INSTRUCTION
for medical use of the medicinal product
DICLOFENAC - DONATION
(DICLOFENAC-DARNITSA)
Storage:
active substance: 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.
Medicinal form. Solution for injection.
Main physicochemical properties: transparent, colorless or slightly yellowish liquid with a slight specific smell.
Pharmacotherapeutic group. Non-steroidal anti-inflammatory and anti-rheumatic drugs. Acetic acid derivatives and related compounds. ATX code M01A B05.
Pharmacological properties.
Pharmacodynamics.
Diclofenac-Darnytsia contains diclofenac sodium, a non-steroidal compound with pronounced anti-rheumatic, anti-inflammatory, analgesic and antipyretic properties. Suppression of the biosynthesis of prostaglandins, which play an important role in the occurrence of inflammation, pain and pain, 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 joint swelling; there is also a noticeable improvement in motor function.
Diclofenac has a pronounced analgesic effect on moderate and severe pain of non-rheumatic origin within 15-30 minutes.
Diclofenac also demonstrated a significant effect on migraine attacks.
In post-traumatic and post-operative conditions with inflammation, diclofenac rapidly relieves spontaneous pain and pain during movement and reduces swelling caused by inflammation and wounds.
When using the drug 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-Darnytsia, a solution for injections in ampoules, is especially necessary for the treatment of inflammatory and degenerative rheumatic diseases and pain syndrome due to inflammation of non-rheumatic origin.
Pharmacokinetics.
Absorption. Following administration of 75 mg of diclofenac by intramuscular injection, absorption begins immediately, and mean peak plasma concentrations of approximately 2.5 μg/mL (8 μmol/L) are reached approximately 20 minutes later. The volume of absorption may depend linearly on the dose.
In the event that 75 mg of diclofenac must be administered by intravenous infusion over 2 hours, the mean maximum 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. Following 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 about twice as large as after oral or rectal administration, because about half of the active substance is metabolized during the first passage through the liver ("first-pass" effect) in the event that the drug the drug is administered orally or rectally.
Pharmacokinetic properties do not change after repeated administration. As long as the recommended dosing intervals are followed, the drug does not accumulate.
Distribution. 99.7% of diclofenac binds to serum proteins, mainly to albumin (99.4%). The volume of distribution is 0.12-0.17 l/kg.
Diclofenac enters the synovial fluid, where maximum concentrations are established 2-4 hours after reaching the peak value in the blood plasma. The expected elimination half-life from the synovial fluid is from 3 to 6 hours. 2 hours after peak plasma concentrations of diclofenac in synovial fluid exceed those in plasma and remain higher for 12 hours.
Diclofenac was detected at low concentrations (100 ng/ml) in the breast milk of a lactating woman. The estimated amount of the drug entering the body of an infant with breast milk is equivalent to 0.03 mg/kg/day.
Biotransformation. Biotransformation of diclofenac occurs partly by glucuronidation of the intact molecule, but mainly by single and multiple hydroxylation and methoxylation, which leads to the formation of several phenolic metabolites (3'-hydroxy-, 4'-hydroxy-, 5-hydroxy-, 4',5- dihydroxy-, and 3'-hydroxy-4'-methoxy-diclofenac), most of which are converted into glucuronide conjugates. Two of these phenolic metabolites are biologically active, but their action is much less pronounced than that of diclofenac.
Breeding. The total systemic clearance of diclofenac in blood plasma is 263 ± 56 ml/min (mean value ± standard deviation). The terminal half-life in plasma is 1-2 hours. Four metabolites, including two active ones, also have a short plasma elimination half-life of 1-3 hours. One metabolite, 3'-hydroxy-4'-methoxy-diclofenac, has a much longer plasma half-life. However, this metabolite is actually 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. Residues of the dose are eliminated in the form of metabolites through bile and feces.
Special groups of patients.
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 50% higher plasma concentrations than observed in young healthy subjects.
