ARTIFLEKS UL'TRA

INSTRUCTIONS for medical use of the medicinal product DICLESEL (DISLASEL)

Composition

active substances: sodium diclofenac, lidocaine hydrochloride; 1 ml contains: 37.5 mg of sodium diclofenac and 10 mg of lidocaine hydrochloride; excipients: disodium edetate, acetylcysteine, propylene glycol, polyethylene glycol 400, sodium hydroxide, water for injection.

Pharmaceutical form

Solution for injection.

Main physical and chemical properties

Clear, colorless or slightly yellowish-brown liquid.

Pharmacotherapeutic group

Nonsteroidal anti-inflammatory and anti-rheumatic agents.

ATC code M01AE55.

Pharmacological properties

Pharmacodynamics

The medicinal product Diclasel contains sodium diclofenac - a nonsteroidal active substance with pronounced anti-rheumatic, anti-inflammatory, analgesic, and antipyretic properties. The suppression of prostaglandin biosynthesis is considered the main mechanism of its action. Prostaglandins play a significant role in the occurrence of inflammation, pain, and increased temperature.

In rheumatic diseases, the anti-inflammatory and analgesic properties of the medicinal product cause a pronounced clinical response, which is characterized by the disappearance of pain at rest, pain during movement, morning stiffness, and swelling of the joints, as well as an improvement in the functional properties of the joints.

In post-traumatic/postoperative inflammation, sodium diclofenac quickly reduces sudden pain and pain during movement, as well as reduces swelling caused by inflammation and injuries.

When used simultaneously for the treatment of postoperative pain, sodium diclofenac significantly reduces the need for opioids. The medicinal product Diclasel has a pronounced analgesic effect in moderate and severe pain of non-rheumatic origin within 15-30 minutes after administration - it can be used for initial therapy of inflammatory and degenerative rheumatic diseases, as well as for the treatment of pain caused by non-rheumatic inflammation.

Pharmacokinetics

Absorption. After intramuscular administration, the maximum plasma concentration is reached within 10-20 minutes. The therapeutic concentration of the medicinal product Diclasel in plasma is 0.7-2.0 mcg/ml. Repeated administration of the medicinal product does not cause any changes in the kidneys. With adherence to the recommended intervals between administrations of the medicinal product, its accumulation in the body is not observed.

Distribution. 99.7% of diclofenac is bound to plasma proteins, mainly to albumin (99.4%). The average volume of distribution of sodium diclofenac is 0.12-0.17 L/kg.

The medicinal product penetrates into the synovial fluid, where its maximum concentration is determined within 2-4 hours after reaching peak plasma concentrations. At the same time, the half-life of elimination from the synovial fluid is 3-6 hours. Due to this, even 4-6 hours after administration of the medicinal product, the concentrations of the active substance in the synovial fluid are higher than in plasma and remain at higher levels for 12 hours.

Metabolism. Approximately half of the total amount of the administered active substance undergoes first-pass metabolism. As a result, the values of the area under the concentration-time curve (AUC) after oral or rectal administration of the medicinal product are approximately twice as low as the AUC values after parenteral administration of an equivalent dose of the medicinal product.

The biotransformation of the medicinal product occurs partially through glucuronidation and methoxylation. Two of the phenolic metabolites formed during this process are pharmacologically active, but to a lesser extent than sodium diclofenac itself.

Elimination. Sodium diclofenac is eliminated from the plasma with a systemic clearance of 263 ± 56 ml/min (mean level ± standard deviation). The final half-life of the medicinal product is 1-2 hours. Approximately 60% of the administered dose of the medicinal product is excreted by the kidneys in the form of metabolites, and less than 1% - in unchanged form. The remaining part of the administered dose is excreted in a metabolized form with bile and then with feces.

Linearity/Nonlinearity. Plasma concentration shows a linear dependence on the dose.

Pharmacokinetics in special patient groups. No significant differences in absorption, metabolism, and elimination of the medicinal product were observed in elderly patients. In patients with impaired renal function, after administration of the usual dose of the medicinal product, no increase in the amount of unchanged active substance was observed. If the creatinine clearance was less than 10 ml/min, the level of metabolites in plasma at a steady state was approximately 4 times higher than in healthy volunteers. Nevertheless, the metabolites were ultimately eliminated with bile. In cases of impaired liver function (chronic hepatitis, compensated cirrhosis of the liver), the pharmacokinetics and metabolism of the medicinal product did not differ from those in patients with normal liver function.

Clinical characteristics

Indications

To be used in the form of intramuscular injections in such conditions:

• inflammatory or 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, inflammation, and swelling after injuries and surgical interventions;
• severe migraine attacks.

