Diclofenac

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DICLOFENAC (DICLOFENAC)

Composition:

active substance: diclofenac;

1 tablet contains: sodium diclofenac (calculated as dry substance) 0.05 g;

excipients: microcrystalline cellulose, lactose monohydrate, potato starch, colloidal anhydrous silicon dioxide, calcium stearate.

Pharmaceutical form. Tablets.

main physico-chemical properties: white tablets with a score line and beveled edge.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Acetic acid derivatives and related substances.

ATC code M01A B05.

Pharmacological properties.

Pharmacodynamics.

Has pronounced anti-inflammatory, analgesic, and moderate antipyretic effects. The mechanism of action is associated with inhibition of prostaglandin synthesis. Inhibits platelet aggregation. Reduces pain at rest and during movement, morning stiffness, and joint swelling, improving joint functional capacity. In inflammatory processes following surgery or trauma, rapidly alleviates both spontaneous pain and pain during movement.

Pharmacokinetics.

Diclofenac sodium is rapidly absorbed into the bloodstream—the maximum plasma concentration is reached within 1–2 hours. Plasma protein binding exceeds 99%. It penetrates well into tissues and synovial fluid, where its concentration increases gradually, reaching higher levels than in plasma after 4 hours. Food may slow the rate of absorption without affecting the extent of absorption. Bioavailability is approximately 50%.

The elimination half-life from plasma is 1–2 hours and from synovial fluid is 3–6 hours. Approximately 35% is excreted as metabolites in feces; about 65% is metabolized in the liver and excreted by the kidneys as inactive metabolites, and about 1% is excreted unchanged.

Clinical characteristics.

Indications.

• Inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritides);
• Spinal pain syndromes;
• Rheumatic diseases of soft tissues outside the joints;
• 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 underlying disease should be treated with disease-modifying agents. Fever alone is not an indication for the use of this medication.

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 the past (two or more distinct episodes of confirmed ulcer or bleeding).
• Pregnancy.
• Inflammatory bowel diseases (e.g., Crohn’s disease or ulcerative colitis).
• Renal failure (creatinine clearance < 15 mL/min/1.73 m²).
• Hepatic failure.
• Severe heart failure (Stage III–IV heart failure).
• Congestive heart failure (Functional Class II–IV heart failure).
• Ischemic heart disease in patients with angina or history of myocardial infarction.
• Cerebrovascular diseases in patients with history of stroke or transient ischemic attacks.
• Peripheral arterial disease.
• Treatment of postoperative pain following coronary artery bypass grafting (or use of cardiopulmonary bypass).
• Diclofenac, like other nonsteroidal anti-inflammatory drugs, is contraindicated in patients who have experienced asthma attacks, angioedema, urticaria, or acute rhinitis, nasal polyps, or other allergic symptoms in response to ibuprofen, acetylsalicylic acid, or other NSAIDs.
• Coagulation disorders.

Interaction with other medicinal products and other types of interactions.

The interactions listed below have been observed with diclofenac administered as enteric-coated tablets and/or other dosage forms of diclofenac.

Lithium. Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.

Digoxin. Diclofenac may increase plasma digoxin concentrations when used concomitantly. Monitoring of serum digoxin levels is recommended.

Diuretics and antihypertensive agents. Concomitant use of diclofenac with diuretics and antihypertensive agents [e.g., β-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 monitoring of renal function is advised both at the start and during concomitant therapy due to increased risk of nephrotoxicity.

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

Anticoagulants and antithrombotic agents. Concomitant use increases the risk of bleeding, and preventive measures are recommended. Although clinical studies have not shown a significant effect of diclofenac on anticoagulant activity, isolated reports indicate an increased risk of bleeding in patients receiving diclofenac and anticoagulants simultaneously. Therefore, close monitoring of such patients is recommended to ensure no dosage adjustments of anticoagulants are needed. Like other NSAIDs, high-dose diclofenac may transiently inhibit platelet aggregation.