Patients with impaired renal function. Accumulation of the active substance may not be expected in patients with impaired renal function following the usual dosing regimen. At a creatinine clearance of less than 10 ml/min, the levels of hydroxy metabolites in blood plasma at steady state are approximately 4 times higher than in patients with normal renal function.
Therefore, metabolites are finally excreted in bile.
Patients with liver diseases. In patients with chronic hepatitis or compensated cirrhosis, the kinetics and metabolism of diclofenac are the same as in healthy volunteers.
Clinical characteristics.
Indication.
The medicinal product for intramuscular administration 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 operations;
- severe migraine attacks.
The medicinal product when administered as an intravenous infusion 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 non-steroidal 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 bleeding or perforation of the gastrointestinal tract associated with previous NSAID treatment.
- Active peptic ulcer/bleeding or a history of recurrent peptic ulcer/bleeding (two or more separate episodes of established ulceration or bleeding).
- Inflammatory bowel diseases (for example, Crohn's disease or ulcerative colitis).
- Liver failure.
- Kidney failure.
- Congestive heart failure (II-IV functional class according to the NYHA - New York Heart Association classification).
- Ischemic heart disease in patients (angina, previous myocardial infarction).
- Cerebrovascular diseases in patients who have suffered a stroke or have episodes of transient ischemic attacks.
- Diseases of peripheral arteries.
- Treatment of perioperative pain in coronary artery bypass grafting (or the use of an artificial blood circulation device).
- High risk of postoperative bleeding, blood clotting disorders, hemostasis disorders, hematopoietic disorders or cerebrovascular bleeding.
- III trimester of pregnancy.
In this dosage form, the drug is contraindicated for children.
Intravenous infusions are contraindicated in:
- simultaneous use of NSAIDs or anticoagulant (including low doses of heparin);
- hemorrhagic diathesis in the anamnesis or confirmed/suspected cerebrovascular bleeding in the anamnesis;
- surgical interventions with a high risk of bleeding;
- history of bronchospasm and bronchial asthma;
- moderate or severe renal insufficiency (creatinine level in blood serum > 160 mmol/l);
- hypovolemia or dehydration of various genesis.
Interaction with other medicinal products and other types of interactions.
Below are the interactions that have been observed with the use of diclofenac preparations in the form of a solution for injections and/or other dosage forms.
Lithium. Under the conditions of simultaneous use, diclofenac can increase the concentration of lithium in the blood plasma. Monitoring of serum lithium levels is recommended.
Digoxin. Under the conditions of simultaneous use, diclofenac can increase the concentration of digoxin in the blood plasma. Monitoring of serum digoxin levels is recommended.
Diuretics and antihypertensive drugs. As with other NSAIDs, concomitant use of diclofenac with diuretics or antihypertensive agents [for example, β-blockers, angiotensin-converting enzyme (ACE) inhibitors] can lead to a decrease in their antihypertensive effect due to inhibition of the synthesis of vasodilating prostaglandins. Therefore, such a combination should be used with caution, and patients, especially the elderly, should be closely monitored for blood pressure.
Patients should receive adequate hydration, and monitoring of renal function is also recommended after initiation of concomitant therapy and regularly thereafter, especially with regard to the effects of diuretics and ACE inhibitors due to the increased risk of nephrotoxicity.
Drugs that cause hyperkalemia. Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increased serum potassium levels, so patients should be monitored more frequently.
Other NSAIDs and corticosteroids. Simultaneous use of diclofenac and other systemic NSAIDs or corticosteroids may increase the frequency of side effects from the gastrointestinal tract. The simultaneous use of two or more NSAIDs should be avoided.
Anticoagulants and antithrombotics. Precautions are recommended, as concomitant use increases the risk of bleeding. Although clinical studies do not indicate 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 at the same time. Therefore, close monitoring of such patients is recommended. Like other NSAIDs, diclofenac in high doses can temporarily inhibit platelet aggregation.
