Diclocaine

INSTRUCTIONS FOR MEDICAL USE|consumption| OF THE MEDICINAL PRODUCT DICLOCAIN (DICLOCAIN)

Composition:

Active substances: diclofenac, lidocaine;

1 ml| of solution contains^^:: sodium diclofenac 37.5 mg, lidocaine hydrochloride | 10 mg;

Excipients: water for injections, propylene glycol|, ethanol 96%, sodium metabisulfite (E 223), disodium edetate, 0.1 M solution of sodium hydroxide.

Pharmaceutical form. Solution for injection.

Main physico-chemical|physico-chemical| properties: clear colorless|colorless| or slightly yellowish solution.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents.

ATC code M01AB55.

Pharmacological Properties

Pharmacodynamics. The drug contains sodium diclofenac, a non-steroidal active substance with pronounced anti-rheumatic, anti-inflammatory, analgesic, and antipyretic properties. Inhibition of prostaglandin biosynthesis is considered the main mechanism of its action. Prostaglandins play a significant role in the development of inflammation, pain, and fever.

In rheumatic diseases, the anti-inflammatory and analgesic properties of the drug determine the clinical response, characterized by marked reduction or disappearance of signs and symptoms: pain at rest, pain on movement, morning stiffness, joint swelling, as well as improvement in joint functional properties. In post-traumatic or postoperative inflammation, diclofenac induces rapid reduction of acute pain and pain on movement, and also reduces edema caused by inflammation and injury.

When used concomitantly for treatment of postoperative pain, diclofenac significantly reduces the need for opioids. The drug may enhance the pronounced analgesic effect on moderate to severe non-rheumatic pain within 15–30 minutes after administration.

The drug is particularly effective when used for initial therapy of inflammatory and degenerative rheumatic diseases, as well as for treatment of pain caused by non-rheumatic inflammation.

Pharmacokinetics. The mean volume of distribution of sodium diclofenac is 0.12–0.17 L/kg; binding to plasma proteins exceeds 99%.

The therapeutic concentration of diclofenac in plasma is 0.7–2 µg/mL.

Repeated administration of the drug does not cause any renal changes. When recommended intervals between doses are observed, no drug accumulation occurs in the body.

Diclofenac penetrates into synovial fluid, where its Cmax is reached 2–4 hours after peak plasma concentration; the half-life (T½) in synovial fluid is 3–6 hours. Therefore, even 4–6 hours after administration, diclofenac concentrations in synovial fluid are higher than in plasma and remain elevated for up to 12 hours.

Approximately half of the administered sodium diclofenac undergoes first-pass metabolism. As a result, the area under the concentration-time curve (AUC) after oral or rectal administration of sodium diclofenac is approximately two times lower than the AUC observed after parenteral administration of an equivalent dose.

Biotransformation of diclofenac occurs partially via glucuronidation and methoxylation. Two of the resulting phenolic metabolites are pharmacologically active, although to a lesser extent than diclofenac itself.

Diclofenac is eliminated from plasma with a systemic clearance of 263 ± 56 mL/min (mean ± standard deviation). The terminal half-life (T½) of the drug is 1–2 hours. Approximately 60% of the administered dose is excreted by the kidneys as metabolites, with less than 1% excreted unchanged. The remainder of the dose is excreted in metabolized form via bile and feces.

No significant differences in absorption, metabolism, and elimination of the drug depending on patient age have been observed.

In patients with impaired renal function, administration of the usual dose did not result in increased levels of unchanged diclofenac. However, when creatinine clearance was below 10 mL/min, the calculated steady-state plasma concentration of metabolites was approximately four times higher than in patients with normal renal function. Despite this, metabolites were ultimately eliminated via bile.

In cases of hepatic impairment (chronic hepatitis, compensated liver cirrhosis), the pharmacokinetics and metabolism of the drug do not differ from those in patients with normal liver function.

Clinical characteristics.

