Instructions for Argett Rapid hard capsules 75 mg No. 20
Composition
active ingredient: diclofenac sodium;
1 capsule contains 75 mg of diclofenac sodium;
excipients:
capsule contents: talc, microcrystalline cellulose, povidone K 25, colloidal anhydrous silica, propylene glycol, methacrylate copolymer (type A);
capsule shell: gelatin, erythrosine (E 127), titanium dioxide (E 171), yellow iron oxide (E 172), sodium lauryl sulfate.
Dosage form
Enteric-coated hard capsules.
Main physicochemical properties: hard gelatin capsules, size 2; capsule cap and body are opaque, red in color; capsule contents: white to cream-colored granules.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs; acetic acid derivatives and related substances. ATX code M01A B05.
Pharmacological properties
Pharmacodynamics
ARGETT rapid contains diclofenac sodium, a nonsteroidal compound that has a pronounced anti-inflammatory, analgesic and antipyretic effect. The main mechanism of action of diclofenac is considered to be inhibition of prostaglandin biosynthesis. Prostaglandins play an important role in the genesis of inflammation, pain and fever.
In vitro, diclofenac sodium at concentrations equivalent to those achieved in the treatment of patients does not inhibit the biosynthesis of cartilage proteoglycans.
Pharmacokinetics
After oral administration of the enteric-coated capsule, the maximum plasma level is reached depending on the duration of passage through the stomach, on average after 1–2 hours.
Serum protein binding is 99.7%, mainly to albumin (99.4%). The apparent volume of distribution is 0.12–0.17 l/kg.
Diclofenac penetrates into the synovial fluid, where its maximum concentration is reached 2-4 hours later than in blood plasma. The apparent half-life from the synovial fluid is 3-6 hours. 2 hours after reaching the maximum plasma concentration, the concentration of diclofenac in the synovial fluid is higher than in plasma, and its values remain higher for 12 hours.
The metabolism of diclofenac is carried out partly by glucuronidation of the unchanged molecule, mainly by single and multiple methoxylation, which leads to the formation of several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxydiclofenac), most of which are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, but to a much lesser extent than diclofenac.
The total systemic plasma clearance of diclofenac is 263 ± 56 ml/min. The terminal half-life is 1–2 hours. The 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 half-life, but this metabolite is completely inactive.
About 60% of the administered dose is excreted in the urine as glucuronide conjugates of the unchanged active substance, as well as in the form of metabolites, most of which are glucuronide conjugates. Less than 1% of diclofenac is excreted unchanged. The rest of the administered dose is excreted in the form of metabolites with bile and feces.
Pharmacokinetics in certain groups of patients.
In patients with impaired renal function, when using ARGETT rapid in usual single doses, no accumulation of diclofenac was observed. In the case when creatinine clearance is less than 10 ml/min, the estimated equilibrium concentrations of diclofenac hydroxymetabolites are approximately 4 times higher than in healthy volunteers. However, the metabolites are ultimately excreted in the bile.
In patients with chronic hepatitis or compensated cirrhosis, the pharmacokinetics of diclofenac are similar to those in patients without liver disease.
Indication
Symptomatic treatment of pain and inflammation in:
– rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, pain syndrome of various localization, extra-articular rheumatism;
– edema with pain syndrome or post-traumatic inflammation.
