Diclofenac euro

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

Composition:

Active ingredient: sodium diclofenac;

1 tablet contains 50 mg of sodium diclofenac;

Excipients: lactose monohydrate, maize starch, talc, magnesium stearate, colloidal anhydrous silicon dioxide, sodium croscarmellose, methacrylic acid copolymer dispersion, sodium hydroxide, diethyl phthalate, polysorbate 80 (Tween 80), titanium dioxide (E 171), colouring agent Sunset Yellow FCF (E 110).

Pharmaceutical form. Enteric-coated tablets.

Main physicochemical properties: orange, round, biconvex tablets coated with an enteric coating.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents.

ATC code M01AB05.

Pharmacological properties.

Pharmacodynamics.

Diclofenac sodium, the active ingredient of the drug, is a non-steroidal compound with pronounced antipyretic, analgesic, and anti-inflammatory properties. Diclofenac sodium, as a non-selective inhibitor of COX-1 and COX-2, interferes with arachidonic acid metabolism and inhibits prostaglandin biosynthesis by suppressing the activity of prostaglandin synthetase enzyme, thereby significantly reducing the manifestations of inflammation and increasing the sensitivity of nerve endings to mechanical stimuli and the action of biologically active substances produced at the site of inflammation.

In rheumatic diseases, the anti-inflammatory and analgesic effects of Diclofenac Euro reduce the intensity of pain (both at rest and during movement), morning stiffness, joint swelling, and thus improve the patient's functional status.

In injuries and the post-traumatic period, diclofenac reduces pain and inflammatory edema.

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

Pharmacokinetics.

Diclofenac is rapidly and completely absorbed from enteric-coated tablets. After a single oral dose of Diclofenac Euro 50 mg, maximum plasma concentration (Cmax) is reached in approximately 2–3 hours and amounts to 1.5 μg/mL. The plasma concentration of the substance is linearly proportional to the dose. No changes in diclofenac pharmacokinetics were observed with repeated administration; the drug does not accumulate when the recommended dosing interval is maintained.

The bioavailability of diclofenac is 50%. Protein binding in blood is 95–98% (primarily to albumin). Diclofenac Euro penetrates into synovial fluid, where maximum concentration is reached 2–4 hours later than in plasma. The elimination half-life from synovial fluid is 3–6 hours (the concentration of the active substance in synovial fluid 4–6 hours after administration is higher than in plasma and remains higher for the subsequent 12 hours).

Approximately 50% of the active substance undergoes "first-pass" metabolism in the liver. The area under the concentration-time curve (AUC) after oral administration is approximately half that observed after parenteral administration of the same dose. Diclofenac metabolism occurs mainly via single hydroxylation and conjugation with glucuronic acid. The CYP2C9 enzyme P450 system is also involved in the drug's metabolism. The pharmacological activity of metabolites is lower than that of diclofenac.

Systemic clearance of diclofenac is 260 mL/min. The elimination half-life from plasma is 1–2 hours. 60% of the administered dose is excreted via the kidneys into urine as metabolites, in the form of glucuronide conjugates of the intact molecule and as metabolites, most of which are also converted into glucuronide conjugates; less than 1% is excreted unchanged; the remainder of the dose is excreted in the form of metabolites via bile.

In patients with severe renal impairment (creatinine clearance less than 10 mL/min), the relative proportion of metabolite excretion via bile increases. Calculated steady-state plasma concentrations of hydroxylated metabolites were approximately four times higher than in healthy volunteers. In elderly individuals and in patients with chronic hepatitis and compensated liver cirrhosis, no significant changes in diclofenac pharmacokinetics were observed.

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 accompanied by inflammation and edema, e.g. following dental or orthopedic procedures;
• pain and/or inflammation associated with inflammatory gynecological conditions, such as primary dysmenorrhea or adnexitis;
• as an adjunctive agent in severe inflammatory ENT disorders accompanied by pain, e.g. pharyngotonsillitis, otitis.

