Instructions Diclofenac-Darnitsa solution for injection 2.5% ampoule 3 ml No. 10
Composition
active ingredient: diclofenac;
1 ml of solution contains diclofenac sodium 25 mg;
Excipients: mannitol (E 421), sodium metabisulfite (E 223), benzyl alcohol, propylene glycol, sodium hydroxide, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: transparent, colorless or slightly yellowish liquid with a slight specific odor.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related compounds. ATC code M01A B05.
Pharmacological properties
Pharmacodynamics.
Diclofenac-Darnitsa contains diclofenac sodium, a non-steroidal compound with pronounced antirheumatic, anti-inflammatory, analgesic and antipyretic properties. Inhibition of the biosynthesis of prostaglandins, which play an important role in the occurrence of inflammation, pain and fever, is considered the main mechanism of action of the drug. In rheumatic diseases, the anti-inflammatory and analgesic properties of the drug cause a clinical response, which is characterized by the disappearance of signs and symptoms: pain at rest and during movement, morning stiffness and swelling of the joints; also a noticeable improvement in motor function.
Diclofenac has a pronounced analgesic effect on moderate to severe pain of non-rheumatic origin within 15−30 minutes.
Diclofenac has also demonstrated a significant effect on migraine attacks.
In post-traumatic and postoperative conditions with inflammation, diclofenac quickly relieves spontaneous pain and pain during movement and reduces swelling caused by inflammation and wounds.
When used simultaneously with opioid analgesics for postoperative pain relief, diclofenac significantly reduces the need for them.
Diclofenac sodium in vitro at concentrations equivalent to those achieved in humans does not inhibit the synthesis of proteoglycans in cartilage tissue.
Diclofenac-Darnitsa, solution for injection in ampoules, is especially necessary for the initiation of treatment of inflammatory and degenerative rheumatic diseases and pain syndrome due to inflammation of non-rheumatic origin.
Pharmacokinetics.
Absorption: After administration of 75 mg diclofenac by intramuscular injection, absorption begins immediately and mean peak plasma concentrations of approximately 2.5 μg/ml (8 μmol/l) are reached after approximately 20 minutes. The extent of absorption may be linearly related to the dose.
When 75 mg diclofenac is to be administered by intravenous infusion over 2 hours, the mean peak plasma concentrations are approximately 1.9 μg/ml (5.9 μmol/l). Shorter infusion times lead to higher peak plasma concentrations, while longer infusions lead to concentrations proportional to the infusion rate after 3-4 hours. After intramuscular injection or administration of gastro-resistant tablets or suppositories, plasma concentrations decrease rapidly once peak levels are reached.
Bioavailability. The area under the concentration curve (AUC) after intramuscular or intravenous administration is approximately twice as large as after oral or rectal administration, because approximately half of the active substance is metabolized during the first passage through the liver (the "first-pass effect") when the drug is administered orally or rectally.
Pharmacokinetic properties do not change after repeated administration. If the recommended dosing intervals are observed, accumulation of the drug does not occur.
Distribution: 99.7% of diclofenac is bound to serum proteins, mainly albumin (99.4%). The volume of distribution is 0.12-0.17 l/kg.
Diclofenac enters the synovial fluid, where maximum concentrations are reached 2-4 hours after peak plasma levels. The expected elimination half-life from synovial fluid is 3 to 6 hours. 2 hours after peak plasma levels, diclofenac concentrations in synovial fluid exceed those in plasma and remain higher for 12 hours.
Diclofenac has been detected in low concentrations (100 ng/ml) in the breast milk of a breastfeeding woman. The estimated amount of drug reaching the infant via breast milk is equivalent to 0.03 mg/kg/day.
Elimination. The total systemic clearance of diclofenac from plasma is 263 ± 56 ml/min (mean ± standard deviation). 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. One metabolite, 3'-hydroxy-4'-methoxy-diclofenac, has a much longer plasma half-life. However, this metabolite is virtually inactive.
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. However, in some elderly patients, a 15-minute intravenous infusion resulted in plasma concentrations that were 50% higher than those observed in young healthy subjects.
Patients with renal impairment. In patients with renal impairment, no accumulation of the active substance is expected when the usual dosage regimen is followed. With a creatinine clearance of less than 10 ml/min, the plasma levels of the hydroxy metabolites at steady state are approximately 4 times higher than in patients with normal renal function.
Therefore, 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 healthy volunteers.
Indication
The drug, when administered intramuscularly, is intended for the treatment of:
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 intravenous infusions, is intended for the treatment or prevention of postoperative pain.