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, and corticosteroids. Concurrent 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 therapeutic efficacy. However, there are some reports of both hypoglycemia and hyperglycemia requiring dosage adjustments of antidiabetic agents during diclofenac therapy. Therefore, blood glucose monitoring is recommended during combination therapy.

There are also isolated reports of metabolic acidosis occurring 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 or after methotrexate administration, as this may increase methotrexate plasma concentrations and enhance its toxicity. Serious cases of toxicity have been reported when methotrexate and NSAIDs, including diclofenac, were administered within 24 hours of each other. This interaction occurs due to methotrexate accumulation resulting from 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, lower doses of diclofenac should be used in patients receiving cyclosporine.

Tacrolimus. Concomitant use of NSAIDs with tacrolimus increases the risk of nephrotoxicity, possibly due to the renal anti-prostaglandin effects of NSAIDs and the calcineurin inhibitor.

Quinolone antibiotics. Seizures may occur in patients receiving quinolone derivatives and NSAIDs concomitantly, regardless of history of epilepsy or seizures. Therefore, caution is advised when prescribing quinolones to 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 effects.

Cholestyramine and colestipol. These agents 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 cholestyramine/colestipol.

Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs in patients may exacerbate heart failure, reduce glomerular filtration rate (GFR), and increase plasma levels of glycosides.

Mifepristone. NSAIDs should not be used within 8–12 days after mifepristone administration, as NSAIDs may reduce the efficacy of mifepristone.

CYP2C9 inhibitors. Caution is required when co-administering diclofenac with CYP2C9 inhibitors (e.g., voriconazole), as this may lead to a significant increase in plasma maximum concentrations and exposure to diclofenac.

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

Special precautions for use.

Careful medical monitoring is required in patients who have complaints indicating gastrointestinal disorders, or who have a history of peptic ulceration of the stomach or intestine; patients with ulcerative colitis or Crohn's disease, as well as patients with impaired liver function.

With prolonged use of diclofenac, as with other NSAIDs, systematic monitoring of the peripheral blood picture is recommended.

Diclofenac, like other NSAIDs, may temporarily inhibit platelet aggregation. Therefore, careful monitoring of appropriate laboratory parameters is necessary in patients with coagulation disorders.

Caution is required when administering diclofenac to elderly patients, especially those who are debilitated or have low body weight; such patients should be prescribed the lowest effective dose.

Alcoholic beverages should be avoided during diclofenac treatment. If diclofenac is used prior to surgery, the physician or dentist should be informed.

Premature discontinuation of the medication may lead to recurrence of painful symptoms.

To minimize adverse effects, the lowest effective dose should be used for the shortest duration necessary to control symptoms. The patient's need for diclofenac therapy to relieve symptoms and response to treatment should be periodically reviewed.

Placebo-controlled studies have shown an increased risk of thrombotic cardiovascular and cerebrovascular complications with certain selective COX-2 inhibitors. It is currently unknown whether this risk is directly correlated with selective COX-1/COX-2 inhibitors or individual NSAIDs. Since comparative clinical data on long-term treatment with maximum-dose diclofenac are currently unavailable, the possibility of a similar increased risk cannot be excluded. Until such data become available, a careful benefit-risk assessment should be performed before using diclofenac in patients with clinically confirmed ischemic heart disease, cerebrovascular disorders, peripheral arterial disease, or significant risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking). Therefore, the lowest effective dose should also be used for the shortest possible treatment duration.

As with other NSAIDs, allergic reactions—including anaphylactic/anaphylactoid reactions—may occur.

Diclofenac, like other NSAIDs, may mask signs of infection.

The medication contains lactose. This medication should not be administered to patients with rare hereditary galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.