According to generally accepted approaches to the treatment of infectious-inflammatory diseases, etiotropic agents should also be used. Fever alone is not an indication for the use of this drug.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients;
• active gastric and/or duodenal ulcer, gastrointestinal hemorrhage or perforation;
• gastrointestinal bleeding or perforation in medical history related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
• active peptic ulcer disease/bleeding, or recurrent peptic ulcer disease/bleeding in history (two or more separate episodes of diagnosed ulcer or bleeding);
• inflammatory bowel diseases (Crohn's disease or ulcerative colitis);
• third trimester of pregnancy;
• hepatic failure;
• renal failure (glomerular filtration rate (GFR) < 15 mL/min/1.73 m²);
• congestive heart failure (NYHA functional class 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 in whom administration of ibuprofen, acetylsalicylic acid, or other nonsteroidal anti-inflammatory drugs triggers attacks of bronchial asthma, angioedema, urticaria, or acute rhinitis, nasal polyps, or other allergic symptoms.

Interaction with other medicinal products and other forms of interactions.

The interactions listed below have been observed during the use of Diclofenac Euro and/or diclofenac in other dosage forms and doses.

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 NSAIDs, including diclofenac, with diuretics or antihypertensive agents (e.g., beta-blockers, angiotensin-converting enzyme [ACE] inhibitors) may reduce antihypertensive effects by inhibiting the synthesis of vasodilatory prostaglandins. Therefore, such combinations should be used with caution, especially in elderly patients: blood pressure should be carefully monitored. Patients should receive adequate fluid intake, and renal function should be monitored after initiation of combination therapy and regularly thereafter, particularly when diuretics and ACE inhibitors are used, due to an 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 recommended.

Anticoagulants and antithrombotic agents: should be prescribed with caution, as concomitant use with diclofenac increases the risk of bleeding. Although clinical studies do not indicate that diclofenac affects the action of anticoagulants, there have been isolated reports of increased bleeding risk in patients receiving diclofenac and anticoagulants simultaneously. Therefore, to ensure that 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 systemically acting NSAIDs or corticosteroids may increase the frequency of gastrointestinal adverse reactions (gastrointestinal bleeding or ulceration). Concomitant use of two or more NSAIDs should be avoided.

Selective serotonin reuptake inhibitors (SSRIs). Concomitant administration of systemically acting NSAIDs, including diclofenac, with SSRIs increases the risk of gastrointestinal bleeding.

Antidiabetic agents. Clinical studies have shown that diclofenac can be administered concomitantly with oral antidiabetic agents without affecting their clinical efficacy. However, there have been some reports of both hypoglycemia and hyperglycemia, necessitating dose adjustments of antidiabetic agents during diclofenac treatment. Therefore, blood glucose monitoring is recommended during combination therapy.

There have also been isolated reports of metabolic acidosis with concomitant use of diclofenac, particularly in patients with pre-existing renal impairment.

Methotrexate. Diclofenac Euro may inhibit renal tubular clearance of methotrexate, leading to elevated methotrexate levels. NSAIDs should be used with caution at least 24 hours before or after methotrexate administration, as methotrexate blood concentrations may increase and enhance 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. Diclofenac Euro, like other NSAIDs, may increase cyclosporine nephrotoxicity due to effects on renal prostaglandins; therefore, diclofenac should be administered at lower doses than in patients not receiving cyclosporine.

Tacrolimus. Concomitant use of NSAIDs with tacrolimus increases the risk of nephrotoxicity, possibly mediated by NSAID-induced anti-prostaglandin effects in the kidneys and the calcineurin inhibitor.

Quinolone antibiotics. There have been isolated reports of seizures possibly associated with concomitant use of quinolones and NSAIDs. Seizures 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 potential for increased phenytoin effects.

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, 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. Diclofenac should be used with caution concomitantly with CYP2C9 inhibitors (such as sulfaphenazole and voriconazole), as this may lead to a significant increase in plasma concentration and effect of diclofenac due to inhibition of its metabolism.

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 concentration and efficacy of diclofenac.

Special precautions for use.

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

Concomitant use of the medicinal product Diclofenac Euro and other systemically acting NSAIDs, including selective COX-2 inhibitors, should be avoided due to the lack of evidence for synergistic effects and the potential for additive adverse effects.

Placebo-controlled studies have shown an increased risk of thrombotic cardiovascular and cerebrovascular complications with the use of certain selective COX-2 inhibitors. A direct correlation between this risk and the COX-1/COX-2 selectivity of individual NSAIDs has not yet been established. Due to the absence of comparable clinical trial data on long-term treatment with maximum doses of diclofenac, a similar increased risk cannot be excluded. A careful benefit-risk assessment should be performed before prescribing diclofenac to patients with clinically confirmed ischemic heart disease, cerebrovascular disorders, peripheral arterial occlusive disease, or significant risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, or smoking). The lowest effective dose should be used for the shortest possible duration of treatment.

