Olphen®-100 sr depocaps

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Olfen®-100 SR Depocaps (Olfen®-100 SR Depocaps)

Composition:

Active substance: sodium diclofenac;

Each prolonged-release capsule contains sodium diclofenac 100 mg;

Excipients: lactose monohydrate, microcrystalline cellulose, sodium carboxymethylcellulose–microcrystalline cellulose, glyceryl trimyristate, titanium dioxide (E 171), aqueous dispersion of ammonio-methacrylate copolymer (type B), triethyl citrate, colloidal anhydrous silicon dioxide;

Capsule shell: gelatin, titanium dioxide (E 171), black iron oxide (E 172), red iron oxide (E 172), erythrosine (E 127).

Pharmaceutical form. Prolonged-release capsules.

Main physicochemical properties: hard gelatin capsules with a pink cap and white opaque body, marked with "100", containing white or almost white pellets.

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

Pharmacological properties.

Pharmacodynamics.

The medicinal product Olphen®-100 SR Depocaps contains sodium diclofenac—a non-steroidal compound exerting anti-inflammatory, analgesic, and antipyretic effects. The primary mechanism of action of diclofenac 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 inhibit 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 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®-100 SR Depocaps induced rapid reduction of spontaneous pain and pain on movement, as well as decreased inflammatory swelling and wound edema.

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

In primary dysmenorrhea, the drug Olphen®-100 SR Depocaps reduces pain symptoms and the intensity of menstrual bleeding.

Pharmacokinetics.

Absorption. After a single dose of 1 capsule of Olphen®-100 SR Depocaps, the maximum plasma concentration of diclofenac is reached within 4 hours, with a mean value of 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 mean plasma concentration of diclofenac 24 hours after administration of 1 capsule of Olphen®-100 SR Depocaps is 13 ng/mL (40 nmol/L).

After administration of 1 capsule of Olphen®-100 SR Depocaps once daily, the minimum drug concentrations are approximately 22 ng/mL (70 nmol/L).

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

Diclofenac penetrates into synovial fluid, where the maximum drug concentration is achieved 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 concentrations of the active substance in synovial fluid are higher than in plasma and remain at elevated levels for up to 12 hours.

Metabolism. Biotransformation of diclofenac occurs partially via glucuronidation of the unchanged molecule, but mainly through single and multiple hydroxylations and methoxylations, 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 further converted into glucuronide conjugates. Two of these phenolic metabolites are pharmacologically active, although 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 the two pharmacologically active ones, is also short, ranging from 1 to 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 diclofenac excreted unchanged. The remainder of the administered dose is excreted as metabolites via bile into feces.

Pharmacokinetics in specific patient groups. 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 pharmacokinetic profile 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. Nevertheless, 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.

Relief of pain and reduction of inflammation of varying degrees in different conditions, including:

• Joint disorders: rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute gout attacks;
• Acute musculoskeletal disorders such as periarthritis (e.g. periarthritis of the shoulder), tendinitis, tenosynovitis, bursitis;
• Other pathological conditions caused by trauma, including fractures, low back pain, sprains, dislocations, orthopedic, dental, and other minor surgical procedures.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product; acute gastric or intestinal ulcer; gastrointestinal hemorrhage or perforation; history of gastrointestinal bleeding or perforation associated with previous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs); active peptic ulcer disease/bleeding or recurrent peptic ulcer disease/bleeding in history; as with other NSAIDs, diclofenac is contraindicated in patients in whom administration of ibuprofen, acetylsalicylic acid, or other NSAIDs induces attacks of bronchial asthma, angioedema, 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; perioperative pain management in coronary artery bypass grafting (or use of cardiopulmonary bypass); third trimester of pregnancy.

Interaction with other medicinal products and other forms of interaction.

When using the medicinal product Olfen®-100 SR Depocaps and/or other diclofenac preparations, the following interactions may occur.

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

Diuretics and other antihypertensive agents. As with other NSAIDs, concomitant use of sodium diclofenac with diuretics or antihypertensive agents (e.g. beta-blockers, angiotensin-converting enzyme [ACE] inhibitors) may reduce the antihypertensive effect of these agents (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 elderly patients. Adequate fluid intake should be maintained. Renal function should be monitored at the beginning of concomitant therapy and periodically during treatment, particularly when diuretics and ACE inhibitors are used, due to the increased risk of nephrotoxicity (see section "Special precautions for use").

