Olfen 100 SR depocaps prolonged-release capsules 100 mg 20 pcs.

Pharmacodynamics

The drug Olfen contains diclofenac sodium salt – a substance of non-steroidal structure, which exhibits anti-inflammatory, analgesic and antipyretic effects. The main mechanism of action of diclofenac, demonstrated in experimental conditions, is considered to be inhibition of the biosynthesis of prostaglandins, which play an important role in the occurrence of inflammation, pain and fever. In in vitro studies, diclofenac sodium in concentrations equivalent to those achieved in the treatment of patients did not inhibit the biosynthesis of proteoglycans in cartilage tissue.

In rheumatic diseases, the anti-inflammatory and analgesic properties of Olfen provide the most pronounced clinical effect, characterized by a significant reduction in the severity of symptoms such as pain at rest and with movement, morning stiffness and swelling of the joints, as well as improved joint function.

In post-traumatic or postoperative inflammation, Olfen caused a rapid reduction in the severity of spontaneous pain and pain during movement, and also reduced inflammatory swelling and wound edema.

The pronounced analgesic effect of Olfen was demonstrated in clinical trials for moderate and severe non-rheumatic pain syndrome.

Olfen reduces the pain and intensity of menstrual bleeding in primary dysmenorrhea.

When used concomitantly for the treatment of postoperative pain, diclofenac sodium significantly reduces the need for opioids.

Olfen-75 exhibits a pronounced analgesic effect in moderate and severe pain of non-rheumatic origin 15-30 minutes after administration. The drug Olfen-75 can be used for the initial therapy of inflammatory and degenerative rheumatic diseases, as well as for the treatment of pain caused by non-rheumatic inflammation.

Pharmacokinetics

Absorption. Olfen-50 Lactab. After passing through the stomach, diclofenac is rapidly and completely absorbed from Olfen-50 Lactab tablets, which are resistant to the action of gastric juice. Although absorption is rapid, its onset may be delayed due to the presence of a gastro-resistant coating on the tablet. After a single dose of 1 Olfen-50 Lactab tablet, C _max in blood plasma is on average 1.5 μg/ml (5 μmol/l).

If you take a diclofenac tablet during or after a meal, its passage through the stomach is slowed down (compared to taking it on an empty stomach), but this does not have a negative effect on the amount of active substance absorbed.

Olfen-75. The average volume of distribution of diclofenac sodium is 0.12-0.17 l/kg. The binding of the drug to plasma proteins is more than 99%. After i / m administration, C _max in blood plasma is achieved after 10-20 minutes. The therapeutic concentration of Olfen-75 in blood plasma is 0.7-2 μg/ml. Repeated administration of the drug does not cause any changes in the kidneys. If the recommended intervals between doses of the drug are observed, its cumulation in the body is not observed.

Olfen-100 SR Depocaps. After a single dose of 1 capsule of Olfen-100 SR Depocaps, C _max of diclofenac in blood plasma is reached after 4 hours, and its average value is 0.5 μg/ml (1.6 μmol/l). Food intake has no clinically significant effect on the absorption and systemic bioavailability of the drug.

The average concentration of diclofenac in the blood plasma 24 hours after taking 1 capsule of Olfen-100 SR Depocaps is 13 ng / ml (40 nmol / l). After taking 1 capsule of Olfen-100 SR Depocaps once a day, the lowest concentration level at the end of the dosing period is about 22 ng / ml (70 nmol / l).

Distribution: Diclofenac is 99.7% bound to plasma proteins, mainly albumin (99.4%). The apparent volume of distribution is 0.12-0.17 l/kg body weight.

Diclofenac penetrates into the synovial fluid, where C _max is reached 2-4 hours later than in blood plasma. The observed T _½ from the synovial fluid is 3-6 hours. Due to this, even 2 hours after administration of the drug, the concentration of the active substance in the synovial fluid is higher than in blood plasma, and remains 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, AUC levels after oral or rectal administration of the drug are approximately 2 times lower than the AUC observed after parenteral administration of an equivalent dose of the drug.

