Olfen®-50 lactab

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT Olfen®-50 Lactab (Olfen®-50 Lactab)

Composition:

Active substance: diclofenac sodium;

1 enteric-coated tablet contains 50 mg of sodium diclofenac;

Excipients: sodium starch glycolate, microcrystalline cellulose, sodium stearyl fumarate, colloidal anhydrous silicon dioxide, talc, hypromellose;

Enteric coating: methacrylic acid copolymer dispersion, triethyl citrate, talc;

Colored coating: hypromellose, titanium dioxide (E 171), talc, quinoline yellow (E 104), iron oxide yellow (E 172), macrogol 6000.

Pharmaceutical form. Enteric-coated tablets.

Main physicochemical characteristics: biconvex tablets, film-coated, yellowish-brown in color, with the imprint “mp” on one side and “O 50” on the other.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents.
ATC code M01AB05.

Pharmacological properties.

Pharmacodynamics.

The Olphen®-50 Lactab preparation contains sodium diclofenac—a nonsteroidal compound exhibiting anti-inflammatory, analgesic, and antipyretic effects. The primary mechanism of action of diclofenac, demonstrated under experimental conditions, is considered to be the inhibition of prostaglandin biosynthesis, which play a key role in the development of inflammation, pain, and elevated body temperature. In in vitro studies, sodium diclofenac at concentrations equivalent to those achieved during patient treatment did not suppress proteoglycan biosynthesis in cartilage tissue.

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

In post-traumatic and postoperative inflammation, Olphen®-50 Lactab rapidly reduces spontaneous pain and pain on movement, and also decreases inflammatory swelling and wound edema.

In clinical studies, the drug has also demonstrated a pronounced analgesic effect in moderate and severe non-rheumatic pain syndromes.

In primary dysmenorrhea, Olphen®-50 Lactab reduces pain symptoms and the intensity of menstrual bleeding.

Pharmacokinetics.

Absorption. After passing through the stomach, diclofenac is rapidly and completely absorbed from Olphen®-50 Lactab tablets, which are resistant to gastric juice. Although absorption occurs rapidly, its onset may be delayed due to the presence of a gastro-resistant coating on the tablet. After a single dose of one Olphen®-50 Lactab tablet, the maximum plasma concentration averages 1.5 µg/mL (5 µmol/L).

When the tablet is taken during or after a meal, its passage through the stomach is slowed (compared to administration on an empty stomach), but this does not negatively affect the total amount of active substance absorbed.

Distribution. Diclofenac binding to plasma proteins is 99.7%, primarily to albumin (99.4%). The observed volume of distribution is 0.12–0.17 L/kg.

Diclofenac penetrates into synovial fluid, where maximum drug concentration is reached 2–4 hours later than in plasma. The observed elimination half-life from synovial fluid is 3–6 hours. As a result, even 2 hours after administration, the concentration of the active substance in synovial fluid is higher than in plasma and remains at elevated levels for up to 12 hours.

Diclofenac has been detected at low concentrations (100 ng/mL) in the breast milk of one woman. The estimated amount of drug transferred to the infant via breast milk corresponds to a dose of 0.03 mg/kg/day.

Metabolism. Biotransformation of diclofenac occurs partially via glucuronidation of the unchanged molecule, but mainly through mono- and repeated hydroxylation and methoxylation, leading to the formation of several phenolic metabolites (3-hydroxy-, 4-hydroxy-, 5-hydroxy-, 4,5-dihydroxy-, and 3-hydroxy-4-methoxy-diclofenac), most of which are converted into glucuronide conjugates. Two of the phenolic metabolites formed are pharmacologically active, but to a lesser extent than sodium diclofenac itself.

Elimination. Total systemic clearance of diclofenac is 263 ± 56 mL/min (mean value ± SD). The terminal elimination half-life is 1–2 hours. The elimination half-life of four metabolites, including two pharmacologically active ones, is also short and ranges from 1–3 hours. The practically inactive metabolite 3-hydroxy-4-methoxy-diclofenac has a longer elimination half-life. Approximately 60% of the administered dose is excreted in urine as metabolites, with less than 1% of unchanged diclofenac excreted. The remainder of the administered dose is excreted as metabolites via bile into feces.

Pharmacokinetics in specific patient populations.