Medicinal products causing hyperkalemia. Concomitant therapy with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may be associated with increased serum potassium levels; therefore, more frequent monitoring of patients is recommended (see section "Special 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 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 precautions for use"). Although clinical studies have not demonstrated evidence of an effect of diclofenac on anticoagulant activity, reports have been received of increased bleeding risk in patients taking diclofenac and anticoagulants concomitantly. Therefore, careful monitoring of patients receiving diclofenac and anticoagulants simultaneously is recommended, and dose adjustment of anticoagulants may be necessary if required. 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 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 with concomitant use of diclofenac, particularly in patients with pre-existing renal impairment.

Metotrexate. 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. Serious cases of toxicity have been reported when the interval between methotrexate and NSAID (including diclofenac) administration was within 24 hours. This interaction is mediated by methotrexate accumulation 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 effect on renal prostaglandins. Therefore, the medicinal product should be administered at lower doses than in patients not receiving cyclosporine or tacrolimus.

Quinolone antibacterial agents. 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 administered concomitantly with diclofenac, monitoring of plasma phenytoin concentrations is recommended due to the expected increase in phenytoin effects.

Cholestyramine and colestipol. These agents may delay or reduce absorption of diclofenac. Therefore, it is recommended to administer diclofenac 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 glycoside levels in plasma.

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

CYP2C9 inhibitors. Caution is required when co-prescribing 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-prescribing 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, the lowest effective dose should be used for the shortest duration necessary to control symptoms.

Concomitant use of the medicinal product Olfen®-100 SR Depocaps with systemic NSAIDs, such as selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided due to lack of evidence for synergistic effect and potential for additive adverse effects.

Placebo-controlled trials 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 COX-1/COX-2 selectivity of individual NSAIDs has not been established. Due to the lack of comparable clinical trial data on long-term treatment with maximum doses of diclofenac, 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 treatment duration.

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.

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 include chest pain occurring in combination with an allergic reaction to diclofenac.

Olfen®-100 SR Depocaps, like other NSAIDs, may mask signs and symptoms of infection.

Elderly patients (aged 65 years and older). Caution is required when prescribing the drug to patients over 65 years of age. Although the pharmacokinetics of diclofenac are not significantly altered in elderly patients to a clinically relevant extent, nonsteroidal anti-inflammatory drugs should be used with particular caution in this population, as they are generally more susceptible to adverse reactions. Specifically, the lowest effective dose is recommended for frail elderly patients or those with low body weight. Patients should also be evaluated for gastrointestinal bleeding during NSAID therapy.

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

Medical monitoring and special caution are mandatory for patients receiving NSAIDs, including diclofenac, who present with symptoms suggesting gastrointestinal tract disorders. The risk of bleeding, ulceration, or perforation increases with higher NSAID doses, including diclofenac, and in patients with a history of peptic ulcers, particularly complicated by bleeding or perforation. Elderly patients are more likely to experience adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, which may be fatal.

To reduce the risk of such 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 that may increase gastrointestinal risk, consideration should be given to combination therapy with protective agents (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 ulceration 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 risk of gastrointestinal anastomotic leakage increases with NSAID use, including diclofenac. Close medical monitoring is required when diclofenac is used after gastrointestinal surgery.

Hepatic effects. Close medical monitoring is required when Olfen®-100 SR Depocaps is administered to patients with impaired liver function, as their condition may worsen. With NSAIDs, including diclofenac, levels of one or more liver enzymes may increase. This elevation is usually reversible upon discontinuation of the drug.

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

During long-term treatment with Olfen®-100 SR Depocaps, regular monitoring of liver function and liver enzyme levels is recommended. If liver function abnormalities persist or worsen, or if clinical signs or symptoms of progressive liver disease or other manifestations (e.g., eosinophilia, rash) occur, Olfen®-100 SR Depocaps 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, some of which were fatal.

Hepatitis may occur with diclofenac without prodromal symptoms. Caution is required when administering Olfen®-100 SR Depocaps to patients with hepatic porphyria, due to the potential to provoke an attack.

Diclofenac is contraindicated in patients with hepatic failure. No specific studies have been conducted in patients with impaired liver function, and no dose adjustment recommendations are available. Diclofenac should be used with caution in patients with mild or moderate hepatic impairment.

