Instructions Diclofenac-Teva solution for injection 75 mg/3 ml ampoule 3 ml No. 5
Composition
active ingredient: diclofenac sodium;
1 ampoule (3 ml) contains 75 mg of diclofenac sodium;
Excipients: benzyl alcohol, disodium edetate, acetylcysteine, propylene glycol, mannitol (E 421), sodium hydroxide, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent colorless or slightly greenish-yellow solution.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related compounds. ATX code M01A B05.
Pharmacological properties
Pharmacodynamics
Diclofenac-Teva is a nonsteroidal drug with pronounced analgesic/anti-inflammatory properties. It is an inhibitor of prostaglandin synthetase (cyclooxygenase). Diclofenac sodium in vitro at concentrations equivalent to those achieved in humans does not inhibit the biosynthesis of proteoglycans in cartilage tissue. If the drug is used simultaneously with opioids for the relief of postoperative pain, it significantly reduces the need for opioids.
Pharmacokinetics
Absorption
After administration of 75 mg diclofenac by intramuscular injection, absorption begins immediately and the mean maximum plasma concentration of approximately 2.558 ± 0.968 μg/ml (2.5 μg/ml = 8 μmol/l) is reached after approximately 20 minutes. The extent of absorption is linearly proportional to the dose.
When 75 mg diclofenac is administered by intravenous infusion over 2 hours, the mean maximum plasma concentration is approximately 1.875 ± 0.436 μg/ml (1.9 μg/ml = 5.9 μmol/l). Shorter infusion times lead to higher maximum plasma concentrations (Cmax), while longer infusions lead to a plateau concentration proportional to the infusion rate after 3-4 hours. In contrast to oral administration, when the drug is administered as a suppository or intramuscular injection, its plasma concentration decreases rapidly after reaching maximum levels.
Bioavailability
The area under the concentration curve (AUC) after intramuscular or intravenous administration is approximately twice as large as after oral or rectal administration, as these routes of administration avoid first-pass metabolism through the liver.
Distribution
99.7% of diclofenac binds to plasma proteins, mainly albumin (99.4%).
Diclofenac penetrates into the synovial fluid, where Cmax is reached 2-4 hours after reaching the peak plasma concentration. The expected half-life from the synovial fluid is 3-6 hours. Two hours after reaching Cmax, the concentration of diclofenac in the synovial fluid exceeds that in the blood plasma and remains higher for a period of up to 12 hours.
Diclofenac was detected in low concentrations (100 ng/ml) in breast milk from one breastfeeding woman. The estimated amount of drug reaching the infant in breast milk is equivalent to 0.03 mg/kg/day.
Metabolism
The biotransformation of diclofenac occurs partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and methoxylation, leading to the formation of several phenolic metabolites, most of which are converted to glucuronide conjugates. Two of these phenolic metabolites are biologically active, but their activity is much less pronounced than for diclofenac.
Breeding
The total systemic clearance of diclofenac in plasma is 263 ± 56 ml/min (mean ± SD). The terminal plasma half-life is 1–2 hours. Four metabolites, including two active ones, also have short plasma half-lives of 1–3 hours. Approximately 60% of the administered dose is excreted in the urine as the glucuronide conjugate of the intact molecule and as metabolites, most of which are also converted to glucuronide conjugates. Less than 1% is excreted as unchanged substance. The remainder of the dose is eliminated as metabolites via the bile and feces.
Special patient groups
Elderly patients: No age-related differences in drug absorption, metabolism, or excretion were observed, except that in five elderly patients, a 15-minute intravenous infusion resulted in plasma concentrations that were 50% higher than those observed in young healthy volunteers.
Patients with renal impairment. In patients with renal impairment, no accumulation of unchanged active substance is expected based on the kinetics of the drug after a single dose when the usual dosage regimen is followed. In conditions of creatinine clearance less than 10 ml/min, the levels of hydroxymetabolites in the blood plasma are approximately 4 times higher than in healthy volunteers. However, the metabolites are ultimately excreted in the bile.
Patients with liver disease: In patients with chronic hepatitis or compensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.
Indication
inflammatory and degenerative forms of rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, vertebral pain syndrome, non-articular rheumatism; acute attacks of gout; renal and biliary colic; pain and swelling after injuries and surgeries; severe migraine attacks.
The drug, when administered as an intravenous infusion, is intended for the treatment or prevention of postoperative pain.