Contraindications

Hypersensitivity to the active substances or to any other components of the medicinal product;

increased individual sensitivity to lidocaine or to other amide local anesthetics;

seizures in the anamnesis caused by the use of lidocaine;

porphyria;

myasthenia;

anticoagulant therapy;

bleeding or perforation of the gastrointestinal tract in the anamnesis, associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);

active form of peptic ulcer / bleeding or recurrent peptic ulcer / bleeding in the anamnesis (two or more separate episodes of confirmed ulcer or bleeding);

active peptic ulcer and / or duodenal ulcer, gastrointestinal bleeding or perforation;

as well as other NSAIDs, diclofenac is also contraindicated in patients in whom the use of ibuprofen, acetylsalicylic acid, or other NSAIDs provokes attacks of bronchial asthma, bronchospasm, angioedema, urticaria, acute rhinitis, nasal polyps, or symptoms similar to allergy;

inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis);

liver failure (class C according to the Child-Pugh scale);

renal failure (glomerular filtration rate (GFR) <15 ml/min/1.73 m2);

congestive heart failure [II-IV functional class according to the NYHA (New York Heart Association) classification];

ischemic heart disease in patients who have had angina pectoris, myocardial infarction;

cerebrovascular diseases in patients who have had a stroke or have had episodes of transient ischemic attacks;

peripheral artery disease;

contraindicated for the treatment of perioperative pain in coronary artery bypass grafting (or when using a heart-lung machine);

severe conduction disorders of the heart, atrioventricular block II and III degree, sick sinus syndrome, Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, complete transverse block of the heart, bradycardia, cardiogenic or hypovolemic shock, pronounced arterial hypotension;

high risk of postoperative bleeding, coagulation disorders, incomplete hemostasis, hematopoietic disorders, or cerebrovascular bleeding.

Interactions with other medicinal products and other types of interactions

Such interactions of the medicinal product Diclasel or other pharmaceutical forms of diclofenac may be observed.

Diclofenac may increase the concentrations of lithium and digoxin in plasma. In case of concomitant use, it is recommended to monitor the levels of lithium and digoxin in the blood serum.

Taking diclofenac sodium simultaneously with diuretics or antihypertensive agents (e.g., beta-blockers, angiotensin-converting enzyme inhibitors [ACE inhibitors]) may cause a decrease in the antihypertensive effect. Such combinations should be used with caution, and blood pressure in these patients, especially the elderly, should be carefully monitored. Patients need to take adequate fluid. It is recommended to monitor renal function at the beginning of combination therapy and regularly thereafter, especially when taking diuretics and ACE inhibitors, due to the increased risk of nephrotoxicity.

Medicinal products that cause hyperkalemia. Concomitant treatment with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with an increased level of potassium in the blood serum, so the assessment of the patient's condition should be performed more frequently.

Concomitant administration of diclofenac and other systemic NSAIDs, in particular selective inhibitors of cyclooxygenase-2 (COX-2), or corticosteroids increases the risk of gastrointestinal bleeding or ulcers. It is recommended to avoid concomitant use of two or more NSAIDs.

It is recommended to take diclofenac sodium with anticoagulants and antiplatelet agents with caution, as their combined use increases the risk of bleeding. Although there is no evidence of the effect of diclofenac on the action of anticoagulants, there have been individual reports of the risk of hemorrhagic complications in patients who took diclofenac and anticoagulants simultaneously. Therefore, careful monitoring of patients who take diclofenac and anticoagulants simultaneously is recommended, and if necessary, correction of the anticoagulant dosage. Like other NSAIDs, diclofenac in high doses can reversibly inhibit platelet aggregation.

Concomitant use of systemic NSAIDs and selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding.

Antidiabetic medicinal products. It has been established that diclofenac sodium can be prescribed together with oral hypoglycemic agents, and this does not affect their clinical effects. However, there are individual reports of hypoglycemic and hyperglycemic reactions after the appointment of diclofenac sodium, which required a change in the dosage of hypoglycemic preparations. In connection with this, it is recommended to monitor the level of glucose in the blood during such combination therapy. It is also known about individual cases of metabolic acidosis when diclofenac and metformin are used simultaneously, especially in patients with impaired renal function.

Diclofenac may inhibit the clearance of methotrexate in renal tubules, leading to an increase in the level of methotrexate. In case of NSAID administration, including diclofenac, less than 24 hours before methotrexate administration, it is recommended to be cautious, as the concentration of methotrexate in the blood may increase and the toxicity of this substance may increase. There have been reports of serious toxicity when methotrexate and NSAIDs, including diclofenac, were used with an interval of within 24 hours. This interaction is mediated by the accumulation of methotrexate due to impaired renal excretion in the presence of NSAIDs.

Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine and tacrolimus through its effect on renal prostaglandins. In connection with this, it should be used in lower doses than for patients who do not receive cyclosporine and tacrolimus.

There have been individual reports of the development of seizures, which may be the result of concomitant use of quinolone antibiotics and NSAIDs. Seizures are possible in patients with and without a history of epilepsy or seizures. Therefore, caution should be exercised when using quinolones in patients who are already taking NSAIDs.

When using phenytoin simultaneously with diclofenac, it is recommended to monitor the concentration of phenytoin in the blood plasma due to the expected increase in phenytoin exposure.

Cholestyramine and colestipol may cause a delay or decrease in the absorption of diclofenac, so it is recommended to prescribe diclofenac at least 1 hour before or 4-6 hours after the administration of cholestyramine/colestipol.

Concomitant use of cardiac glycosides and NSAIDs may enhance heart failure, reduce glomerular filtration rate, and increase the levels of glycosides in plasma.

NSAIDs should not be used for 8-12 days after the use of mifepristone, as NSAIDs may reduce its effect.

Caution is required when prescribing diclofenac in combination with CYP2C9 inducers (e.g., rifampicin). This may lead to a significant decrease in plasma concentration and exposure to diclofenac.

It is recommended to prescribe diclofenac with caution in combination with potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole), as this may lead to a significant increase in peak plasma concentration and enhancement of the effect of diclofenac due to the inhibition of its metabolism.

Alcohol. The use of NSAIDs and simultaneous consumption of alcohol may enhance the side effects of the active substance, especially on the gastrointestinal tract or central nervous system (CNS).

Interactions related to the content of lidocaine hydrochloride may also be observed.

In case of the use of lidocaine in combination with antiarrhythmic agents, beta-blockers, or calcium antagonists, one should take into account the additive inhibitory effect on atrioventricular conduction, intraventricular conduction, and the strength of contraction.

Beta-blockers, propranolol, and others, as well as cimetidine, peptidin, bupivacaine, quinidine, disopyramide, amitriptyline, nortriptyline, chlorpromazine, and imipramine increase the level of lidocaine in the blood serum, reducing its liver metabolism.

In case of digitalis intoxication, lidocaine may enhance the severity of atrioventricular (AV) block. Lidocaine weakens the cardiotonic effect of cardiac glycosides.

In case of concomitant use with antiarrhythmic agents (amiodarone, verapamil, quinidine, etc.) or anticonvulsant agents (hydantoin derivatives) and phenytoin, the cardiodepressive effect of lidocaine is enhanced.

In case of concomitant use with sedatives and hypnotics, anesthetics (hexobarbital, thiopental sodium intravenously), it is possible to enhance the suppressive effect on the CNS.

In case of concomitant use with procainamide, hallucinations are possible. Lidocaine may enhance the effect of agents that block neuromuscular transmission, as the latter reduce the conduction of nerve impulses.

Ethanol enhances the suppressive effect of lidocaine on respiration.

Norepinephrine, mexiletine - the toxicity of lidocaine is enhanced (the clearance of lidocaine is reduced).

Isadrin and glucagon - the clearance of lidocaine is increased.

Midazolam moderately increases the concentration of lidocaine in the blood.

Monoamine oxidase inhibitors, aminazine, bupivacaine, amitriptyline, nortriptyline, imipramine - when combined with lidocaine, the risk of developing arterial hypotension and prolongation of the local anesthetic effect of the latter increases.

Narcotic analgesics (e.g., morphine) - when combined with lidocaine, the analgesic effect of narcotic analgesics is enhanced, but the suppression of respiration is also enhanced.

Phenylamine - the risk of developing ventricular arrhythmia of the "pirouette" type increases.

Propafenone - it is possible to increase the duration and severity of side effects from the CNS.

Rifampicin - it is possible to reduce the concentration of lidocaine in the blood.

Polymyxin B - it is necessary to monitor respiratory function.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) - when combined with lidocaine, they contribute to the slowing down of lidocaine absorption and prolongation of its effect. Guanadrel, guanethidine, mecamylamine, trimethaphan - when combined for spinal and epidural anesthesia, the risk of pronounced hypotension and bradycardia increases. Acetazolamide, thiazide, and loop diuretics - when combined with lidocaine, they cause hypokalemia and reduce the effect of the latter.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin) - when combined with lidocaine, the risk of bleeding development increases.

Special warnings and precautions for use

General recommendations. During treatment with NSAIDs, including selective or non-selective COX-2 inhibitors, ulcers, bleeding, or perforation of the gastrointestinal tract may occur, regardless of the presence or absence of warning symptoms or serious gastrointestinal events in the anamnesis. Undesirable effects can be minimized by using the lowest effective dose for the shortest possible period necessary to control symptoms.