Gastrointestinal effects

Cases of gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation have been reported during treatment with all NSAIDs, including diclofenac. These events can be fatal and may occur at any time during therapy, with or without prior warning symptoms, or in patients with a history of serious gastrointestinal complications. These events generally have more serious consequences in elderly patients. If signs of gastrointestinal bleeding or ulceration occur in patients receiving diclofenac, the drug should be discontinued.

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

The use of NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic dehiscence. Close monitoring and caution are recommended when using diclofenac after gastrointestinal surgery.

Inform your physician if you have recently undergone or are planning to undergo surgery on the stomach or intestines before using diclofenac, as diclofenac may sometimes impair intestinal wound healing after surgery.

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 GI toxicity, treatment should be initiated and maintained at the lowest effective doses. For such patients, as well as those requiring concomitant use of medications containing low-dose acetylsalicylic acid (ASA/aspirin) or other drugs likely to increase the risk of GI adverse effects, consideration should be given to combination therapy with protective agents (e.g., 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 when treating 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.

Hepatic effects

Careful medical monitoring is required if diclofenac is administered to patients with impaired liver function, as their condition may worsen. During NSAID use, including diclofenac, levels of one or more liver enzymes may increase. This has been observed very frequently in diclofenac studies (approximately 15% of patients), but rarely accompanied by clinical symptoms. In most cases, increases were to borderline levels. In addition to elevated liver enzymes, serious hepatic reactions, including jaundice, fulminant hepatitis, hepatic necrosis, and liver failure—some fatal—have been reported rarely.

It should be noted that diclofenac is recommended only for short-term treatment (no more than 2 weeks). During prolonged therapy, regular monitoring of liver function and liver enzyme levels is recommended as a precautionary measure. If liver function abnormalities persist or worsen, or if clinical symptoms may be related to progressive liver disease, or if other manifestations occur (e.g., eosinophilia, rash), diclofenac should be discontinued. Diseases such as hepatitis may progress without prodromal symptoms. Caution is necessary when administering diclofenac to patients with hepatic porphyria due to the potential risk of provoking an attack.

Renal effects

Prolonged use of high-dose NSAIDs often leads to fluid retention and hypertension.

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 hypertension, elderly patients, patients receiving concomitant diuretic therapy or drugs that significantly affect renal function, and patients with significant extracellular fluid volume depletion due to any cause, such as before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure. After discontinuation of therapy, patients' conditions usually normalize.

Skin effects

Serious skin reactions (some of which were fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and Lyell's syndrome, have been reported very rarely in association with NSAID use, including diclofenac. The highest risk of these reactions occurs early in the treatment course, with most cases appearing within the first month of therapy. Allergic reactions, including anaphylactic/anaphylactoid reactions, may occur rarely with diclofenac and other NSAIDs, even without prior exposure. Allergic reactions may progress to severe allergic reactions—such as Kounis syndrome—which may lead to myocardial infarction. Symptoms may include chest pain associated with an allergic reaction to diclofenac. Diclofenac should be discontinued at the first sign of skin rash, mucosal lesions, or any other signs of hypersensitivity.

SLE and mixed connective tissue diseases

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

As with all analgesics, prolonged use of the medication for headache treatment may lead to improvement or worsening of the condition (medication-overuse headache). If headache develops due to excessive analgesic use, the analgesic dose should not be increased; instead, treatment should be discontinued. Medication-overuse headache should be suspected in patients with frequent or daily headache attacks occurring despite (or because of) regular analgesic use.

Cardiovascular and cerebrovascular effects

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

Clinical and epidemiological data indicate that diclofenac use, particularly at high doses (150 mg/day) and during long-term treatment, slightly increases the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke).

Diclofenac is not recommended for patients with uncontrolled hypertension, mild to moderate congestive heart failure, stable ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. If use is necessary, it should only be considered after careful risk-benefit assessment and at a dose not exceeding 100 mg daily, since cardiovascular risks of diclofenac may increase with dose and duration of treatment (it should be used for the shortest possible duration and at the lowest effective dose).

