Sodium diclofenac-kv

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SODIUM DICLOFENAC-KV (DICLOFENAC SODIUM-KV)

Composition:

Active substance: diclofenac sodium;

1 capsule contains 25 mg of diclofenac sodium;

Excipients: lactose monohydrate;

Capsule shell composition: gelatin, indigo carmine (E 132), titanium dioxide (E 171).

Pharmaceutical form. Hard capsules.

Main physicochemical properties: hard gelatin capsules with a blue cap and a white body. The contents of the capsules are a white crystalline powder.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Acetic acid derivatives and related substances. ATC code M01AB05.

Pharmacological Properties

Pharmacodynamics

Sodium diclofenac-KV contains sodium diclofenac, a nonsteroidal compound exerting pronounced analgesic and anti-inflammatory effects.

It is an inhibitor of prostaglandin synthetase (cyclooxygenase).

In vitro, sodium diclofenac at concentrations equivalent to those achieved during patient treatment does not suppress proteoglycan biosynthesis in cartilage tissue.

Pharmacokinetics

Absorption. Although absorption is complete, the onset of action may be delayed due to passage through the stomach, which can be influenced by food intake that slows gastric emptying. Mean peak plasma concentrations of 1.48 ± 0.65 µg/mL (1.5 µg/mL = 5 µmol/L) are reached on average within 2 hours after administration of a 50 mg dose.

Bioavailability. Approximately half of the administered diclofenac undergoes metabolism during the first pass through the liver (first-pass effect); the area under the concentration-time curve (AUC) after oral administration is approximately half that obtained with an equivalent parenteral dose.

The pharmacokinetic characteristics of the drug do not change upon repeated administration. Accumulation does not occur when the recommended dosage regimen is followed.

Plasma concentrations in children receiving equivalent doses (mg/kg body weight) are similar to those observed in adults.

Distribution. Protein binding of diclofenac to plasma proteins is 99.7%, and to albumin is 99.4%.

Diclofenac penetrates into synovial fluid, where its maximum concentration is achieved 2–4 hours later than in plasma. The half-life in synovial fluid is 3–6 hours. Two hours after peak plasma concentrations are reached, diclofenac concentrations in synovial fluid remain higher; this phenomenon persists for up to 12 hours.

There is one report of detection of diclofenac at low concentrations (100 ng/mL) in breast milk. The estimated amount of drug transferred to the infant via breast milk corresponds to a dose of 0.03 mg/kg/day.

Metabolism. Diclofenac is partially metabolized by glucuronidation of the unchanged molecule, but primarily by single and multiple hydroxylations and methoxylations, 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 significantly less so than diclofenac.

Elimination. Total systemic plasma clearance of diclofenac is 263 ± 56 mL/min (mean ± standard deviation). The terminal half-life in plasma is 1–2 hours. The half-life in plasma of four metabolites, including two pharmacologically active ones, is also short and ranges from 1–3 hours. Approximately 60% of the administered dose is excreted in urine as glucuronide conjugates of the intact molecule and as metabolites, most of which are also converted into glucuronide conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the administered dose is excreted in feces as metabolites.

Pharmacokinetics in Specific Patient Groups

Elderly Patients. No significant effect of patient age on absorption, metabolism, or elimination of the drug has been observed, except for one finding: in five elderly patients, a 15-minute intravenous infusion resulted in plasma concentrations 50% higher than expected compared to young healthy volunteers.

Patients with Renal Impairment. In patients with impaired renal function receiving therapeutic doses, accumulation of the unchanged active substance is not expected based on the drug's kinetics after single administration. In patients with creatinine clearance below 10 mL/min, calculated steady-state plasma concentrations of hydroxylated metabolites were approximately four times higher than in healthy volunteers. However, ultimately, all metabolites were excreted via bile.

Patients with Liver Disease. In patients with chronic hepatitis or compensated cirrhosis of the liver, pharmacokinetic parameters and diclofenac metabolism are similar to those in patients without liver disease.

Clinical characteristics.

Indications.

• Inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritides);
• Spinal pain syndromes;
• Rheumatic diseases of periarticular soft tissues;
• Acute gout attacks;
• Post-traumatic and postoperative pain syndromes associated with inflammation and edema, e.g., following dental or orthopedic procedures;
• Gynecological conditions associated with pain and inflammation, e.g., primary dysmenorrhea or adnexitis;
• As an adjunctive agent in severe inflammatory diseases of the ear, nose, and throat (ENT) organs accompanied by pronounced pain, e.g., pharyngotonsillitis, otitis. According to general therapeutic principles, the primary condition should be treated with appropriate basic therapy. Fever as a symptom is not an indication for use of this medicinal product.

Contraindications.

• Hypersensitivity to the active substance or to any other component of the medicinal product;
• Active gastric or intestinal ulcer; gastrointestinal hemorrhage or perforation;
• History of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
• Active peptic ulcer/hemorrhage or recurrent peptic ulcer/hemorrhage in history (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);
• Hepatic insufficiency (Child-Pugh class C, cirrhosis, or ascites);
• Renal insufficiency (creatinine clearance < 15 ml/min/1.73 m²);
• Congestive heart failure (NYHA II–IV);
• Ischemic heart disease in patients with angina pectoris or history of myocardial infarction;
• Cerebrovascular diseases in patients with history of stroke or transient ischemic attacks;
• Peripheral arterial disease;
• Treatment of perioperative pain in coronary artery bypass grafting (CABG) (or use of cardiopulmonary bypass);
• Like other NSAIDs, diclofenac is contraindicated in patients who have experienced attacks of bronchial asthma, angioedema, urticaria, or acute rhinitis, nasal polyps, or other allergic symptoms in response to ibuprofen, acetylsalicylic acid, or other NSAIDs.

Interaction with other medicinal products and other forms of interaction.

The interactions listed below have been observed with diclofenac in capsule and other dosage forms.

Lithium. Concomitant use of diclofenac may increase plasma lithium concentrations. Monitoring of serum lithium levels is recommended.

Digoxin. Concomitant use of diclofenac may increase plasma digoxin concentrations. Monitoring of serum digoxin levels is recommended.

Diuretics and antihypertensive agents. Concomitant use of diclofenac with diuretics and antihypertensive agents (e.g., beta-blockers, angiotensin-converting enzyme [ACE] inhibitors) may reduce their antihypertensive effect by inhibiting the synthesis of vasodilatory prostaglandins. Therefore, such combinations should be used with caution, and patients, especially elderly ones, should be closely monitored for blood pressure. Adequate hydration is recommended, and renal function should be monitored after initiation and regularly during concomitant therapy, particularly with diuretics and ACE inhibitors, due to increased risk of nephrotoxicity.

Agents causing hyperkalemia. Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may lead to increased serum potassium levels; therefore, more frequent monitoring of patients is advised.

Anticoagulants and antithrombotic agents. Concomitant use increases the risk of bleeding, so precautionary measures are recommended. Although clinical studies do not indicate an effect of diclofenac on anticoagulant activity, isolated reports suggest an increased risk of bleeding in patients receiving diclofenac and anticoagulants simultaneously. Therefore, to ensure no dosage adjustments of anticoagulants are needed, careful monitoring of such patients is recommended. Like other nonsteroidal anti-inflammatory drugs, diclofenac at high doses may transiently inhibit platelet aggregation.

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, and corticosteroids.
Concomitant use of diclofenac with other NSAIDs or corticosteroids increases the risk of gastrointestinal bleeding or ulceration. Concomitant use of two or more NSAIDs should be avoided.

Selective serotonin reuptake inhibitors (SSRIs). Concomitant use of NSAIDs and SSRIs increases the risk of gastrointestinal bleeding.

Antidiabetic agents. Clinical studies have shown that diclofenac can be used together with oral antidiabetic agents without altering their therapeutic effect. However, there are some reports of both hypoglycemia and hyperglycemia occurring during such combined use, necessitating dosage adjustments of antidiabetic agents. Therefore, as a precautionary measure, blood glucose levels should be monitored during combination therapy.

Isolated cases of metabolic acidosis have also been reported with concomitant use of diclofenac, particularly in patients with pre-existing renal impairment.