Diclofenac sodium, like other NSAIDs, increases the risk of developing serious cardiovascular thrombotic events, myocardial infarction, and stroke. Placebo-controlled studies have found an increased risk of thrombotic cardiovascular and cerebrovascular complications when using certain selective COX-2 inhibitors. A direct correlation of this risk with the selectivity of individual NSAIDs to COX-1/COX-2 has not been established. Due to the lack of comparative data from clinical studies on long-term treatment with maximum doses of diclofenac, a similar increased risk cannot be excluded. In the absence of relevant data, before using diclofenac, it is necessary to carefully evaluate the risk and benefit for patients with clinically confirmed ischemic heart disease, cerebrovascular pathology, obliterating atherosclerosis of peripheral arteries, or significant risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes, smoking). Diclofenac should only be used after careful analysis of possible risks and benefits of such treatment. It is necessary to introduce the lowest effective dose for the shortest possible period of treatment.

The effect of NSAIDs on the kidneys includes fluid retention with edema and/or arterial hypertension. Due to this, diclofenac should be used with special caution in patients with impaired heart function and other conditions that contribute to fluid retention. It is also necessary to exercise caution in patients who are taking diuretics or ACE inhibitors or are prone to hypovolemia.

Consequences are usually more serious in elderly patients. It is necessary to be cautious when prescribing the medicinal product to elderly patients. In particular, for elderly patients with poor health and low body weight, it is recommended to use the lowest effective doses.

It is necessary to avoid the use of the medicinal product Diclasel with systemic NSAIDs, including selective COX-2 inhibitors, due to the lack of any synergistic benefit and the risk of developing additional side effects.

As in the case of other NSAIDs, when using diclofenac, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur. Reactions of hypersensitivity may also progress to the Coombs syndrome, a severe allergic reaction that can cause myocardial infarction. Symptoms of such a reaction are chest pain that occurs in combination with an allergic reaction to diclofenac.

NSAIDs, due to their pharmacodynamic properties, may mask the signs and symptoms of infection. With prolonged use of analgesics, headache may occur, which cannot be treated by increasing the dose of these drugs.

Effect on the gastrointestinal tract (GI). When using all NSAIDs, including diclofenac, gastrointestinal bleeding, ulcers, or perforation have been reported, which can be fatal and occur at any time during treatment, regardless of the presence or absence of warning symptoms or serious gastrointestinal events in the anamnesis. These events are usually more serious in elderly patients. Diclofenac sodium should be used under medical supervision and with caution in patients with symptoms indicating gastrointestinal diseases or with a history of gastric or intestinal ulcers, bleeding, or perforation of the GI tract. The risk of gastrointestinal bleeding is higher with increased doses of NSAIDs, in patients with a history of ulcers, especially complicated by bleeding or perforation, as well as in the elderly.

If gastrointestinal bleeding or ulcers develop in patients during treatment with the medicinal product Diclasel, the drug should be discontinued.

When using NSAIDs in elderly patients, undesirable reactions occur more frequently, especially gastrointestinal bleeding and perforation, which can be fatal. To reduce the risk of gastrointestinal disorders in patients with a history of ulcers, especially complicated by bleeding or perforation, as well as in the elderly, patients with poor health, or with low body weight, the medicinal product should be used at the minimum effective dose for as short a period as possible. Such patients, as well as patients who regularly take low doses of acetylsalicylic acid/aspirin or other medicinal products that increase the risk of undesirable effects on the GI tract, should be prescribed combination therapy with agents that have a protective effect on the gastric mucosa (e.g., proton pump inhibitors or misoprostol).

Patients with gastrointestinal toxicity in the anamnesis, especially the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Caution is also required for patients who receive concomitant medications that increase the risk of ulcers or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid), or selective serotonin reuptake inhibitors (SSRIs).

When using NSAIDs, including diclofenac, the risk of leakage from the gastrointestinal anastomosis increases - careful medical supervision and caution are necessary when using diclofenac after surgical interventions on the gastrointestinal tract.

Effect on the liver. Patients with impaired liver function who are prescribed diclofenac sodium require careful medical supervision, as their condition may worsen during treatment. During treatment with NSAIDs, including diclofenac, an increase in the level of one or more liver enzymes may occur. Such changes were observed during the use of diclofenac in clinical trials very often (in approximately 15% of patients), but rarely accompanied by clinical symptoms. In most such cases, the increase in these indicators remains within the limit values. Often (in 2.5%), a moderate increase in these indicators above the norm (from ≥ 3 to < 8 × ULN [upper limit of normal]) was noted, while the frequency of a significant increase in the levels of these enzymes (≥ 8 × ULN) was approximately 1%. In 0.5% of patients, in addition to an increase in liver enzyme levels, clinically manifest liver damage (eosinophilia, rash) developed. Elevated enzyme levels were usually reversible after discontinuation of the medicinal product.

