Diclofenac Teva solution for injection 75 mg/3 ml in 3 ml ampoules 5 pcs.

Pharmacodynamics

Diclofenac Teva is a nonsteroidal drug with pronounced analgesic/anti-inflammatory properties, inhibits COX. Diclofenac sodium in vitro at concentrations equivalent to those achieved in humans does not inhibit the biosynthesis of proteoglycans of cartilage tissue in humans. If the drug is used to relieve postoperative pain simultaneously with precipitation, it significantly reduces the need for opioids.

Pharmacokinetics

Absorption: After administration of 75 mg diclofenac by intramuscular injection, absorption begins immediately, and the mean Cmax in plasma, which is ≈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 of diclofenac is administered by intravenous infusion over 2 hours, the mean Cmax in plasma is approximately 1.875 ± 0.436 μg/ml (1.9 μg/ml = 5.9 μmol/l). Shorter infusion times lead to higher Cmax _in plasma, while longer infusions lead to a plateau concentration proportional to the infusion rate after 3-4 hours. In contrast to the corresponding results for oral administration, when the drug is administered as a suppository or intramuscularly, the plasma concentration decreases rapidly immediately after reaching maximum levels.

Bioavailability. AUC after IM or IV administration is approximately twice that after oral or rectal administration, because this route avoids first-pass metabolism through the liver.

Distribution: 99.7% of diclofenac is bound to proteins, mainly to albumin (99.4%).

Diclofenac penetrates into the synovial fluid, where Cmax is reached 2-4 hours after reaching the peak value in the blood plasma. The expected T½ _from the synovial fluid is 3-6 hours. 2 hours after reaching Cmax in the blood plasma, the concentration of diclofenac in the synovial fluid exceeds this value in the blood plasma and remains higher for 12 hours.

Diclofenac has been detected in low concentrations (100 ng/mL) in breast milk from one breastfeeding woman. The estimated amount of drug that reaches 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 that of diclofenac.

Elimination: The total systemic clearance of diclofenac in plasma is 263 ± 56 ml/min (mean ± SD). The terminal T½ _from plasma is 1-2 h. Four metabolites, including two active ones, also have short T½ _from plasma – 1-3 h.

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 in the feces.

Special patient groups: Elderly patients. No differences in absorption, metabolism, or excretion of the drug were observed depending on the age of the patient, except that in 5 elderly patients, a 15-minute intravenous infusion resulted in plasma concentrations 50% higher than those 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. With a creatinine clearance of 10 ml/min, the plasma levels of hydroxymetabolites 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 of the liver, the kinetics and metabolism of diclofenac are the same as in patients without liver disease.

With i / m administration:

• inflammatory and degenerative forms of rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, vertebral pain syndrome, extra-articular rheumatism;
• acute attacks of gout;
• renal and hepatic colic;
• pain and swelling after injuries and surgeries;
• severe migraine attacks.

In the form of IV infusions: treatment or prevention of postoperative pain.

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 2 days. If necessary, treatment can be continued with diclofenac sodium tablets or suppositories.

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 (1 ampoule) administered by deep injection into the upper outer quadrant 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 of diclofenac sodium (e.g. tablets, suppositories) up to a total maximum daily dose of 150 mg.

In the setting of a migraine attack, clinical experience is limited to cases with the initial use of 1 ampoule of 75 mg, the dose is administered if possible immediately after the use of suppositories of 100 mg on the same day (if necessary). The total daily dose should not exceed 175 mg on the 1st day.

There are no available data on the use of diclofenac sodium for the treatment of migraine attacks for 1 day.

In / in infusion. Immediately before the start of the / in 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, treatment can be repeated after 4-6 hours, but the dose should not exceed 150 mg/day;
• for the prevention of postoperative pain: 15 min-1 h after surgery, a loading dose of 25-50 mg should be administered, after which a continuous infusion of ≈5 mg/h should be applied 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.

• Known hypersensitivity to the active substance or any component of the drug; history of gastrointestinal bleeding or perforation associated with previous NSAID treatment; active ulcer/bleeding or history of recurrent ulcer/bleeding (≥2 separate episodes of diagnosed ulcer or bleeding); 3rd 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 BA, 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 disorders, hemostasis disorders, hematopoietic disorders or cerebrovascular bleeding; treatment of perioperative pain during coronary artery bypass grafting (or the use of a cardiopulmonary bypass machine); coronary artery disease in patients with angina pectoris, myocardial infarction; cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks; peripheral arterial disease.

In this dosage form, the drug is contraindicated in children.

For intravenous use only:

• concomitant use of NSAIDs or anticoagulants (including low-dose heparin);
• history of hemorrhagic diathesis, confirmed or suspected cerebrovascular bleeding in history;
• surgical interventions associated with a high risk of bleeding;
• History of asthma;
• moderate or severe renal impairment (plasma creatinine 160 μmol/l);
• hypovolemia or dehydration from any cause.

Adverse drug reactions are listed according to frequency: 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 unknown (cannot be estimated from the available data).