Contraindication
– Hypersensitivity to the active substance or to any of the excipients of the drug;
– active gastric and/or duodenal ulcer or history of recurrent ulcer/bleeding (two or more separate episodes of established ulceration or bleeding); history of gastrointestinal bleeding or perforation related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
– Argett Rapid, like other NSAIDs, is contraindicated in patients with a history of allergic reactions in the form of asthma attacks, bronchospasm, angioedema, urticaria or acute rhinitis, nasal polyps and other allergic symptoms provoked by taking ibuprofen, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs;
– III trimester of pregnancy and breastfeeding period;
– proctitis, hemorrhoidal symptoms, rectal bleeding or other active bleeding;
– severe renal failure (creatinine clearance
– cerebrovascular diseases in patients who have had a stroke or have episodes of transient ischemic attacks;
– unexplained disorders of hematopoiesis;
– congestive heart failure (NYHAII-IV);
– ischemic heart disease in patients with angina pectoris or previous myocardial infarction;
– peripheral artery disease;
– treatment of perioperative pain during coronary artery bypass grafting (or use of a cardiopulmonary bypass machine);
– inflammatory bowel diseases (Crohn's disease or ulcerative colitis);
– children under 18 years of age;
– uncontrolled arterial hypertension.
Interaction with other medicinal products and other types of interactions
Other NSAIDs, including salicylates:
Concomitant use of several NSAIDs may increase the risk of gastrointestinal (GI) adverse reactions such as gastrointestinal ulcers and bleeding due to synergistic effects. Therefore, concomitant use of diclofenac and other NSAIDs is not recommended (see section 4.4).
Corticosteroids:
Concomitant use may increase the risk of gastrointestinal adverse reactions such as gastrointestinal ulcers and bleeding (see section "Special warnings and precautions for use")
Selective serotonin reuptake inhibitors (SSRIs):
Concomitant use may increase the risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").
Anticoagulants and antiplatelet agents:
It should be used with caution, as concomitant use may increase the risk of bleeding (see section "Special warnings and precautions for use"). Although clinical studies have not shown that diclofenac affects the action of anticoagulants, there are reports of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly. Close monitoring of such patients is recommended.
Digoxin, phenytoin, lithium:
Concomitant use of diclofenac and digoxin, phenytoin or lithium preparations may increase the serum levels of these substances. Monitoring of serum lithium levels is necessary. Monitoring of serum digoxin and phenytoin levels is recommended.
Diuretics and antihypertensives:
As with other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensive drugs (e.g. beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists) may lead to a decrease in their antihypertensive effect. Therefore, the combination should be used with caution and blood pressure should be monitored periodically in patients, particularly the elderly. Patients should be adequately hydrated and renal function should be monitored after initiation of concomitant use and periodically thereafter, particularly for diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity. Concomitant treatment with potassium-sparing diuretics may be associated with increases in serum potassium, therefore regular monitoring is necessary (see section 4.4).
Antidiabetic drugs:
In clinical studies, it has been shown that diclofenac can be used concomitantly with oral antidiabetic agents without affecting their clinical effect. However, there have been isolated reports of hypoglycemic and hyperglycemic effects requiring a change in the dosage of the antidiabetic agent during treatment with diclofenac. In this regard, blood glucose monitoring is recommended as a precautionary measure during concomitant treatment.
Methotrexate:
Diclofenac may inhibit the renal tubular clearance of methotrexate, thereby increasing methotrexate levels. Caution should be exercised if NSAIDs, in particular diclofenac, are administered less than 24 hours before or after treatment with methotrexate, as the blood concentration of methotrexate may increase, leading to increased toxicity of this substance.
Probenecid or sulfinpyrazone:
Medicines containing probenecid or sulfinpyrazone may delay the excretion of diclofenac.
Tacrolimus:
NSAIDs such as diclofenac may increase the renal toxicity of tacrolimus.
Cyclosporine:
Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine through its effects on renal prostaglandins. Therefore, it should be used at lower doses than those used in patients not receiving concomitant cyclosporine treatment.
Quinolone antibacterial agents:
There have been isolated reports of convulsions that may have been associated with the concomitant use of quinolones and NSAIDs.
Colestipol and cholestyramine:
These agents may induce a delay or decrease in the absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4-6 hours after colestipol/cholestyramine.
Potent CYP2C9 inhibitors:
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 for 8-12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.
Application features
General information:
Concomitant use of the drug with systemic NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to the lack of evidence demonstrating synergistic benefit and the possibility of additive side effects.