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

In patients with impaired renal function receiving therapeutic doses, accumulation of unchanged active substance is not expected, based on the drug's kinetics after single administration. When creatinine clearance is less than 10 mL/min, calculated steady-state concentrations of diclofenac metabolites are approximately four times higher than in healthy volunteers. Despite this, metabolites are ultimately excreted solely via bile.

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

Clinical characteristics.

Indications.

• Inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritides);
• Spinal pain syndromes;
• Rheumatic diseases of soft periarticular tissues;
• Acute gout attacks;
• Post-traumatic and postoperative pain syndromes associated with inflammation and edema, e.g. following dental or orthopedic procedures;
• Gynecological conditions associated with pain and inflammation, e.g. primary dysmenorrhea or adnexitis;
• As an adjunctive agent in severe inflammatory ENT disorders accompanied by pronounced pain, e.g. pharyngotonsillitis, otitis.

According to general therapeutic principles, the underlying disease should be treated with disease-modifying agents. Fever alone is not an indication for use of this medicinal product.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product;
• Active gastric or intestinal ulcer; gastrointestinal hemorrhage or perforation;
• History of gastrointestinal bleeding or perforation related to 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);
• As with other NSAIDs, diclofenac is contraindicated in patients in whom administration of ibuprofen, acetylsalicylic acid, or other NSAIDs induces attacks of bronchial asthma, angioneurotic edema, urticaria, acute rhinitis, nasal polyps, or other allergic symptoms;
• Inflammatory bowel diseases (e.g. Crohn’s disease or ulcerative colitis);
• Hepatic failure;
• Renal failure (glomerular filtration rate <15 mL/min/1.73 m²);
• 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;
• Treatment of perioperative pain in coronary artery bypass grafting (CABG) (or use of cardiopulmonary bypass);
• Third trimester of pregnancy.

Interaction with other medicinal products and other types of interactions.

When using the medicinal product Olfen®-50 Lactab and/or other diclofenac preparations, the following interactions may occur.

Litium, digoxin. Diclofenac may increase plasma concentrations of lithium and digoxin when used concomitantly with these medicinal products. Monitoring of lithium and digoxin serum levels is recommended.

Diuretics and other antihypertensive agents. As with other NSAIDs, co-administration of sodium diclofenac with diuretics or antihypertensive agents (e.g. beta-blockers, angiotensin-converting enzyme [ACE] inhibitors) may reduce the antihypertensive effect of these drugs (due to inhibition of vasodilatory prostaglandin synthesis). Such combinations should be used with caution, and blood pressure should be monitored in these patients, especially in the elderly. Adequate hydration is recommended. Renal function should also be monitored at the beginning and periodically during concomitant therapy, particularly when diuretics and ACE inhibitors are used, due to the increased risk of nephrotoxicity.

Agents 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 (see section "Special warnings and precautions for use").

Other NSAIDs, including selective cyclooxygenase-2 inhibitors, and corticosteroids. Concomitant use of diclofenac with other NSAIDs or corticosteroids may increase the frequency of gastrointestinal adverse effects (e.g. gastrointestinal bleeding or ulcers). Concomitant use of two or more NSAIDs should be avoided (see section "Special warnings and precautions for use").

Anticoagulants and antiplatelet agents. Caution should be exercised when using sodium diclofenac with anticoagulants and antiplatelet agents, as their combined use may increase the risk of bleeding (see section "Special warnings and precautions for use"). Although clinical studies have not demonstrated evidence of an effect of diclofenac on anticoagulant activity, there have been reports of increased bleeding risk in patients receiving diclofenac and anticoagulants simultaneously. Therefore, careful monitoring of patients receiving diclofenac and anticoagulants is recommended, and dose adjustment of anticoagulants may be necessary. 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 (see section "Special warnings and precautions for use").

Antidiabetic agents. Clinical studies have shown that sodium diclofenac can be administered together with oral antidiabetic agents without affecting their clinical efficacy. However, isolated reports of hypoglycemic and hyperglycemic reactions have been reported after administration of sodium diclofenac, requiring adjustment of antidiabetic agent doses. Therefore, monitoring of blood glucose levels is recommended during such combination therapy.

There have also been isolated reports of metabolic acidosis when used concomitantly with diclofenac, particularly in patients with pre-existing renal impairment.