Methotrexate. Diclofenac may inhibit renal tubular clearance of methotrexate, leading to elevated methotrexate levels. Caution is advised when prescribing NSAIDs, including diclofenac, within 24 hours before methotrexate administration, as this may increase methotrexate plasma concentrations and enhance its toxicity. Serious toxicity cases have been reported when the interval between methotrexate and NSAID (including diclofenac) administration was within 24 hours. This interaction is mediated by methotrexate accumulation due to impaired renal excretion in the presence of NSAIDs.

Cyclosporine. The effect of diclofenac, like other NSAIDs, on prostaglandin synthesis in the kidneys may potentiate the nephrotoxicity of cyclosporine; therefore, diclofenac should be administered at lower doses in patients receiving cyclosporine compared to those not receiving cyclosporine.

Tacrolimus. Concomitant use of NSAIDs with tacrolimus increases the risk of nephrotoxicity, possibly mediated by renal anti-prostaglandin effects of NSAIDs and calcineurin inhibitors.

Quinolone antibacterial agents. Seizures may occur in patients receiving quinolone derivatives and NSAIDs concomitantly. This may occur in patients both with and without a history of epilepsy or seizures. Therefore, caution should be exercised when considering quinolone use in patients already receiving NSAIDs.

Phenytoin. When phenytoin is used concomitantly with diclofenac, monitoring of plasma phenytoin concentrations is recommended due to the expected increase in phenytoin effect.

Cholestyramine and colestipol. These agents may delay or reduce absorption of diclofenac. Therefore, diclofenac should be administered at least 1 hour before or 4–6 hours after cholestyramine/colestipol administration.

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 within 8–12 days after mifepristone administration, as NSAIDs may reduce the efficacy of mifepristone.

Strong CYP2C9 inhibitors. Caution is recommended when co-prescribing diclofenac with strong CYP2C9 inhibitors (e.g., voriconazole), as this may lead to a significant increase in plasma maximum concentrations and exposure of diclofenac due to inhibition of its metabolism.

CYP2C9 inducers. Caution is required when co-prescribing diclofenac with CYP2C9 inducers (e.g., rifampicin), as this may lead to a significant decrease in plasma concentrations and exposure of diclofenac.

Special precautions for use.

The patient's need for diclofenac therapy to relieve symptoms and response to treatment should be periodically reassessed.

To minimize adverse effects, treatment should be initiated with the lowest effective dose, administered for the shortest duration necessary to control symptoms.

Concomitant use of the medicinal product Sodium diclofenac-KV with systemic NSAIDs, such as selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to lack of evidence for synergistic effects and potential for additive adverse effects. An increased risk of thrombotic cardiovascular and cerebrovascular complications has been observed with certain selective COX-2 inhibitors. At present, it is not definitively known whether this risk is directly correlated with the COX-1/COX-2 selectivity of individual NSAIDs.

Caution is required in elderly patients. Use with caution in patients over 65 years of age. In particular, the lowest effective dose is recommended for frail elderly patients or those with low body weight.

The effect of NSAIDs on the kidneys may lead to fluid retention and edema and/or arterial hypertension; therefore, diclofenac should be used with caution in patients with cardiac impairment or other conditions predisposing to fluid retention. The medicinal product should be used with caution in patients who are concurrently receiving diuretics or angiotensin-converting enzyme (ACE) inhibitors or who have an increased risk of hypovolemia.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even in the absence of prior exposure to diclofenac.

Hypersensitivity reactions may also progress to Kounis syndrome—a serious allergic reaction that may lead to myocardial infarction. One possible manifestation is chest pain occurring in the context of an allergic reaction to diclofenac.

Sodium diclofenac-KV, like other NSAIDs, may mask signs of infection.

Gastrointestinal effects

When using all NSAIDs, including diclofenac, cases of gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation have been reported. These events may be fatal and may occur at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal events. These effects generally have more severe consequences in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the medicinal product should be discontinued.