Like other NSAIDs, diclofenac may mask the signs and symptoms of infection due to its pharmacodynamic properties.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may also occur without prior exposure to diclofenac.
Adverse reactions can be minimized by using the lowest effective dose for the shortest period necessary to control symptoms (see section “Method of administration and dosage” and risks of gastrointestinal and cardiovascular reactions below).
As with other NSAIDs, in rare cases, diclofenac may cause allergic reactions, including anaphylactic/anaphylactoid reactions, in individuals who have not previously taken it. Hypersensitivity reactions may progress to the development of Kounis syndrome (acute allergic coronary syndrome), which can lead to myocardial infarction. Symptoms of this type of allergic reaction to diclofenac include chest pain.
Elderly patients:
In view of general medical principles, caution is advised when treating elderly patients. In particular, it is recommended to use the lowest effective dose in frail elderly patients or those with low body weight. Elderly patients have an increased frequency of adverse reactions to NSAIDs, in particular gastrointestinal bleeding and perforation, which can be fatal (see section "Method of administration and dosage").
Use the drug with caution in patients over 65 years of age.
Gastrointestinal reactions:
Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal, have been reported with all NSAIDs, including diclofenac, at any time during treatment, with or without warning symptoms or with or without a previous history of serious gastrointestinal events. They generally have a more serious outcome in the elderly.
When using diclofenac, careful medical supervision is mandatory. Particular caution should be exercised when prescribing to patients with symptoms indicating gastrointestinal disorders or a history of ulceration, intestinal bleeding (see section "Adverse reactions"). The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing doses of NSAIDs in patients with a history of ulceration, particularly if complicated by bleeding or perforation (see section "Contraindications"), as well as in elderly patients.
To reduce the risk of gastrointestinal toxicity in patients with a history of ulcer, especially 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 patients who require concomitant use of low doses of acetylsalicylic acid or other drugs that may increase the risk for the gastrointestinal tract, the possibility of using combination therapy with protectors (e.g. misoprostol or proton pump inhibitors) should be considered (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 advised to report any unusual gastrointestinal symptoms (including gastrointestinal bleeding), especially during the initial stages of treatment.
Patients taking concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants such as warfarin, SSRIs or antiplatelet agents such as acetylsalicylic acid, should use the drug with caution (see section "Contraindications").
Close medical supervision and caution are also recommended when using the drug in patients with ulcerative colitis or Crohn's disease, as their condition may be exacerbated (see section "Adverse reactions").
If gastrointestinal bleeding or ulceration occurs in patients taking diclofenac, treatment should be discontinued.
All NSAIDs, including diclofenac, may be associated with the risk of anastomotic failure and leakage. Close medical supervision and caution are recommended when using diclofenac in patients undergoing gastrointestinal surgery.
In very rare cases, serious skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported after the use of NSAIDs (see section 4.8). Patients appear to be at highest risk of these reactions at the beginning of therapy, with the majority of reactions occurring within the first month of treatment. Diclofenac should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Reactions from the cardiovascular and cerebrovascular systems:
Appropriate monitoring and counseling are recommended for patients with a history of hypertension and/or mild congestive heart failure (NYHA class I), as fluid retention and edema have been reported following the use of NSAIDs.
Clinical trials and epidemiological data consistently point to an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) associated with the use of diclofenac, particularly at high doses (150 mg/day) and in the case of long-term treatment (see sections "Contraindications" and "Special warnings and precautions for use").
Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) should receive diclofenac only after careful clinical evaluation.
Since the cardiovascular risks of diclofenac may increase with increasing dose and duration of use, the drug should be used for the shortest possible time and at the lowest effective daily dose. Patients should be periodically assessed for symptom relief and response to treatment.