NSAID effects on the kidneys include fluid retention with edema and/or arterial hypertension. Therefore, diclofenac should be used with caution in patients with impaired cardiac function and other conditions predisposing to fluid retention. Caution is also required if the patient is concurrently taking diuretics or ACE inhibitors, or is prone to hypovolemia.

These effects are generally more serious in elderly patients. Caution should be exercised when prescribing the drug to elderly individuals (over 65 years of age). In particular, the lowest effective dose is recommended for frail elderly patients and those with low body weight.

If gastrointestinal bleeding or ulcers occur in patients undergoing treatment with Diclofenac Euro, its use should be discontinued.

Allergic reactions (including anaphylactic/anaphylactoid reactions) may rarely occur with diclofenac, as with other NSAIDs, even without prior exposure to diclofenac.

Hypersensitivity reactions may progress to Kounis syndrome, a serious allergic reaction that may lead to myocardial infarction. Symptoms of such reactions may include chest pain occurring in combination with an allergic reaction to diclofenac.

Like other NSAIDs, Diclofenac Euro, due to its pharmacodynamic properties, may mask signs and symptoms of infection.

Enteric-coated tablets of Diclofenac Euro contain lactose. Diclofenac Euro should not be administered to patients with rare hereditary galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.

Gastrointestinal tract (GIT) effects.

When using all NSAIDs, whether COX-2 selective or not, including diclofenac, cases of gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation, which may be fatal, have been reported. These events may occur at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal events. These effects generally have more serious consequences in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.

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

As with other NSAIDs, careful medical supervision and special caution are required when prescribing Diclofenac Euro to patients with symptoms indicating gastrointestinal disorders or with a history of ulcers, gastrointestinal bleeding, or perforation. The risk of gastrointestinal bleeding increases with higher NSAID doses, in patients with a history of peptic ulcer (especially if complicated by bleeding or perforation), and in elderly patients. To reduce the risk of gastrointestinal toxicity in such patients, treatment should be initiated and maintained at the lowest effective doses. For such patients, as well as for those requiring concomitant use of acetylsalicylic acid (ASA/aspirin)-containing drugs or other agents increasing the risk of gastrointestinal 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, particularly elderly individuals, should inform their physician about any unusual abdominal symptoms (especially gastrointestinal bleeding). The drug should be prescribed with caution to patients who are concurrently taking medications that increase the risk of ulceration or bleeding (systemic corticosteroids, anticoagulants (e.g., warfarin), antiplatelet agents (e.g., ASA), or selective serotonin reuptake inhibitors).

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

Hepatic effects.

Patients with hepatic impairment should be under continuous medical supervision, as their condition may worsen.

When using NSAIDs, including diclofenac, liver enzyme levels may increase. These elevations were generally reversible upon discontinuation of the drug.

This phenomenon was observed very frequently in clinical trials with diclofenac (approximately in 15% of patients), but rarely accompanied by clinical symptoms. In most cases, increases were within borderline levels. Moderate increases (≥ 3 to < 8 times the upper limit of normal) were observed frequently (in 2.5% of cases), while pronounced increases (≥ 8 times the upper limit of normal) occurred in approximately 1% of cases. Elevated liver enzymes were associated with clinically evident liver injury in 0.5% of cases in the aforementioned clinical trials.

It should be noted that Diclofenac Euro is recommended only for short-term treatment (not more than 2 weeks). In cases of prolonged diclofenac use, preventive measures include regular monitoring of liver function and liver enzyme levels. The use of this drug should be discontinued if liver function impairment or deterioration occurs, if clinical signs or symptoms suggest liver disease development, or if other symptoms such as eosinophilia or rash appear.

In addition to elevated liver enzymes, rare cases of severe hepatic reactions, including jaundice, fulminant hepatitis, hepatic necrosis, and hepatic failure, some resulting in fatal outcomes, have been reported.

The course of diseases such as hepatitis may occur without prodromal symptoms. Diclofenac should be used with caution in patients with hepatic porphyria due to the potential risk of provoking an attack.

Renal effects.

NSAIDs, including diclofenac, reduce prostaglandin levels, which are important for maintaining renal blood flow.