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

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking) only after careful clinical evaluation and only at a dose ≤100 mg daily if treatment duration does not exceed four weeks. Since cardiovascular risks increase with dose and duration of diclofenac use, it should be used for the shortest possible duration and at the lowest effective dose. The patient's need for diclofenac therapy and response to treatment should be periodically reviewed. Use with caution in patients aged 65 years and older.

Hematological effects

The medication is recommended only for short-term treatment.

With prolonged use of this medication, as with other NSAIDs, a complete blood count is recommended.

Diclofenac may temporarily inhibit platelet aggregation. Patients with coagulation disorders, hemorrhagic diathesis, or hematological disorders should be carefully monitored.

History of asthma

Patients with asthma, seasonal allergic rhinitis, nasal mucosal swelling (i.e., nasal polyps), chronic obstructive pulmonary diseases, or chronic respiratory infections (especially those associated with allergic, rhinitis-like symptoms) are more likely to experience NSAID-related reactions, such as asthma exacerbation (so-called analgesic intolerance/analgesic-induced asthma), Quincke's edema, or urticaria. Therefore, special precautionary measures (readiness for emergency intervention) are recommended. This also applies to patients with allergic reactions to other substances, such as rash, pruritus, or urticaria.

Like other agents that inhibit prostaglandin synthetase activity, sodium diclofenac may provoke bronchospasm in patients with bronchial asthma or a history of bronchial asthma.

Use during pregnancy or breastfeeding.

Pregnancy.

Use during pregnancy is contraindicated.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage and of congenital heart defects and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy.

Animal studies have shown that administration of a prostaglandin synthesis inhibitor increases pre- and post-implantation loss and embryonic/fetal mortality.

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

From the 20th week of pregnancy, diclofenac use may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation of the drug. Prenatal monitoring for oligohydramnios should be considered if diclofenac is used for several days starting from the 20th week of pregnancy. Diclofenac use should be discontinued if oligohydramnios is detected.

During the third trimester, all prostaglandin synthesis inhibitors may cause:

Risks to the fetus:

• Cardio-pulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• Impaired renal function (see above);

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

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

Lactation period.

Like other NSAIDs, diclofenac is excreted in small amounts into breast milk. Therefore, diclofenac should not be used by women during breastfeeding to avoid potential adverse effects on the infant.

Fertility.

Like other NSAIDs, diclofenac may negatively affect female fertility and is therefore not recommended for women attempting to conceive. For women experiencing infertility or undergoing infertility evaluation, discontinuation of diclofenac should be considered.

Ability to affect reaction speed when driving or operating machinery.

Patients should refrain from driving or operating potentially hazardous machinery requiring heightened attention and rapid reaction, as visual disturbances, dizziness, vertigo, somnolence, central nervous system disorders, lethargy, or increased fatigue may occur during treatment.

Method of Administration and Dosage

For oral use.

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

Tablets should be taken during or after meals, without chewing, with a sufficient amount of water.

The dosage and duration of treatment are determined by a physician depending on the nature and course of the disease, the patient's response to the drug, and the therapeutic effect achieved.

Adults and children aged 14 years and older.

The usual initial dose is 100–150 mg daily. For mild symptoms and long-term therapy, a dose of 75–100 mg/day is usually sufficient. The daily dose should be divided into 2–3 administrations. For primary dysmenorrhea, the daily dose should be individually adjusted and typically ranges from 50–150 mg. The initial dose may be 50–100 mg, but if necessary, it can be increased over several menstrual cycles up to the maximum dose of 200 mg per day. Treatment should begin as soon as the first painful symptoms appear and continue for several days, depending on the clinical response.

For children aged 14 to 18 years, the recommended daily dose is 75–150 mg, administered in two or three divided doses.

The recommended maximum daily dose of Diclofenac is 150 mg.

Elderly patients.

