Ortofen-zdorovya forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ORTOPHEN- ZDOROVYE FORTE

Composition:

Active ingredient: 1 tablet contains 50 mg of sodium diclofenac;

Excipients: monohydrate lactose; crospovidone; microcrystalline cellulose; sodium croscarmellose; magnesium stearate; colloidal anhydrous silicon dioxide; dry mixture "Acryl-eze white" containing talc, titanium dioxide (E 171), methacrylate copolymer (type C), sodium lauryl sulfate, sodium bicarbonate, silicon dioxide; macrogol 6000; Ponceau 4R (E 124); azorubine (E 122).

Medicinal form. Enteric-coated tablets.

Main physicochemical properties: enteric-coated tablets, from pink to pink with a reddish hue. Two layers are visible in cross-section.

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

ATC code M01AB05.

Pharmacological properties.

Pharmacodynamics. The drug contains sodium diclofenac, a non-steroidal 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 inhibit proteoglycan biosynthesis in cartilage tissue.

Pharmacokinetics. Although absorption is complete, the onset of action may be delayed due to passage through the stomach, which can be influenced by food intake, slowing 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 tablet.

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 following administration of an equivalent parenteral dose.

The pharmacokinetic characteristics of the drug do not change upon repeated administration. Accumulation does not occur under recommended dosing regimens.

Diclofenac binding to plasma proteins is 99.7%, with albumin binding at 99.4%.

Diclofenac penetrates into synovial fluid, where its Cmax is reached 2–4 hours later than in plasma. The half-life (T½) from synovial fluid is 3–6 hours. Two hours after reaching Cmax in plasma, diclofenac concentration in synovial fluid remains higher; this phenomenon persists for 12 hours.

Diclofenac was detected at low concentrations (100 ng/mL) in breast milk in one woman. The estimated amount of drug transferred to the infant via breast milk is equivalent to a dose of 0.03 mg/kg/day.

Diclofenac is partially metabolized via glucuronidation of the unchanged molecule, but primarily through single and multiple hydroxylations and methoxylation, leading to the formation of several phenolic metabolites, most of which form conjugates with glucuronic acid. Two of these phenolic metabolites are biologically active, but significantly less so than diclofenac.

Total systemic clearance of diclofenac from plasma is 263 ± 56 mL/min (mean value ± SD). The terminal T½ from plasma is 1–2 hours. The T½ in plasma of four metabolites, including two pharmacologically active ones, is also short, ranging from 1–3 hours. Approximately 60% of the administered dose is excreted in urine as the glucuronide conjugate 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.

No significant effect of patient age on absorption, metabolism, and elimination of the drug has been observed, except for the finding that in five elderly patients, a 15-minute intravenous infusion resulted in a 50% higher plasma concentration of the drug than expected in young healthy individuals.

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 less than 10 mL/min, calculated steady-state concentrations of hydroxylated metabolites in plasma were approximately four times higher than in healthy individuals. However, ultimately, all metabolites were excreted via bile.

In patients with chronic hepatitis or compensated liver cirrhosis, 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, spondyloarthritis);
• Spinal pain syndromes;
• Rheumatic diseases of soft tissues surrounding joints;
• Acute gout attacks;
• Post-traumatic and postoperative pain syndromes accompanied by 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 basic therapy agents. Fever alone is not an indication for use of this drug.

Contraindications.

• Hypersensitivity to the components of the drug.
• Active gastric or intestinal ulcer; gastrointestinal bleeding or perforation.
• History of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs).
• Active peptic ulcer disease of the stomach or duodenum/bleeding, or recurrent peptic ulcer/bleeding 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.
• Renal insufficiency (glomerular filtration rate < 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 diseases.
• Treatment of perioperative pain in aortocoronary bypass surgery (or use of cardiopulmonary bypass apparatus).
• The drug, like other NSAIDs, is contraindicated in patients who have experienced attacks of bronchial asthma, angioedema, urticaria, or rhinitis, nasal polyps, or other allergic symptoms in response to ibuprofen, acetylsalicylic acid, or other NSAIDs.

Interaction with other medicinal products and other types of interactions. The interactions listed below have been observed with diclofenac in tablet form and/or other dosage forms.