The biotransformation of diclofenac occurs partly by glucuronidation of the unchanged molecule, but mainly by single and multiple hydroxylation and methoxylation, leading to the formation of several phenolic metabolites (3-hydroxy-, 4-hydroxy-, 5-hydroxy-, 4,5-hydroxy- and 3-hydroxy-4-methoxydiclofenac), most of which are converted to glucuronide conjugates. Two of the phenolic metabolites formed are pharmacologically active, but to a lesser extent than diclofenac sodium itself.

Elimination. The total systemic clearance of diclofenac is 263 ± 56 ml/min (mean ± standard deviation). The terminal T½ _is 1-2 h. The T½ _of 4 metabolites, including 2 pharmacologically active ones, is also short and is 1-3 h. The practically inactive metabolite, 3-hydroxy-4-methoxydiclofenac, has a longer T½ _. About 60% of the dose of the drug is excreted in the urine as metabolites and 1% of diclofenac – in unchanged form. The remaining part of the administered dose is excreted in metabolized form with bile, and then with feces.

Pharmacokinetics in individual patient groups. After taking the drug, no significant differences in absorption, metabolism and excretion of the drug related to the age of the patients were noted.

In patients with impaired renal function, when using standard or individually selected doses, no increase in the amount of unchanged active substance was detected. At a creatinine clearance of 10 ml/min, the estimated equilibrium concentrations of diclofenac metabolites are approximately 4 times higher than in healthy volunteers. Despite this, the metabolites are ultimately excreted only with bile.

In patients with impaired liver function (chronic hepatitis, compensated cirrhosis), the kinetics and metabolism of diclofenac are similar to those in patients with normal liver function.

Olfen-50 Lactab:

• inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritis);
• pain syndromes in the spine;
• rheumatic diseases of extra-articular soft tissues;
• acute attacks of gout;
• post-traumatic and postoperative pain syndromes accompanied by inflammation and swelling, for example, after dental and orthopedic interventions;
• gynecological diseases accompanied by pain and inflammation, such as primary dysmenorrhea or adnexitis;
• as an adjuvant for severe inflammatory diseases of the ENT organs, accompanied by severe pain syndrome, for example, with pharyngotonsillitis, otitis.

According to general therapeutic principles, the underlying disease should be treated with basic therapy. Fever in itself is not an indication for the use of the drug.

Olfen-75. The drug is used in the form of i / m injections for the following 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 surgeries;
• severe migraine attacks.

Olfen-100 SR Depocaps. Pain relief and reduction of inflammation of varying degrees in various conditions, including:

• joint pathology: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute attacks of gout;
• acute musculoskeletal diseases such as periarthritis (e.g., shoulder scapular periarthritis), tendinitis, tendovaginitis, bursitis;
• other pathological conditions caused by injuries, including fractures, back pain, sprains, dislocations, orthopedic, dental and other minor surgical interventions.

According to general therapeutic principles, the underlying disease should be treated with basic therapy. Fever in itself is not an indication for the use of the drug.

The dose is selected individually. The drug should be used in the minimum effective doses for the shortest period of time, taking into account the goal of treatment in each specific patient.

The drug is not used in children.

Olfen-50 Lactab. Adults. The initial daily dose of diclofenac sodium is usually 100-150 mg, i.e. 2-3 tablets of Olfen-50 Lactab. In less severe cases and with long-term therapy, it is usually sufficient to use 75-100 mg/day (a dose of 75 mg is used in the appropriate dosage). The daily dose is usually divided into 2-3 doses.

To prevent night pain and morning stiffness, taking Olfen-50 Lactab during the day can be combined with the administration of rectal capsules before bedtime, but the maximum daily dose of diclofenac should not exceed 150 mg.

In primary dysmenorrhea, the daily dose is selected individually and is usually 50-150 mg. The initial dose may be 50-100 mg and, if necessary, may be increased over several menstrual cycles, but not higher than 200 mg/day. Treatment should be started at the first symptoms and continued for several days, depending on the dynamics of symptom regression.

Elderly patients. Although the pharmacokinetics of Olfen-50 Lactab are not impaired to any clinically significant extent in elderly patients, NSAIDs should be used with caution in such patients, as they are generally more susceptible to adverse reactions. In particular, it is recommended to use the minimum effective dose for debilitated elderly patients or those with low body weight; patients should also be monitored for gastrointestinal bleeding during treatment with NSAIDs.

