Olfen® -75

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Olfen®-75 (Olfen®-75)

Composition:

Active substances: diclofenac sodium, lidocaine hydrochloride monohydrate;

1 ampoule (2 ml) contains: diclofenac sodium 75 mg and lidocaine hydrochloride monohydrate 20 mg;

Excipients: disodium edetate, acetylcysteine, propylene glycol, polyethylene glycol 400, sodium hydroxide, water for injections.

Medicinal form. Solution for injection.

Main physicochemical characteristics: clear solution, practically colorless to slightly yellow.

Pharmacotherapeutic group. Nonsteroidal anti-inflammatory and antirheumatic agents.
ATC code M01AB55.

Pharmacological properties.

Pharmacodynamics.

The medicinal product Olphen®-75 contains sodium diclofenac, a non-steroidal active substance with pronounced anti-rheumatic, anti-inflammatory, analgesic and antipyretic properties. Inhibition of prostaglandin biosynthesis, which play a significant role in the development of inflammation, pain and fever, is considered the main mechanism of its action. In rheumatic diseases, the anti-inflammatory and analgesic properties of the medicinal product result in a clinical response characterized by marked disappearance of signs and symptoms (pain at rest and during movement, morning stiffness and joint swelling), as well as noticeable improvement in motor function.

In post-traumatic and postoperative conditions associated with inflammation, sodium diclofenac rapidly reduces acute pain and pain on movement, and also decreases edema caused by inflammation and injury. When used concomitantly with opioids for postoperative pain management, sodium diclofenac significantly reduces the need for opioids. The medicinal product Olphen®-75 demonstrates pronounced analgesic effect within 15–30 minutes after administration in moderate to severe non-rheumatic pain. It can be used for initial treatment of inflammatory and degenerative rheumatic diseases, as well as for management of pain caused by non-rheumatic inflammation.

Pharmacokinetics.

Absorption. After intramuscular administration of 75 mg diclofenac, maximum plasma concentration, averaging 2.5 µg/mL, is reached within 20 minutes. The therapeutic concentration of Olphen®-75 in plasma ranges from 0.7 to 2.0 µg/mL. Repeated administration of the drug does not cause any renal-related changes. Pharmacokinetic properties remain unchanged after repeated dosing. No accumulation of the drug in the body has been observed when recommended dosing intervals are maintained.

Distribution. 99.7% of diclofenac is bound to plasma proteins, primarily to albumin (99.4%). The apparent volume of distribution of sodium diclofenac is 0.12–0.17 L/kg. The medicinal product Olphen®-75 penetrates into synovial fluid, where maximum concentration is achieved 2–4 hours after peak plasma concentration. The half-life in synovial fluid is 3–6 hours. As a result, even 4–6 hours after administration, the concentration of the active substance in synovial fluid exceeds that in plasma and remains higher for up to 12 hours.

Metabolism. Approximately half of the administered dose undergoes first-pass metabolism. Consequently, the area under the concentration-time curve (AUC) after oral or rectal administration is approximately half that observed after parenteral administration of an equivalent dose.

Biotransformation of diclofenac occurs via glucuronidation and hydroxylation, forming several phenolic metabolites, two of which are pharmacologically active but less potent than sodium diclofenac itself.

Elimination. Sodium diclofenac is eliminated from plasma with a systemic clearance of 263 ± 56 mL/min (mean ± standard deviation). The terminal half-life in plasma 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 into feces.

Linearity/non-linearity. Plasma concentration demonstrates linear dependence on dose.

Pharmacokinetics in specific patient populations. No significant differences in absorption, metabolism, or elimination of the drug were observed in elderly patients. In patients with impaired renal function, after administration of the usual dose, no increase in unchanged active substance was observed. However, when creatinine clearance was less than 10 mL/min, the theoretical steady-state plasma metabolite levels were approximately four times higher than in healthy volunteers. Despite this, metabolites were ultimately eliminated via bile. In patients with hepatic impairment (chronic hepatitis, compensated cirrhosis), the pharmacokinetics and metabolism of the drug do not differ from those in patients with normal liver function.

Clinical characteristics.

Indications.

The medicinal product is indicated for intramuscular injection in the following conditions:

− inflammatory or degenerative forms of rheumatism, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis, vertebral pain syndrome, periarticular rheumatism;

− acute attacks of gout;

− renal and hepatic colic;

− pain, inflammation, and edema following trauma and surgical interventions;

− severe migraine attacks.

