Argette rapid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ARGETT rapid (ARGETT rapid)

Composition:

Active substance: sodium diclofenac;

1 capsule contains 75 mg of sodium diclofenac;

Excipients:

Capsule contents: talc, microcrystalline cellulose, povidone K 25, colloidal anhydrous silicon dioxide, propylene glycol, methacrylate copolymer (type A);

Capsule shell: gelatin, erythrosine (E 127), titanium dioxide (E 171), yellow iron oxide (E 172), sodium lauryl sulfate.

Pharmaceutical form. Hard enteric-coated capsules.

Main physico-chemical properties: hard gelatin capsules, size 2; capsule cap and body are opaque and red-colored; contents of capsules: granules from white to cream-colored.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic drugs; acetic acid derivatives and related substances. ATC code M01A B05.

Pharmacological properties.

Pharmacodynamics.

The medicinal product ARGETT Rapid contains diclofenac sodium – a non-steroidal compound exerting pronounced anti-inflammatory, analgesic and antipyretic effects. The main mechanism of action of diclofenac is considered to be inhibition of prostaglandin biosynthesis. Prostaglandins play an important role in the pathogenesis of inflammation, pain and fever.

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

Pharmacokinetics.

After oral administration of the enteric-coated capsule, maximum plasma concentration is reached depending on gastric emptying time, on average within 1–2 hours.

Protein binding to plasma proteins is 99.7%, occurring predominantly with albumin (99.4%). The apparent volume of distribution is 0.12–0.17 L/kg.

Diclofenac penetrates into synovial fluid, where its maximum concentration is achieved 2–4 hours later than in plasma. The apparent elimination half-life from synovial fluid is 3–6 hours. Two hours after reaching maximum plasma concentration, the concentration of diclofenac in synovial fluid exceeds that in plasma, and remains higher for up to 12 hours.

Metabolism of diclofenac occurs partially via glucuronidation of the unchanged molecule, mainly through single and multiple methoxylation, leading to the formation of several phenolic metabolites (3’-hydroxy-, 4’-hydroxy-, 5’-hydroxy-, 4’,5-dihydroxy-, and 3’-hydroxy-4’-methoxy-diclofenac), most of which are converted into glucuronide conjugates. Two of these phenolic metabolites are biologically active, but significantly less so than diclofenac.

Total systemic plasma clearance of diclofenac is 263 ± 56 mL/min. The terminal elimination half-life is 1–2 hours. The elimination half-life of four metabolites, including two pharmacologically active ones, is also short – 1–3 hours. One of the metabolites, 3’-hydroxy-4’-methoxydiclofenac, has a longer elimination half-life, but this metabolite is completely inactive.

Approximately 60% of the administered dose is excreted in urine as glucuronide conjugates of the unchanged active substance as well as metabolites, most of which are glucuronide conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the administered dose is excreted via bile and feces as metabolites.

Pharmacokinetics in specific patient groups

In patients with impaired renal function, administration of ARGETT Rapid at usual single doses does not result in accumulation of diclofenac. However, when creatinine clearance is less than 10 mL/min, calculated steady-state concentrations of hydroxymetabolites of diclofenac are approximately four times higher than in healthy volunteers. Ultimately, however, these metabolites are excreted via bile.

In patients with chronic hepatitis or compensated liver cirrhosis, pharmacokinetic parameters of diclofenac are similar to those in patients without liver disease.

Clinical characteristics.

Indications.

Symptomatic treatment of pain and inflammation in:

• Rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, pain syndromes of various localizations, periarticular rheumatism;
• Swelling with pain or post-traumatic inflammatory conditions.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product;
• Active gastric or duodenal ulcer or recurrent peptic ulcer disease/bleeding in history (two or more separate episodes of confirmed ulcer or bleeding); gastrointestinal bleeding or tract perforation in history associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
• AРGETT rapid, like other NSAIDs, is contraindicated in patients with a history of allergic reactions such as asthma attacks, bronchospasm, angioedema, urticaria, or acute rhinitis, nasal polyps, or other allergic symptoms provoked by intake of ibuprofen, acetylsalicylic acid, or other NSAIDs;
• Third trimester of pregnancy and breastfeeding period;
• Proctitis, hemorrhoidal symptoms, rectal bleeding, or other active bleeding;
• Severe renal impairment (creatinine clearance < 30 mL/min);
• Hepatic impairment (Child-Pugh class C);
• Cerebrovascular diseases in patients who have experienced stroke or transient ischemic attacks;
• Unexplained disorders of hematopoiesis;
• Congestive heart failure (NYHA II-IV);
• Ischemic heart disease in patients with angina pectoris or history of myocardial infarction;
• Peripheral arterial disease;
• Treatment of perioperative pain in coronary artery bypass grafting (CABG) (or use of cardiopulmonary bypass);
• Inflammatory bowel diseases (Crohn's disease or ulcerative colitis);
• Pediatric population under 18 years of age;
• Uncontrolled arterial hypertension.