Olfen-75. Before using the drug Olfen-75, it is mandatory to conduct a skin test for hypersensitivity to lidocaine hydrochloride. Olfen-75 should be used as an intramuscular injection. Due to the possible occurrence of anaphylactic reactions, up to the development of shock, after the administration of the drug Olfen-75, the patient should be under supervision for at least 1 hour, and the necessary means for providing emergency medical care should be available.

The usual single dose of the drug is the contents of 1 ampoule (i.e. 75 mg of diclofenac sodium), which is administered intramuscularly once a day 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 should be discarded.

In case of severe pain (e.g. colic), the drug can be administered 2 times a day with an interval of several hours, necessarily changing the injection site. The combination of parenteral administration of Olfen-75 with other dosage forms of Olfen drugs (tablets, capsules, rectal capsules, gel or patch) is permissible provided that the maximum daily dose of diclofenac sodium does not exceed 150 mg.

In the setting of a migraine attack, clinical experience is limited to cases with the initial use of one 75 mg ampoule, the dose should be administered if possible immediately after the use of 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 data available on the use of Olfen-75 for the treatment of migraine attacks for more than one day.

The duration of parenteral use of Olfen-75 should not exceed 2 days. If necessary, treatment can be continued with Olfen-50 Lactab, Olfen-100 CP Depocaps.

Olfen-75 is not used for intravenous injection/infusion.

Elderly patients: No dose adjustment is required, but elderly patients should be monitored closely due to the possible occurrence of adverse reactions.

Patients with renal or hepatic impairment: No dose reduction is required in patients with mild to moderate renal or hepatic impairment.

Olfen-100 SR Depocaps. Adults. Olfen-100 SR Depocaps should be taken before meals. Swallow the capsules without chewing, with a glass of water.

The daily dose of the drug is usually 1 capsule of Olfen-100 SR Depocaps. In mild cases and with long-term treatment, the appointment of 1 capsule of Olfen-100 SR Depocaps per day is usually sufficient. If it is necessary to use a dose of 50 mg or 150 mg of diclofenac sodium, treatment with Olfen-100 SR Depocaps should be combined with taking Olfen-50 Lactab.

In cases where the symptoms of the disease are most pronounced at night or in the morning, it is advisable to take Olfen-100 SR Depocaps at night.

Olfen-50 Lactab, Olfen-100 SR Depocaps:

• hypersensitivity to the active or auxiliary substances of the drug;
• history of gastrointestinal bleeding or perforation related to previous NSAID treatment;
• active ulcer/bleeding or history of recurrent ulcer/bleeding (2 or more separate episodes of established ulcer or bleeding);
• Like other non-steroidal anti-inflammatory drugs, diclofenac is also contraindicated in patients in whom the use of ibuprofen, acetylsalicylic acid or other non-steroidal anti-inflammatory drugs provokes attacks of bronchial asthma, angioedema, urticaria or acute rhinitis;
• inflammatory bowel diseases (such as Crohn’s disease or ulcerative colitis);
• liver failure;
• renal failure;
• congestive heart failure (NYHA II-IV);
• CHD in patients with angina pectoris or previous myocardial infarction;
• cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks;
• peripheral artery disease;
• treatment of perioperative pain during coronary artery bypass grafting (or the use of a cardiopulmonary bypass machine).

Olfen-75:

• hypersensitivity to the active substances or any components of the drug;
• hypersensitivity to lidocaine or other amide local anesthetics;
• history of seizures caused by the use of lidocaine;
• WPW-s-m;
• porphyria;
• myasthenia gravis;
• anticoagulant therapy;
• history of gastrointestinal bleeding or perforation related to previous NSAID treatment;
• active peptic ulcer/bleeding or history of recurrent peptic ulcer/bleeding (2 or more separate episodes of established ulceration or bleeding);
• like other nonsteroidal anti-inflammatory drugs, diclofenac is also contraindicated in patients in whom the use of ibuprofen, acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs provokes attacks of bronchial asthma, angioedema, urticaria or acute rhinitis;
• inflammatory bowel diseases (such as Crohn’s disease or ulcerative colitis);
• liver failure;
• renal failure;
• congestive heart failure (NYHA II-IV);
• CHD in patients with angina pectoris or previous myocardial infarction;
• cerebrovascular disease in patients who have had a stroke or have episodes of transient ischemic attacks;
• peripheral artery disease;
• contraindicated for the treatment of perioperative pain during coronary artery bypass grafting (or when using a cardiopulmonary bypass machine);
• AV block II and III degree, sick sinus syndrome, Adams-Stokes syndrome, severe arterial hypotension, bradycardia, cardiogenic or hypovolemic shock, complete transverse heart block;
• high risk of postoperative bleeding, blood clotting disorders, incomplete hemostasis, hematopoiesis disorders, or cerebrovascular bleeding.