Contraindication
Known hypersensitivity to the active substance or to any of the other ingredients of the drug. History of gastrointestinal bleeding or perforation related to previous treatment with non-steroidal anti-inflammatory drugs (NSAIDs). Active peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (two or more separate episodes of established ulceration or bleeding). Third trimester of pregnancy. Like other NSAIDs, diclofenac is also contraindicated in patients in whom the use of ibuprofen, acetylsalicylic acid or other NSAIDs provokes attacks of bronchial asthma, angioedema, urticaria or acute rhinitis. Inflammatory bowel diseases (e.g. Crohn's disease or ulcerative colitis). Hepatic failure. Renal failure. Congestive heart failure (NYHA II–IV). High risk of postoperative bleeding, blood clotting, hemostasis disorders, hematopoietic disorders or cerebrovascular bleeding. Treatment of perioperative pain in coronary artery bypass grafting (or the use of an artificial circulatory device). Ischemic heart disease in patients with angina pectoris, myocardial infarction. Cerebrovascular disease in patients with stroke or transient ischemic attacks. Peripheral arterial disease.
In this dosage form, the drug is contraindicated in children.
Contraindications for intravenous use
Concomitant use of NSAIDs or anticoagulants (including low-dose heparin). History of hemorrhagic diathesis, confirmed or suspected cerebrovascular bleeding in history. Operations associated with a high risk of bleeding. History of bronchial asthma. Moderate or severe renal impairment (serum creatinine
>160 µmol/L). Hypovolemia or dehydration from any cause.
Interaction with other medicinal products and other types of interactions
The following interactions may occur with Diclofenac-Teva and/or other diclofenac preparations.
Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.
Digoxin: Diclofenac may increase the plasma concentration of digoxin when used concomitantly. Monitoring of serum digoxin levels is recommended.
Diuretics and antihypertensives. As with other NSAIDs, concomitant use of diclofenac with diuretics and antihypertensives (e.g. beta-blockers, angiotensin-converting enzyme (ACE) inhibitors) may lead to a reduction in their antihypertensive effect due to inhibition of the synthesis of vasodilator prostaglandins. Therefore, such a combination should be used with caution and patients, especially elderly patients, should be closely monitored for blood pressure. Patients should be adequately hydrated and monitoring of renal function is recommended after initiation of concomitant therapy and regularly thereafter, especially with diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity (see Precautions).
Drugs causing hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may be associated with increases in serum potassium, therefore patients should be monitored more frequently (see Precautions).
Anticoagulants and antithrombotic agents: Caution is advised as concomitant administration may increase the risk of bleeding (see Precautions). Although clinical studies have not shown an effect of diclofenac on the activity of anticoagulants, there is some evidence of an increased risk of bleeding in patients receiving diclofenac and anticoagulants concomitantly.
Therefore, close monitoring of these patients is recommended to ensure that no changes in anticoagulant dosage are necessary. Like other NSAIDs, diclofenac in high doses may temporarily inhibit platelet aggregation.
Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. Concomitant administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. The concomitant use of two or more NSAIDs should be avoided (see Precautions).
Antidiabetic agents. Clinical studies have shown that diclofenac can be used together with oral antidiabetic agents without affecting their clinical effect. However, isolated cases of both hypoglycemic and hyperglycemic effects have been reported, requiring a change in the dosage of antidiabetic agents during treatment with diclofenac. In such cases, monitoring of blood glucose levels is necessary as a precautionary measure during concomitant therapy.
Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. Caution is advised when NSAIDs, including diclofenac, are administered less than 24 hours before methotrexate treatment, as this may increase the blood concentration of methotrexate and increase its toxicity. Serious toxicity has been reported when methotrexate and diclofenac have been administered within 24 hours of each other. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.
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 in patients not receiving cyclosporine.
Tacrolimus: There is a possible increased risk of nephrotoxicity when NSAIDs are used with tacrolimus, which may be mediated through the renal antiprostaglandin effects of the NSAID and the calcineurin inhibitor.
Quinolone antibacterials. There are isolated reports of seizures that may result from the concomitant use of quinolones and NSAIDs. This may occur in patients with or without a history of epilepsy or seizures. Therefore, caution should be exercised when quinolones are used 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 exposure.
Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended that diclofenac be administered at least 1 hour before or 4–6 hours after colestipol/cholestyramine.
Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma glycoside levels.