Renal effects. NSAIDs, including diclofenac, reduce prostaglandin levels, which are important for maintaining renal blood flow. Fluid retention, edema, and hypertension have been frequently (1–10%) reported during treatment with NSAIDs, including diclofenac. Therefore, special attention should be given to patients with cardiac or renal impairment, history of arterial hypertension, elderly patients, patients receiving concomitant diuretics or drugs that significantly affect renal function, and patients with significant reduction in extracellular fluid volume due to any cause (e.g., before or after major surgery) (see section "Contraindications"). As a precautionary measure, monitoring of renal function is recommended in such cases. Discontinuation of therapy usually results in return to the pre-treatment state.

Diclofenac is contraindicated in patients with renal failure (glomerular filtration rate <15 mL/min/1.73 m²). No specific studies have been conducted in patients with impaired renal function, and no dose adjustment recommendations are available. Diclofenac should be used with caution in patients with renal impairment.

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 with the use of NSAIDs, including Olfen®-100 SR Depocaps (see section "Adverse reactions"). The highest risk of these reactions occurs early in the course of treatment, with most cases appearing within the first month of therapy. Treatment with Olfen®-100 SR Depocaps 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 aseptic meningitis.

Cardiovascular and cerebrovascular effects. Diclofenac treatment is generally not recommended for patients with diagnosed cardiovascular 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 if treatment exceeds 4 weeks. Since cardiovascular risks with diclofenac may increase with higher doses and longer duration of treatment, it should be used for the shortest possible time and at the lowest effective dose. The need for diclofenac and the patient's response to therapy should be periodically reviewed, especially if treatment lasts longer than 4 weeks.

Appropriate monitoring and advice are necessary for patients with a history of arterial hypertension and/or mild to moderate congestive heart failure, as fluid retention and edema have been reported with NSAIDs, including diclofenac. Diclofenac should be used with caution in patients receiving concomitant diuretics or ACE inhibitors, or those at risk of hypovolemia.

Clinical and epidemiological data indicate that diclofenac use, particularly at high doses (150 mg/day) and during long-term treatment, may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Patients should be informed about the possibility of serious thrombotic events (chest pain, dyspnea, weakness, speech disturbances), which may occur without warning symptoms. In such cases, immediate medical attention should be sought.

Hematological effects. With prolonged use of this drug, as with other NSAIDs, monitoring of 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.

Respiratory effects (asthma history). In 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), reactions to NSAIDs such as asthma exacerbation (so-called analgesic intolerance/analgesic-induced asthma), Quincke's edema, or urticaria occur more frequently. 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 in 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.

The product contains lactose. This medicinal product should not be used by patients with rare hereditary forms of galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption.

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, congenital heart defects, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of cardiovascular malformations increases 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 has been associated with increased pre- and post-implantation loss and embryonic/fetal mortality. Furthermore, in animals treated with a prostaglandin synthesis inhibitor during organogenesis, an increased incidence of various malformations, including cardiovascular abnormalities, has been observed.

From the 20th week of pregnancy, use of diclofenac may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after initiation of treatment and is usually reversible upon discontinuation. Additionally, there have been reports of ductus arteriosus 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 as low as possible and the duration of treatment as short as possible. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after diclofenac use for several days starting from the 20th week of pregnancy. If oligohydramnios or ductus arteriosus 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 risks such as cardiopulmonary toxicity (premature constriction/closure of the ductus arteriosus and pulmonary hypertension), renal dysfunction (see above); and expose the mother and newborn to risks such as prolonged bleeding time (an effect related to inhibition of platelet aggregation, which may occur even with very low doses), and inhibition of uterine contractions leading to delayed or prolonged labor.

Breastfeeding. Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, to avoid 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®-100 SR Depocaps may negatively affect female fertility and is therefore not recommended for women attempting to conceive. Consideration should be given to discontinuing the medicinal product in women who are unable to conceive or 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 affect reaction speed when driving or operating machinery.

Patients who experience visual disturbances, dizziness, vertigo, somnolence, lethargy, increased fatigue, or other central nervous system disorders during treatment with Olfen®-100 SR Depocaps should refrain from driving or operating machinery.

Dosage and Administration

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

Adults

Olfen®-100 SR Depocaps should be taken during a meal. The capsules should be swallowed whole with a small amount of liquid and not chewed.