Diclofenac should only be prescribed to patients with significant cardiovascular risk factors (such as hypertension, hyperlipidemia, diabetes mellitus, smoking) after careful clinical evaluation and only at a dose ≤100 mg daily, if treatment is not continued for more than four weeks. Since the cardiovascular risks of diclofenac may increase with increasing dose and duration of treatment, it should be used for the shortest possible period and at the lowest effective dose. The patient's need for diclofenac to relieve symptoms and the response to therapy should be reassessed periodically. Patients should be alert for the appearance of serious signs and symptoms of atherothrombosis (e.g. chest pain, shortness of breath, weakness, speech disorders), which may occur without warning. Patients should be warned that in such cases they should seek medical advice immediately.
Liver reactions:
Close medical supervision is necessary if diclofenac is prescribed to patients with impaired liver function, as their condition may be aggravated.
As with other NSAIDs, including diclofenac, elevations of one or more liver enzymes may occur. During prolonged or repeated use of diclofenac, regular monitoring of liver function is indicated as a precautionary measure. If abnormal liver function tests persist or worsen, if clinical signs or symptoms consistent with liver disease develop, or if other manifestations occur (e.g. eosinophilia, rash), diclofenac should be discontinued immediately. Hepatitis may occur with diclofenac without prodromal symptoms.
Caution should be exercised when using diclofenac in patients with hepatic porphyria, as it may precipitate an attack.
Renal and cardiac dysfunction:
Since fluid retention has been reported with NSAIDs, including diclofenac, special caution should be exercised in patients with impaired cardiac or renal function, a history of hypertension, elderly patients receiving concomitant diuretics or medicinal products that may significantly impair renal function, and patients with significant extracellular volume depletion from any cause, e.g. before and after major surgery (see section 4.3). Monitoring of renal function is recommended as a precautionary measure if diclofenac is used in the following situations. After discontinuation of the drug, recovery to pre-treatment status is always achieved.
Cases of acute renal failure have been reported after initiation of high doses or multiple NSAIDs in patients receiving tenofovir disoproxil fumarate and with risk factors for renal impairment. If tenofovir disoproxil fumarate is used concomitantly with NSAIDs, renal function should be monitored appropriately.
Reactions from the blood system:
Like other NSAIDs, diclofenac may temporarily inhibit platelet aggregation. Patients with hemostatic defects should be closely monitored.
In case of long-term treatment with diclofenac, monitoring of blood counts is recommended.
In patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially if associated with allergic rhinitis-like symptoms), reactions to NSAIDs such as exacerbation of asthma (so-called analgesic intolerance/asthma after analgesic use), angioedema or urticaria occur more frequently than in other patients. Therefore, special precautions (emergency medical attention) are recommended for such patients. This also applies to patients who have allergic reactions to other substances, e.g. skin reactions, itching or urticaria.
Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other NSAIDs can provoke the development of bronchospasm in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.
Other precautions:
Diclofenac should only be used in patients with the following conditions after careful benefit/risk assessment:
– induced porphyria;
– systemic lupus erythematosus (SLE) and mixed connective tissue disease.
Particularly careful medical supervision is necessary in the following cases:
– patients with gastrointestinal disorders;
– patients with disorders of the cardiovascular system;
– patients with pre-existing renal failure;
– patients with impaired liver function;
– patients who have just undergone major surgery;
– elderly patients;
– patients with respiratory disorders and allergies;
– patients who have allergic reactions to other substances;
– patients with disorders of the blood system;
– patients at risk of infection.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may also occur in rare cases after the use of diclofenac in patients who have not previously used the drug. At the first sign of a hypersensitivity reaction after use of the drug, treatment should be discontinued. A person with appropriate special training should initiate medically necessary procedures appropriate to the symptoms.
Other information
In case of long-term use of diclofenac, regular monitoring of liver and kidney function and blood count is necessary.
In case of prolonged use of analgesics, a headache may occur, which cannot be treated by increasing the dose of the drug.