Mifepristone: Diclofenac sodium should not be used within 8–12 days of mifepristone administration, as it may reduce the effect of the latter.
Potent CYP2C9 inhibitors: Caution is advised when co-administering diclofenac with potent CYP2C9 inhibitors (e.g. voriconazole and sulfinpyrazone), which may lead to a significant increase in plasma Cmax and exposure to diclofenac due to inhibition of its metabolism.
Application features
General recommendations
Undesirable effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
The use of Diclofenac with systemic NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to the lack of any synergistic benefit and the possibility of additional side effects.
Caution should be exercised when prescribing the drug to elderly patients. In particular, it is recommended to use the lowest effective dose in elderly patients with frail health and patients with low body mass index.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may also occur without prior exposure to diclofenac. Hypersensitivity reactions may also progress to Kounis syndrome, a severe allergic reaction that may cause myocardial infarction, the symptoms of which are chest pain associated with an allergic reaction to diclofenac.
Diclofenac sodium, due to its pharmacodynamic properties, may mask the signs and symptoms of infection.
Effects on the digestive system
With the use of diclofenac, as with other NSAIDs, cases of gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and occur at any time during treatment, with or without warning symptoms, and in the presence of a history of serious gastrointestinal events, have been reported. These events usually have a more serious consequence in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
Elderly patients have an increased frequency of adverse reactions when using NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
To reduce the risk of gastrointestinal toxicity in patients with a history of ulcer, especially those 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 patients who require concomitant use of medicinal products containing low doses of acetylsalicylic acid (ASA) or other medicinal products likely to increase the risk of adverse effects on the digestive system, combination therapy with protective medicinal products (e.g. proton pump inhibitors or misoprostol) should be considered.
Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant medications that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agents (e.g. ASA) or SSRIs (see Interactions with other medicinal products and other forms of interaction).
Patients with ulcerative colitis or Crohn's disease require close medical supervision and caution, as their condition may worsen. NSAIDs, including diclofenac, may increase the risk of gastrointestinal anastomotic leakage, and close medical supervision is necessary when using diclofenac after gastrointestinal surgery.
Effect on the liver
Careful medical supervision is required when using the drug in patients with impaired liver function, as their condition may worsen.
As with other NSAIDs, diclofenac may increase the level of one or more liver enzymes. During long-term treatment with Diclofenac, regular monitoring of liver function is necessary as a precautionary measure.
If liver function abnormalities persist or worsen, if clinical signs or symptoms suggestive of progressive liver disease, or if other manifestations are observed (e.g. eosinophilia, rash), Diclofenac should be discontinued.
When using diclofenac, hepatitis may occur without prodromal symptoms.
Caution is necessary if Diclofenac-Teva is used in patients with hepatic porphyria, due to the possibility of provoking an attack.
Effects on the kidneys
Since fluid retention and edema have been reported with diclofenac, special care should be taken in patients with impaired cardiac or renal function, a history of hypertension, the elderly, patients receiving concomitant therapy with diuretics or drugs that significantly affect renal function, and patients with a significant decrease in extracellular fluid volume for any reason, such as before or after major surgery (see Contraindications). In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually results in a return to pre-treatment status.
Effects on the skin
When using diclofenac sodium, as with other NSAIDs, serious skin reactions (some of them fatal) have been reported very rarely, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (see "Adverse reactions"). The highest risk of developing these reactions is observed at the beginning of the course of therapy, in most cases - during the first month of treatment. The use of the drug Diclofenac-Teva should be discontinued at the first appearance of skin rashes, mucosal lesions or any other signs of hypersensitivity.
Systemic lupus erythematosus (SLE) and mixed connective tissue diseases
Patients with SLE and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.
Cardiovascular and cerebrovascular effects
Diclofenac should only be prescribed to patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus, smoking) after careful clinical evaluation. 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 should be periodically reviewed for symptom relief and response to therapy. Use with caution in patients over 65 years of age.
Clinical trial data and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and for long periods, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).
Diclofenac is not recommended for use in patients with uncontrolled hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease; if necessary, use is possible only after a careful risk-benefit assessment and only at a dosage not exceeding 100 mg/day. A similar assessment should be carried out before starting long-term treatment in patients with risk factors for cardiovascular events (e.g., hypertension, hyperlipidemia, diabetes mellitus, and smoking).