In case of adverse reactions, you should consult a doctor.

The following adverse reactions may occur with both long-term and short-term use of the drug.

From the blood and lymphatic system: thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic), agranulocytosis.

Immune system disorders: hypersensitivity reactions (anaphylactic and anaphylactoid reactions, including hypotension and shock), angioedema (including facial swelling), sensation of heat, cold or numbness of the extremities.

Psychiatric: disorientation, depression, insomnia, nightmares, irritability, psychotic disorders.

From the nervous system: headache, dizziness, drowsiness, paresthesia, memory impairment, convulsions, anxiety, tremor, aseptic meningitis, taste disturbance, stroke, sensory disturbances, fatigue, confusion, hallucinations, general malaise.

For Olfen-75 also: loss of consciousness up to coma, muscle cramps, motor block, dysarthria, dysphagia, nystagmus.

From the organ of vision: visual impairment, blurred vision, diplopia, optic neuritis.

For Olfen-75 also: blinking of “flies”, photophobia, conjunctivitis.

From the side of the organs of hearing and vestibular apparatus: vertigo, tinnitus, hearing impairment.

For Olfen-75 also: hyperacusis.

Cardiovascular system: palpitations, chest pain, myocardial infarction, heart failure, hypertension, hypotension, vasculitis, arrhythmia, bradycardia.

For Olfen-75 also: slowing of cardiac conduction, transverse heart block, cardiac arrest, collapse, tachycardia, hot flashes.

Respiratory: asthma (including shortness of breath), bronchospasm, pneumonitis, respiratory depression or arrest.

For Olfen-75 also: rhinitis.

On the part of the digestive system: abdominal pain, nausea, vomiting, diarrhea, abdominal cramps, dyspepsia, flatulence, anorexia, gastritis, gastrointestinal bleeding, vomiting with blood, hemorrhagic diarrhea, melena, gastric and intestinal ulcers with or without bleeding and 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, 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 eruptions, eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), exfoliative dermatitis, alopecia, photosensitivity, purpura, allergic purpura, pruritus.

On the part of the kidneys and urinary tract: fluid retention in the body, edema, acute renal failure, hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, renal papillary necrosis.

From the reproductive system: impotence.

General disorders: edema.

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/day) and with long-term use.

For Olfen-75 also: general disorders and reactions at the injection site: general malaise, malignant hyperthermia, weakness, reactions at the site of i / m injection, such as pain, a slight burning sensation or tissue induration, swelling, necrosis at the injection site, abscess at the injection site.

General: To minimize side effects, treatment should be initiated at the lowest effective dose for the shortest period of time necessary to control symptoms.

The use of Olfen with systemic NSAIDs, such as selective COX-2 inhibitors, should be avoided due to the lack of any evidence of a synergistic effect and due to potential additive side effects.

Caution is advised in elderly patients. In particular, it is recommended to use the lowest effective dose in frail elderly patients with a low body mass index.

As with other non-steroidal anti-inflammatory drugs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac.

Due to its pharmacodynamic properties, diclofenac sodium, like other NSAIDs, may mask the signs and symptoms of infection.

Gastrointestinal effects: Gastrointestinal bleeding (hemorrhage, melena), ulceration or perforation, which can be fatal and may occur at any time during treatment with or without warning symptoms or a previous history of serious gastrointestinal events, have been reported with all NSAIDs, including diclofenac. These events are usually more severe in the elderly. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.

As with other NSAIDs, including diclofenac, medical supervision and special caution are required in patients with symptoms suggestive of gastrointestinal disorders. The risk of gastrointestinal bleeding, ulceration or perforation increases with increasing dose of NSAIDs, including diclofenac.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which can be fatal.