The usual daily dose is 1 capsule of Olfen®-100 SR Depocaps. In mild cases and during long-term treatment, this dose is generally sufficient. If a dose of 50 mg or 150 mg of sodium diclofenac is required, treatment with Olfen®-100 SR Depocaps should be combined with Olfen®-50 Lactab.

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

Elderly patients (aged 65 years and older). The medicinal product should be used with caution in these patients (see section "Special Warnings and Precautions for Use").

Cardiovascular diseases or significant risk factors. Diclofenac should only be prescribed after careful clinical evaluation (see section "Special Warnings and Precautions for Use").

Patients with renal impairment. The medicinal product is contraindicated in patients with renal insufficiency (glomerular filtration rate <15 ml/min/1.73 m²). There are no dosage adjustment recommendations; use with caution (see section "Special Warnings and Precautions for Use").

Patients with hepatic impairment. The medicinal product is contraindicated in patients with hepatic insufficiency. There are no dosage adjustment recommendations; use with caution (see section "Special Warnings and Precautions for Use").

Children

The medicinal product should not be used in children due to the high content of active substance.

Overdose

Symptoms. Typical clinical symptoms of sodium diclofenac overdose are not well known. In case of overdose, the following may occur: headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, diarrhea, dizziness, disorientation, excitation, coma, somnolence, tinnitus, or convulsions. In cases of severe poisoning, acute renal failure and liver damage are possible.

Treatment. Management of acute poisoning with NSAIDs (including diclofenac) consists of supportive and symptomatic therapy. This includes treatment of manifestations such as arterial hypotension, renal failure, convulsions, gastrointestinal disturbances, and respiratory depression. Specific treatments such as forced diuresis, hemodialysis, or hemoperfusion are not particularly effective for 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 overdose results from ingestion of a dose that poses a potential life-threatening risk, gastric lavage (induction of emesis or stomach washing) should be performed.

Adverse Reactions

The following adverse reactions may occur both during long-term and short-term use of medications containing sodium diclofenac. Adverse reactions are categorized by frequency as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data).

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

Immune system disorders: rare – hypersensitivity reactions, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock); very rare – angioedema (including facial swelling).

Psychiatric disorders: very rare – disorientation, depression, insomnia, nightmares, irritability, psychotic disorders.

Nervous system disorders: common – headache, dizziness; rare – somnolence, fatigue; very rare – paresthesia, memory impairment, convulsions, restlessness, tremor, aseptic meningitis, taste disturbances, stroke; frequency not known – confusion, hallucinations, sensory disturbances, malaise.

Eye disorders: very rare – visual disturbances, blurred vision, diplopia; frequency not known – optic neuritis.

Ear and labyrinth disorders: common – vertigo; very rare – tinnitus, hearing impairment.

Cardiovascular disorders: common – arterial hypertension; uncommon* – palpitations, chest pain, heart failure, myocardial infarction, arterial hypotension; very rare – vasculitis; frequency not known – Kounis syndrome.

Respiratory system disorders: rare – asthma (including dyspnea); very rare – pneumonitis.

Gastrointestinal disorders: common – nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, anorexia; rare – gastritis, gastrointestinal bleeding, hematemesis, hemorrhagic diarrhea, melena, gastric and intestinal ulcers with bleeding, gastrointestinal stenosis, perforation, or without such complications (sometimes fatal, especially in elderly patients), which may lead to peritonitis; very rare – 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: common – elevated transaminase levels; rare – hepatitis, jaundice, liver disorders; very rare – fulminant hepatitis, liver necrosis, liver failure.

Skin and subcutaneous tissue disorders: common – rash; rare – urticaria; very rare – 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: common – fluid retention, edema; very rare – acute kidney injury (acute renal failure), hematuria, proteinuria, interstitial nephritis, nephrotic syndrome, renal papillary necrosis.

Reproductive system disorders: very rare – impotence.

General disorders: rare – edema.

*Frequency data are based on long-term use at high doses (150 mg/day).

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 during 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 related compounds, which may disrupt retinal blood flow regulation and contribute to visual disturbances. If such symptoms occur during diclofenac treatment, an ophthalmological examination should be performed to rule out other possible causes.

Shelf life. 3 years.

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

Packaging.

10 capsules per blister, 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. Acino Pharma AG.

Manufacturer’s address and location of business operations.

Birsstrasse 2, 4253 Liesberg, Switzerland.