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

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

Diuretics and antihypertensive agents. As with other NSAIDs, 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 under close monitoring for blood pressure. Adequate hydration is recommended, and monitoring of renal function is advised after initiation and on a regular basis during concomitant therapy, particularly with diuretics and ACE inhibitors, due to increased risk of nephrotoxicity.

Agents causing hyperkalemia. Concomitant therapy with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increased serum potassium levels; therefore, more frequent monitoring of patients is recommended.

Anticoagulants and antiplatelet agents. Concomitant use may increase the risk of bleeding, so precautionary measures are recommended. Although existing clinical data do not indicate an effect of diclofenac on anticoagulant activity, there are isolated reports of increased bleeding risk in patients taking diclofenac and anticoagulants simultaneously. Therefore, to ensure no dosage adjustments are needed, careful monitoring of such patients is recommended. Like other NSAIDs, diclofenac at high doses may temporarily inhibit platelet aggregation.

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

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

Antidiabetic agents. Diclofenac may be used together with oral antidiabetic agents without altering their therapeutic effect. However, there are some reports of both hypoglycemia and hyperglycemia, necessitating dosage adjustments of antidiabetic agents during diclofenac use. Therefore, as a precaution, blood glucose monitoring is recommended during combination therapy.

There are also isolated reports of metabolic acidosis when diclofenac is used concomitantly, particularly in patients with pre-existing renal dysfunction.

Methotrexate. Diclofenac may inhibit renal tubular clearance of methotrexate, leading to elevated methotrexate levels. Caution is advised when prescribing NSAIDs, including diclofenac, less than 24 hours before or after methotrexate administration, as this may increase methotrexate blood concentration and enhance its toxic effects. 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 and tacrolimus. The effect of diclofenac, like other NSAIDs, on prostaglandin synthesis in the kidneys may enhance the nephrotoxicity of cyclosporine and tacrolimus. Therefore, diclofenac should be used at lower doses than in patients not receiving cyclosporine or tacrolimus.

Quinolone antibacterials. 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 is advised when considering quinolone use in patients already receiving NSAIDs.

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

Cholestyramine and colestipol. These agents may delay or reduce diclofenac absorption. 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 glycoside plasma levels.

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 recommended when co-prescribing diclofenac with CYP2C9 inhibitors (e.g., voriconazole), which may lead to a significant increase in plasma Cmax and exposure to diclofenac.

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

Special precautions for use.

General.

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

Concomitant use of the drug with systemic NSAIDs, such as selective COX-2 inhibitors, should be avoided due to lack of evidence for synergistic effects and potential for additive adverse effects.
Placebo-controlled studies have shown an increased risk of thrombotic cardiovascular and cerebrovascular complications with certain selective COX-2 inhibitors. Since there are no comparative clinical data on long-term use of diclofenac at maximum doses, a similar risk cannot be excluded. A direct correlation between this risk and the COX-1/COX-2 selectivity of individual NSAIDs has not yet been established. In the absence of such data, a careful risk-benefit assessment should be performed before prescribing diclofenac to patients with clinically confirmed ischemic heart disease, cerebrovascular disorders, peripheral arterial occlusive diseases, or significant risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). Due to this risk, the lowest effective dose should be used for the shortest possible duration.

The effect of NSAIDs on the kidneys includes fluid retention with edema and/or arterial hypertension. Diclofenac should be used with caution in patients with cardiac dysfunction or other conditions predisposing to fluid retention. This is also recommended for patients concurrently taking diuretics or ACE inhibitors or those prone to hypovolemia.

Consequences are generally more serious in elderly patients. Caution is required when prescribing the drug to elderly individuals. Special caution is advised for patients over 65 years of age. In particular, the lowest effective dose is recommended for frail elderly patients or those with low body weight.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur even without prior exposure to diclofenac. Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that may cause myocardial infarction. Symptoms of such reactions may include chest pain occurring in combination with an allergic reaction to diclofenac.

Due to its pharmacodynamic properties, the drug, like other NSAIDs, may mask signs and symptoms of infection.

The drug contains lactose; therefore, patients with known sugar intolerance should consult their physician before taking this medication.