Selective serotonin reuptake inhibitors (SSRIs). Simultaneous administration of systemic NSAIDs and SSRIs increases the risk of bleeding in the digestive tract.
Antidiabetic drugs. Clinical studies have shown that diclofenac can be used together with oral antidiabetic agents without affecting their clinical effect. However, individual cases of both hypoglycemic and hyperglycemic effects after administration of diclofenac are known, requiring a change in the dosage of antidiabetic agents during treatment with diclofenac. In this case, monitoring of blood glucose levels is required.
Probenecid. Medicinal products containing probenecid can delay the elimination of diclofenac.
Colestipol and cholestyramine. The simultaneous use of diclofenac and cholestipol or cholestyramine reduces the absorption of diclofenac by approximately 30% and 60%, respectively.
Therefore, it is recommended that diclofenac be administered at least 1 hour before or 4 to 6 hours after colestipol/cholestyramine.
Drugs that stimulate drug-metabolizing enzymes. Drugs that stimulate enzymes, such as rifampicin, carbamazepine, phenytoin, St. John's wort (Hypericum perforatum), are theoretically capable of reducing the concentration of diclofenac in the blood plasma.
Methotrexate. Caution is recommended when administering NSAIDs less than 24 hours before or after taking methotrexate, as the concentration of methotrexate in the blood may increase and the toxicity of this substance may increase. Diclofenac can inhibit the clearance of methotrexate in the renal tubules, which leads to an increase in the level of methotrexate. This interaction is mediated through the accumulation of methotrexate as a result of impaired renal excretion when using NSAIDs.
Cyclosporine and tacrolimus. Diclofenac, like other NSAIDs, can increase the nephrotoxicity of cyclosporine due to its effect on renal prostaglandins. The same risk occurs with tacrolimus treatment. In this regard, it should be used in lower doses than in patients who do not receive cyclosporine and tacrolimus.
Antibacterial quinolones. The development of convulsions is possible in patients who simultaneously used quinoline derivatives and NSAIDs, regardless of the presence or absence of epilepsy or convulsions in the anamnesis. Therefore, caution should be exercised when considering the use of quinoline in patients already receiving NSAIDs.
Phenytoin. When using phenytoin simultaneously with diclofenac, it is recommended to monitor the concentration of phenytoin in blood plasma due to the expected increase in exposure to phenytoin.
Cardiac glycosides. The simultaneous use of cardiac glycosides and NSAIDs can aggravate heart failure, reduce the rate of glomerular filtration and increase the level of glycosides in the blood plasma.
Mifepristone. NSAIDs should not be used for 8-12 days after mifepristone administration, as NSAIDs may reduce its effect.
Potent inhibitors of CYP2C9. Caution is recommended when diclofenac is co-administered with strong CYP2C9 inhibitors (for example, voriconazole), which can lead to a significant increase in the maximum plasma concentration and exposure of diclofenac due to inhibition of its metabolism.
Inductors CYP2C9. Caution is necessary in case of simultaneous appointment of diclofenac with inducers of CYP2C9 (for example, rifampicin). This can lead to a significant decrease in the plasma concentration and exposure of diclofenac.
Features of application.
Undesirable effects can be minimized by using the minimum effective dose for the shortest possible time required to control symptoms.
The use of the drug with systemic NSAIDs, including selective inhibitors of cyclooxygenase-2, should be avoided due to the lack of any synergistic benefit and the possibility of the development of additional side effects.
Care should be taken when prescribing the drug to elderly patients. In particular, the lowest effective doses should be used for elderly patients in poor health and for patients with low body mass index.
As with the use of other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid, may also occur when using diclofenac. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can cause myocardial infarction. A symptom of such a reaction may be chest pain that occurs in combination with an allergic reaction to diclofenac.
Like other NSAIDs, diclofenac, due to its pharmacodynamic properties, can mask the signs and symptoms of infection.