To reduce the risk of such gastrointestinal toxicity, treatment should be initiated and maintained at the lowest effective dose. For such patients, as well as those requiring concomitant use of medicinal products containing low doses of acetylsalicylic acid or other medicinal products likely to increase the risk of gastrointestinal adverse effects, additional protective measures (e.g. proton pump inhibitors or misoprostol) should be considered. Patients with a history of gastrointestinal toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially gastrointestinal bleeding). Precautions should also be taken in patients receiving concomitant medicinal products that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g. warfarin), antithrombotic agents (e.g. acetylsalicylic acid) or selective serotonin reuptake inhibitors.

Effects on the liver. Careful medical supervision is required when Olfen is prescribed to patients with impaired liver function, as their condition may worsen.

As with other nonsteroidal anti-inflammatory drugs, including diclofenac, the level of one or more liver enzymes may increase.

During long-term treatment with Olfen, regular monitoring of liver function and liver enzyme levels is prescribed as a precautionary measure. If liver function abnormalities persist or worsen and if clinical signs or symptoms that may be associated with progressive liver disease or if other manifestations are observed (e.g. eosinophilia, rash), the use of Olfen should be discontinued. The course of diseases such as hepatitis may occur without prodromal symptoms. Precautions are necessary if Olfen is to be used in patients with hepatic porphyria due to the possibility of provoking an attack.

Renal effects. Since fluid retention and oedema have been reported with NSAIDs, including diclofenac, special care should be taken in patients with impaired cardiac or renal function, a history of hypertension, the elderly, patients receiving diuretic therapy or drugs that significantly affect renal function, and in individuals with significant depletion of extracellular fluid volume for any reason, such as before or after major surgery. In such cases, monitoring of renal function is recommended as a precautionary measure. Discontinuation of therapy usually results in a return to pre-treatment status.

Skin effects. In connection with the use of NSAIDs, including diclofenac sodium, serious skin reactions (some of them fatal) have been reported in very rare cases, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis. Patients are at greatest risk of developing these reactions at the beginning of therapy: the onset of the reaction is noted in most cases during the first month of treatment. The use of the drug Olfen should be discontinued at the first appearance of skin rashes, mucosal lesions or any other signs of hypersensitivity.

Systemic lupus erythematosus and mixed connective tissue diseases: Patients with systemic lupus erythematosus and mixed connective tissue diseases may be at increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects: Appropriate monitoring and advice should be given to patients with a history of hypertension and/or mild to moderate congestive heart failure, as fluid retention and oedema have been reported in association with the use of NSAIDs, including diclofenac.

Clinical trial data and epidemiological data suggest that the use of diclofenac, especially at high doses (150 mg/day) and with long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke).

Diclofenac is not recommended for use in patients with uncontrolled hypertension, congestive heart failure, stable coronary artery disease, peripheral arterial disease and/or cerebrovascular disease, and should only be used after careful risk/benefit assessment and only at doses not exceeding 100 mg/day. A similar assessment should be made before initiating long-term treatment in patients with risk factors for cardiovascular events (e.g. hypertension, hyperlipidemia, diabetes mellitus and smokers).

Patients should be informed of the possibility of serious thrombotic events (chest pain, shortness of breath, weakness, speech disorders), which may occur at any time. In this case, a doctor should be consulted immediately.

Effect on hematological parameters. With prolonged use of this drug, as with other NSAIDs, monitoring of complete blood counts is recommended.

Olfen may temporarily inhibit platelet aggregation. Patients with impaired hemostasis, hemorrhagic diathesis, or hematological disorders should be carefully monitored.

History of asthma. Patients with bronchial asthma, seasonal allergic rhinitis, nasal mucosal edema (i.e. nasal polyps), chronic obstructive pulmonary disease or chronic respiratory tract infections (especially those associated with allergic rhinitis-like symptoms) are more likely to experience reactions to NSAIDs, such as exacerbation of asthma (so-called analgesic intolerance/analgesic asthma), angioedema, urticaria. Therefore, special precautions (emergency preparedness) are recommended for such patients. This also applies to patients with allergic reactions to other substances, such as rash, itching, urticaria.