Habitual use of analgesics, particularly combinations of several analgesic drugs, can generally lead to irreversible kidney damage with an associated risk of renal failure (analgesic nephropathy).
The use of NSAIDs simultaneously with alcohol can provoke side effects caused by the active substance, especially 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 be at increased risk of developing aseptic meningitis.
Use during pregnancy or breastfeeding
Pregnancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetal development.
Epidemiological data suggest an increased risk of miscarriage and of cardiac malformations and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations has been reported to increase from less than 1% to approximately 1.5%. The risk is thought to increase with increasing dose and duration of treatment.
Prostaglandin synthesis inhibitor use in animals has been shown to result in pre- and post-implantation loss and embryo/fetal death. In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis.
During the first and second trimesters of pregnancy, the drug should be used only if clearly needed. If the drug is used by a woman attempting to conceive or pregnant during the first and second trimesters of pregnancy, the dose should be kept as low as possible and the duration of treatment should be as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may
· cause in the fetus:
- cardiopulmonary toxicity (with premature closure of the foramen ovale 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 blood clotting time, antiplatelet effect, which can occur even when taking very low doses;
- suppression of uterine contractions, causing delayed or prolonged labor.
Therefore, the drug 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 side effects in the newborn.
Diclofenac may affect female reproductive function and is therefore not recommended for use in women attempting to conceive. In women who have difficulty conceiving or who are undergoing infertility investigations, discontinuation of the drug should be considered.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience visual disturbances, vertigo, drowsiness or CNS disturbances while taking diclofenac, especially in combination with alcohol, should refrain from driving or operating other machinery.
Method of administration and doses
A single dose of the drug is 75 mg of diclofenac sodium (1 capsule), the total daily dose should not exceed 150 mg of diclofenac sodium (2 capsules).
The duration of use is determined by the doctor.
In case of rheumatic disease, it may be necessary to use the drug for a long time. In case of long-term use, the total daily dose should be reduced, if possible, to 75 mg diclofenac sodium, depending on the therapeutic response.
Adverse reactions can be minimized by using the lowest effective dose for the shortest period necessary to control symptoms (see section "Special warnings and precautions for use").
Special patient groups
Elderly patients:
No specific dose adjustment is required. Due to the potential side effect profile, elderly patients should be under special medical supervision (see section 4.4 for information on the use of the drug in the treatment of elderly patients).
Kidney failure:
No dose adjustment is necessary in patients with mild or moderate renal impairment (see section 4.3 for information on the use of the drug in patients with severe renal impairment).
Hepatic impairment (see Pharmacokinetics section):
No dose adjustment is necessary for patients with mild or moderate hepatic impairment (see section 4.3 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 the section "Contraindications").
Overdose
Symptoms
There is no typical clinical picture characteristic of diclofenac overdose. Overdose can cause CNS disorders 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 case of severe poisoning, acute renal failure and liver damage are possible. Hypotension, respiratory depression and cyanosis may occur.
Treatment
There is no specific antidote.
Treatment of acute diclofenac poisoning consists mainly of supportive measures and symptomatic treatment. Supportive measures and symptomatic treatment are necessary in the event of complications such as hypotension, renal failure, convulsions, gastrointestinal disorders and respiratory depression.
Specific measures such as forced diuresis, dialysis or hemoperfusion are unlikely to aid in the elimination of diclofenac due to its high protein binding and extensive metabolism.
Activated charcoal can be used after a potentially toxic overdose, and gastric lavage is only possible within 60 minutes of a life-threatening overdose.
Adverse reactions
Adverse reactions are listed according to the following classification of their frequency of occurrence:
very common (≥ 1/10); common (≥ 1/100 to uncommon (≥ 1/1000 to rare (≥ 1/10,000 to very rare (frequency not known (cannot be estimated from the available data).
It should be noted that the listed adverse reactions are mainly dose-dependent and vary between patients, in particular the risk of gastrointestinal bleeding (gastritis, erosion, ulcer) depends on the dose range and duration of use.