When using NSAIDs, including diclofenac, in patients with symptoms suggesting gastrointestinal (GI) tract disorders, medical monitoring and special caution are mandatory. The risk of GI bleeding, ulceration, or perforation increases with higher NSAID doses, including diclofenac.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

To reduce the risk of such GI 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-dose acetylsalicylic acid (ASA/aspirin) or other drugs increasing the risk of GI adverse effects, consideration should be given to combination therapy including proton pump inhibitors or misoprostol. Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (particularly GI bleeding). Caution is also required in patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), antiplatelet agents (e.g., ASA), or selective serotonin reuptake inhibitors (SSRIs).

The use of NSAIDs, particularly diclofenac, is associated with an increased risk of gastrointestinal anastomotic insufficiency. Careful medical monitoring and caution are recommended when using diclofenac after gastrointestinal surgery.

Hepatic effects

Close medical monitoring is required when prescribing Sodium diclofenac-KV to patients with impaired liver function, as their condition may worsen. With the use of NSAIDs, including diclofenac, the levels of one or more liver enzymes may increase. This phenomenon has been observed very frequently with diclofenac, but rarely accompanied by clinical symptoms of liver injury. In most cases, enzyme levels rise to borderline values. Elevations in liver enzyme levels have been associated with clinical signs of liver injury. Increases in enzyme levels are usually reversible upon discontinuation of the medicinal product.

During long-term treatment with Sodium diclofenac-KV, regular monitoring of liver function and liver enzyme levels is required.

If liver function impairment persists or worsens, if clinical symptoms suggest progressive liver disease, or if other manifestations occur (e.g., eosinophilia, rash), use of Sodium diclofenac-KV should be discontinued. The course of diseases such as hepatitis may occur without prodromal symptoms. In addition to elevated liver enzyme levels, rare severe hepatic reactions have been reported, including jaundice, fulminant hepatitis, hepatic necrosis, and hepatic failure, some of which have been fatal. Caution is necessary when prescribing Sodium diclofenac-KV to patients with hepatic porphyria (due to the potential to provoke an attack).

Renal effects

Since fluid retention and edema have been reported during treatment with NSAIDs, including diclofenac, particular attention should be paid to patients with impaired cardiac or renal function, a history of arterial hypertension, elderly patients, patients receiving concomitant diuretic therapy or other drugs significantly affecting renal function, and patients with marked reduction in extracellular fluid volume for any reason (e.g., before or after major surgery). As a precautionary measure, monitoring of renal function is recommended in such cases. Discontinuation of therapy usually results in return to the pre-treatment state.

Skin reactions

Serious skin reactions (some of which have been fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) have been very rarely reported in association with the use of NSAIDs, including Sodium diclofenac-KV. The highest risk of these reactions occurs early in the course of treatment, with most cases appearing within the first month of therapy. The medicinal product Sodium diclofenac-KV should be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of hypersensitivity.

Systemic lupus erythematosus (SLE) and mixed connective tissue disorders

Patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders have an increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking) only after careful clinical evaluation. Since cardiovascular risks of diclofenac increase with higher doses and longer treatment duration, it should be used for the shortest possible duration and at the lowest effective dose.

Patients with a history of arterial hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and counseling, as fluid retention and edema have been reported with NSAID use, including diclofenac.

Clinical trial data and epidemiological evidence suggest that a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke) may be associated with diclofenac use, particularly at high doses (150 mg/day) and during prolonged treatment.

Diclofenac is not recommended for patients with uncontrolled arterial hypertension, congestive heart failure, established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. If use is necessary, it should be considered only after careful risk/benefit assessment and at a dose not exceeding 100 mg daily. A similar risk/benefit assessment should be performed before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g., patients with hypertension, hyperlipidemia, diabetes, or who smoke).

Patients should be informed about the possibility of serious adverse reactions (chest pain, dyspnea, weakness, speech disturbances), which may develop at any time. In such cases, immediate medical attention is required.

Hematological effects

With prolonged use of this and other NSAIDs, regular complete blood counts are recommended.

Sodium diclofenac-KV may temporarily inhibit platelet aggregation. Close monitoring is required in patients with coagulation disorders, hemorrhagic diathesis, or hematological disorders.