Patients should be informed about the possibility of serious events (chest pain, shortness of breath, weakness, speech disorders) that may occur at any time. In this case, a doctor should be consulted immediately.
Effect on hematological parameters
With prolonged use of the drug, as with other NSAIDs, blood test monitoring is recommended.
Like other NSAIDs, Diclofenac may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis or hematological disorders should be carefully monitored.
History of asthma
Patients with bronchial asthma, seasonal allergic rhinitis, patients with swelling of the nasal mucosa (nasal polyps), chronic obstructive pulmonary disease or chronic respiratory infections (especially those associated with allergic rhinitis-like symptoms) are more likely than others to experience reactions to NSAIDs that resemble asthma exacerbations (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. In this regard, special precautions (emergency medical readiness) are recommended for such patients. This also applies to patients with allergies to other substances, manifested by skin reactions, itching or urticaria.
Like other drugs that inhibit the activity of prostaglandin synthetase, diclofenac sodium can provoke the development of bronchospasm in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.
Diclofenac should be used with extreme caution intravenously in patients with bronchial asthma, as its symptoms may be exacerbated.
Fertility in women
The use of Diclofenac may impair female fertility and is not recommended in women attempting to conceive. Discontinuation of the drug should be considered in women who may have difficulty conceiving or who are undergoing investigation of infertility.
Intramuscular injections
Instructions for intramuscular injections must be strictly followed to avoid adverse reactions at the injection site, which may lead to muscle weakness, muscle paralysis, hypoesthesia and necrosis at the injection site.
Children
Diclofenac in the form of a solution for injection should not be administered to premature infants or newborns. The use of benzyl alcohol may lead to toxic and anaphylactoid reactions in children under 3 years of age.
Ability to influence reaction speed when driving vehicles or other mechanisms
Patients who experience visual disturbances, dizziness, vertigo, drowsiness or other central nervous system disorders during treatment with Diclofenac-Teva should refrain from driving or operating other machinery.
Use during pregnancy or breastfeeding
Pregnancy
In the I and II trimesters of pregnancy, Diclofenac-Teva can be prescribed only if the expected benefit to the mother outweighs the potential risk to the fetus, only in the minimum effective dose. The duration of treatment should be as short as possible. Like other NSAIDs, the drug is contraindicated in the III trimester of pregnancy (possible inhibition of uterine contractility and premature closure of the ductus arteriosus in the fetus).
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryo/foetal development. Epidemiological data suggest an increased risk of miscarriage and/or cardiac malformations and gastroschisis following exposure to a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformations has increased from less than 1% to approximately 1.5%.
It is possible that the risk increases with increasing dose and duration of treatment. It has been documented that in animals, administration of a prostaglandin synthesis inhibitor leads to increased pre- and post-implantation losses and embryo/fetal lethality.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may affect the fetus in the following ways:
Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure with oligohydramnios.
The effect of diclofenac on the mother and newborn, as well as at the end of pregnancy:
Possible: prolongation of bleeding time; antiplatelet effect, which may be observed 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 period
Like other NSAIDs, diclofenac sodium passes into breast milk in small amounts. Therefore, the drug should not be used during breastfeeding to avoid undesirable effects on the infant.
Fertility
Like other NSAIDs, diclofenac sodium may affect female fertility. The drug is not recommended for women attempting to conceive. Women who have difficulty conceiving or who have undergone investigation for infertility should discontinue use of the drug.
Method of administration and doses
The drug should be used in the lowest effective dose for the shortest period of time, taking into account the goal of treatment for each individual patient.
Adults
Diclofenac sodium, solution for injection, should not be used for more than 2 days. If necessary, treatment can be continued with diclofenac sodium in tablet or suppository form.
Intramuscular injection
To prevent damage to nerves or other tissues at the site of intramuscular injection, the following rules must be followed.
The usual dose is 75 mg (one ampoule) per day, administered by deep injection into the upper outer sector of the gluteus maximus muscle. In severe cases (e.g. colic), the daily dose may be increased to two 75 mg injections, several hours apart (one injection in each buttock). Alternatively, the 75 mg solution for injection may be combined with other dosage forms (e.g. tablets or suppositories) up to a maximum total daily dose of 150 mg diclofenac sodium.
In the setting of a migraine attack, clinical experience is limited to cases with the initial use of one 75 mg ampoule, the dose being administered if possible immediately after the use of 100 mg suppositories on the same day (if necessary). The total daily dose should not exceed 175 mg on the first day.