Interaction with other medicinal products and other forms of interaction.

Other NSAIDs, including salicylates

Concomitant use of multiple NSAIDs may increase the risk of adverse gastrointestinal (GI) events such as gastrointestinal ulcers and bleeding due to synergistic effects. Therefore, concomitant use of diclofenac and other NSAIDs is not recommended (see section "Special precautions for use").

Corticosteroids

Concomitant use may increase the risk of adverse GI events such as gastrointestinal ulcers and bleeding (see section "Special precautions for use").

Selective serotonin reuptake inhibitors (SSRIs)

Concomitant use may increase the risk of gastrointestinal bleeding (see section "Special precautions for use").

Anticoagulants and antiplatelet agents

Should be used with caution, as concomitant use may increase the risk of bleeding (see section "Special precautions for use"). Although clinical studies do not indicate that diclofenac affects the action of anticoagulants, there are reports of increased bleeding risk in patients receiving diclofenac and anticoagulants simultaneously. Close monitoring of such patients is recommended.

Digoxin, phenytoin, lithium

Concomitant use of diclofenac with digoxin, phenytoin, or lithium-containing preparations may increase serum levels of these substances. Monitoring of serum lithium levels is required. Monitoring of serum digoxin and phenytoin levels is recommended.

Diuretics and antihypertensive agents

As with other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensive agents (e.g., beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists) may reduce their antihypertensive effect. Therefore, such combinations should be used with caution, and blood pressure should be monitored periodically, especially in elderly patients. Patients should be adequately hydrated, and renal function monitoring should be considered after initiation of concomitant therapy and periodically thereafter, particularly with diuretics and ACE inhibitors due to increased risk of nephrotoxicity. Concomitant treatment with potassium-sparing diuretics may lead to elevated serum potassium levels; therefore, regular monitoring is necessary (see section "Special precautions for use").

Antidiabetic agents

Clinical studies have shown that diclofenac can be used together with oral antidiabetic agents without affecting their clinical efficacy. However, isolated reports of hypoglycemic and hyperglycemic effects requiring dosage adjustment of antidiabetic agents during diclofenac treatment exist. Therefore, monitoring of blood glucose levels is recommended as a precautionary measure during concomitant therapy.

Methotrexate

Diclofenac may inhibit renal tubular clearance of methotrexate, thereby increasing methotrexate levels. Caution is required when NSAIDs, including diclofenac, are used less than 24 hours before or after methotrexate administration, as this may increase methotrexate blood concentration and enhance its toxicity.

Probenecid or sulfinpyrazone

Medicinal products containing probenecid or sulfinpyrazone may delay elimination of diclofenac.

Tacrolimus

NSAIDs such as diclofenac may increase renal toxicity of tacrolimus.

Cyclosporine

Diclofenac, like other NSAIDs, may increase cyclosporine nephrotoxicity due to effects on renal prostaglandins. Therefore, it should be administered at lower doses compared to doses used in patients not receiving concomitant cyclosporine therapy.

Quinolone antibacterial agents

There are isolated reports of seizures possibly associated with concomitant use of quinolones and NSAIDs.

Cholestyramine and colestipol

These medicinal products may induce delayed or reduced absorption of diclofenac. Therefore, diclofenac should be administered at least 1 hour before or 4–6 hours after administration of cholestyramine/colestipol.

Potent CYP2C9 inhibitors

Caution is required when using diclofenac concomitantly with potent CYP2C9 inhibitors (such as sulfinpyrazone or voriconazole), as this may lead to a significant increase in plasma diclofenac concentrations and effects due to inhibition of diclofenac metabolism.

Cardiac glycosides

Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase glycoside levels in plasma.

Mifepristone

The medicinal product AРGETT rapid should not be used within 8–12 days after administration of mifepristone, as NSAIDs may reduce the effect of mifepristone.

Special precautions for use.