Contraindications.

• Hypersensitivity to the active substances or to any of the other components of the medicinal product;
• increased individual sensitivity to lidocaine or to other amide-type local anesthetics;
• history of seizures induced by lidocaine;
• porphyria;
• myasthenia gravis;
• anticoagulant therapy;
• gastrointestinal bleeding or perforation in history related to previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
• active peptic ulcer disease/gastrointestinal bleeding or recurrent peptic ulcer disease/bleeding in history (two or more separate episodes of confirmed ulcer or bleeding);
• active gastric and/or duodenal ulcer, gastrointestinal bleeding or perforation;
• as with other NSAIDs, diclofenac is contraindicated in patients in whom administration of ibuprofen, acetylsalicylic acid, or other NSAIDs induces attacks of bronchial asthma, bronchospasm, angioedema, urticaria, acute rhinitis, nasal polyps, or allergy-like symptoms;
• inflammatory bowel diseases (e.g., Crohn’s disease or ulcerative colitis);
• hepatic insufficiency (Child-Pugh class C);
• renal insufficiency (glomerular filtration rate [GFR] < 15 mL/min/1.73 m²);
• congestive heart failure [NYHA functional class II–IV (New York Heart Association)];
• 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 the treatment of perioperative pain in coronary artery bypass grafting (CABG) (or when using cardiopulmonary bypass);
• severe disturbances of the cardiac conduction system, second- or third-degree atrioventricular block, sick sinus syndrome, Adams-Stokes syndrome, Wolff-Parkinson-White syndrome, complete heart block, bradycardia, cardiogenic or hypovolemic shock, pronounced arterial hypotension;
• high risk of postoperative bleeding, coagulation disorders, incomplete hemostasis, hematopoietic disorders, or cerebrovascular hemorrhage.

Interaction with other medicinal products and other types of interactions.

The following interactions may occur with the medicinal product Olfen®-75 and/or other diclofenac formulations.

Concomitant use of diclofenac may increase plasma concentrations of lithium and digoxin. Monitoring of serum lithium and digoxin levels is recommended.

Concomitant administration of sodium diclofenac with diuretics or antihypertensive medicinal products (e.g., β-blockers, angiotensin-converting enzyme [ACE] inhibitors) may reduce antihypertensive efficacy. Such combinations should be used with caution, and blood pressure should be carefully monitored, especially in elderly patients. Adequate fluid intake is recommended. Renal function should be monitored at the start of concomitant therapy and regularly thereafter, particularly when diuretics and ACE inhibitors are used, due to increased risk of nephrotoxicity.

Medicinal products causing hyperkalemia. Concomitant use of potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may lead to increased serum potassium levels; therefore, more frequent monitoring of patients is recommended.

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

Sodium diclofenac should be used with caution in combination with anticoagulants and antiplatelet agents, as their combined use increases the risk of bleeding. Although no evidence of diclofenac affecting anticoagulant action has been established, isolated reports of hemorrhagic complications have occurred in patients taking diclofenac and anticoagulants simultaneously. Close monitoring of patients receiving both diclofenac and anticoagulants is recommended, with dose adjustment of anticoagulants if necessary. Like other NSAIDs, high-dose diclofenac may 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 sodium diclofenac can be administered together with oral hypoglycemic agents without affecting their clinical efficacy. However, isolated reports of hypoglycemic and hyperglycemic reactions following sodium diclofenac administration have required adjustment of hypoglycemic agent doses. Therefore, blood glucose monitoring is recommended during such combination therapy. Isolated cases of metabolic acidosis have also been reported with concomitant use of diclofenac and metformin, particularly in patients with pre-existing renal impairment.

Diclofenac may inhibit renal tubular clearance of methotrexate, leading to elevated methotrexate levels. Caution is advised when administering NSAIDs, including diclofenac, within 24 hours before or after methotrexate treatment, as this may increase methotrexate plasma 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.

Diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine and tacrolimus due to effects on renal prostaglandins. Therefore, it should be used at lower doses than in patients not receiving cyclosporine or tacrolimus.

Isolated reports exist of seizures possibly associated with concomitant use of quinolone antibiotics and NSAIDs. Seizures may occur in patients both with and without a history of epilepsy or seizures. Therefore, caution is advised when considering quinolone use in patients already receiving NSAIDs.