Like other drugs that inhibit prostaglandin synthetase activity, diclofenac sodium and other nonsteroidal anti-inflammatory drugs can provoke the development of bronchospasm when used in patients with bronchial asthma or a history of asthma.

Olfen-75. Since Olfen-75 contains lidocaine hydrochloride, a skin test for individual sensitivity must be performed before use. Lidocaine can only be administered by medical professionals.

Like other lidocaine-containing drugs, the drug should be prescribed with caution to patients with epilepsy, impaired cardiac conduction, and respiratory failure.

It should also be noted that when treating the injection site with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of soreness and swelling increases.

Since lidocaine has a pronounced arrhythmogenic effect, the drug should be used with caution in individuals with complaints of arrhythmia in the past.

Use with caution in patients with moderate heart failure, moderate arterial hypotension, incomplete AV block, impaired intraventricular conduction, moderate liver and kidney function (creatinine clearance 10 ml/min), impaired respiratory function, epilepsy, increased convulsive readiness, myasthenia gravis, after heart surgery, with a genetic predisposition to hyperthermia, debilitated patients and elderly patients; when injecting into an inflamed (infected) area.

ECG monitoring is mandatory when using lidocaine. In case of sinus node dysfunction, prolongation of the PQ interval, widening of the QRS complex, or the development of a new arrhythmia, the dose should be reduced or the drug should be discontinued.

Before using lidocaine for heart disease (hypokalemia reduces the effectiveness of lidocaine), it is necessary to normalize the level of potassium in the blood.

Olfen-75 contains 1 mmol (23 mg) of sodium per dose, i.e. it is practically sodium-free.

May cause symptoms similar to those caused by alcohol consumption due to the presence of propylene glycol.

Olfen-100 SR Depocaps. The drug contains lactose. Patients with rare hereditary forms of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug.

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo-fetal development. Epidemiological data indicate an increased risk of miscarriage, cardiac malformations and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. This risk is believed to increase with increasing dose and duration of therapy.

Diclofenac sodium should not be used in the first and second trimesters of pregnancy unless clearly necessary. If diclofenac sodium is used by a woman attempting to conceive, or during the first or second trimester of pregnancy, the dose should be kept as low and the duration of treatment as short as possible.

Diclofenac sodium is contraindicated in the third trimester of pregnancy due to the fact that all prostaglandin synthesis inhibitors can:

expose the fetus to the following risks:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and development of pulmonary hypertension);
• renal dysfunction, which progresses to renal failure with oligohydramnios;

expose mother and child to the following risks:

• possible prolonged bleeding – an effect associated with inhibition of platelet aggregation, which can occur even when taking very low doses of the drug;
• Inhibition of uterine muscle contractions, which leads to delay or prolongation of labor.

The use of Olfen-75, like other drugs containing lidocaine hydrochloride, is contraindicated during pregnancy.

Breastfeeding. Due to the penetration of NSAIDs into breast milk, diclofenac sodium is not prescribed to women who are breastfeeding. If such treatment is absolutely necessary, breastfeeding should be discontinued.

Female fertility. Olfen may affect female fertility and is therefore not recommended for women attempting to conceive. Discontinuation of the drug should be considered in women who are unable to conceive or who are undergoing investigation for infertility.

Patients with visual disturbances, dizziness, drowsiness, lethargy or increased fatigue or other CNS disorders should refrain from driving or operating machinery.

When using Olfen and/or other diclofenac preparations, the following interactions may occur.

Lithium, digoxin. When used simultaneously with these drugs, diclofenac may increase the plasma concentrations of lithium and digoxin. It is recommended to monitor the plasma levels of lithium and digoxin.

Diuretics and other antihypertensive drugs. As with other non-steroidal anti-inflammatory drugs, the concomitant use of diclofenac sodium with diuretics or antihypertensive drugs (e.g. β-blockers, ACE inhibitors) may result in a reduction in the antihypertensive effect of these drugs. Such combinations should be used with caution, and blood pressure should be monitored in these patients, especially in the elderly. Patients should be adequately hydrated and renal function should be monitored at the start of concomitant therapy and periodically during treatment, especially when diuretics and ACE inhibitors are used, given the increased risk of nephrotoxicity.