General information

Concomitant use of the medicinal product ARGETT Rapid with systemic NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to lack of evidence demonstrating synergistic benefit and potential for additive adverse reactions.

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

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur even without prior exposure to diclofenac.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and gastrointestinal and cardiovascular risks below).

As with other NSAIDs, administration of diclofenac may in rare cases trigger allergic reactions, including anaphylactic/anaphylactoid reactions, even in patients who have not previously taken it. Hypersensitivity reactions may progress to development of Kounis syndrome (acute allergic coronary syndrome), which may lead to myocardial infarction. Symptoms of such allergic reactions to diclofenac include chest pain.

Elderly patients

In accordance with general medical principles, caution is recommended when treating elderly patients. In particular, the lowest effective dose should be used in frail elderly patients or those with low body weight. Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal (see section "Dosage and administration").

Use with caution in patients aged 65 years and older.

Gastrointestinal (GI) reactions

When using all NSAIDs, including diclofenac, gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation, which may be fatal, have been reported at any time during treatment, with or without warning symptoms, and with or without serious gastrointestinal events in history. Generally, these outcomes are more severe in elderly patients.

Careful medical monitoring is mandatory when using diclofenac. Particular caution is required when prescribing the medicinal product to patients with symptoms indicating gastrointestinal disorders or with a history of peptic ulcer, intestinal bleeding (see section "Adverse reactions"). The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially if complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients.

To reduce the risk of gastrointestinal toxicity in patients with a history of peptic ulcer, particularly if complicated by bleeding or perforation, and in elderly patients, treatment should be initiated and maintained at the lowest effective dose.

For such patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that may increase gastrointestinal risk, consideration should be given to using combination therapy with gastroprotective agents, such as misoprostol or proton pump inhibitors (see below and section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be informed about unusual gastrointestinal symptoms (including gastrointestinal bleeding), especially during initial stages of treatment.

Caution is required when administering the product to patients receiving concomitant medicinal products that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), SSRIs, or antiplatelet agents (e.g., acetylsalicylic acid) (see section "Contraindications").

Careful medical monitoring and caution are also recommended when using the product in patients with ulcerative colitis or Crohn’s disease, as their condition may worsen (see section "Adverse reactions").

If gastrointestinal bleeding or ulceration occurs in patients taking diclofenac, treatment must be discontinued.

Use of all NSAIDs, including diclofenac, may be associated with a risk of anastomotic dehiscence and leakage. Careful medical monitoring and caution are recommended when using diclofenac in patients after gastrointestinal surgery.

Skin reactions

Very rarely, serious skin reactions (some of which are fatal), including exfoliative dermatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis, and generalized bullous fixed drug eruption, have been reported in association with diclofenac use (see section "Adverse reactions"). The highest risk of such reactions generally occurs at the beginning of treatment, with most cases developing within the first month of therapy. The medicinal product ARGETT Rapid should be discontinued immediately at the first signs of skin rash, mucosal lesions, or any other signs of hypersensitivity.

Cardiovascular and cerebrovascular reactions

Appropriate monitoring and medical advice are recommended for patients with a history of arterial hypertension and/or mild (NYHA class I) congestive heart failure, as fluid retention and edema have been reported after NSAID use.

Clinical trials and epidemiological data consistently highlight an increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) associated with diclofenac use, particularly at high doses (150 mg daily) and with long-term treatment (see sections "Contraindications" and "Special precautions for use").

Patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) may receive diclofenac only after careful clinical evaluation.

Since cardiovascular risks of diclofenac may increase with higher doses and longer duration of use, the product should be used for the shortest possible time and at the lowest effective daily dose. The need for symptom relief and response to treatment should be periodically reassessed.

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 a dose ≤ 100 mg daily if treatment lasts no more than four weeks. As cardiovascular risks of diclofenac may increase with higher doses and longer treatment duration, it should be used for as short a period as possible and at the lowest effective dose.

The patient’s need for diclofenac for symptom relief and response to therapy should be periodically reviewed. Patients should be vigilant for serious signs and symptoms of atherothrombosis (e.g., chest pain, dyspnea, weakness, speech disturbances), which may occur without warning. Patients should be warned to seek immediate medical attention if such symptoms occur.

Hepatic reactions

Careful medical monitoring is required if diclofenac is prescribed to patients with impaired liver function, as their condition may worsen.