If liver function impairment persists or worsens during treatment, if clinical signs or symptoms of liver disease (e.g., hepatitis) or other manifestations (e.g., eosinophilia, rash) occur, diclofenac sodium should be discontinued. The course of diseases such as hepatitis may be without prodromal symptoms. It is necessary to use the medicinal product Diclasel with caution in patients with liver porphyria due to the possible provocation of an attack.

Effect on the kidneys. Due to the importance of prostaglandins for maintaining renal blood flow, prolonged use of high doses of NSAIDs, including diclofenac, often (1-10%) leads to fluid retention, edema, and arterial hypertension.

Special attention should be paid to patients with impaired heart or kidney function, arterial hypertension in the anamnesis, elderly patients, patients receiving concomitant therapy with diuretics or agents that significantly affect renal function, and patients with significant reduction in extracellular fluid volume for any reason, for example, before or after serious surgical intervention. In such cases, monitoring of renal function is recommended. Discontinuation of therapy usually leads to a return to the state that preceded treatment. Frequent and regular use of analgesics, especially combinations of several analgesic preparations, can lead to persistent kidney damage, which is accompanied by the risk of developing renal failure ("analgesic nephropathy").

Effect on the skin and subcutaneous tissue. Very rarely, in connection with the use of NSAIDs, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, sometimes with a fatal outcome, may occur. The highest risk of such reactions in patients exists at the beginning of the treatment course, and in most cases, these reactions occur within the first month of treatment. At the first signs of a rash on the skin, lesions of the mucous membranes, or other manifestations of hypersensitivity, the medicinal product Diclasel should be discontinued. As with other NSAIDs, diclofenac can rarely cause allergic reactions, including anaphylactic/anaphylactoid reactions, in patients who have not previously taken it.

Reactions at the injection site. There have been reports of reactions at the injection site after intramuscular administration of diclofenac, including necrosis at the injection site and medicamentous embolism, also known as Nicolau's syndrome (especially after accidental subcutaneous administration). When administering diclofenac intramuscularly, it is necessary to choose the appropriate needle and injection technique (see the "Method of administration and dosage" section).

Systemic lupus erythematosus (SLE) and mixed connective tissue diseases. In patients with SLE and mixed connective tissue diseases, the risk of developing aseptic meningitis associated with NSAID treatment is increased.

Effect on the cardiovascular system and cerebral vessels. Diclofenac should be prescribed to patients with significant risk factors for cardiovascular events (e.g., arterial hypertension, hyperlipidemia, diabetes, smoking) only after careful clinical evaluation.

As a rule, diclofenac is not recommended for patients with cardiovascular disease (heart failure, ischemic heart disease, peripheral artery disease) or uncontrolled arterial hypertension. In case of necessity, patients with cardiovascular disease or uncontrolled arterial hypertension or with significant risk factors for cardiovascular diseases should receive treatment with diclofenac only after careful evaluation of risks and benefits and only in doses up to 100 mg/day, if the treatment course exceeds 4 weeks (see the "Special warnings and precautions for use" section).

Patients should be informed about the signs and symptoms of serious arterial thromboembolic events (e.g., chest pain, shortness of breath, weakness, speech disorders), which can occur without warning symptoms. In such a case, it is necessary to seek medical attention immediately. In the presence of congestive heart failure (II-IV functional class according to the NYHA classification), the use of the medicinal product is contraindicated.

Effect on hematological parameters. Since NSAIDs can temporarily inhibit platelet aggregation, during prolonged use of diclofenac sodium, as well as other NSAIDs, it is recommended to monitor hematological parameters. Patients with coagulation disorders, hemorrhagic diathesis, or hematological abnormalities require careful supervision.

Asthma in the anamnesis. In patients with bronchial asthma, seasonal allergic rhinitis, nasal congestion (nasal polyps), chronic obstructive pulmonary disease, or chronic respiratory tract infections (especially if they are associated with symptoms similar to allergic rhinitis), allergic reactions to NSAIDs, such as exacerbation of asthma (so-called analgesic intolerance, leukotriene asthma, aspirin asthma), Quincke's edema, or urticaria, occur more frequently than in other patients. In connection with this, special precautions are recommended for such patients (readiness to provide emergency care). This also applies to patients with allergies to other substances that manifest as skin reactions, itching, or urticaria.

As with other medicinal products that inhibit prostaglandin synthetase activity, diclofenac sodium may provoke the development of bronchospasm in patients who suffer from bronchial asthma or have a history of bronchial asthma.