There are no data available on the use of diclofenac sodium for the treatment of migraine attacks lasting more than one day.
Intravenous infusions
Immediately before starting intravenous infusion, diclofenac sodium should be diluted in 100–500 ml of 0.9% sodium chloride solution or 5% glucose solution.
Only clear solutions can be used.
Diclofenac sodium, solution for injection, should not be administered as an intravenous bolus injection.
Recommended alternative dosage regimens for diclofenac sodium, solution for injection:
For the treatment of moderate to severe postoperative pain, 75 mg should be administered continuously for 30 minutes to 2 hours; if necessary, the treatment can be repeated after 4–6 hours, but the dose should not exceed 150 mg/day; for the prevention of postoperative pain, a loading dose of 25–50 mg should be administered 15 minutes to 1 hour after surgery, followed by a continuous infusion of approximately 5 mg/hour up to a maximum daily dose of 150 mg.
Elderly patients
No dose adjustment is required, but elderly patients should be monitored closely due to the possible occurrence of adverse reactions.
The recommended maximum daily dose of diclofenac sodium is 150 mg.
Children
Not intended for use in children.
Overdose
Symptoms. Typical clinical symptoms of diclofenac sodium overdose are unknown. In case of overdose, headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, agitation, coma, drowsiness, tinnitus, loss of consciousness or convulsions may occur. In case of severe poisoning, acute renal failure and liver damage are possible.
Treatment. Treatment of acute poisoning with NSAIDs, including diclofenac, consists of supportive measures and symptomatic therapy, as necessary to eliminate complications such as hypotension, renal failure, convulsions, gastrointestinal disorders, respiratory depression. Special measures such as forced diuresis, dialysis or hemoperfusion are unlikely to be effective in eliminating NSAIDs, including diclofenac, due to their high protein binding and extensive metabolism.
Activated charcoal should be considered within 1 hour of ingestion of a potentially toxic amount of the drug. In addition, gastric lavage should be considered in adults within 1 hour of ingestion of a potentially toxic amount of the drug. Diazepam should be administered intravenously if seizures are frequent or prolonged. Other measures may be indicated depending on the clinical condition of the patient. Treatment is symptomatic.
Adverse reactions
Adverse drug reactions are listed by frequency: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency unknown (cannot be estimated from the available data).
The following undesirable effects include those associated with the administration of diclofenac sodium under conditions of short-term and long-term use.
Blood and lymphatic system disorders: very rarely - thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), agranulocytosis.
Immune system disorders: Rare: hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension and shock); very rare: angioedema (including facial edema).
Mental disorders: very rarely - disorientation, depression, insomnia, nightmares, irritability and other mental disorders.
From the nervous system: often - headache, dizziness; rarely - drowsiness, fatigue; very rarely - paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disturbance, stroke; frequency unknown - confusion, hallucinations, sensory disturbances, general malaise.
On the part of the organs of vision: very rarely - visual disturbances, blurred vision, diplopia; frequency unknown - optic neuritis.
From the side of the organs of hearing and labyrinth: often - vertigo; very rarely - tinnitus, hearing impairment.
Cardiac disorders: very rarely - palpitations, chest pain, heart failure, myocardial infarction; frequency unknown - Kounis syndrome.
From the vascular system: very rarely - arterial hypertension, arterial hypotension, vasculitis.
Respiratory, thoracic and mediastinal disorders: rarely - asthma (including dyspnoea); very rarely - pneumonitis.
On the part of the digestive system: often - nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia; rarely - 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); very rarely - colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal disorders, membranous intestinal strictures, pancreatitis; frequency unknown - ischemic colitis.
Hepatobiliary disorders: often - increased transaminase levels; rarely - hepatitis, jaundice, impaired liver function; very rarely - transient hepatitis, hepatonecrosis, hepatic failure.
Skin and subcutaneous tissue disorders: common: rash; rare: urticaria; very rare: bullous rash, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, hair loss, photosensitivity reaction, purpura, allergic purpura, pruritus.
Renal and urinary disorders: very rarely - acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.
General disorders and administration site conditions: common: injection site reaction, pain, induration; rare: injection site edema, injection site necrosis; very rare: injection site abscess.
From the reproductive system and mammary glands: very rarely - impotence.
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/day) and with long-term use.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 30 °C out of the reach of children.
Store ampoules in the box.
Pack