When phenytoin is administered concomitantly with diclofenac, monitoring of plasma phenytoin concentrations is recommended due to expected increased phenytoin exposure.

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

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

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

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

Concomitant administration of diclofenac with strong CYP2C9 inhibitors (such as sulfaphenazole and voriconazole) is recommended with caution, as this may lead to a significant increase in peak plasma concentration and enhanced effect of diclofenac due to inhibition of its metabolism.

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

Interactions related to the presence of lidocaine hydrochloride monohydrate may also occur.

When lidocaine is used in combination with antiarrhythmic agents, β-blockers, or calcium antagonists, additive inhibitory effects on atrioventricular conduction, intraventricular conduction, and myocardial contractility should be considered.

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

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

Concomitant use with antiarrhythmic agents (amiodarone, verapamil, quinidine, etc.) or anticonvulsants (hydantoin derivatives) and phenytoin enhances the cardiodepressant effect of lidocaine. Concomitant use with sedatives and hypnotics, or anesthetic agents (hexobarbital, intravenous sodium thiopental) may enhance CNS depression.

Concomitant use with procainamide may cause delirium and hallucinations. Lidocaine may potentiate the effects of medicinal products causing neuromuscular blockade, as they reduce nerve impulse conduction. Ethanol enhances the respiratory depressant effect of lidocaine.

Norepinephrine, mexiletine – increase lidocaine toxicity (reduced lidocaine clearance). Isadrine and glucagon – increase lidocaine clearance. Midazolam moderately increases lidocaine blood concentration.

Monoamine oxidase inhibitors, chlorpromazine, bupivacaine, amitriptyline, nortriptyline, imipramine – when used concomitantly with lidocaine, increase the risk of arterial hypotension and prolong the local anesthetic effect of lidocaine.

Narcotic analgesics (e.g., morphine) – when used concomitantly with lidocaine, enhance the analgesic effect of narcotic analgesics but also enhance respiratory depression. Pretilamine – increases the risk of ventricular arrhythmia of the "torsades de pointes" type. Propafenone – may increase the duration and severity of CNS-related adverse effects. Rifampicin – may reduce lidocaine blood concentration.

Polymyxin B – respiratory function should be monitored. Vasoconstrictors (epinephrine, methoxamine, phenylephrine) – when used concomitantly with lidocaine, slow lidocaine absorption and prolong its effect. Guanadrel, guanethidine, mecamylamine, trimethaphan – when used concomitantly for spinal or epidural anesthesia, increase the risk of severe hypotension and bradycardia. Acetazolamide, thiazide and loop diuretics – when used concomitantly with lidocaine, cause hypokalemia and reduce lidocaine's effect. Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin, and others) – when used concomitantly with lidocaine, increase the risk of bleeding.

Special precautions.

General recommendations. During treatment with NSAIDs, both selective and non-selective COX-2 inhibitors, peptic ulcers, gastrointestinal bleeding, or gastrointestinal perforation may occur, regardless of the presence or absence of prior warning symptoms or serious gastrointestinal events in history. Adverse effects can be minimized by using the lowest effective dose for the shortest possible duration required to control symptoms.

Sodium diclofenac, like other NSAIDs, increases the risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke. Placebo-controlled studies have demonstrated an increased risk of thrombotic cardiovascular and cerebrovascular complications with certain selective COX-2 inhibitors. A direct correlation between this risk and the selectivity of individual NSAIDs for COX-1/COX-2 has not yet been established. Due to the lack of comparative clinical trial data on long-term treatment with maximum doses of diclofenac, a similar increased risk cannot be excluded. In the absence of such data, a careful benefit-risk assessment should be performed before using diclofenac in patients with clinically confirmed ischemic heart disease, cerebrovascular disease, peripheral arterial disease, or significant risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). Diclofenac should be used only after careful evaluation of potential risks and benefits. Because of this risk, the lowest effective dose should be used for the shortest possible duration of treatment.

The effects of NSAIDs on the kidneys include fluid retention with edema and/or arterial hypertension. Therefore, diclofenac should be used with particular caution in patients with impaired cardiac function and other conditions predisposing to fluid retention. Caution is also advised in patients concurrently taking diuretics or ACE inhibitors, or those prone to hypovolemia.