Since fluid retention, edema, and hypertension have been frequently (1–10%) reported during treatment with NSAIDs, including diclofenac, special attention should be paid to patients with impaired cardiac or renal function, a history of arterial hypertension, elderly patients, patients concurrently taking diuretics or drugs significantly affecting renal function, and patients with a substantial reduction in extracellular fluid volume for any reason (e.g., pre-/post-surgery). Monitoring of renal function is recommended when prescribing Diclofenac Euro in such cases. Discontinuation of therapy usually results in return to the pre-treatment state.

Skin effects.

Serious skin reactions (some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) have been very rarely reported in association with the use of NSAIDs, including the medicinal product Diclofenac Euro. The highest risk of these reactions occurs early in the course of therapy; reactions typically appear within the first month of treatment. The use of Diclofenac Euro 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 diseases.
Patients with systemic lupus erythematosus (SLE) and mixed connective tissue diseases have an increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects.

Treatment with Diclofenac Euro is generally not recommended for patients with diagnosed cardiovascular diseases (heart failure, ischemic heart disease, peripheral arterial disease) or uncontrolled arterial hypertension.

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation and only at doses up to 100 mg daily if treatment exceeds 4 weeks. Since cardiovascular risks increase with higher doses and longer duration of diclofenac treatment, it should be used for the shortest possible duration and at the lowest effective dose. The patient's need for diclofenac use for symptom relief and response to therapy should be periodically reviewed, especially when treatment lasts longer than 4 weeks.

Appropriate monitoring and recommendations are necessary for patients with a history of arterial hypertension and/or mild to moderate congestive heart failure, as fluid retention and edema have been reported with the use of NSAIDs, including diclofenac.

Diclofenac Euro should be used with caution in patients taking concomitant diuretics or ACE inhibitors and in patients at increased risk of hypovolemia.

Clinical trial data and epidemiological evidence suggest that the use of diclofenac, particularly at high doses (150 mg/day) and for prolonged periods, slightly increases the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Diclofenac should not be prescribed to patients with uncontrolled arterial hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. If use is necessary, it may only be considered after careful risk-benefit assessment and only at a dosage not exceeding 100 mg daily for no more than 4 weeks.

Patients should be informed about the possibility of serious thrombotic events (chest pain, dyspnea, weakness, speech disturbances) occurring at any time during treatment. In such cases, immediate medical attention is required.

Hematological effects.

The medicinal product Diclofenac Euro is recommended only for short-term treatment. If this drug is prescribed for a longer period, regular monitoring of the hemogram is recommended (as with other NSAIDs).

Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation; therefore, careful monitoring is required in patients with coagulation disorders, hemorrhagic diathesis, or hematological disorders.

History of asthma.

In patients with bronchial asthma, seasonal allergic rhinitis, nasal mucosal edema (e.g., nasal polyps), chronic obstructive pulmonary diseases (COPD), or chronic respiratory tract infections (especially those associated with allergic, rhinitis-like symptoms), adverse effects such as bronchial asthma exacerbation ("analgesic intolerance" or analgesic-induced asthma), Quincke's edema, or urticaria occur more frequently with NSAID use than in other patients. Therefore, special precautions (readiness for emergency care) are required. The above also applies to patients with allergic reactions to other drugs, e.g., rash, pruritus, urticaria.

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

The product contains the colorant sunset yellow FCF (E 110), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy.
From the 20th week of pregnancy, the use of Diclofenac Euro may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after the start of treatment and is usually reversible upon discontinuation of treatment. Diclofenac Euro should not be used during the first and second trimesters of pregnancy, except when the potential benefit to the mother outweighs the potential risk to the fetus. For women planning pregnancy or during the first or second trimester, the dose of the medicinal product should be as low as possible, and the duration of treatment as short as possible. Prenatal monitoring for oligohydramnios should be considered after exposure to Diclofenac Euro for several days starting from the 20th week of pregnancy. Diclofenac Euro use should be discontinued if oligohydramnios is detected.

Like other NSAIDs, the drug is contraindicated during the third trimester of pregnancy (due to possible inhibition of uterine contractility and premature closure of the fetal arterial duct) (see section "Contraindications").

Inhibition of prostaglandin synthesis may adversely affect the course of pregnancy and/or embryonic/fetal development. Epidemiological data suggest an increased risk of miscarriage and/or congenital heart defects and gastroschisis after 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 a prostaglandin synthesis inhibitor leads to increased 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, was observed.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus as follows:

• cardiopulmonary toxicity (with premature closure of the arterial duct and pulmonary hypertension);
• impaired renal function (see above).