Effect on the digestive system
With the use of all NSAIDs, including diclofenac, cases of gastrointestinal bleeding (vomiting blood, melena), ulceration or perforation have been reported, which can be fatal and can be observed at any time during treatment, both with warning symptoms and without them, as well as in the presence of serious events from the gastrointestinal tract in the anamnesis. These phenomena usually have more serious consequences in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.
When using all NSAIDs, including diclofenac, careful medical supervision is necessary; Caution should be exercised when prescribing diclofenac to patients with symptoms suggestive of gastrointestinal disturbances, or with a history of gastric or intestinal ulceration, 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 ulceration, especially with bleeding or perforation complications.
Elderly patients have an increased incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.
To reduce the risk of gastrointestinal toxicity in patients with a history of ulceration, especially complications of 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 likely to increase the risk of adverse effects on the digestive system, combination therapy with protective drugs (eg, proton pump inhibitors or misoprostol).
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 (eg, warfarin), antithrombotic agents (eg, acetylsalicylic acid), or selective serotonin reuptake inhibitors.
The use of NSAIDs, including diclofenac, may be associated with an increased risk of anastomotic failure. Careful monitoring of patients and caution when using after surgical interventions on organs of the gastrointestinal tract are recommended.
Effect on the liver
Careful medical supervision is required if diclofenac is prescribed to patients with liver damage, as their condition may worsen.
As with other NSAIDs, the level of one or more liver enzymes may be elevated. Liver function should be monitored regularly during long-term treatment.
If hepatic impairment persists or worsens, if clinical signs or symptoms are suggestive of progressive liver disease, or if other manifestations (e.g., eosinophilia, rash) occur, the drug should be discontinued.
During treatment with diclofenac sodium, the course of hepatitis can pass without prodromal symptoms.
Precautions are necessary if the drug is used in patients with hepatic porphyria, due to the possibility of provoking an attack.
Effect on kidneys
Since fluid retention and edema have been reported during treatment with NSAIDs, including diclofenac, special attention should be paid to patients with impaired heart or kidney function, a history of hypertension, elderly patients, 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.
Effect on the skin
Serious skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely with the use of NSAIDs, including diclofenac. Obviously, 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 diclofenac should be stopped at the first appearance of skin rashes, lesions of the mucous membrane or any other signs of hypersensitivity.
Systemic lupus erythematosus (SLE) and mixed connective tissue diseases
Patients with SLE and mixed connective tissue diseases have an increased risk of developing aseptic meningitis.
Cardiovascular and cerebrovascular effects
Diclofenac should be prescribed to patients with significant risk factors for cardiovascular events (eg, hypertension, hyperlipidemia, diabetes, smoking) only after careful clinical evaluation. Because the cardiovascular risks of diclofenac may increase with increasing dose and duration of treatment, it should be used for the shortest 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 arterial hypertension and/or congestive heart failure of mild or moderate severity, appropriate monitoring and recommendations are necessary, as cases of fluid retention and edema have been reported in connection with the use of NSAIDs, including diclofenac.
Data from clinical trials and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and for a long time, may be associated with some increased risk of arterial thrombotic events (eg, myocardial infarction or stroke).
Diclofenac is not recommended for patients with uncontrolled hypertension, congestive heart failure, stable coronary heart disease, peripheral artery disease and/or cerebrovascular disease. If necessary, use is possible only after a careful risk-benefit assessment and only in a dosage not exceeding 100 mg per day. A similar assessment should be performed before starting long-term treatment in patients with risk factors for the development of cardiovascular events (eg, hypertension, hyperlipidemia, diabetes, and smoking).
Patients should be informed of the possibility of serious complications (chest pain, shortness of breath, weakness, slurred speech) that may occur at any time. In this case, you should immediately consult a doctor.
Effect on hematological parameters
With long-term use of the drug, blood analysis monitoring is recommended.