Consequences are generally more serious in elderly patients. Caution should be exercised when prescribing the medicinal product to elderly patients. In particular, for frail elderly patients and those with low body weight, the lowest effective doses are recommended.

Concomitant use of the medicinal product Olfen®-75 with systemic NSAIDs, including selective COX-2 inhibitors, should be avoided due to the lack of any synergistic benefit and the risk of additional adverse effects.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur during diclofenac use. Hypersensitivity reactions may also progress to Kounis syndrome, a severe allergic reaction that may lead to myocardial infarction. Symptoms include chest pain occurring in combination with an allergic reaction to diclofenac.

Nonsteroidal anti-inflammatory drugs, due to their pharmacodynamic properties, may mask signs and symptoms of infection. Prolonged use of analgesics may lead to medication-overuse headache, which cannot be treated by increasing the dose of these drugs.

Gastrointestinal (GI) tract effects. Gastrointestinal bleeding, ulcers, or perforation have been reported during treatment with all NSAIDs, including diclofenac, and may be fatal, occurring at any time during therapy, regardless of the presence or absence of prior warning symptoms or serious GI events in history. These events generally have more serious consequences in elderly patients. Sodium diclofenac should be used under medical supervision and with caution in patients with symptoms indicating gastrointestinal disorders, or with a history of gastric or intestinal ulcers, GI bleeding, or GI perforation. The risk of gastrointestinal bleeding is higher with increased NSAID doses, in patients with a history of ulcers, especially complicated by bleeding or perforation, and in elderly patients. If gastrointestinal bleeding or GI ulceration occurs during treatment with Olfen®-75, the drug should be discontinued.

In elderly patients, adverse reactions occur more frequently during NSAID use, particularly gastrointestinal bleeding and perforation, which may be fatal. To reduce the risk of gastrointestinal disturbances in patients with a history of ulcers, especially complicated by bleeding or perforation, in elderly patients, frail patients, or those with low body weight, the drug should be used at the lowest effective dose for the shortest possible duration. For such patients, as well as those regularly taking low-dose acetylsalicylic acid/aspirin or other drugs increasing the risk of GI adverse effects, combination therapy with agents providing mucosal protection (e.g., proton pump inhibitors or misoprostol) is advisable.

Patients with a history of gastrointestinal toxicity, especially elderly patients, should report any unusual abdominal symptoms (particularly gastrointestinal bleeding). Caution is also required in patients receiving 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 SSRIs.

The use of NSAIDs, including diclofenac, increases the risk of leakage from gastrointestinal anastomoses; careful medical monitoring and caution are required when using diclofenac after gastrointestinal surgery.

Hepatic effects. Patients with impaired liver function require careful medical supervision when prescribed sodium diclofenac, as their condition may worsen during treatment. During therapy with NSAIDs, including diclofenac, the levels of one or more liver enzymes may increase. Such changes were observed very commonly (approximately 15% of patients) in clinical trials with diclofenac but were rarely associated with clinical symptoms. In most cases, these elevations remain within borderline limits. Moderate increases above normal (≥ 3 to < 8 × ULN [upper limit of normal]) were frequently observed (in 2.5%), while significant elevations (≥ 8 × ULN) occurred in approximately 1%. Clinically apparent liver injury (e.g., eosinophilia, rash) developed in 0.5% of patients, in addition to elevated liver enzymes. Elevated enzyme concentrations were generally reversible after discontinuation of the drug.

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 medicinal product Olfen®-75 should be used with caution in patients with hepatic porphyria due to the potential risk of provoking an attack.

Renal effects. Because prostaglandins play an important role in maintaining renal blood flow, prolonged use of high doses of NSAIDs, including diclofenac, frequently (1–10%) leads to fluid retention, edema, and arterial hypertension.

Particular attention should be paid to patients with impaired cardiac or renal function, a history of arterial hypertension, elderly patients, patients receiving concomitant therapy with diuretics or drugs significantly affecting renal function, and patients with significant extracellular fluid volume depletion due to any cause, such as before or after major surgery. In such cases, monitoring of renal function is recommended. Discontinuation of therapy usually results in return to the pre-treatment state. Frequent and regular use of analgesics, especially combinations of several analgesic drugs, may lead to persistent kidney damage, with a risk of renal failure ("analgesic nephropathy").