Female fertility. The medicinal product Diclasel may affect female fertility and is therefore not recommended for women who plan to become pregnant. The question of discontinuing the use of the medicinal product should be considered in women who have difficulty conceiving, as well as in women who are undergoing examination for infertility.

Lidocaine. Lidocaine can only be administered by medical personnel. As with other lidocaine-containing preparations, the medicinal product Diclasel should be used with caution in patients with epilepsy, impaired cardiac conduction, or respiratory failure.

Since the medicinal product Diclasel contains lidocaine, it should be taken into account that when processing the injection site with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of pain and swelling increases. Lidocaine has a pronounced arrhythmogenic effect, so it is necessary to use the medicinal product with caution in patients with a history of arrhythmias.

Cautious use is recommended in patients with moderate heart failure, arterial hypotension of moderate severity, incomplete atrioventricular block, atrioventricular block I degree, impaired intraventricular conduction, impaired liver and kidney function of moderate severity (creatinine clearance 10 ml/min), impaired respiratory function, epilepsy, increased convulsive readiness, severe myasthenia, after heart surgery, with a genetic predisposition to hyperthermia, weakened patients, and elderly patients, when injecting into an inflamed (infected) area.

During the use of lidocaine, mandatory ECG monitoring is required. In case of impaired activity of the sinus node, prolongation of the PQ interval, widening of the QRS complex, or development of a new arrhythmia, the dose of the medicinal product should be reduced or the medicinal product should be discontinued. Before the use of lidocaine, it is necessary to normalize the potassium level in the blood in case of cardiac diseases (hypokalemia reduces the effectiveness of lidocaine).

Other. Due to the presence of propylene glycol in the composition, the medicinal product Diclasel may cause symptoms similar to those that occur when consuming alcohol.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding

Pregnancy period

Starting from the 20th week of pregnancy, the use of diclofenac may cause oligohydramnios due to impaired renal function of the fetus. This disorder can occur soon after the start of treatment and is usually reversible after discontinuation of treatment. During the first and second trimesters of pregnancy, diclofenac should not be prescribed, except in cases of extreme necessity. If diclofenac is used in women who are trying to become pregnant or during the first and second trimesters of pregnancy, the dose should be as low as possible, and the duration of treatment should be as short as possible. Prenatal monitoring for oligohydramnios may be justified after exposure to diclofenac for several days, starting from the 20th week of pregnancy. The use of diclofenac should be discontinued if oligohydramnios is detected.

Breastfeeding period

Like other nonsteroidal anti-inflammatory drugs, diclofenac penetrates into breast milk in small amounts. Therefore, to avoid undesirable effects on the infant, diclofenac should not be used in women during breastfeeding. If treatment is considered necessary, the baby should be transferred to artificial feeding.

Fertility

Diclofenac may affect female fertility. The medicinal product is not recommended for women who plan to become pregnant. Women who have difficulty conceiving or who are undergoing examination for infertility should discontinue the use of diclofenac.

Based on the available data from animal studies, it is impossible to exclude reproductive function disorders in males. The relevance of these data to humans has not been established.

Influence on the ability to drive vehicles and operate machinery

Patients who have developed vision disorders, dizziness, drowsiness, fatigue, increased fatigue, or other disorders of the central nervous system should refrain from driving a car or working with other mechanisms.

Method of administration and dosage

The dose is selected by the doctor individually. The medicinal product should be used in the smallest effective doses for the shortest possible period, taking into account the purpose of treatment for each individual patient.

Since there is a risk of anaphylactic reactions, including the development of shock, after the administration of the medicinal product Diclasel, the patient should be under supervision for at least 1 hour, with means for providing emergency medical care on standby.

The medicinal product Diclasel should be administered in the form of intramuscular injections. To avoid damage to nerves or other tissues at the injection site, the following instructions should be followed. Such damage can lead to muscle weakness, paralysis of muscles, and hypesthesia, medicamentous embolism (Nicolau's syndrome), and necrosis at the injection site.

The usual single dose of the medicinal product is 1 ampoule (i.e., 75 mg of sodium diclofenac), which is administered intramuscularly once a day by deep injection into the upper outer quadrant of the gluteal muscle under aseptic conditions.

The solution should be used immediately after opening the ampoule. Any unused solution should be disposed of.

In case of severe pain (e.g., colic), as an exception, the medicinal product can be administered 2 times a day with an interval of several hours, necessarily changing the injection site. The combination of parenteral administration of the medicinal product Diclasel with other pharmaceutical forms of diclofenac (tablets, capsules, rectal capsules, gel, or plaster) is permissible provided that the maximum daily dose of diclofenac sodium does not exceed 150 mg.