Like other NSAIDs, diclofenac can temporarily inhibit platelet aggregation. Patients with hemostasis disorders, hemorrhagic diathesis or hematological disorders should be carefully monitored.
Asthma in history
Patients with bronchial asthma, seasonal allergic rhinitis, patients with swelling of the nasal mucosa (nasal polyps), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially associated with allergic, rhinitis-like symptoms) more often than others, reactions to NSAIDs similar to an exacerbation of asthma (so-called intolerance to analgesics/analgesic asthma), angioedema or urticaria occur. In this regard, such patients are recommended to take special precautions (readiness to provide emergency care). This also applies to patients with allergies to other substances, manifested by skin reactions, itching or hives.
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.
Injection site reactions
Injection site reactions have been reported following intramuscular administration of diclofenac, including injection site necrosis and drug-induced embolism, also known as Nicolaou syndrome (especially after inadvertent subcutaneous administration). When diclofenac is administered intramuscularly, appropriate needle selection and injection technique should be followed (see section "Method of administration and dosage").
Important information about excipients.
The drug contains sodium metabisulfite (E 223), which can rarely cause hypersensitivity reactions and bronchospasm.
Use during pregnancy or breastfeeding.
Pregnancy. In the I and II trimesters of pregnancy, the drug Diclofenac-Darnytsia can be prescribed only if the expected benefit to the mother exceeds the potential risk to the fetus, and 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 last trimester of pregnancy (possible suppression of the contractile ability of the uterus and premature closure of the ductus arteriosus in the fetus).
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/fetus development. Data from epidemiological studies indicate an increased risk of miscarriage and/or the risk of developing heart defects and gastroschisis after using a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular disease increases from less than 1% to about 1.5%.
It is possible that the risk increases with an increase in the dose and duration of treatment. It has been shown that in animals, administration of a prostaglandin synthesis inhibitor leads to an increase in pre- and post-implantation losses and embryo/fetal lethality.
In addition, in animals treated with prostaglandin synthesis inhibitor during the period of organogenesis, an increased frequency of various malformations, including those of the cardiovascular system, was registered. Starting from the 20th week of pregnancy, the use of diclofenac can cause oligohydroamnion due to impaired fetal kidney function. This may occur soon after starting treatment and is usually reversible after stopping treatment. If Diclofenac-Darnytsia is used by women who are trying to get pregnant, or in the I or II trimester of pregnancy, the dose of the drug should be as low as possible, and the duration of treatment should be as short as possible. Antepartum monitoring for oligohydramnios should be considered after diclofenac exposure for several days beginning at 20 weeks' gestation. Diclofenac should be discontinued if oligohydramnios is detected.
During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis can affect the fetus in the following way:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- impaired kidney function (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, which leads to delay or prolongation of childbirth.
Therefore, Diclofenac-Darnytsia is contraindicated in the 3rd trimester of pregnancy.
Breastfeeding period. Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, to avoid unwanted effects on the baby, Diclofenac-Darnytsia should not be used during breastfeeding.
Fertility. Like other NSAIDs, Diclofenac-Darnytsia can affect a woman's fertility. The drug should not be used by women who are planning to become pregnant. If a woman has difficulty conceiving or is undergoing an examination for infertility, it is necessary to stop using the drug Diclofenac-Darnytsia.
The ability to influence the speed of reaction when driving vehicles or other mechanisms.
Patients who experience visual disturbances, dizziness, vertigo, drowsiness or other disturbances of the central nervous system during treatment with Diclofenac-Darnytsia should refrain from driving vehicles and working with other mechanisms.
Method of application and dosage.
The drug should be used in the smallest recommended doses for the shortest period of time, taking into account the goal of therapy for each patient individually.
Do not use for more than 2 days. If necessary, the treatment can be continued with Diclofenac-Darnytsia tablets.
Intramuscular injection.
To prevent damage to nerves or other tissues at the site of an intramuscular injection, the following recommendations should be followed.