Effects on skin and subcutaneous tissue. Very rarely, severe skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, sometimes fatal, may occur with NSAID use. The highest risk of these reactions occurs at the beginning of treatment; in most cases, these reactions appear within the first month of therapy. Olfen®-75 should be discontinued at the first signs of skin rash, mucosal lesions, or any other signs of hypersensitivity. As with other NSAIDs, diclofenac may rarely cause allergic reactions, including anaphylactic/anaphylactoid reactions, even in patients who have not previously taken it.

Patients with systemic lupus erythematosus and mixed connective tissue disease have an increased risk of aseptic meningitis.

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

Generally, diclofenac is not recommended for patients with cardiovascular disease (heart failure, ischemic heart disease, peripheral arterial disease) or uncontrolled arterial hypertension. If diclofenac use is necessary in patients with cardiovascular disease or uncontrolled arterial hypertension, or in those with significant risk factors for cardiovascular disease (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking), a careful risk/benefit assessment is required, and the drug should be prescribed at doses not exceeding 100 mg daily if treatment exceeds 4 weeks.

Since cardiovascular risks with diclofenac increase with higher doses and longer treatment duration, it should be used for the shortest possible time and at the lowest effective dose. The patient's need for diclofenac and response to therapy should be periodically reviewed, especially if treatment lasts longer than 4 weeks. Use with caution in patients aged 65 years and older.

For patients with a history of arterial hypertension and/or mild to moderate congestive heart failure, appropriate monitoring and recommendations are necessary, as fluid retention and edema have been reported with NSAID use, including diclofenac. Clinical and epidemiological data indicate that diclofenac use, particularly at high doses (150 mg/day) and over prolonged periods, slightly increases 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 disease, and/or cerebrovascular disease. If use is necessary, it may be considered only after careful risk/benefit assessment and at doses not exceeding 100 mg/day. A similar assessment should be performed before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Patients should be informed about signs and symptoms of serious arterial thromboembolic events (e.g., chest pain, dyspnea, weakness, speech disturbances), which may occur without prior warning symptoms. In such cases, immediate medical attention is required. The medicinal product is contraindicated in patients with congestive heart failure (NYHA functional class II–IV).

Hematological effects. Since NSAIDs may temporarily inhibit platelet aggregation, hematological parameters should be monitored during prolonged use of sodium diclofenac and other NSAIDs. Patients with coagulation disorders, hemorrhagic diathesis, or hematological abnormalities require close monitoring.

History of asthma. In patients with bronchial asthma, seasonal allergic rhinitis, nasal mucosal edema (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 ("analgesic intolerance," leukotriene asthma, aspirin-induced asthma), Quincke's edema, or urticaria occur more frequently than in other patients. Therefore, special precautions (readiness for emergency care) are recommended for such patients. This also applies to patients with allergies to other substances manifesting as skin reactions, pruritus, or urticaria.

Like other drugs that inhibit prostaglandin synthase activity, sodium diclofenac and other NSAIDs may provoke bronchospasm in patients with bronchial asthma or a history of bronchial asthma.

Female fertility. The medicinal product Olfen®-75 may affect female fertility and therefore is not recommended for women planning pregnancy. Consideration should be given to discontinuing the drug in women experiencing difficulty conceiving or undergoing infertility evaluation.

Lidocaine. Lidocaine administration should be performed only by healthcare professionals. As with other lidocaine-containing preparations, Olfen®-75 should be used with caution in patients with epilepsy, cardiac conduction disorders, or respiratory insufficiency.

Since Olfen®-75 contains lidocaine, it should be noted that using disinfectant solutions containing heavy metals at the injection site increases the risk of local reactions such as pain and swelling. Lidocaine has a pronounced arrhythmogenic effect; therefore, 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, first-degree AV block, intraventricular conduction disturbances, moderate liver and kidney dysfunction (creatinine clearance 10 mL/min), respiratory function disorders, epilepsy, increased seizure susceptibility, severe myasthenia gravis, after cardiac surgery, in patients with genetic predisposition to hyperthermia, debilitated patients, elderly patients, and when injecting into inflamed (infected) areas.

ECG monitoring is mandatory during lidocaine use. If sinus node dysfunction, PQ interval prolongation, QRS widening, or new arrhythmia occurs, the dose should be reduced or the drug discontinued. Before using lidocaine in cardiac conditions (hypokalemia reduces lidocaine efficacy), serum potassium levels should be normalized.