History of asthma

In patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (e.g., nasal polyps), chronic obstructive pulmonary diseases, or chronic respiratory infections (particularly those associated with allergic, rhinitis-like symptoms), reactions to NSAIDs such as asthma exacerbation (so-called analgesic intolerance/analgesic-induced asthma), Quincke's edema, or urticaria occur more frequently. Therefore, special precautions (readiness for emergency intervention) are recommended. This also applies to patients with allergic reactions to other substances.

Like other drugs that inhibit prostaglandin synthetase activity, sodium diclofenac may provoke bronchospasm when administered to patients with bronchial asthma or a history of bronchial asthma.

The medicinal product contains lactose. Patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Use during pregnancy or breastfeeding.

Pregnancy. Sodium diclofenac-KV may be prescribed during the first and second trimesters of pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus, and only at the lowest effective dose, with treatment duration as short as possible. Like other NSAIDs, sodium diclofenac is contraindicated during the last three months of pregnancy (possible inhibition of uterine contractility and premature closure of the fetal ductus arteriosus).

Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and congenital heart defects and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%.

The risk may increase with higher doses and longer duration of treatment. Animal studies have shown that administration of prostaglandin synthesis inhibitors leads to increased pre- and post-implantation loss and embryonic/fetal mortality.

Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of various developmental abnormalities, including cardiovascular defects, has been observed.

From the 20th week of pregnancy, the use of diclofenac may cause oligohydramnios due to fetal renal dysfunction. This effect may occur soon after starting treatment and is usually reversible upon discontinuation. There have also been reports of ductus arteriosus constriction after second-trimester treatment, mostly reversible after stopping the drug. Therefore, diclofenac should not be prescribed during the first and second trimesters unless absolutely necessary. If Sodium diclofenac-KV is prescribed to women attempting to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and treatment duration as short as possible. Prenatal monitoring for oligohydramnios and ductus arteriosus constriction may be advisable after diclofenac exposure for several days starting from the 20th gestational week. If oligohydramnios or ductus arteriosus constriction is detected, diclofenac should be discontinued.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose risks to the fetus:

• cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction (see above);

and risks to the mother at the end of pregnancy and to the newborn:

• prolonged bleeding time, anti-aggregatory effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, Sodium diclofenac-KV is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding. Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, Sodium diclofenac-KV should not be used during breastfeeding to avoid potential adverse effects on the infant. If treatment is essential, breastfeeding should be discontinued.

Female fertility. Like other NSAIDs, diclofenac may negatively affect female fertility. Therefore, the drug is not recommended for women planning pregnancy. For women experiencing infertility or undergoing fertility investigations, discontinuation of Sodium diclofenac-KV should be considered.

Ability to affect reaction speed when driving or operating machinery.

Patients who experience visual disturbances, dizziness, vertigo, somnolence, central nervous system disorders, lethargy, or fatigue during treatment with Sodium diclofenac-KV should not drive or operate machinery.

Dosage and Administration

The medicinal product should be used at the lowest effective dose for the shortest duration necessary, taking into account the individual treatment goals for each patient.

Capsules should preferably be taken after meals with liquid.

The usual initial dose is 100–150 mg per day. For mild symptoms and during long-term therapy, a daily dose of 75–100 mg is sufficient. The daily dose should be divided into 2–3 administrations. The daily dose must not exceed 150 mg.

In primary dysmenorrhea, the daily dose should be individually adjusted and usually ranges from 50–150 mg. The initial dose may be 50–100 mg per day; however, if necessary, it can be increased over several menstrual cycles up to the maximum, but not exceeding 200 mg/day. Treatment should begin after the onset of the first pain symptoms and continue for several days, depending on the clinical response and symptom regression.

Children aged 5–14 years

25 mg capsules may be administered to children aged 5 years and older, as prescribed by a physician, at a daily dose of 0.5–2 mg/kg body weight, depending on symptom severity; this dose should be divided into 2–3 administrations. In the treatment of juvenile rheumatoid arthritis, the daily dose may be increased up to 3 mg/kg body weight in several divided doses.

For example, in a child weighing 30 kg, the daily dose may range from 15 to 60 mg. Based on this range, the medicinal product may be administered as 1 capsule (25 mg) twice daily.

Children aged 14 years and older should receive the medicinal product in doses ranging from 75 to 150 mg per day, divided into 2 or 3 doses.