Effects of prostaglandin synthesis inhibitors on the mother and newborn at the end of pregnancy:

• possible 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, Diclofenac Euro is contraindicated during the third trimester of pregnancy.

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

If treatment is necessary, breastfeeding should be discontinued.

Female fertility.
Like other NSAIDs, Diclofenac Euro may negatively affect female fertility; therefore, it is not recommended for women planning pregnancy. For women experiencing infertility or undergoing fertility investigations, discontinuation of Diclofenac Euro should be considered.

Based on animal studies, impairment of male reproductive function cannot be excluded. The relevance of these findings to humans has not been established.

Ability to affect reaction speed when driving vehicles or operating machinery.

Generally, no effect on reaction speed is observed when the drug is taken at recommended doses and for short-term treatment. However, patients who experience visual disturbances, dizziness, vertigo, somnolence, other central nervous system disorders, lethargy, or fatigue during treatment with Diclofenac Euro should refrain from driving vehicles or operating machinery.

Method of Administration and Dosage

According to general recommendations, the drug should be used at the lowest effective dose sufficient to relieve disease symptoms for the shortest possible duration.

Tablets should be swallowed whole, without chewing, with a small amount of water, during or after meals.

For adults: the recommended dose is 100–150 mg daily. The daily dose should be divided into 2–3 doses. After achieving the optimal therapeutic effect, the dose may be gradually reduced to a maintenance level of 75–100 mg daily. The daily dose of the drug should not exceed 150 mg.

In primary dysmenorrhea, the daily dose of Diclofenac Euro should be individually adjusted. The daily dose usually ranges from 50–150 mg. The initial dose may be 50–100 mg; however, if necessary, the dose may be increased during the following menstrual cycles up to the maximum dose of 200 mg daily. Treatment with Diclofenac Euro tablets should begin at the onset of the first symptoms and continue for several days depending on the patient's response and symptom severity.

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

Elderly patients: although the pharmacokinetics of Diclofenac Euro in elderly patients is not clinically significantly impaired, special caution is required because these patients are more prone 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 during NSAID therapy.

Cardiovascular diseases or significant risk factors

Diclofenac is contraindicated in patients with congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disorders.

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation. Since cardiovascular risks increase with higher doses and longer duration of diclofenac treatment, the drug should be used for the shortest possible duration and at the lowest effective dose. The need for diclofenac use to relieve symptoms and the patient's response to therapy should be reviewed regularly.

Renal function impairment

Diclofenac is contraindicated in patients with renal insufficiency (GFR < 15 mL/min/1.73 m²).

No specific studies have been conducted in patients with renal impairment, and no dose adjustment recommendations are available. Diclofenac should be prescribed with caution to patients with moderate or severe renal impairment.

Hepatic function impairment

Diclofenac is contraindicated in patients with hepatic insufficiency.

No specific studies have been conducted in patients with hepatic impairment, and no dose adjustment recommendations are available. Diclofenac should be prescribed with caution to patients with moderate or severe hepatic impairment.

Children

The drug is not administered to children at this dosage strength due to the high content of active substance.

Overdose.

Symptoms. There is no specific clinical picture characteristic of diclofenac overdose. Overdose may cause symptoms such as dizziness, disorientation, headache, drowsiness, coma, nausea, vomiting, diarrhea, abdominal pain, epigastric pain, gastrointestinal bleeding, psychomotor agitation, tinnitus, seizures, and loss of consciousness. In cases of severe poisoning, acute renal failure and liver damage may occur.

Treatment of acute NSAID poisoning, including diclofenac, consists of supportive and symptomatic therapy. This includes management of arterial hypotension, renal failure, seizures, gastrointestinal complications, and respiratory depression. Specific treatments such as forced diuresis, dialysis, or hemoperfusion are unlikely to be beneficial in eliminating Diclofenac Euro, as the active substances of the drug are highly protein-bound and undergo extensive metabolism.

Activated charcoal may be administered after ingestion of potentially toxic doses. After ingestion of potentially life-threatening doses, gastric decontamination (e.g., induced emesis, gastric lavage) may be performed.

Side effects.

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

Blood and lymphatic system disorders: agranulocytosis, hemolytic anemia; aplastic anemia; anemia associated with internal bleeding; ecchymosis; leukopenia; neutropenia; thrombocytopenia, with or without purpura; pancytopenia. Initial symptoms may include fever, pharyngitis, superficial oral ulcers, flu-like symptoms, severe lethargy, nosebleeds, and skin bleeding.