Methotrexate. Diclofenac may inhibit renal tubular clearance of methotrexate, leading to elevated methotrexate levels. Caution should be exercised when prescribing NSAIDs, including diclofenac, less than 24 hours before or after methotrexate administration, as this may increase methotrexate blood concentration and enhance its toxic effects. Cases of severe toxicity have been reported when the interval between methotrexate and NSAID (including diclofenac) administration was within 24 hours. This interaction is mediated via accumulation of methotrexate due to impaired renal excretion in the presence of NSAIDs.

Cyclosporine and tacrolimus. Sodium diclofenac, like other NSAIDs, may increase the nephrotoxicity of cyclosporine or tacrolimus due to its effects on renal prostaglandins. Therefore, the medicinal product should be administered at lower doses in patients receiving cyclosporine or tacrolimus.

Antibacterial quinolones. Seizures may occur in patients receiving quinolone derivatives and NSAIDs concomitantly. Seizures may occur in patients both with and without a history of epilepsy or seizures. Therefore, caution should be exercised when considering the use of quinolones in patients already receiving NSAIDs.

Phenytoin. When phenytoin is used concomitantly with diclofenac, monitoring of plasma phenytoin concentrations is recommended due to the expected increase in phenytoin effect.

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

Cardiac glycosides. Concomitant use of cardiac glycosides and NSAIDs may exacerbate heart failure, reduce glomerular filtration rate (GFR), and increase serum glycoside levels.

Mifepristone. NSAIDs should not be used within 8–12 days after mifepristone administration, as NSAIDs may reduce the efficacy of mifepristone.

CYP2C9 inhibitors. Caution is required when co-administering diclofenac with CYP2C9 inhibitors (e.g. voriconazole, sulfaphenazole). This may lead to a significant increase in maximum plasma concentration and exposure to diclofenac.

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

Special precautions for use.

General

To minimize adverse effects, treatment should be initiated with the lowest effective dose for the shortest duration necessary to control symptoms.

Concomitant use of the medicinal product Olfen®-50 Lactab with systemic NSAIDs, such as selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to the lack of evidence for synergistic effects and the potential for additive adverse effects.

Placebo-controlled studies have shown an increased risk of thrombotic cardiovascular and cerebrovascular complications with the use of certain selective COX-2 inhibitors. A direct correlation between this risk and the selectivity of individual NSAIDs for COX-1/COX-2 has not been established. Due to the lack of comparative clinical data on long-term, high-dose diclofenac therapy, the possibility of a similar increased risk cannot be excluded. Therefore, a careful benefit-risk assessment should be performed before prescribing diclofenac to patients with clinically confirmed ischemic heart disease, cerebrovascular disorders, peripheral arterial occlusive disease, or significant risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking). Given this risk, the lowest effective dose should be used for the shortest possible duration of treatment.

NSAIDs affect the kidneys, causing fluid retention with edema and/or arterial hypertension. Therefore, diclofenac should be used with caution in patients with impaired cardiac function and other conditions predisposing to fluid retention. Caution is also advised in patients receiving concomitant diuretics or angiotensin-converting enzyme (ACE) inhibitors, or those prone to hypovolemia.

Adverse effects are generally more serious in elderly patients. Caution should be exercised when prescribing the drug to individuals aged 65 years and older. In particular, the lowest effective dose is recommended for frail elderly patients or those with low body weight.

As with other NSAIDs, allergic reactions, including anaphylactic/anaphylactoid reactions, may occur, even without prior exposure to diclofenac. Hypersensitivity reactions may also progress to Kounis syndrome, a severe allergic reaction that may lead to myocardial infarction. Symptoms of such a reaction include chest pain occurring in conjunction with an allergic reaction to diclofenac.

Olfen®-50 Lactab, like other NSAIDs, may mask signs and symptoms of infection.

Gastrointestinal effects

When using all NSAIDs (including selective COX-2 inhibitors), including diclofenac, cases of gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation have been reported. These events can be fatal and may occur at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal events. These events generally have more serious consequences in elderly patients. If gastrointestinal bleeding or ulceration occurs in patients receiving diclofenac, the drug should be discontinued.

When using NSAIDs, including diclofenac, medical supervision and special caution are mandatory in patients with symptoms indicating gastrointestinal disorders. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, including diclofenac, and in patients with a history of peptic ulcers, especially complicated by bleeding or perforation. Elderly patients more frequently experience adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

To reduce the risk of gastrointestinal toxicity, treatment should be initiated and maintained at the lowest effective doses. For such patients, as well as those requiring concomitant low-dose acetylsalicylic acid (ASA/aspirin) or other drugs increasing the risk of gastrointestinal adverse effects, consideration should be given to additional protective measures (e.g., proton pump inhibitors or misoprostol). 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., ASA), or selective serotonin reuptake inhibitors (see section "Interaction with other medicinal products and other forms of interaction").