Indications. The drug is indicated for the following conditions:

• Acute exacerbations of inflammatory or degenerative forms of rheumatism: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, vertebral pain syndromes, periarticular rheumatism;
• Acute gout attacks;
• Renal and hepatic colic;
• Pain, inflammation, and edema following trauma and surgical interventions.

Contraindications.

• Hypersensitivity to the active substances or to any other components of the drug;
• Increased individual sensitivity to lidocaine or to other amide-type local anesthetics;
• History of seizures associated with lidocaine use;
• Wolff–Parkinson–White syndrome;
• Porphyria;
• Myasthenia;
• Anticoagulant therapy;
• Bleeding or perforation in the gastrointestinal tract in history, associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
• Active peptic ulcer disease/bleeding or recurrent peptic ulcer disease/bleeding in history (two or more separate episodes of confirmed ulcer or bleeding);
• History of episodes of bronchospasm, acute rhinitis, nasal polyps, urticaria, or other allergic disorders caused by acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs (NSAIDs);
• Inflammatory bowel diseases (e.g., Crohn’s disease or ulcerative colitis);
• Hepatic insufficiency;
• Renal insufficiency;
• Congestive heart failure (NYHA II–IV);
• Ischemic heart disease in patients with angina pectoris or history of myocardial infarction;
• Cerebrovascular diseases in patients with history of stroke or transient ischemic attacks;
• Peripheral arterial disease;
• Contraindicated for treatment of perioperative pain in coronary artery bypass grafting (or when using cardiopulmonary bypass equipment);
• Second- and third-degree atrioventricular block, sinus node weakness syndrome, Adams–Stokes syndrome, marked arterial hypotension, bradycardia, cardiogenic or hypovolemic shock, complete transverse heart block;
• High risk of postoperative bleeding, coagulation disorders, incomplete hemostasis, hematopoiesis disorders, or cerebrovascular hemorrhage.

Interaction with other medicinal products and other types of interactions. Interactions involving sodium diclofenac may occur.

Lithium, digoxin. When used concomitantly, diclofenac may increase plasma concentrations of lithium and digoxin. Monitoring of lithium and digoxin levels in serum is recommended.

Diuretics and other antihypertensive agents. As with other NSAIDs, concomitant use of sodium diclofenac with diuretics or antihypertensive agents [e.g., β-blockers, angiotensin-converting enzyme (ACE) inhibitors] may reduce the antihypertensive effect of these agents. Such combinations should be used with caution; blood pressure in these patients, especially elderly patients, should be monitored periodically. Patients should consume adequate fluid. Monitoring of renal function is recommended at the beginning of concomitant therapy and periodically thereafter, particularly when diuretics and ACE inhibitors are used, due to the increasing risk of nephrotoxicity.

Medicinal products causing hyperkalemia. Concomitant therapy with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increased serum potassium levels; therefore, more frequent monitoring of patients is required.

Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. Concomitant administration of diclofenac and other systemic NSAIDs or corticosteroids may increase the risk of gastrointestinal bleeding or ulceration. Simultaneous use of two or more NSAIDs should be avoided.

Anticoagulants and antithrombotic agents. Sodium diclofenac should be used with caution in combination with anticoagulants and antiplatelet agents, as their combined use may increase the risk of bleeding. Although evidence of diclofenac’s effect on anticoagulant activity is lacking, isolated reports of hemorrhagic complications have been reported in patients receiving diclofenac and anticoagulants simultaneously. Therefore, close monitoring of patients receiving diclofenac and anticoagulants is recommended, and, if necessary, adjustment of anticoagulant dosage. Like other nonsteroidal anti-inflammatory drugs, diclofenac at high doses may reversibly inhibit platelet aggregation.

Selective serotonin reuptake inhibitors (SSRIs). Concomitant use of systemic NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.

Antidiabetic agents. It has been established that sodium diclofenac can be administered together with oral hypoglycemic agents without affecting their clinical efficacy. However, isolated reports of hypoglycemic and hyperglycemic reactions after administration of sodium diclofenac have required changes in hypoglycemic agent dosages. Therefore, blood glucose monitoring is recommended during such combined therapy.