Ponceau 4R (E 124) and azorubine (E 122) may cause allergic reactions.

Gastrointestinal (GI) tract effects. Cases of gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation have been reported with all NSAIDs, including COX-2-selective and non-selective agents such as diclofenac. These events may be fatal and may occur at any time during treatment, with or without warning symptoms or prior history of serious GI events. These events generally have more serious consequences in elderly patients. If GI bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.

As with other NSAIDs, special medical supervision and caution are required for patients with symptoms indicating GI disturbances when diclofenac is prescribed. The risk of GI bleeding, ulceration, or perforation increases with higher NSAID doses, particularly diclofenac.

Elderly patients have a higher frequency of adverse reactions to NSAIDs, especially 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 doses. For such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid (ASA/aspirin) or other drugs capable of increasing GI adverse effects, consideration should be given to combined therapy with protective agents (e.g., proton pump inhibitors or misoprostol). Patients with a history of GI toxicity, especially elderly ones, should report any unusual abdominal symptoms (particularly GI bleeding). Caution is also required for patients receiving concomitant medications that may 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).

Use of NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic insufficiency. Careful medical monitoring is recommended when using diclofenac after gastrointestinal surgery.

Hepatic effects. Close medical supervision is required if the drug is prescribed to patients with impaired liver function, as their condition may worsen.
As with other NSAIDs, one or more liver enzymes may increase during diclofenac use. Such increases were generally reversible upon discontinuation of the drug.

Elevated liver enzymes were very commonly observed in clinical trials with diclofenac (approximately 15% of patients), but rarely accompanied by clinical symptoms. Most cases involved borderline increases. Moderate increases (≥3 to <8 times the upper limit of normal) occurred frequently (in 2.5% of cases), while marked 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.

Regular monitoring of liver function and liver enzyme levels is recommended as a precaution during long-term treatment. The drug should be discontinued if liver function abnormalities persist or worsen, if clinical signs or symptoms suggest progressive liver disease, or if other manifestations occur (e.g., eosinophilia, rash). In addition to elevated liver enzymes, rare reports of severe hepatic reactions have been documented, including jaundice, fulminant hepatitis, hepatic necrosis, and hepatic failure, which in some cases led to death.

Diseases such as hepatitis may progress without prodromal symptoms. Caution is required when prescribing the drug to patients with hepatic porphyria due to the potential to provoke 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 NSAID treatment, including diclofenac, special attention should be paid to patients with cardiac or renal dysfunction, history of arterial hypertension, elderly patients, patients receiving concomitant diuretic therapy or drugs significantly affecting renal function, and patients with significant extracellular fluid volume depletion from any cause, e.g., before or after major surgery. In such cases, monitoring of renal function is recommended as a precaution. Discontinuation of therapy usually results in return to the pre-treatment state.

Skin effects. Rare but serious skin reactions have been reported with diclofenac use (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), generalized bullous fixed drug eruption, and drug hypersensitivity syndrome with eosinophilia and systemic symptoms (DRESS). The highest risk for these reactions occurs early in therapy, with most cases appearing within the first month of treatment. The drug 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 may have an increased risk of aseptic meningitis.

Cardiovascular and cerebrovascular effects. Treatment with the drug is generally not recommended in 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 (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation and at doses not exceeding 100 mg daily if treatment exceeds 4 weeks. Since cardiovascular risks associated with diclofenac may increase with dose and duration of treatment, it should be used for the shortest possible duration and at the lowest effective dose. The need for diclofenac and response to therapy should be periodically reviewed, especially if treatment exceeds 4 weeks.

Patients with a history of arterial 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.

The drug should be used with caution in patients taking concomitant diuretics or ACE inhibitors or those at increased risk of hypovolemia.

Available data indicate that diclofenac, particularly at high doses (150 mg/day) and with prolonged use, may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Diclofenac is not recommended for patients with uncontrolled arterial hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial diseases, and/or cerebrovascular disease. If use is necessary, it may be considered only after careful risk-benefit assessment and at a dose 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), which may occur at any time. In such cases, immediate medical attention is required.

Hematological effects. With prolonged use of this drug, as with other NSAIDs, monitoring of blood count with leukocyte formula is recommended.