Since concomitant use with potassium-sparing diuretics may lead to hyperkalemia, it is necessary to monitor the level of potassium in the blood plasma.

Other NSAIDs, selective COX-2 inhibitors and corticosteroids. Concomitant use of diclofenac and other non-steroidal anti-inflammatory drugs or glucocorticoids may increase the risk of gastrointestinal bleeding or ulceration. The concomitant use of two or more NSAIDs should be avoided.

Anticoagulants and antiplatelet agents: It is recommended to take diclofenac sodium with anticoagulants and antiplatelet agents with caution, as their combined use may increase the risk of bleeding.

Although clinical studies have not shown evidence of an effect of diclofenac on the action of anticoagulants, there have been isolated reports of a risk of hemorrhagic complications in patients taking diclofenac and these drugs simultaneously. Therefore, careful monitoring of patients taking diclofenac and these drugs is recommended and, if necessary, adjustment of the anticoagulant dose. Like other nonsteroidal anti-inflammatory drugs, diclofenac in high doses can reversibly inhibit platelet aggregation.

Selective serotonin reuptake inhibitors: Concomitant use of systemic NSAIDs and selective serotonin reuptake inhibitors may increase the risk of gastrointestinal bleeding.

Antidiabetic drugs: Clinical studies have shown that diclofenac sodium can be administered concomitantly with oral hypoglycemic drugs, as it does not affect their clinical effects. However, there have been isolated reports of hypo- and hyperglycemic reactions after the administration of diclofenac sodium, which required a change in the dose of hypoglycemic drugs.

In this regard, it is recommended to monitor blood glucose levels during such combination therapy.

Methotrexate. Diclofenac may inhibit the renal tubular clearance of methotrexate, leading to increased methotrexate levels. Caution should be exercised when NSAIDs, including diclofenac, are administered less than 24 hours before methotrexate, as this may increase the blood concentration of methotrexate and increase its toxicity. Serious toxicity has been reported when the interval between administration of methotrexate and NSAIDs, including diclofenac, was within 24 hours. This interaction is mediated by accumulation of methotrexate as a result of impaired renal excretion in the presence of NSAIDs.

Cyclosporine and tacrolimus: Diclofenac sodium, like other NSAIDs, may increase the nephrotoxicity of cyclosporine or tacrolimus due to its effects on renal prostaglandins. Therefore, the drug should be prescribed in doses lower than in patients not receiving cyclosporine or tacrolimus.

Quinolone antibiotics. Convulsions may occur in patients receiving quinolones and NSAIDs. Convulsions may occur in patients with or without a history of epilepsy and seizures. Therefore, caution should be exercised when considering the use of quinolones in patients already receiving NSAIDs.

Phenytoin: 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 the exposure of phenytoin.

Colestipol and cholestyramine. These drugs may delay or reduce the absorption of diclofenac. Therefore, it is recommended to administer diclofenac at least 1 hour before or 4-6 hours after colestipol/cholestyramine.

Drugs that induce drug-metabolizing enzymes. Drugs that induce enzymes, such as rifampicin, carbamazepine, phenytoin, St. John’s wort (Hypericum perforatum), are theoretically capable of reducing the plasma concentration of diclofenac.

Cardiac glycosides. Concomitant use of cardiac glycosides and nonsteroidal anti-inflammatory drugs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma glycoside levels.

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

Potent CYP 2C9 inhibitors: Caution is advised when co-administering diclofenac with potent CYP 2C9 inhibitors (e.g. voriconazole), which may lead to a significant increase in plasma Cmax and diclofenac exposure due to inhibition of diclofenac metabolism _.

Drugs known to cause hyperkalemia. Concomitant treatment with potassium-sparing diuretics, ciclosporin, tacrolimus or trimethoprim may be associated with increases in plasma potassium levels, therefore patients should be monitored more frequently.

Diclofenac resinate. Due to the fact that the resinate is the main ion exchanger, it is generally necessary to take into account the inhibition of absorption of other drugs for oral administration.