Methotrexate. Diclofenac may inhibit methotrexate clearance in renal tubules, leading to elevated methotrexate levels. Caution is recommended when administering NSAIDs, including diclofenac, less than 24 hours before methotrexate therapy, as this may increase methotrexate blood concentration and its toxicity. Serious toxicity cases have been reported when methotrexate and NSAIDs, including diclofenac, were administered within 24 hours of each other. This interaction is mediated by methotrexate accumulation due to impaired renal excretion in the presence of NSAIDs.

Cyclosporine. Diclofenac, like other NSAIDs, may increase cyclosporine nephrotoxicity due to effects on renal prostaglandins. Therefore, it should be administered at lower doses than in patients not receiving cyclosporine.

Tacrolimus. Concomitant use of NSAIDs with tacrolimus may increase the risk of nephrotoxicity, possibly mediated by renal antiprostaglandin effects of NSAIDs and calcineurin inhibitors.

Antibacterial quinolones. Isolated reports exist of seizures possibly resulting from concomitant use of quinolones and NSAIDs. This may occur in patients both with and without a history of epilepsy or seizures. Therefore, quinolones should be prescribed cautiously to patients already receiving NSAIDs.

Phenytoin. When phenytoin is used concomitantly with diclofenac, monitoring of phenytoin plasma concentration is recommended due to expected increased phenytoin exposure.

Cholestyramine and colestipol. These agents may delay or reduce diclofenac absorption. Therefore, diclofenac should be administered at least 1 hour before or 4–6 hours after cholestyramine/colestipol.

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

Mifepristone. NSAIDs should not be used within 8–12 days after mifepristone administration, as NSAIDs may reduce its effect.

Potent CYP2C9 inhibitors. Diclofenac should be prescribed with caution concomitantly with strong CYP2C9 inhibitors (such as sulfaphenazole and voriconazole), as this may lead to a significant increase in plasma peak concentration and enhanced diclofenac effects due to inhibition of its metabolism.

Alcohol. Concomitant use of NSAIDs and alcohol may exacerbate adverse effects of the active substance, particularly on the gastrointestinal tract or central nervous system.

Interactions related to lidocaine hydrochloride content may also occur.

β-adrenergic blockers, propranolol and others, as well as cimetidine, pethidine, bupivacaine, quinidine, disopyramide, amitriptyline, nortriptyline, chlorpromazine, imipramine increase lidocaine levels in serum by reducing its hepatic metabolism.

In cardiac glycoside intoxication, lidocaine may exacerbate the severity of AV block. Lidocaine reduces the cardiotonic effect of cardiac glycosides.

Concomitant use with antiarrhythmic agents (amiodarone, verapamil, quinidine, etc.) or anticonvulsants (hydantoin derivatives) enhances cardiodepressive effects.

Concomitant use with sedatives and hypnotics, anesthetic agents (hexobarbital, intravenous sodium thiopental) may enhance central nervous system depressant effects.

Phenytoin enhances the cardiodepressive effect of lidocaine.

Concomitant use with procainamide may cause delirium, hallucinations.

Lidocaine may enhance the effects of agents causing neuromuscular blockade, as the latter reduce nerve impulse conduction.

Ethanol enhances lidocaine’s respiratory depressant effect.

Norepinephrine, mexiletine – increase lidocaine toxicity (reduced lidocaine clearance).

Isadrine and glucagon – increase lidocaine clearance.

Midazolam moderately increases lidocaine blood concentration.

Monoamine oxidase inhibitors, aminazine, bupivacaine, amitriptyline, nortriptyline, imipramine – combined use with lidocaine increases the risk of arterial hypotension and prolongs the local anesthetic effect of the latter.

Narcotic analgesics (e.g., morphine) – combined use with lidocaine enhances the analgesic effect of narcotic analgesics, but also enhances respiratory depression.