As with other NSAIDs, including diclofenac, levels of one or more liver enzymes may increase. Regular monitoring of liver function is recommended as a precaution during prolonged or repeated use of diclofenac. Diclofenac must be discontinued immediately if abnormal liver test results persist or worsen, if clinical signs or symptoms suggest liver disease, or if other manifestations occur (e.g., eosinophilia, rash). Hepatitis may occur with diclofenac use without prodromal symptoms.

Caution is advised when using diclofenac in patients with hepatic porphyria, as it may provoke an attack.

Renal and cardiac function impairment

Since fluid retention has been reported after use of NSAIDs, including diclofenac, particular caution is required when treating patients with impaired cardiac or renal function, a history of arterial hypertension, elderly patients, patients receiving diuretics or medicinal products that may significantly impair renal function, and patients with significant extracellular fluid volume depletion due to any cause, e.g., before and after major surgical procedures (see section "Contraindications"). Monitoring of renal function is recommended as a precautionary measure when diclofenac is used in the situations listed below. Renal function typically returns to pre-treatment levels after discontinuation of the drug.

Cases of acute renal failure have been reported after initiation of high doses or multiple NSAIDs in patients receiving tenofovir disoproxil fumarate and having risk factors for impaired renal function. Renal function should be appropriately monitored when tenofovir disoproxil fumarate is used concomitantly with NSAIDs.

Blood system reactions

Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with coagulation disorders should be under close supervision.

Monitoring of blood parameters is recommended during prolonged diclofenac treatment.

Respiratory disorders and allergic reactions

In patients with asthma, seasonal allergic rhinitis, mucosal swelling of the nose (e.g., nasal polyps), chronic obstructive pulmonary disease, or chronic respiratory tract infections (especially if associated with allergic rhinitis-like symptoms), reactions to NSAIDs such as asthma exacerbation (so-called analgesic intolerance/analgesic-induced asthma), Quincke’s edema, or urticaria occur more frequently than in other patients. Therefore, special precautions (readiness for emergency intervention) are recommended for such patients. This also applies to patients with allergic reactions to other substances, e.g., skin reactions, pruritus, or urticaria.

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

Other precautions

Diclofenac should be used in patients with the following conditions only after careful benefit-risk assessment:

• porphyria induced by drugs;
• systemic lupus erythematosus (SLE) and mixed connective tissue disease.

Particularly careful medical monitoring is required in the following cases:

• patients with gastrointestinal disorders;
• patients with cardiovascular disorders;
• patients with pre-existing renal impairment;
• patients with impaired liver function;
• patients who have recently undergone major surgery;
• elderly patients;
• patients with respiratory disorders and allergies;
• patients with allergic reactions to other substances;
• patients with blood system disorders;
• patients at risk of infection.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may also occur rarely after diclofenac use, even without prior exposure. If the first signs of hypersensitivity occur after administration of the medicinal product, treatment must be discontinued. A person with appropriate training should initiate medically necessary procedures appropriate to the symptoms.

Other information

Regular monitoring of liver and kidney function and blood parameters is required during prolonged use of diclofenac.

Prolonged use of analgesics may lead to medication-overuse headache, which cannot be treated by increasing the dose of the medicinal product.

Chronic use of analgesics, particularly combinations of several analgesic medicinal products, may generally lead to irreversible kidney damage with associated risk of renal failure (analgesic nephropathy).

Concomitant use of the medicinal product ARGETT Rapid with alcohol may provoke adverse reactions caused by the active substance, particularly those affecting the gastrointestinal tract or central nervous system (CNS).

SLE and mixed connective tissue diseases

Patients with SLE and mixed connective tissue diseases may have an increased risk of developing aseptic meningitis.

Use during pregnancy or breastfeeding

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development.

Epidemiological data indicate an increased risk of miscarriage and 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 is considered to increase with higher doses and longer duration of treatment.

Administration of a prostaglandin synthesis inhibitor to animals has been shown to cause pre- and post-implantation loss and embryonic/fetal death. In addition, increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis.

From the 20th week of pregnancy, use of the drug may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after initiation of treatment and is usually reversible upon discontinuation of therapy. The medicinal product should be used during the first and second trimesters of pregnancy only if absolutely necessary. If the medicinal product is used by a woman trying to conceive or during the first and second trimesters of pregnancy, the dose should be kept as low as possible and the duration of treatment as short as possible. Fetal monitoring for oligohydramnios may be advisable if exposure occurred over several days starting from the 20th week of pregnancy. The medicinal product should be discontinued if oligohydramnios is detected.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may

• cause in the fetus:
  • cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
  • impaired renal function, which may progress to renal failure with oligohydramnios;
• in the mother and newborn (at the end of pregnancy):
  • 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.