Contraindication
Hypersensitivity to the active substance, sodium metabisulfite or to any other components of the medicinal product.
Like other nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac is also contraindicated in patients in whom the use of ibuprofen, acetylsalicylic acid or other NSAIDs provokes an attack of bronchial asthma, angioedema, urticaria, acute rhinitis, nasal polyps or allergy-like symptoms.
History of gastrointestinal bleeding or perforation related to previous NSAID treatment.
Active ulcer/bleeding or history of recurrent ulcer/bleeding (two or more separate episodes of established ulceration or bleeding).
Inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
Liver failure.
Kidney failure.
Congestive heart failure (II-IV functional class according to the NYHA classification - New York Heart Association).
Ischemic heart disease in patients (angina pectoris, previous myocardial infarction).
Cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks.
Peripheral artery disease.
Treatment of perioperative pain in coronary artery bypass grafting (or the use of a cardiopulmonary bypass machine).
High risk of developing postoperative bleeding, blood clotting disorders, hemostasis disorders, hematopoietic disorders, or cerebrovascular bleeding.
Third trimester of pregnancy.
In this dosage form, the drug is contraindicated in children.
Intravenous infusions are contraindicated in:
concomitant use of NSAIDs or anticoagulants (including low-dose heparin);
history of hemorrhagic diathesis or confirmed/suspected cerebrovascular bleeding in history;
surgical interventions with a high risk of bleeding;
bronchospasm and bronchial asthma in history;
moderate or severe renal insufficiency (serum creatinine level > 160 mmol/l);
hypovolemia or dehydration of various origins.
Interaction with other medicinal products and other types of interactions
The following are interactions observed with diclofenac preparations in the form of a solution for injection and/or other dosage forms.
Lithium: Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.
Diuretics and antihypertensives. As with other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensives [e.g. β-blockers, angiotensin-converting enzyme (ACE) inhibitors] may lead to a reduction in their antihypertensive effect due to inhibition of vasodilator prostaglandin synthesis. Therefore, such a combination should be used with caution and patients, especially the elderly, should be closely monitored for blood pressure. Patients should be adequately hydrated and renal function should be monitored 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 serum potassium levels, and patients should be monitored more frequently.
Other NSAIDs and corticosteroids: Concomitant use of diclofenac and other systemic NSAIDs or corticosteroids may increase the incidence of gastrointestinal adverse reactions. The concomitant use of two or more NSAIDs should be avoided.
Anticoagulants and antithrombotic agents. Caution is advised as concomitant use increases 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 anticoagulants concomitantly. Therefore, close monitoring of such patients is recommended. Like other NSAIDs, diclofenac in high doses may transiently inhibit platelet aggregation.
Selective serotonin reuptake inhibitors (SSRIs). Concomitant administration of systemic NSAIDs and SSRIs increases the risk of gastrointestinal bleeding.
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 after administration of diclofenac have been reported, which necessitates a change in the dosage of antidiabetic agents during treatment with diclofenac. In such cases, monitoring of blood glucose levels is necessary.
Probenecid: Medicines containing probenecid may delay the elimination of diclofenac.
Colestipol and cholestyramine: Concomitant administration of diclofenac and colestipol or cholestyramine reduces the absorption of diclofenac by approximately 30% and 60%, respectively.
Therefore, it is recommended to administer diclofenac at least 1 hour before or 4–6 hours after colestipol/cholestyramine.
Drugs that induce drug-metabolizing enzymes: Drugs that induce enzymes, such as rifampicin, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum), are theoretically capable of reducing diclofenac plasma concentrations.
Methotrexate. Caution is advised when NSAIDs are administered less than 24 hours before or after methotrexate, as methotrexate blood concentrations and toxicity may increase. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. This interaction is mediated by methotrexate accumulation as a result of impaired renal excretion with NSAIDs.
Cyclosporine and tacrolimus. Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine through its effects on renal prostaglandins. The same risk also occurs with tacrolimus treatment. In this regard, it should be used in lower doses than in patients not receiving cyclosporine and tacrolimus.
Quinolone antibacterials: Convulsions may occur in patients receiving quinoline derivatives and NSAIDs concomitantly, with or without a history of epilepsy or seizures. Therefore, caution should be exercised when considering the use of quinolines 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.
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 its effect.
Potent CYP2C9 inhibitors: Caution is recommended when co-administering diclofenac with potent CYP2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in maximum plasma concentrations and exposure to diclofenac due to inhibition of its metabolism.