The use of NSAIDs, including diclofenac, increases the risk of gastrointestinal anastomotic leakage; careful medical monitoring is necessary when using diclofenac after gastrointestinal surgery.

Hepatic effects

Close medical monitoring is required when Olfen®-50 Lactab is prescribed to patients with impaired liver function, as their condition may worsen.

When using NSAIDs, including diclofenac, levels of one or more liver enzymes may increase. Such elevations are usually reversible upon discontinuation of the drug.

This phenomenon was very frequently observed in clinical trials with diclofenac (approximately in 15% of patients), but rarely associated with clinical symptoms. Most of these cases involved borderline increases. Moderate elevations (≥3 to <8 times the upper limit of normal) were frequently observed (in 2.5% of cases), while marked elevations (≥8 times the upper limit of normal) occurred in approximately 1% of cases. Clinically evident liver injury associated with elevated liver enzymes occurred in 0.5% of cases in the aforementioned clinical trials.

During long-term treatment with Olfen®-50 Lactab, regular monitoring of liver function and liver enzyme levels is recommended as a precautionary measure. If liver function abnormalities persist or worsen, if clinical signs or symptoms of progressive liver disease or other manifestations (e.g., eosinophilia, rash) occur, Olfen®-50 Lactab should be discontinued.

In addition to elevated liver enzymes, rare cases of severe hepatic reactions have been reported, including jaundice, fulminant hepatitis, hepatic necrosis, and hepatic failure, which in some cases led to death.

Hepatitis may occur with diclofenac use without prodromal symptoms. Caution is required when Olfen®-50 Lactab is used in patients with hepatic porphyria, due to the potential risk of provoking an attack.

Renal effects

NSAIDs, including diclofenac, reduce prostaglandin levels, which are important for maintaining renal blood flow.

Since fluid retention, edema, and hypertension have been frequently (1–10%) reported during treatment with NSAIDs, including diclofenac, particular attention should be paid to patients with impaired cardiac or renal function, a history of arterial hypertension, elderly patients, patients receiving concomitant diuretic therapy or drugs significantly affecting renal function, and patients with substantial reduction in extracellular fluid volume for any reason, such as before or after major surgery (see section "Contraindications"). In such cases, monitoring of renal function is recommended as a precaution. Discontinuation of therapy usually leads to reversal to the pre-treatment state.

Skin effects

Serious skin reactions (some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) have been very rarely reported in association with the use of NSAIDs, including Olfen®-50 Lactab (see section "Adverse reactions"). The highest risk of these reactions occurs early in the course of treatment; reactions typically appear within the first month of therapy. Treatment with Olfen®-50 Lactab should be discontinued at the first appearance of skin rash, mucosal lesions, or any other signs of hypersensitivity.

Systemic lupus erythematosus (SLE) and mixed connective tissue disorders

Patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders have an increased risk of developing aseptic meningitis.

Cardiovascular and cerebrovascular effects

Diclofenac treatment is generally not recommended for patients with diagnosed cardiovascular diseases (heart failure, ischemic heart disease, peripheral arterial disease) or uncontrolled arterial hypertension.

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation and only at doses up to 100 mg daily for treatment courses exceeding 4 weeks. Since cardiovascular risks with diclofenac may increase with higher doses and longer treatment duration, it should be used for as short a period as possible and at the lowest effective dose. The need for diclofenac and the patient's response to therapy should be periodically reviewed, especially if treatment exceeds 4 weeks.

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

Diclofenac should be used with caution in patients receiving concomitant diuretics or ACE inhibitors or those at increased risk of hypovolemia.

Clinical trial data and epidemiological evidence suggest that the use of diclofenac, particularly at high doses (150 mg/day) and during prolonged treatment, may be associated with a small increased 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 should only be considered after careful benefit-risk assessment and at a dosage not exceeding 100 mg daily for no more than 4 weeks.

Patients should be informed about the possibility of serious thrombotic events (chest pain, dyspnea, weakness, speech disturbances) at any time during treatment. In such cases, immediate medical attention should be sought.

Hematological effects

With prolonged use of this drug, as with other NSAIDs, monitoring of a complete blood count is recommended.