Therefore, the medicinal product is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding period

Diclofenac and its metabolites are excreted in small amounts in breast milk. Therefore, diclofenac should not be used during breastfeeding to avoid adverse effects in the newborn.

Fertility

Use of diclofenac may affect fertility in women; therefore, it is not recommended for use in women attempting to conceive. In women experiencing difficulty conceiving or undergoing infertility investigations, discontinuation of the medicinal product should be considered.

Ability to affect reaction speed when driving or operating machinery

Patients who experience visual disturbances, vertigo, drowsiness, or central nervous system (CNS) disorders during diclofenac use, especially in combination with alcohol, should refrain from driving or operating machinery.

Method of administration and dosage.

The single dose of the drug is 75 mg of sodium diclofenac (1 capsule); the total daily dose should not exceed 150 mg of sodium diclofenac (2 capsules).

The duration of treatment is determined by a physician.

In the case of rheumatic diseases, prolonged administration of the drug may be necessary. During long-term use, the total daily dose should be reduced, if possible, to 75 mg of sodium diclofenac, depending on the therapeutic response.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to relieve disease symptoms (see section "Special instructions").

Special patient groups

Elderly patients

No separate dose adjustment is required. Due to the profile of potential adverse reactions, elderly patients should be under special medical supervision (see section "Special instructions" for information on the use of the drug in elderly patients).

Renal impairment

Dose adjustment is not necessary in patients with mild to moderate renal impairment (see section "Contraindications" for information on the use of the drug in patients with severe renal impairment).

Hepatic impairment (see section "Pharmacokinetics")

Dose adjustment is not necessary in patients with mild to moderate hepatic impairment (see section "Contraindications" for information on the use of the drug in patients with severe hepatic impairment).

Children

The drug is contraindicated in children and adolescents (see also section "Contraindications").

Overdose.

Symptoms

There is no typical clinical picture characteristic of diclofenac overdose. Overdose may cause central nervous system disturbances such as headache, dizziness, drowsiness, tinnitus, convulsions (myoclonic convulsions are also possible in children), and loss of consciousness, as well as abdominal pain, nausea, vomiting, gastrointestinal bleeding, and diarrhea. In cases of severe poisoning, acute renal failure and hepatic injury may occur. Further complications may include arterial hypotension, respiratory depression, and cyanosis.

Treatment

There is no specific antidote.

Treatment of acute diclofenac poisoning primarily consists of supportive measures and symptomatic therapy. Supportive care and symptomatic treatment are required in cases of complications such as arterial hypotension, renal failure, convulsions, gastrointestinal disturbances, and respiratory depression.

Specific interventions such as forced diuresis, dialysis, or hemoperfusion are unlikely to enhance diclofenac elimination due to its high degree of protein binding and extensive metabolism.

Activated charcoal may be administered after a potentially toxic overdose, and gastric lavage may be considered only within 60 minutes after a life-threatening overdose.

Adverse Reactions

Adverse reactions are listed according to the following frequency classification:

Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from available data).

It should be noted that the listed adverse reactions are predominantly dose-dependent and may vary among individual patients. In particular, the risk of gastrointestinal bleeding (gastritis, erosion, ulcer) depends on the dose range and duration of treatment.

The most commonly observed adverse reactions are of gastrointestinal origin.

Peptic ulcers, perforations, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special Warnings and Precautions for Use"). Nausea, vomiting, diarrhea, abdominal distension, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, and exacerbation of colitis or Crohn’s disease have been reported following administration of the drug (see section "Special Warnings and Precautions for Use"). Gastritis has been observed less frequently.

Edema, hypertension, and heart failure have been reported in association with NSAID therapy.

Clinical trial and epidemiological data indicate an increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) associated with diclofenac use, particularly at high doses (150 mg daily) and with prolonged treatment duration (see sections "Contraindications" and "Special Warnings and Precautions for Use").

Infections and infestations

Very rare: Worsening of infection-related inflammation (e.g., development of necrotizing fasciitis), which may coincide with systemic NSAID use. This may be related to the mechanism of action of NSAIDs.

If signs of infection develop for the first time or worsen during diclofenac treatment, patients are advised to seek immediate medical attention.