The side effects presented below include those associated with the administration of diclofenac sodium in short-term and long-term use.

From the blood and lymphatic system: very rarely – thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), agranulocytosis.

On the part of the immune system: rarely – hypersensitivity, anaphylactic and anaphylactoid reactions (including hypotension); very rarely – angioedema (including facial edema).

Mental disorders: very rarely – disorientation, depression, insomnia, nightmares, irritability, 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 organ of vision: very rarely – visual impairment, blurred vision, diplopia; frequency unknown – optic neuritis.

From the side of the organs of hearing and labyrinth: often – vertigo; very rarely – tinnitus, hearing impairment.

On the part of the heart: very rarely – palpitations, chest pain, heart failure, myocardial infarction.

From the vascular system: very rarely – arterial hypertension, arterial hypotension, vasculitis.

From the respiratory system, thoracic organs and mediastinum: rarely – asthma (including dyspnea), bronchospasm; 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.

On the part of the liver: sometimes – increased transaminase levels, rarely – hepatitis, jaundice, impaired liver function; very rarely – fulminant hepatitis, hepatonecrosis, liver 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, purpura, allergic purpura, pruritus.

From the kidneys and urinary tract: 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.

General recommendations: Undesirable effects can be reduced by using the lowest effective dose for the shortest duration necessary to control symptoms.

The use of Diclofenac Teva with systemic NSAIDs, including selective COX-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, for elderly patients with frail health and for patients with low body mass index, it is recommended to use the minimum effective dose.

As with other non-steroidal anti-inflammatory drugs, allergic reactions, including anaphylactic/anaphylactoid reactions, may also occur without prior exposure to diclofenac.

Diclofenac sodium, due to its pharmacodynamic properties, may mask the signs and symptoms of infection.

Gastrointestinal effects. Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and may occur at any time during treatment with or without warning symptoms, and in patients with a history of serious gastrointestinal events, have been reported with all NSAIDs, including diclofenac. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.

As with all NSAIDs, including diclofenac, close medical supervision is necessary; special care should be taken when prescribing diclofenac to patients with symptoms suggestive of gastrointestinal disorders, or with a history of gastric or intestinal ulcer, bleeding or perforation. The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing doses of NSAIDs, including diclofenac, and in patients with a history of ulcer, especially if complicated by bleeding or perforation.

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

To reduce the risk of toxic effects on the digestive system in patients with a history of ulcer, especially with complications in the form of bleeding or perforation, and in elderly patients, treatment is initiated and maintained at the minimum effective dose.

For such patients, as well as patients who require concomitant use of medicinal products containing low doses of acetylsalicylic acid 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 the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required in patients receiving concomitant therapy with drugs that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agents (e.g. acetylsalicylic acid) or selective serotonin reuptake inhibitors.

Effects on the liver. When taking the drug in patients with impaired liver function, close medical supervision is necessary, as their condition may worsen. As with other non-steroidal anti-inflammatory drugs, including diclofenac, the level of one or more liver enzymes may increase. During long-term treatment with Diclofenac Teva, 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 (e.g. eosinophilia, rash) occur, Diclofenac should be discontinued.

The course of diseases such as hepatitis can occur without prodromal symptoms.

Caution is required if Diclofenac is used in patients with hepatic porphyria, due to the possibility of provoking an attack.

Renal effects: Since fluid retention and oedema have been reported with NSAIDs, including diclofenac, special care should be taken in patients with impaired cardiac or renal function, a history of hypertension, the elderly, patients receiving concomitant diuretic therapy or drugs that significantly affect renal function, and patients with significant volume depletion from any cause, such as before or after major surgery. 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.

Skin effects. Serious skin reactions (some of which were fatal) have been reported very rarely in association with the use of NSAIDs, including diclofenac sodium, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The highest risk of these reactions is observed at the beginning of the course of therapy, in most cases – during the first month of treatment. The use of Diclofenac Teva should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.

Systemic lupus erythematosus and mixed connective tissue diseases: Patients with systemic lupus erythematosus 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 sodium for symptom relief should be periodically reviewed and the response to therapy monitored. Use with caution in patients ≥65 years of age.

For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and advice should be provided, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.

Clinical trial data and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) 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 coronary artery disease, peripheral arterial disease and/or cerebrovascular disease, and should only be used after careful risk/benefit assessment at a dose not exceeding 100 mg/day. A similar assessment should be made before initiating 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, you should immediately consult a doctor.

Effect on hematological parameters. With prolonged use of the drug, as with other NSAIDs, blood test monitoring is recommended. Like other nonsteroidal anti-inflammatory drugs, Diclofenac Teva 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), COPD or chronic respiratory infections (especially those associated with allergic rhinitis-like symptoms) are more likely than others to experience reactions to NSAIDs that resemble exacerbations of asthma (so-called analgesic intolerance/analgesic asthma), angioedema or urticaria. Therefore, special precautions (emergency medical attention) 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 with bronchial asthma or in patients with a history of bronchial asthma.

Fertility in women: 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.