Prenylamine – increases the risk of developing ventricular arrhythmia of the "torsade de pointes" type.

Propafenone – possible increase in duration and severity of central nervous system side effects.

Rifampicin – possible reduction in lidocaine blood concentration.

Polymyxin B – respiratory function should be monitored.

Digitalis glycosides – in intoxication, lidocaine may exacerbate the severity of AV block.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) – combined use with lidocaine slows lidocaine absorption and prolongs its effect.

Guanadrel, guanethidine, mecamylamine, trimethaphan – combined use for spinal and epidural anesthesia increases the risk of severe hypotension and bradycardia.

Acetazolamide, thiazide and loop diuretics – combined use with lidocaine causes hypokalemia and reduces its effect.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin, and others) – combined use with lidocaine increases the risk of bleeding.

Special precautions for use.

Adverse effects can be minimized by using the lowest effective dose for the shortest possible duration required to control symptoms.

Treatment with NSAIDs may cause gastrointestinal ulcers, bleeding, or perforation, regardless of the presence of warning symptoms or serious gastrointestinal events in history.

Sodium diclofenac, like other NSAIDs, may increase the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke.

Caution is required when prescribing the drug to elderly patients. In particular, for frail elderly patients and those with low body weight, the lowest effective doses are recommended.

As with other lidocaine-containing medicinal products, the drug should be prescribed cautiously to patients with epilepsy, cardiac conduction disorders, or respiratory insufficiency.

Avoid concomitant use with systemic NSAIDs, including selective cyclooxygenase-2 inhibitors, due to lack of synergistic benefit and potential for additional adverse effects.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur with diclofenac use.

NSAIDs, due to their pharmacodynamic properties, may mask signs and symptoms of infection.

Prolonged use of analgesics may cause headache, which cannot be treated by increasing the dose of these agents.

Effect on the gastrointestinal tract. Gastrointestinal bleeding, ulceration, or perforation have been reported, which may be fatal and may occur at any time during treatment, regardless of the presence or absence of warning symptoms or serious gastrointestinal events in history, associated with all NSAIDs, including diclofenac. Sodium diclofenac should be prescribed under medical supervision and with caution to patients with symptoms indicating gastrointestinal disorders, or with history of gastric or intestinal ulcer, gastrointestinal bleeding, or perforation. The risk of gastrointestinal bleeding is higher with increased NSAID doses in patients with ulcer history, especially complicated by bleeding or perforation, and in elderly patients. If gastrointestinal bleeding or ulceration develops in patients during treatment, the drug should be discontinued.

To reduce the risk of gastrointestinal disorders in patients with ulcer history, especially complicated by bleeding or perforation, and in elderly patients, frail patients, or those with low body weight, the drug should be prescribed at the lowest effective dose for the shortest possible duration. Such patients, as well as those regularly taking low-dose acetylsalicylic acid/aspirin or other agents increasing the risk of gastrointestinal adverse effects, should be given combination therapy with agents having protective effects on gastric mucosa (e.g., proton pump inhibitors or misoprostol).

In elderly patients, NSAID treatment may have more serious consequences. Therefore, such patients should inform their physician of any unusual gastrointestinal symptoms (especially gastrointestinal bleeding). This also applies to patients receiving concomitant agents that may increase the risk of ulcer or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid), or selective serotonin reuptake inhibitors.

Effect on the liver. Patients with impaired liver function require careful medical supervision when receiving sodium diclofenac, as symptoms of liver disease may worsen during treatment.

During NSAID treatment, levels of one or more liver enzymes in blood may increase. Such changes are rarely accompanied by clinical symptoms. In most cases, increases in these parameters remain within borderline values. Moderate increases above normal (from ≥3 to <8 × upper limit of normal) are frequently observed, while significant increases (≥8 × upper limit of normal) occur in approximately 1% of cases. In 0.5% of patients, in addition to elevated liver enzyme levels, clinically manifest liver injury developed (eosinophilia, rash). After discontinuation of the drug, elevated levels of these parameters usually return to normal.