The need for anti-infective therapy/antibiotics should be confirmed.

Very rare: Symptoms of aseptic meningitis, including neck stiffness, headache, nausea, vomiting, fever, or altered consciousness. Patients with autoimmune disorders (e.g., systemic lupus erythematosus, mixed connective tissue disease) appear to be more susceptible.

Blood and lymphatic system disorders

Very rare: Hematopoietic disorders (anemia, including hemolytic and aplastic anemia, leukopenia, agranulocytosis, thrombocytopenia, pancytopenia).

Initial symptoms may include fever, sore throat, oral mucosal ulcers, influenza-like symptoms, severe fatigue, epistaxis, and subcutaneous hemorrhages.

Regular blood monitoring is recommended during long-term treatment.

Immune system disorders

Uncommon: Hypersensitivity, anaphylactic and anaphylactoid reactions, including arterial hypotension, tachycardia, and shock.

Very rare: Angioedema, including facial, lingual, and laryngeal edema with airway obstruction and dyspnea.

In the event of any of the listed reactions (possibly after the first dose), immediate medical attention is required.

Psychiatric disorders

Very rare: Disorientation, insomnia, restlessness, agitation, irritability, psychotic disorders, depression, anxiety, and nightmares.

Nervous system disorders

Common: Central nervous system disturbances such as headache and dizziness.

Uncommon: Somnolence, fatigue.

Very rare: Cerebrovascular disorders, paresthesia, taste disturbances, memory impairment, seizures, tremor, stroke, aseptic meningitis, anxiety.

Frequency not known: Confusion, hallucinations, sensory disturbances, general 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 disorders

Very rare: Tachycardia, chest pain, heart failure, edema, myocardial infarction.

Frequency not known: Kounis syndrome.

Vascular disorders

Very rare: Arterial hypertension, arterial hypotension, vasculitis.

Clinical trial 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 daily) and with prolonged treatment.

Respiratory, thoracic and mediastinal disorders

Uncommon: Asthma, including dyspnea.

Very rare: Pneumonitis.

Gastrointestinal disorders

Common: Nausea, vomiting, diarrhea, dyspepsia, flatulence, abdominal pain, anorexia, loss of appetite.

Uncommon: Gastritis, gastrointestinal bleeding, hematemesis, hemorrhagic diarrhea, melena, gastric or intestinal ulcer (with or without bleeding or perforation, sometimes fatal, particularly in elderly patients), which may lead to peritonitis.

Very rare: Pancreatitis, colitis (including hemorrhagic colitis), exacerbation of ulcerative colitis or Crohn’s disease (see section "Special Warnings and Precautions for Use"), stomatitis (including ulcerative stomatitis), glossitis, esophageal disorders, constipation, diaphragm-like intestinal strictures.

Frequency not known: Ischemic colitis.

Patients should be informed of the need to discontinue the drug and seek immediate medical attention in case of severe upper abdominal pain, melena, or hematemesis.

Hepatobiliary disorders

Common: Increased serum transaminase levels.

Uncommon: Hepatitis, jaundice, liver disorders.

Very rare: Fulminant hepatitis, hepatic necrosis, liver failure.

Therefore, liver function parameters should be monitored regularly.

Skin and subcutaneous tissue disorders

Common: Rash.

Uncommon: Urticaria.

Very rare: Exanthema, bullous reactions, eczema, erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), polymorphic erythema, exfoliative dermatitis, alopecia, photosensitivity, purpura, allergic purpura, pruritus.

Frequency not known: Fixed drug eruption, generalized bullous fixed drug eruption.

Renal and urinary disorders

Common: Development of edema, particularly in patients with systemic arterial hypertension or renal impairment.

Very rare: Acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis. Therefore, renal function should be monitored regularly.

Reproductive system and breast disorders

Very rare: Impotence.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life

4 years.

Storage conditions

Store at temperatures not exceeding 30 °C, in a place inaccessible to children.

Store in the original packaging to protect from moisture.

Packaging

10 capsules per blister; 1, 2, 3, or 5 blisters with patient information leaflet in a cardboard box.

Prescription status

Prescription only.

Manufacturer

Swiss Caps GmbH.

Manufacturer’s address

Grassingerstrasse 9, 83043 Bad Eibing, Germany.

Marketing Authorization Holder

Delta Medical Promotions AG.

Address of Marketing Authorization Holder

Othmarsingerstrasse 26, Zurich CH-8001, Switzerland.