CYP2C9 inducers: Caution is advised when diclofenac is co-administered with CYP2C9 inducers (e.g. rifampicin). This may result in significant reductions in plasma concentrations and exposure to diclofenac.
Application features
The use of the drug with systemic NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to the lack of any synergistic benefit and the possibility of developing additional side effects.
Caution should be exercised when prescribing the drug to elderly patients. In particular, the lowest effective dose should be used for elderly patients with frail health and for patients with low body mass index.
As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may also occur with diclofenac. Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that may cause myocardial infarction. Symptoms of this reaction may include chest pain associated with an allergic reaction to diclofenac.
Like other NSAIDs, diclofenac, due to its pharmacodynamic properties, may mask the signs and symptoms of infection.
Effects on the digestive system
Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal, have been reported with all NSAIDs, including diclofenac, and can occur at any time during treatment, with or without warning symptoms, or with a history of serious gastrointestinal events. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
Close medical supervision is necessary when using all NSAIDs, including diclofenac; 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 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 low doses of acetylsalicylic acid or other drugs that are likely to increase the risk of adverse effects on the digestive system, combination therapy with protective drugs (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 medications that 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.
The use of NSAIDs, including diclofenac, may be associated with an increased risk of anastomotic leakage. Close monitoring of patients and caution are recommended when used after gastrointestinal surgery.
Effect on the liver
Close medical supervision is required if diclofenac is prescribed to patients with liver damage, as their condition may be aggravated.
As with other NSAIDs, one or more liver enzymes may be elevated. During long-term treatment, liver function should be monitored regularly.
If liver dysfunction persists or worsens, if clinical signs or symptoms may be associated with progressive liver disease, or if other manifestations are observed (e.g., eosinophilia, rash), the drug should be discontinued.
When treated with diclofenac sodium, the course of hepatitis may occur without prodromal symptoms.
Caution is necessary if the drug is used in patients with hepatic porphyria, due to the possibility of provoking an attack.
Effects on the kidneys
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 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. In such cases, monitoring of renal function is recommended. Discontinuation of therapy usually results in a return to pre-treatment status.
Serious skin reactions (some of which were fatal) have been reported very rarely in association with the use of NSAIDs, including diclofenac, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. The risk of these reactions appears to be highest at the beginning of therapy, in most cases 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.
Systemic lupus erythematosus (SLE) and mixed connective tissue diseases
Patients with SLE and mixed connective tissue diseases are 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.
For patients with a history of hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and advice is necessary, 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) and for long periods, may be associated with a slightly 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 should only be considered after careful risk-benefit assessment and only at doses 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 complications (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, 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 prostaglandin synthetase activity, diclofenac sodium may provoke the development of bronchospasm in patients suffering from bronchial asthma or in patients with a history of bronchial asthma.
Injection site reactions
Injection site reactions have been reported following intramuscular administration of diclofenac, including injection site necrosis and drug embolism, also known as Nicolau's syndrome (especially after inadvertent subcutaneous injection). When administering diclofenac intramuscularly, appropriate needle selection and injection technique should be observed (see section 4.2).
Important information about excipients.
The medicine contains sodium metabisulfite (E 223), which may rarely cause hypersensitivity reactions and bronchospasm.
Use during pregnancy or breastfeeding
Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryo/foetal development. Epidemiological studies have shown 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 increases from less than 1% to approximately 1.5%.
It is possible that the risk increases with increasing dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation losses and embryo/fetal lethality.
In addition, an increased incidence of various malformations, including cardiovascular, has been reported in animals treated with a prostaglandin synthesis inhibitor during organogenesis. From the 20th week of gestation, the use of diclofenac may cause oligohydramnios due to impaired fetal renal function. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation of treatment. If Diclofenac-Darnitsa is used in women attempting to conceive, or in the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios should be considered after exposure to diclofenac for several days, starting from the 20th week of gestation. Diclofenac should be discontinued if oligohydramnios is detected.
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 impairment (see above).
Effects on the mother and newborn, as well as reactions at the end of pregnancy:
possible prolongation of bleeding time, antiplatelet effect, which can be observed even at very low doses;
inhibition of uterine contractions, leading to delayed or prolonged labor.
Therefore, Diclofenac-Darnitsa is contraindicated in the third trimester of pregnancy.
Breastfeeding. Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, to avoid undesirable effects on the infant, Diclofenac-Darnitsa should not be used during breastfeeding.