In the event of a migraine attack, clinical experience is limited to cases with initial administration of one ampoule of 75 mg, the dose should be administered as soon as possible after the use of suppositories at a dose of 100 mg on the same day (if necessary). The total daily dose should not exceed 175 mg on the first day. There are no available data on the use of the medicinal product Diclasel for the treatment of migraine attacks for more than 1 day. If the patient requires further therapy in subsequent days, the daily dose of diclofenac should not exceed 150 mg (in the form of divided doses administered in the form of suppositories).

The duration of parenteral use of the medicinal product Diclasel should not exceed 2 days.

The medicinal product Diclasel should not be administered for intravenous injection/infusion.

In the presence of cardiovascular disease or significant risk factors for the development of cardiovascular diseases. Treatment with diclofenac is generally not recommended for patients with cardiovascular disease or uncontrolled arterial hypertension. In case of necessity, patients with cardiovascular disease or uncontrolled arterial hypertension or with significant risk factors for cardiovascular diseases should receive treatment with diclofenac only after careful evaluation of risks and benefits and only in doses up to 100 mg/day, if the treatment course exceeds 4 weeks (see the "Special warnings and precautions for use" section).

The use of diclofenac in patients with renal failure is contraindicated (GFR <15 ml/min/1.73 m2). Special studies in patients with impaired renal function have not been conducted, and therefore, no special dosage recommendations can be provided. It is recommended to use the medicinal product with caution in patients with impaired renal function (see the "Special warnings and precautions for use" section).

The use of diclofenac in patients with liver failure is contraindicated (see the "Contraindications" section). Special studies in patients with impaired liver function have not been conducted, and therefore, no special dosage recommendations can be provided. It is recommended to use diclofenac with caution in patients with impaired liver function of mild and moderate severity (see the "Special warnings and precautions for use" section).

Elderly patients do not usually require correction of the initial dose, but it is recommended to exercise caution, especially when prescribing the medicinal product to patients with poor health and low body weight.

Children. The medicinal product should not be used in children (under 18 years of age).

Overdose

Diclofenac

Symptoms. Typical clinical symptoms of overdose of diclofenac sodium are unknown. In case of overdose, headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, abdominal spasms, dyspepsia, flatulence, anorexia, gastritis, vomiting with blood, gastrointestinal bleeding, hemorrhagic diarrhea, melena, gastric and intestinal ulcers, including with bleeding or without, perforation, or gastrointestinal stenosis, which can lead to peritonitis (sometimes with fatal consequences, especially in elderly patients), colitis (including hemorrhagic, ischemic colitis, and exacerbation of nonspecific ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal lesions, diaphragmatic intestinal strictures, and pancreatitis may occur.

Treatment. Within one hour after the administration of a potentially toxic amount of the medicinal product orally, it is recommended to consider the use of activated charcoal. In addition, for adults, it is recommended to consider gastric lavage within 1 hour after the administration of a potentially toxic amount of the medicinal product. Supportive measures and symptomatic treatment should be performed to eliminate such complications as arterial hypotension, renal failure, seizures, irritation of the mucous membrane of the gastrointestinal tract, and respiratory depression. Specific therapy, such as forced diuresis, dialysis, or hemoperfusion, is not significant in the elimination of NSAIDs, given the high level of binding of these drugs to plasma proteins and extensive metabolism. In case of frequent or prolonged seizures, it is necessary to administer diazepam intravenously. Depending on the patient's clinical condition, other measures may be indicated. Treatment is symptomatic.

Lidocaine

Symptoms: numbness of the tongue and lips, excited state, euphoria, anxiety, blurred vision, tremor, depression, drowsiness, dizziness, confusion, respiratory depression or arrest, bradycardia, cardiac conduction disorders, transverse block of the heart, coma, dizziness, general weakness, decreased blood pressure up to the development of shock, tremor, tonic-clonic seizures, coma, collapse, possible atrioventricular block. The first symptoms of overdose in healthy people occur at a lidocaine concentration in the blood of more than 0.006 mg/kg, seizures - at 0.01 mg/kg.

Treatment: discontinuation of the medicinal product administration, oxygen therapy, anticonvulsant agents, vasoconstrictors (noradrenaline, mesaton), in case of bradycardia - cholinolytics (0.5-1 mg of atropine). Intubation, artificial ventilation of the lungs, and resuscitation measures are possible. Dialysis is not effective.

Undesirable effects

In case of undesirable effects, it is necessary to consult a doctor. The list of possible undesirable effects takes into account the data on the action of the active substances that are part of the medicinal product and other pharmaceutical forms of diclofenac under the conditions of short-term and long-term use.