The dose is usually 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 the drug Diclofenac-Darnytsia (for example, tablets) up to a total maximum total daily dose of 150 mg.
In the conditions of a migraine attack, 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 available data on the use of the drug for the treatment of migraine attacks for more than 1 day.
Intravenous infusions
Diclofenac-Darnytsia, solution for injection, should not be administered as an intravenous bolus injection.
Immediately before starting the intravenous infusion of Diclofenac-Darnytsia, 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 injections (0.5 ml of 8.4% or 1 ml of 4.2% solution, or the corresponding volume of another concentration), which was taken from a newly 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 of Diclofenac-Darnytsia, a solution for injection, are recommended:
For the treatment of moderate to severe postoperative pain, 75 mg should be administered continuously over 30 minutes to 2 hours. If necessary, the treatment can be repeated after 4-6 hours, but the dose should not exceed 150 mg per day.
For the prevention of postoperative pain, a loading dose of 25-50 mg should be administered 15 minutes to 1 hour after surgery, after which a continuous infusion of approximately 5 mg per hour should be used up to a maximum daily dose of 150 mg.
Elderly patients
Although in elderly patients, the pharmacokinetics of the drug does not deteriorate to a clinically significant degree, NSAIDs should be used with special caution in such patients, who, as a rule, are more prone to the development of adverse reactions. In particular, for debilitated elderly patients or for patients with a low body weight, it is recommended to use the lowest effective doses (see also the section "Peculiarities of use"); also, patients should be examined for gastrointestinal bleeding during NSAID treatment.
The recommended maximum daily dose of Diclofenac-Darnytsia is 150 mg.
Each ampoule is intended for single use only. The solution should be used immediately after opening the ampoule. Any unused amount must be disposed of.
Children.
Diclofenac-Darnytsia in the medicinal form of a solution for injections is contraindicated for use in children.
Overdose.
Symptoms There is no typical clinical picture of the consequences of an overdose of diclofenac. 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 kidney failure and liver damage are possible.
Treatment. Within 1 hour of using a potentially toxic amount of the drug orally, the use of activated charcoal may be appropriate. Additionally, for adults, gastric lavage should be considered for 1 hour after administration of a potentially toxic amount of the drug. Diazepam should be administered intravenously in case of frequent or prolonged convulsions. Depending on the clinical condition of the patient, other measures may be indicated. Treatment is symptomatic.
Adverse reactions.
Data from clinical studies and epidemiological data indicate an increased risk of arterial thrombotic events (eg, 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 medicinal product Diclofenac-Darnytsia, a solution for injections, and/or other medicinal forms of diclofenac, under the conditions of short-term and long-term treatment.
Adverse reactions are indicated by organ systems and frequency: very often (≥ 1/10), often (≥ 1/100, < 1/10), infrequently (≥ 1/1000, ≤ 1/100), rarely (≥ 1/10000) , ≤ 1/1000), very rare (≤ 1/10000), frequency unknown (cannot be estimated from available data).
On the part of the organs of vision:
very rarely: visual disturbance (blurred vision and diplopia);
frequency unknown: optic neuritis.
Such visual disturbances are effects of the class of NSAIDs and, as a rule, they are reversible after withdrawal of the drug. The most likely mechanism of visual disturbances is the 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 rule out other possible causes.
From the hearing organs and vestibular apparatus:
often: vertigo;
very rarely: tinnitus, hearing impairment.
From the respiratory system, organs of the chest and mediastinum:
rarely: asthma (including dyspnea), bronchospasm;
very rarely: pneumonitis.
From the gastrointestinal tract:
often: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, decreased appetite, anorexia;
rarely: gastritis, gastrointestinal bleeding, vomiting with blood impurities, hemorrhagic diarrhea, melena, stomach or intestinal ulcer with or without bleeding, gastrointestinal stenosis with perforation (sometimes with a fatal outcome, especially in elderly patients), which can lead to peritonitis;
very rarely: colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn's disease), constipation, stomatitis, including ulcerative stomatitis, glossitis, dysphagia, membranous strictures of the small intestine, pancreatitis.