Although the pharmacokinetics of diclofenac are not clinically significantly altered in elderly patients, the drug should be used with caution, as these patients are more susceptible to adverse reactions. In particular, the lowest effective doses are recommended for frail elderly patients and those with low body weight. Patients should also be monitored for gastrointestinal bleeding.

Children.

This dosage form is not recommended for children under 14 years of age. The drug may be used in children aged 14 years and older only if the prescribed dosage can be accurately administered.

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, agitation, 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, seizures, 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 their high degree of plasma protein binding and extensive metabolism. After ingestion of potentially toxic doses, activated charcoal is recommended. After ingestion of potentially life-threatening doses, vomiting should be induced and gastric lavage performed.

Adverse Reactions

The frequency of adverse reactions is defined as follows: very common (>1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

The adverse effects listed below include events reported during short-term or long-term use of the drug.

Blood and lymphatic system disorders: very rare – thrombocytopenia, leukopenia, anemia, including hemolytic anemia and aplastic anemia, agranulocytosis.

Immune system disorders: rare – hypersensitivity, fever, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock); very rare – angioedema (including facial swelling); frequency not known – Kounis syndrome.

Psychiatric disorders: very rare – disorientation, depression, insomnia, irritability, nightmares, psychotic disorders.

Nervous system disorders: common – headache, dizziness; rare – somnolence, fatigue; very rare – paresthesia, memory impairment, convulsions, restlessness, tremor, aseptic meningitis, taste disturbances, stroke, cerebral ischemia; frequency not known – confusion, hallucinations, sensory disturbances, malaise.

Eye disorders: very rare – visual disturbances, blurred vision, diplopia; frequency not known – optic neuritis.

Ear and labyrinth disorders: common – vertigo; very rare – tinnitus, hearing disturbances.

Cardiac and vascular disorders: very rare – general weakness, palpitations, dyspnea, increased pulse rate, increased respiratory rate (RR), chest pain, heart failure, myocardial infarction, arterial hypertension, hypotension, vasculitis.

Respiratory, thoracic and mediastinal disorders: rare – asthma (including dyspnea); very rare – pneumonitis.

Gastrointestinal disorders: common – nausea, vomiting, diarrhea, dyspepsia, heartburn, abdominal distension, loss of appetite, taste disturbances, abdominal pain, flatulence, anorexia; rare – gastritis, gastrointestinal bleeding (hematemesis, melena, bloody diarrhea), gastric and intestinal ulcers with or without bleeding, gastrointestinal stenosis or perforation (sometimes fatal, especially in elderly patients), which may lead to peritonitis; very rare – colitis (including hemorrhagic colitis, ischemic colitis, and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal dysfunction, diaphragm-like intestinal stricture, pancreatitis, gastric erosion, gastroenteropathy with malabsorption syndrome, maldigestion, polyserositis.

Hepatobiliary disorders: common – increased transaminase levels; rare – hepatitis, jaundice, liver disorders; very rare – fulminant hepatitis, liver necrosis, liver failure.

Skin and subcutaneous tissue disorders: common – rashes (maculopapular, urticarial, papular), hyperemia; rare – urticaria; very rare – bullous eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, alopecia, photosensitivity reaction, purpura (including allergic purpura), pruritus.

Renal and urinary disorders: acute kidney injury (acute renal failure), hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.

General disorders: rare – edema.

Reproductive system and breast disorders: very rare – impotence.

Clinical studies and epidemiological data indicate an 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.

Visual disturbances.

Visual disturbances such as impaired vision, worsening of vision, and diplopia are class effects of NSAIDs and 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 retinal blood flow regulation and contribute to the development of visual disturbances. If such symptoms occur during treatment with diclofenac, an ophthalmological examination should be performed to rule out other possible causes.

Shelf life. 3 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

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

Keep out of reach of children.

Packaging.

10 tablets in blisters.

10 tablets in a blister; 1, 3, or 10 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and location of business activity.

1, Gordienkovska Street, Kharkiv, Kharkiv Oblast, 61010, Ukraine.