Fertility. Like other NSAIDs, Diclofenac-Darnitsa may affect female fertility. The drug should not be used in women planning to become pregnant. If a woman has difficulty conceiving or is undergoing investigation for infertility, Diclofenac-Darnitsa should be discontinued.
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-Darnitsa should refrain from driving or operating other mechanisms.
Method of administration and doses
The drug should be used in the lowest recommended doses for the shortest period of time, taking into account the goal of therapy for each individual patient.
Do not use for more than 2 days. If necessary, treatment can be continued with Diclofenac-Darnitsa tablets.
Intramuscular injection.
To prevent damage to nerves or other tissues at the site of intramuscular injection, the following recommendations should be followed.
The usual dose is 75 mg (1 ampoule) per day, which should be administered by deep injection into the upper outer sector of the gluteus maximus muscle. In severe cases, the daily dose can be increased to 2 injections of 75 mg, between which an interval of several hours should be maintained (1 injection in each buttock). Alternatively, 75 mg can be combined with other dosage forms of Diclofenac-Darnitsa (e.g. tablets) up to a total maximum total daily dose of 150 mg.
In the setting of migraine attacks, clinical experience is limited to cases with the initial use of 1 ampoule of 75 mg. The total daily dose should not exceed 175 mg on the first day. There are no data available on the use of the drug for the treatment of migraine attacks for more than 1 day.
Intravenous infusions
Diclofenac-Darnitsa, solution for injection, should not be administered as an intravenous bolus injection.
Immediately before starting the intravenous infusion of Diclofenac-Darnitsa, depending on its required duration, 1 ampoule of the drug should be diluted in 100-500 ml of 0.9% sodium chloride solution or 5% glucose solution, buffered with sodium bicarbonate solution for injection (0.5 ml of 8.4% or 1 ml of 4.2% solution, or the corresponding volume of another concentration), taken from a freshly opened container. Only clear solutions can be used. If there are crystals or sediment in the solution, it cannot be used for infusion.
Two alternative dosing regimens for the drug Diclofenac-Darnitsa, solution for injection, are recommended:
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 per hour up to a maximum daily dose of 150 mg.
Elderly patients
Although the pharmacokinetics of the drug are not impaired to a clinically significant extent in elderly patients, NSAIDs should be used with caution in patients who are generally more susceptible to adverse reactions. In particular, the lowest effective dose is recommended for debilitated elderly patients or patients with low body weight (see also section "Special warnings and precautions for use"); patients should also be monitored for gastrointestinal bleeding during treatment with NSAIDs.
The recommended maximum daily dose of the drug Diclofenac-Darnitsa is 150 mg.
Each ampoule is for single use only. The solution should be used immediately after opening the ampoule. Any unused portion should be discarded.
Children.
Diclofenac-Darnitsa in the dosage form of a solution for injection is contraindicated for use in children.
Overdose
Symptoms. There is no typical clinical picture of the consequences of diclofenac overdose. Overdose may cause symptoms such as headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, agitation, coma, drowsiness, tinnitus, loss of consciousness or convulsions. In case of severe poisoning, acute renal failure and liver damage are possible.
Treatment. Activated charcoal may be considered within 1 hour of ingestion of a potentially toxic amount of the drug. In addition, gastric lavage should be considered for 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.
Side effects
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 therapeutic doses (150 mg per day) and with long-term use.
The following undesirable effects include phenomena associated with the use of the drug Diclofenac-Darnitsa, solution for injection, and/or other dosage forms of diclofenac, under conditions of short-term and long-term treatment.
Adverse reactions are listed by system organ class and 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).
On the part of the organs of vision:
very rare: visual disturbances (blurred vision and diplopia);
frequency unknown: optic neuritis.
Such visual disturbances are class effects of NSAIDs and are usually reversible upon discontinuation of the drug. The most likely mechanism of visual disturbances is inhibition of the synthesis of prostaglandins and other related compounds, which, by disrupting the regulation of retinal blood flow, contribute to the development of visual disturbances. If such symptoms occur during treatment with diclofenac, an ophthalmological examination should be performed to exclude other possible causes.
From the side of the organs of hearing and vestibular apparatus:
common: vertigo;
very rare: tinnitus, hearing impairment.
From the respiratory system, chest organs and mediastinum:
Rare: asthma (including dyspnea), bronchospasm;
very rare: pneumonitis.
From the gastrointestinal tract:
common: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, decreased appetite, anorexia;
Rare: gastritis, gastrointestinal bleeding, vomiting with blood, hemorrhagic diarrhea, melena, gastric or intestinal ulcer with bleeding or ulceration.