If liver function abnormalities persist or worsen during treatment, or if clinical signs or symptoms of liver disease (e.g., hepatitis) or other manifestations (e.g., eosinophilia, rash) occur, sodium diclofenac should be discontinued.

The course of diseases such as hepatitis may proceed without prodromal symptoms.

The drug should be used cautiously in patients with hepatic porphyria due to the possibility of provoking an attack.

Effect on the kidneys. Since fluid retention and edema have been reported during NSAID treatment, including diclofenac, particular attention should be paid to patients with impaired cardiac or renal function, history of arterial hypertension, elderly patients, those receiving concomitant diuretic therapy or agents significantly affecting renal function, and patients with significant extracellular fluid volume depletion for any reason, e.g., before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually leads to return to the pre-treatment state.

Generally, frequent and regular use of analgesics, especially combinations of several analgesic agents, may lead to persistent kidney damage, with risk of renal failure ("analgesic nephropathy").

Effect on skin and subcutaneous tissue. In isolated cases, severe skin reactions, sometimes fatal, including exfoliative dermatitis, Stevens–Johnson syndrome, toxic epidermal necrolysis, and generalized fixed drug eruption, have been reported with diclofenac use. Patients are at high risk of such reactions at the beginning of treatment: reactions develop in most cases within the first month of treatment. If skin rash, mucosal lesions, or any sign of hypersensitivity occur, diclofenac intake should be discontinued.

Injection site reactions. Injection site reactions have been reported after intramuscular administration of diclofenac, including injection site necrosis and drug embolism, also known as Nicolau syndrome (especially after inadvertent subcutaneous injection). Appropriate needle and injection technique should be used for intramuscular diclofenac administration.

Systemic lupus erythematosus (SLE) and mixed connective tissue diseases. Patients with SLE and mixed connective tissue diseases have an increased risk of aseptic meningitis.

Effect on the cardiovascular system and cerebral vessels. Diclofenac may be used in patients with clinically confirmed ischemic heart disease, cerebrovascular disease, peripheral arterial occlusive disease, and patients at risk (e.g., with arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation. Since cardiovascular risks of diclofenac may increase with dose and duration of treatment, it should be used for the shortest possible duration and at the lowest effective dose. The patient's need for diclofenac to relieve symptoms and response to therapy should be reviewed periodically. Use with caution in patients aged 65 years and older.

Patients with history of arterial hypertension and/or mild to moderate congestive heart failure require appropriate monitoring and recommendations, as fluid retention and edema have been reported with NSAID use, including diclofenac.

Diclofenac use, especially at high doses (150 mg/day) and for prolonged periods, may be associated with a slight increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke).

Diclofenac is not recommended for patients with uncontrolled arterial hypertension, congestive heart failure, stable ischemic heart disease, peripheral arterial diseases, and/or cerebrovascular disease. If use is necessary, it may be considered only after careful risk-benefit assessment at a dose not exceeding 100 mg per day.

Patients should be informed about the possible occurrence of serious events (chest pain, shortness of breath, weakness, speech disturbances). In such cases, immediate medical attention is required.

The drug is contraindicated in patients with congestive heart failure (NYHA II–IV).

Effect on hematological parameters. Since NSAIDs may temporarily inhibit platelet aggregation, hematological parameters should be monitored during prolonged use of sodium diclofenac, as with other NSAIDs. Patients with hemostasis disorders, hemorrhagic diathesis, or hematological abnormalities require close monitoring.

Asthma in history. In patients with bronchial asthma, seasonal allergic rhinitis, nasal mucosal edema (i.e., nasal polyps), chronic obstructive pulmonary disease, or chronic respiratory tract infections (especially if associated with symptoms resembling allergic rhinitis), reactions to NSAID intake such as asthma exacerbation (so-called analgesic intolerance, leukotriene asthma, aspirin asthma), Quincke's edema, or urticaria occur more frequently than in other patients. Therefore, special precautions (readiness for emergency assistance) are recommended for such patients. This also applies to patients with allergies to other substances manifesting as skin reactions, itching, or urticaria.

