation category
According to the recipe.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and its business address
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua.