Elderly patients. Although the pharmacokinetics of Diclofenac Sodium-KV are not clinically significantly altered in elderly patients, the drug should be used with particular caution, as elderly patients are more susceptible to adverse reactions. In particular, the lowest effective doses are recommended for frail elderly patients or those with low body weight. Additionally, patients should be monitored for gastrointestinal bleeding during NSAID therapy.

Pediatric population. The medicinal product may be used in children aged 5 years and older.

Overdose.

Symptoms. There is no specific clinical picture characteristic of diclofenac overdose. Overdose may cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, excitation, coma, drowsiness, tinnitus, or convulsions. Acute renal failure and hepatic injury are possible in cases of severe intoxication.

Treatment. Management of acute poisoning with NSAIDs, including diclofenac, consists of supportive and symptomatic therapy. This includes treatment of manifestations such as arterial hypotension, renal failure, convulsions, gastrointestinal disturbances, and respiratory depression. Specific interventions such as forced diuresis, dialysis, or hemoperfusion are unlikely to be effective in eliminating NSAIDs, including diclofenac, due to the high degree of plasma protein binding and extensive metabolism of these agents. After ingestion of potentially toxic doses, activated charcoal may be administered. After ingestion of potentially life-threatening doses, gastrointestinal decontamination (e.g., induced emesis, gastric lavage) should be performed.

Adverse reactions.

The undesirable effects listed below include events reported during short-term or long-term use of the medicinal product.

Blood and lymphatic system disorders: thrombocytopenia, leukopenia, anemia (including hemolytic anemia and aplastic anemia), agranulocytosis.

Immune system disorders: hypersensitivity, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock), angioneurotic edema (including facial swelling).

Psychiatric disorders: disorientation, depression, insomnia, nightmares, irritability, psychotic disorders.

Nervous system disorders: headache, dizziness, somnolence, fatigue, paresthesia, memory impairment, convulsions, restlessness, tremor, aseptic meningitis, taste disturbances, stroke, confusion, hallucinations, sensory disturbances, malaise.

Eye disorders: visual disturbances, blurred vision, diplopia, optic neuritis.

Ear and labyrinth disorders: vertigo, tinnitus, hearing disorders.

Cardiac and vascular disorders: palpitations, chest pain, heart failure, arterial hypertension, arterial 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; Kounis syndrome (frequency unknown).

Respiratory, thoracic and mediastinal disorders: asthma (including dyspnea), pneumonitis.

Gastrointestinal disorders: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia, gastritis, gastrointestinal bleeding (hematemesis, melena, diarrhea with blood), gastric and intestinal ulcers with or without 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, diaphragm-like intestinal stricture, pancreatitis.

Hepatobiliary disorders: increased transaminase levels, hepatitis, jaundice, liver disorders, fulminant hepatitis, liver necrosis, liver failure.

Skin and subcutaneous tissue disorders: rash, urticaria, bullous eruption, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, alopecia, photosensitivity reactions, purpura (including allergic purpura), pruritus.

Renal and urinary system disorders: acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis, fluid retention, edema, arterial hypertension.

Reproductive system disorders: impotence.

Clinical studies and epidemiological data indicate that diclofenac, particularly at high doses (150 mg/day) and with prolonged use, slightly increases the risk of arterial thromboembolic events (e.g. myocardial infarction or stroke).

Visual disturbances.

Visual disturbances, worsening of vision, and diplopia are class effects of NSAIDs, which are usually reversible upon discontinuation of the drug. The most likely mechanism of visual disturbances is inhibition of prostaglandin synthesis and other related compounds, which may disrupt regulation of retinal blood flow and contribute to the development of visual disturbances. If such symptoms occur during treatment with diclofenac, an ophthalmological examination should be performed to exclude other possible causes.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging. 10 capsules per blister; 3 blisters per carton.

Prescription category. Prescription only.

Manufacturer: JSC "KYIV VITAMIN PLANT".

Manufacturer's address and location of its business activity:

38 Kopilivska Street, Kyiv, 04073, Ukraine.

Web-site: www.vitamin.com.ua.