The drug may temporarily inhibit platelet aggregation. Close monitoring is required in patients with coagulation disorders, hemorrhagic diathesis, or hematological disorders.

History of asthma. Patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (i.e., nasal polyps), chronic obstructive lung diseases, or chronic respiratory tract 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 asthma), Quincke's edema, or urticaria. Therefore, special precautionary measures (readiness for emergency care) are recommended for such patients. This also applies to patients with allergic reactions to other substances, such as rash, pruritus, or 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 thereof.

Use during pregnancy or breastfeeding.

Pregnancy. From the 20th week of pregnancy, use of diclofenac may impair fetal renal function, leading to oligohydramnios and, in some cases, neonatal renal failure. These adverse effects are observed on average after several days or weeks of treatment, although oligohydramnios has developed as early as 48 hours after starting NSAID therapy in rare cases. Oligohydramnios often, but not always, resolves after discontinuation of NSAID treatment. Complications of prolonged oligohydramnios may include, for example, limb contractures and pulmonary hypoplasia. In some post-marketing clinical observations, neonatal renal failure required invasive procedures such as exchange transfusion or dialysis.

Additionally, arterial duct constriction has been reported after second-trimester treatment, which resolves in most cases after discontinuation of therapy.

If treatment with the drug lasts more than 48 hours, ultrasound monitoring of amniotic fluid and fetal heart should be considered. If oligohydramnios or arterial duct constriction occurs, the drug should be discontinued and appropriate treatment initiated according to clinical practice.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological studies indicate 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%. This risk is believed to be proportional to the dose and duration of treatment.

Animal studies have shown that prostaglandin synthesis inhibitors increase pre- and post-implantation loss and embryonic/fetal mortality. In animals treated with prostaglandin synthesis inhibitors during organogenesis, increased incidence of various developmental abnormalities, including cardiovascular defects, has been observed.

In the first and second trimesters of pregnancy, the drug may be prescribed only if the expected benefit to the woman outweighs the potential risk to the fetus. If the drug is used by a woman planning pregnancy or during the first or second trimester, the dose should be as low as possible and treatment duration as short as possible.

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, which may progress to renal failure with oligohydramnios (see above).

On the mother and newborn, especially near term:

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

Therefore, the drug is contraindicated during the third trimester of pregnancy.

Breastfeeding. Like other NSAIDs, diclofenac is excreted in small amounts in breast milk. Therefore, the drug should not be used during breastfeeding to avoid adverse effects on the infant. If treatment is necessary, breastfeeding should be discontinued.

Female fertility. Like other NSAIDs, the drug may negatively affect female fertility; therefore, it is not recommended for women planning pregnancy. For women with fertility problems or undergoing infertility evaluation, discontinuation of the drug should be considered. Based on relevant animal studies, impairment of male reproductive function cannot be excluded. The relevance of these data to humans is not established.

Ability to affect reaction rate when driving or operating machinery. Patients who experience visual disturbances, dizziness, vertigo, somnolence, central nervous system disorders, lethargy, or fatigue during treatment should not drive or operate complex machinery.

Method of administration and dosage. To minimize adverse effects, the drug should be used at the lowest effective dose for the shortest duration necessary to control symptoms, considering the treatment goals for each individual patient. Tablets should preferably be taken before meals with liquid; they should not be divided or chewed.

The initial dose is usually 100–150 mg daily. For mild symptoms and long-term therapy, a dose of 75–100 mg daily is sufficient. The daily dose should be divided into 2–3 doses. To prevent nocturnal pain or morning joint stiffness, treatment with diclofenac may be supplemented with rectal suppositories before bedtime. The daily dose should not exceed 150 mg.

For primary dysmenorrhea, the daily dose should be individually adjusted, usually 50–150 mg. The initial dose may be 50–100 mg daily, but if necessary, it may be increased over several menstrual cycles to the maximum of 150 mg daily. The recommended maximum daily dose is 150 mg. Treatment should begin after the onset of the first painful symptoms and continue for several days, depending on symptom regression.

For children aged 14 to 18 years, the drug should be administered at 75–150 mg daily in 2 or 3 doses.

The daily dose should not exceed 150 mg.