The following interactions may also be observed when using Olfen-75, associated with the retention of lidocaine hydrochloride. β-adrenergic blockers, propranolol and others, as well as cimetidine, peptidine, bupivacaine, quinidine sulfate, disopyramide, amitriptyline, nortriptyline, chlorpromazine, imipramine increase the level of lidocaine in the blood plasma, reducing its hepatic metabolism.

In case of intoxication with cardiac glycosides, lidocaine may increase the severity of AV block. Lidocaine reduces the severity of the cardiotonic effect of cardiac glycosides.

When used simultaneously with antiarrhythmic agents (amiodarone, verapamil, quinidine sulfate, etc.) or anticonvulsants (hydantoin derivatives), the cardiodepressive effect is enhanced.

When used simultaneously with sedatives and hypnotics, an increase in the depressing effect on the CNS is possible.

Phenytoin enhances the cardiodepressive effect of lidocaine.

When used simultaneously with procainamide, delusions and hallucinations are possible.

Lidocaine may enhance the effects of drugs that cause neuromuscular blockade, as the latter reduce the conductivity of nerve impulses.

Ethyl alcohol enhances the inhibitory effect of lidocaine on breathing.

Norepinephrine, mexiletine – increases the toxicity of lidocaine (decreases the clearance of lidocaine).

Isadrin and glucagon – increases the clearance of lidocaine.

Midazolam moderately increases the concentration of lidocaine in the blood.

MAO inhibitors, aminazine, bupivacaine, amitriptyline, nortriptyline, imipramine – when used in combination with lidocaine, the risk of developing arterial hypotension increases and the local anesthetic effect of the latter is prolonged.

Narcotic analgesics (e.g. morphine) – when used in combination with lidocaine, the analgesic effect of narcotic analgesics is enhanced, but respiratory depression is also increased.

Prenylamine – increases the risk of developing torsades de pointes ventricular arrhythmia.

Propafenone – possible increase in the duration and severity of CNS side effects.

Rifampicin (digitalis glycosides) – a possible decrease in the concentration of lidocaine in the blood.

Polymyxin B – respiratory function should be monitored.

Procainamide – possible hallucinations.

In case of intoxication with cardiac glycosides, lidocaine may increase the severity of AV block.

Vasoconstrictors (adrenaline, methoxamine, phenylephrine) – when used in combination with lidocaine, they help slow down the absorption of lidocaine and prolong the effect of the latter.

Guanadrel, guanethidine, mecamylamine, trimetaphan – when used in combination for spinal and epidural anesthesia, the risk of severe hypotension and bradycardia increases.

Acetazolamide, thiazide and loop diuretics – when used in combination with lidocaine, cause hypokalemia and reduce the effect of the latter.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin and others) – when used in combination with lidocaine, increase the risk of bleeding.

Typical clinical symptoms of diclofenac sodium overdose are not known. In case of overdose, headache, nausea, epigastric pain, disorientation, agitation, coma, drowsiness, vomiting, gastrointestinal bleeding, diarrhea, dizziness, tinnitus or convulsions may occur. In case of serious poisoning, acute respiratory distress syndrome and liver damage are possible.

Treatment. In case of complications such as hypotension, renal failure, convulsions, irritation of the gastrointestinal mucosa and respiratory depression, supportive and symptomatic treatment is indicated. Specific therapy, such as forced diuresis, hemodialysis or hemoperfusion, is of little value in the elimination of NSAIDs, given the high level of binding of these drugs to plasma proteins and extensive metabolism.

In case of overdose resulting from a potentially toxic dose of the drug, activated charcoal should be used. If the overdose resulted from a dose that is potentially life-threatening, the stomach should be emptied (induce vomiting or perform gastric lavage).

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 heart block, comatose state, dizziness, general weakness, decrease in blood pressure up to the development of shock, tremor, tonic-clonic convulsions, coma, collapse, possible AV block. The first symptoms of overdose in healthy people occur when the concentration of lidocaine in the blood exceeds 0.006 mg/kg, convulsions – at 0.01 mg/kg.

Treatment: discontinuation of the drug, oxygen therapy, anticonvulsants, vasoconstrictors (noradrenaline, mezaton), with bradycardia – anticholinergics (0.5-1 mg of atropine). Intubation, mechanical ventilation, and resuscitation measures are possible. Dialysis is ineffective.

At a temperature not exceeding 25°C.