Immune system disorders: hypersensitivity, anaphylactic/anaphylactoid reactions (including arterial hypotension and shock), angioedema (including facial swelling, tongue swelling, laryngeal edema), allergic vasculitis, and pneumonia.

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

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

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

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

Cardiovascular disorders: arterial hypertension, arterial hypotension, palpitations, arrhythmia, cardialgia, collapse, chest pain, epistaxis, vasculitis, tachycardia, congestive heart failure, myocardial infarction, Kounis syndrome.

Respiratory system disorders: dyspnea (difficulty breathing), asthma (including breathlessness), pneumonitis.

Gastrointestinal disorders: gastropathy (gastralgia and epigastric discomfort, nausea, vomiting, bloating, belching, heartburn, flatulence, diarrhea, hemorrhagic diarrhea, abdominal pain, dyspepsia), erosive-ulcerative gastrointestinal disorders (including esophageal, gastric, peptic ulcer, gastro-intestinal ulcer, with or without bleeding or perforation), multiple gastrointestinal ulcers, gastric or intestinal perforation, peritonitis (severe sharp pain, burning sensation in the epigastrium, blood in stool, melena, vomiting with blood), sometimes fatal, especially in elderly patients; gastritis, gastrointestinal bleeding, nonspecific colitis (with or without bleeding), esophagitis, dry mouth, constipation, toxic hepatitis; less common adverse reactions include vomiting, colitis or exacerbation thereof (including hemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease), decreased appetite or anorexia, dryness and soreness of the oral mucosa, cramping sensation, glossitis, aphthous stomatitis (erosions, ulcers, white coating on the oral mucosa), esophageal dysfunction, development of diaphragm-like intestinal strictures, pancreatitis.

Hepatobiliary disorders: increased serum transaminase levels, fulminant hepatitis, hepatitis with or without jaundice, hepatic dysfunction, fulminant hepatitis, hepatic necrosis, liver failure.

Skin and subcutaneous tissue disorders: pruritus, skin rashes (mainly erythema or urticaria), skin hyperemia, bullous rashes, exanthema, eczema, erythema, exudative multiform erythema including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), erythroderma (exfoliative dermatitis), photosensitivity reactions, photodermatitis (severe sunburn, skin rashes, pigmentation disorders), alopecia, purpura, including allergic purpura.

Renal and urinary system disorders: fluid retention, recurrent vaginal pain of unknown origin, dysmenorrhea, hematuria, cystitis, polyuria, proteinuria, interstitial nephritis, nephrotic syndrome, oliguria or anuria, reduced kidney function, peripheral edema (especially in patients with arterial hypertension or renal insufficiency), renal medullary necrosis, renal papillary necrosis, acute renal failure.

General disorders: edema, injection site abscess.

Reproductive system and breast disorders: impotence.

Infections and infestations: exacerbation of inflammation associated with infections (e.g., development of necrotizing fasciitis) has been reported with systemic use of nonsteroidal anti-inflammatory drugs. This may be due to the mechanism of action of NSAIDs. If signs of infection appear or worsen during diclofenac use, patients should seek immediate medical attention. It is necessary to evaluate whether such condition requires treatment with an antimicrobial agent/antibiotic. Very rarely, symptoms of aseptic meningitis (neck stiffness, headache, nausea, vomiting, fever, or confusion) have been observed during diclofenac use. Patients with autoimmune diseases (systemic lupus erythematosus, mixed connective tissue disease) are considered at higher risk.

Other: changes in laboratory test results.

Clinical and epidemiological data indicate an increased risk of thrombotic complications (e.g., myocardial infarction or stroke) associated with diclofenac use, particularly at high therapeutic doses (150 mg per day) and during prolonged treatment.

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 related compounds, which may disrupt retinal blood flow regulation and lead to visual disturbances. If such symptoms occur during diclofenac treatment, an ophthalmological examination should be performed to rule out other possible causes.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging.

10 tablets in a blister, 1, 2, or 10 blisters in a cardboard box;

10 tablets in each of 2 blisters joined together, 5 combo blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Uniq Pharmaceuticals Laboratories (a division of J. B. Chemicals and Pharmaceuticals Ltd.).

Manufacturer's address and place of business.

Plot No. 215-219, G.I.D.C. Industrial Area, Panoli - 394 116, Bharuch District, India.