Infections and invasions: abscesses at the injection site.

Blood and lymphatic system disorders: thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic), agranulocytosis.

Immune system disorders: hypersensitivity reactions (anaphylactic and anaphylactoid reactions, including arterial hypotension and shock), angioedema (including facial edema), feeling of heat, cold, or numbness of the limbs.

Psychiatric disorders: disorientation, depression, insomnia, nightmares, irritability, restlessness, mental disorders.

Nervous system disorders: headache, dizziness, sleep disturbances, drowsiness, paresthesia, memory impairment, seizures, agitation, tremor, aseptic meningitis, taste disorders, stroke, sensitivity disorders, increased fatigue, confusion, loss of consciousness up to coma, hallucinations, muscle cramps, motor block, dysarthria, dysphagia, nystagmus.

Eye disorders: vision disturbances, blurred vision, diplopia, optic neuritis, flickering "flies", photophobia, conjunctivitis.

Ear and labyrinth disorders: vertigo, tinnitus, hearing impairment, hyperacusis.

Cardiovascular disorders: increased heart rate, chest pain, myocardial infarction, heart failure, arterial hypertension, arterial hypotension, vasculitis, arrhythmia, bradycardia, slowing of cardiac conduction, transverse block of the heart, cardiac arrest, collapse, possible atrioventricular block.

Respiratory, thoracic, and mediastinal disorders: asthma (including shortness of breath), bronchospasm, pneumonia, respiratory depression or arrest, rhinitis.

Gastrointestinal disorders: abdominal pain, nausea, vomiting, diarrhea, abdominal spasms, dyspepsia, flatulence, anorexia, gastritis, vomiting with blood, gastrointestinal bleeding, hemorrhagic diarrhea, melena, gastric and intestinal ulcers, including with bleeding or without, perforation, or gastrointestinal stenosis, which can lead to peritonitis (sometimes with fatal consequences, especially in elderly patients), colitis (including hemorrhagic, ischemic colitis, and exacerbation of nonspecific ulcerative colitis or Crohn's disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal lesions, diaphragmatic intestinal strictures, pancreatitis.

Hepatobiliary disorders: increased transaminase levels, hepatitis, jaundice, liver dysfunction, fulminant hepatitis, liver necrosis, liver failure.

Skin and subcutaneous tissue disorders: rash, urticaria, bullous rash, eczema, erythema, multiform erythema, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), exfoliative dermatitis, alopecia, photosensitivity, purpura, allergic purpura, itching.

Renal and urinary disorders: fluid retention in the body, edema, acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, renal papillary necrosis.

Reproductive system and breast disorders: impotence.

General disorders and administration site conditions: general malaise, malignant hyperthermia, weakness, reactions at the injection site, such as pain, feeling of slight burning or hardening of tissues, swelling, necrosis at the injection site, abscess at the injection site, medicamentous embolism (Nicolau's syndrome).

It has been reported that the use of diclofenac is associated with an increased risk of thrombotic complications (e.g., myocardial infarction or stroke), especially at high therapeutic doses (150 mg/day) and for a long time.

Such visual disturbances as decreased vision, blurred vision, and diplopia may occur after the use of NSAIDs and are usually reversible after discontinuation of treatment. The most likely mechanism of vision disturbances is the inhibition of prostaglandin synthesis 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, it is necessary to perform an ophthalmological examination to exclude other possible causes.

Lidocaine. Rarely, allergic reactions in the form of urticaria, swelling, bronchospasm, or respiratory distress have been described. Due to rapid administration (accidental intravenous injection or injection into tissue with significant blood flow) or overdose, systemic reactions such as dizziness, clouding of consciousness, drowsiness, seizures, confusion, nausea, vomiting, bradycardia, arrhythmia, decreased blood pressure up to shock may occur.

Reporting of suspected adverse reactions

Reporting of adverse reactions after the registration of the medicinal product is important. This allows monitoring the ratio of benefit/risk when using this medicinal product. Medical and pharmaceutical personnel, as well as patients or their authorized representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product through the automated information system for pharmacovigilance at the link: https://aisf.dec.gov.ua.

Shelf life

2 years.

Storage conditions

Store in a refrigerator (at a temperature of +2°C to +8°C). To protect from light, ampoules should be kept in the outer packaging. Store in a place inaccessible to children.

Incompatibility

The medicinal product cannot be mixed with other solutions for injection.

Packaging

2 ml in an ampoule. 5 or 10 ampoules in a cardboard box.

Release category

By prescription.

Manufacturer

LLC "Pharmasel".

Location of the manufacturer and its address

Ukraine, 07408, Kyiv region, Brovary district, village of Kvitneve, Prorizna street, 3.