Diclofenac may temporarily inhibit platelet aggregation. Close monitoring is required in patients with coagulation disorders, hemorrhagic diathesis, or hematological disorders.

History of asthma

Patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (e.g., nasal polyps), chronic obstructive pulmonary diseases, or chronic respiratory tract infections (especially those associated with allergic, rhinitis-like symptoms) are more likely to experience NSAID-related reactions, such as asthma exacerbation (so-called analgesic intolerance/analgesic-induced asthma), Quincke's edema, or urticaria. Therefore, special precautionary measures (readiness for emergency intervention) are recommended for such patients. This also applies to patients with allergic reactions to other substances, such as rash, pruritus, or urticaria.

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

Excipients

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

Use during pregnancy or breastfeeding.

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, cardiac malformations, and gastroschisis after use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increased from less than 1% to approximately 1.5%. This risk is believed to increase with higher drug doses and longer duration of therapy. In animal studies, administration of a prostaglandin synthesis inhibitor led to increased pre- and post-implantation losses and embryonic/fetal mortality. Furthermore, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various malformations, including cardiovascular defects, was observed.

From the 20th week of pregnancy, the use of diclofenac may cause oligohydramnios due to fetal renal dysfunction. This effect may occur soon after initiation of treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction after treatment in the second trimester, most of which resolved after treatment cessation. Therefore, sodium diclofenac should not be used during the first and second trimesters of pregnancy unless absolutely necessary. If sodium diclofenac is used by a woman attempting to conceive or during the first or second trimester of pregnancy, the dose should be minimal and treatment duration as short as possible.

Antenatal monitoring for oligohydramnios and arterial duct constriction may be advisable after diclofenac use for several days starting from the 20th week of pregnancy. If oligohydramnios or arterial duct constriction is detected, diclofenac should be discontinued.

Sodium diclofenac is contraindicated during the third trimester of pregnancy (see section "Contraindications") because all prostaglandin synthesis inhibitors may:

• expose the fetus to the following risks:

  • cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
  • renal dysfunction (see above);

• expose the mother and newborn to the following risks:

• possible prolongation of bleeding time — an effect related to inhibition of platelet aggregation, which may occur even with very low doses;

• inhibition of uterine contractions, leading to delayed or prolonged labor.

Breastfeeding

Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, to prevent adverse reactions in infants, this medicinal product should not be used during breastfeeding. If treatment is necessary, breastfeeding should be discontinued.

Fertility

Like other NSAIDs, Olfen®-50 Lactab may negatively affect female fertility and is therefore not recommended for women planning pregnancy. Consideration should be given to discontinuing the drug in women who are unable to conceive and in women undergoing infertility investigations.

Based on relevant animal studies, impairment of male reproductive function cannot be excluded. The relevance of these findings to humans has not been established.

Ability to influence reaction speed when driving vehicles or operating machinery.

Patients who experience visual disturbances, dizziness, vertigo, somnolence, lethargy, increased fatigue, or other central nervous system disturbances during treatment with Olfen®-50 Lactab should refrain from driving a vehicle or operating machinery.

Administration and Dosage

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

Adults

Tablets should preferably be taken before meals with liquid and must not be divided or chewed.

The usual initial daily dose of sodium diclofenac is 100–150 mg, i.e., 2–3 tablets of Olfen®-50 Lactab. In milder cases and during long-term therapy, a daily dose of 75–100 mg is usually sufficient (to achieve a 75 mg dose, use the medicinal product with the appropriate dosage strength). The daily dose is generally divided into 2–3 doses.

To prevent nocturnal pain and morning stiffness, daytime administration of Olfen®-50 Lactab may be combined with rectal suppositories before bedtime; however, the total daily dose of diclofenac must not exceed 150 mg.

In primary dysmenorrhea, the daily dose is individually adjusted and usually ranges from 50 to 150 mg. The initial dose may be 50–100 mg and, if necessary, may be increased over several menstrual cycles, but not exceeding 150 mg/day. Treatment should begin at the first signs of symptoms and continue for several days, depending on the clinical response.

The recommended maximum daily dose of Olfen®-50 Lactab is 150 mg.