The most commonly observed side effects are gastrointestinal in nature.
Peptic ulcers, perforation or bleeding, sometimes fatal, may occur, especially in elderly patients (see section "Special warnings and precautions for use"). Nausea, vomiting, diarrhea, abdominal distension, constipation, indigestion, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported after use 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 data and epidemiological data suggest an increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke) associated with the use of diclofenac, particularly at high doses (150 mg per day) and in case of long-term use (see sections "Contraindications" and "Special warnings and precautions for use").
Very rare: Worsening of inflammation associated with infection (e.g. development of necrotizing fasciitis) coinciding with the systematic use of NSAIDs. This may be related to the mechanism of action of NSAIDs.
If signs of infection or deterioration develop for the first time while using diclofenac, the patient is advised to seek immediate medical attention.
It is necessary to confirm whether there are indications for the use of anti-infective treatment/antibiotics.
Very rare: symptoms of aseptic meningitis, including stiff neck, headache, nausea, vomiting, fever or confusion. Patients with autoimmune diseases (SLE, mixed connective tissue disease) appear to be predisposed to this.
Blood and lymphatic system disorders
Very rare: haematopoietic disorders (anaemia, particularly haemolytic and aplastic anaemia, leukopenia, agranulocytosis, thrombocytopenia, pancytopenia).
Initial symptoms may include: fever, sore throat, superficial mouth sores, flu-like symptoms, severe exhaustion, nosebleeds, and subcutaneous hemorrhages.
It is necessary to regularly monitor the blood picture during long-term treatment.
On the part of the immune system
Rare: hypersensitivity, anaphylactic and anaphylactoid reactions, including hypotension, tachycardia and shock.
Very rare: angioedema, including swelling of the face, tongue and inner part of the larynx with narrowing of the airways, shortness of breath.
If any of the above problems occur (possibly after the first use of the medicine), you should seek medical attention immediately.
Mental disorders
Very rare: disorientation, insomnia, agitation, irritability, psychotic disorders, depression, anxiety and nightmares.
From the nervous system
Common: CNS disorders such as headache, dizziness.
Rare: drowsiness, fatigue.
Very rare: cerebrovascular accident, paresthesia, taste disturbance, memory impairment, convulsions and tremor, stroke, aseptic meningitis, feeling of anxiety.
Frequency unknown: confusion, hallucinations, sensory disturbances, general malaise.
From the organs of vision
Very rare: visual disturbances, blurred vision, diplopia.
Frequency unknown: optic neuritis.
Hearing and balance disorders
Common: vertigo.
Very rare: tinnitus, hearing impairment.
From the heart
Very rare: palpitations, chest pain, heart failure, edema and myocardial infarction.
Frequency unknown – Kounis Syndrome.
From the vascular side
Very rare: hypertension, hypotension, vasculitis.
Clinical trial data and epidemiological data suggest 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 long-term use.
On the side of the respiratory system, chest and mediastinum
Rare: asthma, particularly dyspnoea.
Very rare: pneumonitis.
From the gastrointestinal tract
Common: nausea, vomiting, diarrhea, dyspepsia, flatulence, abdominal pain, anorexia, loss of appetite.
Rare: gastritis, gastrointestinal bleeding, vomiting with blood, hemorrhagic diarrhea, melena, gastric or intestinal ulcer (with or without bleeding or perforation, sometimes fatal, especially in elderly patients), which may lead to peritonitis.
Very rare: pancreatitis, colitis, including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease (see section "Special warnings and precautions for use"), stomatitis, including ulcerative stomatitis, glossitis, esophageal disorders, constipation, diaphragmatic intestinal strictures.
Frequency unknown: ischemic colitis
Patients should be advised to discontinue the drug and seek immediate medical attention if they experience relatively severe upper abdominal pain, melena, or hematemesis.
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