If diclofenac sodium 75 mg is required, the drug should be used in the appropriate dosage or dosage form.

Elderly patients (aged 65 years and older): Although the pharmacokinetics of the drug are not clinically significantly altered in elderly patients, NSAIDs should be used with particular caution in elderly patients, who are generally more susceptible to adverse reactions. Specifically, the lowest effective doses are recommended for frail elderly patients or those with low body weight; such patients should also be monitored for gastrointestinal bleeding during NSAID therapy.

Existing cardiovascular diseases or significant risk factors: Diclofenac may be prescribed to patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation and, if used for more than 4 weeks, at a maximum daily dose of 100 mg (see "Special precautions for use"). 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. The need for diclofenac and response to therapy should be periodically reviewed.

Patients with impaired renal function: The drug is contraindicated in patients with renal insufficiency (glomerular filtration rate < 15 mL/min/1.73 m²).

No specific studies in patients with impaired renal function have been conducted, and no dosage adjustment recommendations are available. The drug should be prescribed with caution to patients with impaired renal function.

Patients with impaired hepatic function: The drug is contraindicated in patients with hepatic insufficiency.

No specific studies in patients with impaired hepatic function have been conducted, and no dosage adjustment recommendations are available. The drug should be prescribed with caution to patients with moderate to severe hepatic impairment.

Children. The drug should not be used in children under 14 years of age due to the high content of active substance.

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

Treatment. Management of acute NSAID poisoning, including diclofenac, involves supportive and symptomatic therapy. This includes treatment of manifestations such as arterial hypotension, renal failure, seizures, gastrointestinal disturbances, and respiratory depression. Specific measures such as forced diuresis, dialysis, or hemoperfusion are unlikely to be effective in eliminating NSAIDs, including diclofenac, due to extensive protein binding and extensive metabolism. Activated charcoal may be administered after ingestion of potentially toxic doses, and gastric decontamination (e.g., induced emesis, gastric lavage) may be performed after ingestion of potentially life-threatening doses.

Side effects

The undesirable effects listed below have been reported during short-term or long-term use of diclofenac.

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); angioedema (including facial swelling).

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

Nervous system disorders: headache; dizziness; somnolence; fatigue; paresthesia; memory impairment; convulsions; anxiety; 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 disturbances.

Cardiac disorders: palpitations; chest pain; heart failure; myocardial infarction; arterial hypertension; arterial hypotension; vasculitis; Kounis syndrome.

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

Gastrointestinal disorders: nausea; vomiting; diarrhea; dyspepsia; abdominal pain; flatulence; anorexia; gastritis; gastrointestinal bleeding, hematemesis, melena, hemorrhagic diarrhea; gastric and intestinal ulcers, with or without bleeding, gastrointestinal stenosis or perforation (sometimes fatal, especially in elderly patients), which may lead to peritonitis; 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 stricture of the intestine; pancreatitis.

The medicinal product may cause chronic inflammatory conditions with pseudomembranes and strictures in the distal intestine (small and large intestine).

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

Skin and subcutaneous tissue disorders: rash (including with "unknown" frequency: fixed drug eruption, generalized bullous fixed drug eruption); urticaria; bullous rash; eczema; erythema; erythema multiforme; Stevens-Johnson syndrome; Lyell’s syndrome (toxic epidermal necrolysis); exfoliative dermatitis; alopecia; photosensitivity reactions; purpura, including allergic purpura; pruritus; drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

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

Reproductive system and breast disorders: impotence.

Available 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 generally reversible upon discontinuation of the drug. The most likely mechanism of visual disturbances is inhibition of prostaglandin and related compound synthesis, which, due to disruption of retinal blood flow regulation, may alter regulation of intraocular blood pressure and lead to changes in visual acuity. If such symptoms occur during treatment with diclofenac, 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 25°C.

Keep out of reach and sight of children.

Packaging. Tablets No. 10 (10×1), No. 30 (10×3) in blisters, in a carton.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and location of business activity. Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, building 22.

(LIMITED LIABILITY COMPANY "CORPORATION "ZDOROVIYA")

Ukraine, 08301, Kyiv region, city of Boryspil, Shevchenka Street, building 100.

(Limited Liability Company "FARMEKS GROUP")