Elderly Patients (aged 65 years and older)

Although the pharmacokinetics of Olfen®-50 Lactab are not clinically significantly altered in elderly patients, nonsteroidal anti-inflammatory drugs (NSAIDs) should be used with particular caution in this population due to their increased susceptibility to adverse reactions. Specifically, for frail elderly patients or those with low body weight, the lowest effective doses are recommended. Patients should also be monitored for gastrointestinal bleeding during NSAID therapy.

Cardiovascular Disease or Significant Risk Factors

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (such as hypertension, hyperlipidemia, diabetes, smoking) only after careful clinical evaluation. Since cardiovascular risks associated with diclofenac may increase with higher doses and longer treatment duration, it should be used for the shortest possible time and at the lowest effective dose. The need for continued diclofenac use and the patient's response to therapy should be regularly reviewed.

Patients with Renal Impairment

Diclofenac is contraindicated in patients with renal insufficiency (glomerular filtration rate <15 mL/min/1.73 m²).

No specific studies have been conducted in patients with renal impairment, and no dosage adjustment recommendations are available. Diclofenac should be used with caution in patients with moderate or severe renal impairment.

Patients with Hepatic Impairment

Diclofenac is contraindicated in patients with hepatic insufficiency.

No specific studies have been conducted in patients with hepatic impairment, and no dosage adjustment recommendations are available. Diclofenac should be used with caution in patients with moderate or severe hepatic impairment.

Children

Tablets with a 50 mg dose should not be administered to children due to the high content of active substance.

Overdose

Symptoms. The typical clinical symptoms of sodium diclofenac overdose are not well defined. In case of overdose, symptoms may include headache, nausea, vomiting, epigastric pain, gastrointestinal hemorrhage, diarrhea, dizziness, disorientation, agitation, coma, somnolence, tinnitus, or convulsions. In severe poisoning, acute renal failure and hepatic injury may occur.

Treatment. Management of acute NSAID poisoning (including diclofenac) consists of supportive and symptomatic therapy. This includes treatment of manifestations such as arterial hypotension, renal failure, seizures, gastrointestinal disturbances, and respiratory depression. Specific treatments such as forced diuresis, hemodialysis, or hemoperfusion are not particularly effective in eliminating NSAIDs due to their high plasma protein binding and extensive metabolism.

In case of overdose following ingestion of a potentially toxic dose, activated charcoal should be administered. If the overdose involves a potentially life-threatening dose, gastric lavage (induced emesis or stomach washing) should be performed.

Side effects

The following adverse reactions may occur with both long-term and short-term use of medicinal products containing sodium diclofenac.

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), sensation of warmth, coldness, or numbness of extremities.

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

Nervous system disorders: headache, dizziness, somnolence, fatigue, paresthesia, memory impairment, convulsions, restlessness, tremor, aseptic meningitis, taste disturbances, stroke, confusion, hallucinations, sensory disturbances, malaise.

Eye disorders: visual disturbances, blurred vision, diplopia, optic neuritis.

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

Cardiovascular disorders: palpitations, chest pain, myocardial infarction, heart failure, arterial hypertension, arterial hypotension, vasculitis, arrhythmia, bradycardia, Kounis syndrome.

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

Gastrointestinal disorders: nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia, gastritis, gastrointestinal bleeding, hematemesis, hemorrhagic diarrhea, melena, gastric and intestinal ulcers with or without bleeding, gastrointestinal stenosis or perforation (sometimes fatal, especially in elderly patients), which may lead to peritonitis; colitis (including hemorrhagic colitis, ischemic 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, hepatic disorders, fulminant hepatitis, hepatic necrosis, hepatic 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.

Renal and urinary disorders: fluid retention, edema, acute kidney injury (acute renal failure), hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, renal papillary necrosis.

Reproductive system disorders: 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 per day) and with prolonged treatment.

Visual disturbances

Visual disturbances such as impaired vision, worsening of vision, and diplopia are class effects of NSAIDs and are usually reversible upon discontinuation of the drug. The most likely mechanism of visual disturbances is inhibition of prostaglandin synthesis and other related compounds, which may disrupt regulation of retinal blood flow and thereby contribute to the development of visual disturbances. If such symptoms occur during treatment with diclofenac, an ophthalmological examination should be performed to rule out other possible causes.

Shelf life: 5 years.

Storage conditions: Store at a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging: 10 tablets in a blister; 2 blisters per carton.

Prescription status: Prescription only.

Manufacturer: Acino Pharma AG.

Manufacturer’s address and place of business:

Birsstrasse 2, 4253 Liestal, Switzerland.