Other. Due to the presence of propylene glycol, Olfen®-75 may cause symptoms similar to those induced by alcohol consumption.

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. Diclofenac use may cause oligohydramnios due to fetal renal dysfunction; in addition, cases of arterial duct constriction have been reported.

The use of Olfen®-75, as with other medicinal products containing lidocaine hydrochloride monohydrate, is contraindicated during pregnancy.

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

Female fertility. The use of Olfen®-75 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 in those undergoing infertility evaluation. Based on animal studies, impairment of male reproductive function cannot be excluded. The relevance of these findings to humans has not been established.

Ability to affect reaction speed when driving or operating machinery.

Patients experiencing visual disturbances, dizziness, drowsiness, lethargy, increased fatigue, or other central nervous system disorders should refrain from driving or operating machinery.

Method of Administration and Dosage.

The dose is individually adjusted by a physician. The medicinal product should be used at the lowest effective doses for the shortest duration necessary, taking into account the treatment objective for each individual patient.

Due to the possibility of anaphylactic reactions, up to and including shock, after administration of the medicinal product Olfen®-75, the patient must remain under medical supervision for at least 1 hour, with emergency medical equipment and medications immediately available.

Olfen®-75 should be administered as intramuscular injections. To avoid nerve or other tissue damage at the injection site (which may lead to muscle weakness, paralysis, or reduced sensation), the following instructions must be observed. The usual single dose is the contents of 1 ampoule (i.e., 75 mg of sodium diclofenac), administered under aseptic conditions as a deep intramuscular injection once daily into the upper outer quadrant of the gluteal muscle. The solution should be used immediately after opening the ampoule. Any unused portion of the solution must be discarded.

In cases of severe pain (e.g., colic), as an exception, the medicinal product may be administered twice daily, with several hours between doses, and the injection site must be alternated. Parenteral administration of Olfen®-75 in combination with other dosage forms of Olfen® products (tablets, capsules, rectal capsules, gel, or patch) is permissible provided that the total daily dose of sodium diclofenac does not exceed 150 mg.

In acute migraine attacks, clinical experience is limited to cases where one 75 mg ampoule is administered, preferably immediately after using 100 mg suppositories 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 Olfen®-75 for treating migraine attacks for more than 1 day. If further treatment is required on subsequent days, the maximum daily dose should not exceed 150 mg (administered as divided doses in suppository form).

The duration of parenteral administration of Olfen®-75 should not exceed 2 days. If further treatment is needed, therapy may be continued with Olfen®-50 Lactab, Olfen®-100 CP Depocaps, or Olfen®-100 Rectocaps.

Olfen®-75 must not be used for intravenous injection or infusion.

Cardiovascular disease or significant cardiovascular risk factors. Diclofenac therapy is generally not recommended for patients with cardiovascular disease or uncontrolled arterial hypertension. If necessary, patients with cardiovascular disease, uncontrolled arterial hypertension, or significant cardiovascular risk factors should only receive diclofenac therapy after careful risk assessment and only at doses up to 100 mg daily if treatment duration exceeds 4 weeks (see section "Special Warnings and Precautions for Use").

Use of diclofenac in patients with renal impairment is contraindicated (GFR < 15 mL/min/1.73 m²). Specific studies in patients with renal dysfunction have not been conducted; therefore, no specific dosage recommendations can be provided. Diclofenac should be used with caution in patients with impaired renal function (see section "Special Warnings and Precautions for Use").

Use of diclofenac in patients with hepatic impairment is contraindicated (see section "Contraindications"). Specific studies in patients with hepatic dysfunction have not been conducted; therefore, no specific dosage recommendations can be provided. Diclofenac should be used with caution in patients with mild to moderate hepatic impairment (see section "Special Warnings and Precautions for Use").

Elderly patients. Dose adjustment of the initial dose is generally not required; however, caution is recommended, especially when prescribing for frail patients or those with low body weight.

Children. Not intended for use in children.

Overdose.

Diclofenac.

Symptoms. Typical clinical symptoms of sodium diclofenac overdose are not well defined. In case of overdose, symptoms may include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, restlessness, coma, drowsiness, tinnitus, confusion, loss of consciousness, or convulsions. In severe poisoning, acute renal failure and liver damage may occur. Overdose may also lead to arterial hypotension, respiratory depression, and cyanosis.