Like other agents inhibiting prostaglandin synthetase activity, sodium diclofenac and other NSAIDs may provoke bronchospasm in patients with bronchial asthma or history of bronchial asthma.

Lidocaine. Since the drug contains lidocaine, it should be noted that disinfectant solutions containing heavy metals at the injection site increase the risk of local reaction in the form of pain and swelling.

Since lidocaine has a pronounced arrhythmogenic effect, the drug should be used cautiously in individuals with a history of arrhythmia.

Use with caution in patients with moderate heart failure, moderate arterial hypotension, incomplete AV block, intraventricular conduction disorders, moderate liver and kidney dysfunction (creatinine clearance 10 ml/min), respiratory function disorders, epilepsy, increased seizure predisposition, severe myasthenia, after cardiac surgery, in genetic predisposition to hyperthermia, in frail patients and elderly patients; when injecting into inflamed (infected) areas.

During lidocaine use, cardiac function must be monitored by ECG. If sinus node dysfunction, prolonged P–Q interval, widened QRS complex, or new arrhythmia develops, the dose should be reduced or the drug discontinued.

Before lidocaine use in cardiac conditions (hypokalemia reduces lidocaine efficacy), potassium levels in blood should be normalized.

Excipients. The drug contains less than 1 mmol (less than 23 mg)/dose of sodium, i.e., practically sodium-free.

The drug contains 19.01 vol.% ethanol (alcohol), i.e., 300 mg/dose. Harmful for patients with alcoholism. Caution is required when using in patients with liver diseases (except those specified in the "Contraindications" section) and patients with epilepsy.

Use during pregnancy or breastfeeding.

Pregnancy. From the 20th week of pregnancy, diclofenac use may cause oligohydramnios due to fetal kidney dysfunction. Medicinal products containing lidocaine hydrochloride are contraindicated during pregnancy.

Breastfeeding. Since NSAIDs pass into breast milk, sodium diclofenac should not be prescribed to breastfeeding women. If such treatment is absolutely necessary, breastfeeding should be discontinued.

Fertility. The drug may affect female fertility and is therefore not recommended for women planning pregnancy. Consideration should be given to discontinuing the drug in women unable to conceive and women undergoing infertility evaluation.

Ability to affect reaction speed when driving or operating machinery. Patients with visual disturbances, dizziness, drowsiness, lethargy, increased fatigue, or other central nervous system disorders should refrain from driving or operating machinery.

Administration and dosage. The drug is administered as intramuscular injections. The dose should be individualized. The lowest effective dose should be used for the shortest possible duration.

The usual single dose is 1 ampoule (i.e., 75 mg sodium diclofenac), administered intramuscularly once daily by deep injection into the upper outer quadrant of the gluteal muscle. The solution should be used immediately after opening the ampoule. Any unused solution must be discarded.

In cases of severe pain (e.g., colic), the drug may be administered twice daily at several-hour intervals, changing the injection site each time. Parenteral administration may be combined with other dosage forms (tablets, capsules, rectal capsules, gel, or patch), provided the maximum daily dose of sodium diclofenac does not exceed 150 mg.

The duration of parenteral administration should not exceed 2 days.

Do not use the drug for intravenous injection/infusion.

Children. Do not use in children.

Overdose.

Sodium diclofenac.

Symptoms. Typical clinical symptoms of sodium diclofenac overdose are unknown. In case of overdose, headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, excitement, coma, drowsiness, tinnitus, confusion, loss of consciousness, or seizures may occur. In severe poisoning, acute renal failure and liver injury are possible. Overdose may also lead to arterial hypotension, respiratory depression, and cyanosis.