From the side of the liver and biliary tract:
often: an increase in the level of transaminases;
infrequently: impaired liver function, especially with long-term therapy, hepatitis with or without jaundice (in rare cases, instantaneous hepatitis is possible, even without previous symptoms);
very rarely: acute hepatitis, hepatonecrosis, liver failure.
From the kidneys and urinary system:
often: formation of edema, especially in patients with arterial hypertension or with renal failure;
very rarely: acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis.
From the side of the nervous system:
often: headache, dizziness, drowsiness;
rarely: fatigue;
very rarely: paresthesia, taste disorder, memory impairment, convulsions, anxiety, tremor, aseptic meningitis*, stroke;
frequency is unknown: impaired sensitivity, impaired sense of touch.
From the side of the psyche:
very rarely: disorientation, depression, insomnia, night terrors, irritability, mental disorders, confusion, hallucinations.
From the side of the cardiovascular system:
very rarely: palpitations, chest pain, heart failure, myocardial infarction, arterial hypertension, arterial hypotension, vasculitis;
frequency unknown: Kounis syndrome.
From the blood and lymphatic system:
very rarely: thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), agranulocytosis.
From the side of the immune system:
often: hypersensitivity reactions, such as skin rash and itching;
infrequently: urticaria;
rarely: anaphylactic and pseudoanaphylactic reactions (including hypotension and shock)
very rarely: angioedema (including facial edema), allergic vasculitis;
From the side of the skin and subcutaneous tissue:
often: rash;
infrequent: hair loss;
rarely: urticaria;
very rarely: exanthema, eczema, erythema, erythema multiforme, photosensitivity reactions, purpura (including allergic purpura of Schönlein-Henoch), bullous rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), exfoliative dermatitis, pruritus.
From the side of the reproductive system:
very rarely: impotence.
General disorders and administration site conditions:
often: reactions at the injection site, pain and/or hardening at the injection site, general malaise;
rarely: swelling, necrosis at the injection site; very rarely: abscess at the injection site; frequency is unknown: drug-induced embolism of the skin (Nicolau's syndrome).
*Exacerbation of inflammatory processes of infectious origin (for example, the development of necrotizing fasciitis) associated with the systemic use of NSAIDs have been described very rarely. Perhaps this is related to the mechanism of action of NSAIDs. Very rarely, symptoms of aseptic meningitis such as neck stiffness, headache, nausea, vomiting, fever, or confusion have been observed with diclofenac. Patients with autoimmune diseases (systemic lupus erythematosus, mixed connective tissue disease) are prone to such conditions.
Reporting of suspected adverse reactions.
The reporting of suspected adverse reactions after the registration of a medicinal product is an important procedure. This allows for continued monitoring of the benefit/risk ratio for the respective medicinal product. Healthcare professionals should report any suspected adverse reactions through the national reporting system.
Expiration date. 3 years.
Storage conditions.
Store in the original packaging at a temperature not higher than 25 °C. Do not freeze.
Keep out of the reach of children.
Incompatibility.
Diclofenac-Darnytsia, a solution for injections, cannot be mixed with other solutions for injections in the same container.
0.9% sodium chloride solution and 5% glucose solution without sodium bicarbonate as additives pose a risk of oversaturation, which may lead to the formation of crystals or precipitate.
Other solutions for infusion should not be used.
Packaging.
3 ml in an ampoule; 5 ampoules each in a contoured blister pack; 1 or 2 contour envelopes in a pack.
Leave category. By prescription.
Producer. PrJSC "Pharmaceutical firm "Darnytsia".
The location of the manufacturer and the address of the place of its activity.
Ukraine, 02093, Kyiv, st. Boryspilska, 13.