Treatment. Within one hour after ingestion of a potentially toxic amount of the drug, oral administration of activated charcoal should be considered. In addition, gastric lavage should be considered in adults within one hour after ingestion of a potentially toxic dose. Supportive measures and symptomatic treatment should be initiated to manage complications such as arterial hypotension, renal failure, convulsions, gastrointestinal mucosal irritation, and respiratory depression. Specific treatments such as forced diuresis, dialysis, or hemoperfusion are not particularly effective in eliminating NSAIDs due to their high plasma protein binding and extensive metabolism. Intravenous diazepam should be administered in cases of frequent or prolonged convulsions. Other interventions may be indicated depending on the patient's clinical condition. Treatment is symptomatic.

Lidocaine.

Symptoms. Numbness of the tongue and lips, agitation, euphoria, anxiety, blurred vision, tremor, depression, drowsiness, dizziness, confusion, respiratory depression or arrest, bradycardia, cardiac conduction disturbances, atrioventricular block, coma, vertigo, general weakness, decreased arterial pressure up to shock, tremor, tonic-clonic seizures, coma, collapse, and possible atrioventricular block. Initial symptoms of overdose in healthy individuals occur at blood lidocaine concentrations exceeding 0.006 mg/kg; seizures occur at 0.01 mg/kg.

Treatment. Discontinue administration of the drug, provide oxygen therapy, administer anticonvulsants, vasopressors (noradrenaline, mesaton), and in cases of bradycardia, anticholinergics (0.5–1 mg atropine). Endotracheal intubation, artificial ventilation, and resuscitation measures may be required. Dialysis is ineffective.

Adverse Reactions

If adverse effects occur, consult a physician. The list of possible adverse effects includes information on potential actions of active substances contained in the medicinal product, as well as data from other diclofenac dosage forms used for both short-term and long-term treatment.

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 heat, cold, or numbness in the extremities.

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, flickering "floaters", photophobia, conjunctivitis.

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

Cardiac and vascular 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, Kounis syndrome.

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

Gastrointestinal disorders: Abdominal pain, nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, flatulence, anorexia, gastritis, vomiting blood, gastrointestinal bleeding, hemorrhagic diarrhea, melena, gastric and intestinal ulcers (with or without bleeding or perforation), gastrointestinal perforation or gastrointestinal stenosis, which may lead to peritonitis (sometimes fatal, especially in elderly patients), colitis (including hemorrhagic colitis, ischemic colitis, and exacerbation of nonspecific 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, liver failure.

Skin and subcutaneous tissue disorders: Rash, urticaria, bullous rash, 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: Erectile dysfunction.

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

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 daily) and with prolonged use.

Visual disturbances such as blurred vision, visual obscurations, and diplopia may occur after use of NSAIDs and are usually reversible upon discontinuation of therapy. The most likely mechanism of visual disturbances is inhibition of prostaglandin synthesis and related compounds, which may impair retinal blood flow regulation and lead to visual disturbances. If such symptoms occur during treatment with diclofenac, an ophthalmological examination should be performed to rule out other possible causes.

Lidocaine. Allergic reactions such as urticaria, edema, bronchospasm, or dyspnea, and circulatory reactions have been reported infrequently. Systemic reactions such as dizziness, clouding of consciousness, somnolence, seizures, confusion, nausea, vomiting, bradycardia, arrhythmia, decreased arterial pressure up to shock may occur due to rapid administration (accidental intravenous injection, injection into tissue with high blood flow) or overdose.

Reporting suspected adverse reactions. All suspected adverse reactions and lack of therapeutic efficacy should be reported via the following link: https://aisf.dec.gov.ua/.

Shelf life: 5 years.

Storage after opening the ampoule: The ampoule contents must be used immediately after opening; any unused solution must be discarded.

Storage conditions:

Store at a temperature not exceeding 25 °C in the original package to protect from light.

Keep out of reach of children.

Incompatibility: The medicinal product Olfen®-75 must not be mixed with other injectable solutions.

Packaging: 2 ml in an ampoule, 5 ampoules per box.

Prescription category: Prescription only.

Manufacturer: Merckle GmbH.

Manufacturer’s address and place of business:

Ludwig-Merckle-Strasse 3, 89143 Blaubeuren, Germany.