Treatment. Within one hour after ingestion of a potentially toxic amount, oral activated charcoal may be beneficial. Additionally, gastric lavage should be considered for adults within 1 hour after ingestion of a potentially toxic amount. Supportive measures and symptomatic treatment to manage complications such as arterial hypotension, renal failure, seizures, gastrointestinal mucosal irritation, and respiratory depression. Specific therapies such as forced diuresis, dialysis, or hemoperfusion are of limited value in eliminating NSAIDs due to their high plasma protein binding and extensive metabolism. Intravenous diazepam should be administered for frequent or prolonged seizures. Other measures may be indicated depending on the patient's clinical condition. Treatment is symptomatic.

Lidocaine.

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

Treatment: discontinue drug administration, oxygen therapy, anticonvulsants, vasoconstrictors (norepinephrine, mesaton), for bradycardia – cholinolytics (0.5–1 mg atropine). Intubation, artificial ventilation, resuscitation may be performed. Dialysis is ineffective.

Adverse Reactions

If adverse effects occur, consult a physician.

The list of possible adverse effects includes information regarding potential actions of the active ingredients contained in the medicinal product.

Infections and infestations: Injection site abscesses.

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

Immune system disorders: Hypersensitivity reactions (anaphylactic and anaphylactoid reactions, including arterial hypotension and shock), angioneurotic edema (including facial swelling), sensations of warmth, cold, or limb numbness.

Psychiatric disorders: Disorientation, depression, insomnia, nightmares, irritability, restlessness, psychiatric disturbances.

Nervous system disorders: Headache, dizziness, sleep disturbances, somnolence, paresthesia, memory impairment, seizures, anxiety, tremor, aseptic meningitis, taste disturbances, stroke, sensory disturbances, increased fatigue, confusion, loss of consciousness up to coma, hallucinations, muscle twitching, motor block, dysarthria, dysphagia, nystagmus.

Eye disorders: Visual disturbances, blurred vision, diplopia, optic neuritis, floaters, photophobia, conjunctivitis.

Ear and labyrinth disorders: Vertigo, tinnitus, hearing disturbances, hyperacusis.

Cardiac disorders: Palpitations, chest pain, myocardial infarction, heart failure, arterial hypertension, arterial hypotension, vasculitis, arrhythmia, bradycardia, slowed cardiac conduction, atrioventricular block, cardiac arrest, collapse, tachycardia, flushing.

Respiratory, thoracic and mediastinal disorders: Asthma (including dyspnea), bronchospasm, pneumonitis, respiratory depression or arrest, rhinitis.

Gastrointestinal disorders: Abdominal pain, nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, flatulence, anorexia, gastritis, vomiting of blood, gastrointestinal hemorrhage, hemorrhagic diarrhea, melena, gastric and intestinal ulcers (including those with hemorrhage or perforation) (sometimes fatal, especially in elderly patients), colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal lesions, diaphragm-like intestinal strictures, pancreatitis.

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

Skin and subcutaneous tissue disorders: Rash (including with "unknown" frequency: fixed drug eruption, generalized bullous fixed drug eruption), urticaria, eczema, erythema, erythema multiforme, Stevens–Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, alopecia, photosensitivity, purpura, allergic purpura, pruritus.

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

Reproductive system disorders: Impotence.

General disorders and administration site conditions: Malaise, malignant hyperthermia, weakness, reactions at the site of intramuscular injection (e.g., pain, mild burning sensation or tissue induration, swelling), drug embolism (Nicolau syndrome), injection site necrosis.

An increased risk of thrombotic complications (e.g., myocardial infarction or stroke) has been reported with the use of diclofenac, particularly at high therapeutic doses (150 mg per day) and prolonged use.

Shelf life. 5 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.

Incompatibility. Do not mix the medicinal product with other injectable solutions.

Packaging. 2 ml in ampoules, pack of 10 in a partitioned box; № 5×2, № 10 in blister pack in a box.

Prescription status. Prescription only.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and place of business. 22 Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.