IM injection. Injection instructions must be followed closely to prevent injection site reactions, which may include muscle weakness, muscle paralysis, hypoesthesia, and injection site necrosis.

Children. Diclofenac solution for injection should not be administered to premature infants or neonates. The use of benzyl alcohol may cause toxic and anaphylactoid reactions in children under 3 years of age.

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 nonsteroidal anti-inflammatory drugs, the drug is contraindicated in the third trimester of pregnancy (possible inhibition of uterine contractility and premature closure of the ductus arteriosus in the fetus).

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological studies have shown an increased risk of miscarriage and/or heart defects and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular defects increases from less than 1% to approximately 1.5%.

It is possible that the risk increases with dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo/fetal lethality.

In addition, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various malformations, including those of the cardiovascular system, has been reported. If Diclofenac is used in women attempting to conceive or in the first trimester of pregnancy, the dose should be as low as possible and the duration of treatment as short as possible.

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.

Thus, the drug is contraindicated in the third trimester of pregnancy.

Breastfeeding. Like other nonsteroidal anti-inflammatory drugs, diclofenac is excreted in breast milk in small quantities. Therefore, in order to avoid undesirable effects on the infant, the drug should not be used during breastfeeding.

Fertility. Like other nonsteroidal anti-inflammatory drugs, diclofenac sodium may affect female fertility. The drug is not recommended for women planning to become pregnant. Women who have problems conceiving or have undergone investigation for infertility should discontinue use of the drug.

Children: Not intended for use in children.

Ability to influence the reaction rate when driving vehicles or operating 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 vehicles and operating other mechanisms.

The following interactions of the drug Diclofenac Teva and/or other diclofenac drugs may occur.

Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of plasma lithium levels is recommended.

Digoxin: Diclofenac may increase the plasma concentration of digoxin when used concomitantly. Monitoring of digoxin plasma levels is recommended.

Diuretics and antihypertensives. The simultaneous use of diclofenac, as with other NSAIDs, with diuretics and antihypertensives (e.g. β-blockers, ACE inhibitors) may lead to a decrease in their antihypertensive effect by inhibiting the synthesis of vasodilator prostaglandins. Therefore, this combination should be used with caution and patients, especially the elderly, 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.

Drugs causing hyperkalemia: Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus or trimethoprim may be associated with increases in plasma potassium levels, therefore patients should be monitored more frequently.

Anticoagulants and antithrombotic agents: Caution is advised as concomitant administration may increase the risk of bleeding. 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 these drugs concomitantly.

Therefore, close monitoring of such patients is recommended to ensure that any changes in anticoagulant dosage are not necessary. Like other NSAIDs, diclofenac in high doses may temporarily inhibit platelet aggregation.

Other NSAIDs, including selective COX-2 inhibitors, and corticosteroids. Concomitant use of diclofenac and other nonsteroidal anti-inflammatory drugs or glucocorticoids may increase the risk of gastrointestinal bleeding or ulceration. The concomitant use of two or more NSAIDs should be avoided.

Selective serotonin reuptake inhibitors: Concomitant administration of systemic NSAIDs and selective serotonin reuptake inhibitors may increase the risk of gastrointestinal bleeding.

Antidiabetic drugs. Clinical studies have shown that diclofenac can be used together with oral antidiabetic drugs without affecting their therapeutic effect. However, isolated cases of both hypoglycemic and hyperglycemic effects are known, requiring a change in the dosage of antidiabetic drugs during treatment with diclofenac. In such cases, monitoring of blood glucose levels is necessary, which is a preventive 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 NSAIDs, including 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 due to its effects on renal prostaglandins. Therefore, it should be used at lower doses than in patients not taking cyclosporine.

Tacrolimus: The use of NSAIDs with tacrolimus may increase the risk of nephrotoxicity, which may be mediated through the renal antiprostaglandin effects of the NSAID and the calcineurin inhibitor.

Quinolone antibacterials. There have been 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 and seizures. Therefore, caution should be exercised when considering the use of quinolones 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 to administer diclofenac at least 1 hour before or 4-6 hours after colestipol/cholestyramine.

Cardiac glycosides. Concomitant use of cardiac glycosides and nonsteroidal anti-inflammatory drugs 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 its effect.

Potent CYP 2C9 inhibitors: Caution is advised when prescribing diclofenac with potent CYP 2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in plasma Cmax and exposure to diclofenac due to inhibition of its metabolism _.

Incompatibility: Due to the lack of compatibility studies, this medicinal product must not be mixed with other medicinal products.

Symptoms. Typical clinical symptoms of diclofenac sodium overdose are not known. 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 respiratory distress syndrome and liver damage are possible.

Treatment. Within 1 hour after the administration of a potentially toxic amount of the drug orally, the use of activated charcoal should be considered. In addition, in adults, gastric lavage should be considered within 1 hour after the administration of a potentially toxic amount of the drug. In case of frequent or prolonged convulsions, diazepam should be administered intravenously. Other measures may be indicated, taking into account the clinical condition of the patient. Treatment is symptomatic.

At a temperature not exceeding 30°C.

Store ampoules in the box.