INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ORTOPHEN (ORTOPHEN)

Composition:

Active substance: diclofenac;

One tablet contains sodium diclofenac equivalent to 100 % substance 25 mg;

Excipients: lactose monohydrate; sucrose; povidone; potato starch; stearic acid; coating acrylic-iz yellow 93O38159 (containing: methacrylic acid copolymer (type C), talc, titanium dioxide (E 171), triethyl citrate, quinoline yellow (E 104), colloidal anhydrous silicon dioxide, sodium bicarbonate, sodium lauryl sulfate, yellow iron oxide (E 172), Ponceau 4R (E 124)).

Dosage form. Enteric-coated tablets.

Main physicochemical properties: round, biconvex tablets with a film coating ranging from light yellow to yellow. When broken and examined under a magnifying glass, a core surrounded by a continuous layer is visible.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Acetic acid derivatives and related substances. ATC code M01AB05.

Pharmacological Properties.

Pharmacodynamics.

Ortofen contains sodium diclofenac and is a nonsteroidal anti-inflammatory drug (NSAID) with pronounced analgesic, anti-inflammatory, and antipyretic effects. The main mechanism of action is inhibition of prostaglandin biosynthesis (prostaglandin synthetase, cyclooxygenase), which play a key role in the development of inflammation, pain, and fever.

In vitro, at concentrations equivalent to those achieved in humans, diclofenac does not inhibit proteoglycan biosynthesis in cartilage tissue.

Ortofen tablets, due to their rapid absorption, are suitable for the treatment of acute conditions associated with pain and inflammation, where a rapid onset of action (within 30 minutes) is desirable. In post-traumatic pain and inflammation, diclofenac rapidly relieves both spontaneous pain and pain on movement, as well as reduces swelling at the site of inflammation and wound edema.

In addition, the active substance may alleviate pain and reduce bleeding in primary dysmenorrhea. Diclofenac also provides analgesic effects in other conditions associated with moderate to severe pain.

Pharmacokinetics.

Absorption.

Diclofenac is rapidly and completely absorbed. Absorption begins immediately after administration, and the amount of absorbed substance corresponds to that absorbed following administration of an equivalent dose of sodium diclofenac. Administration with food does not affect the total amount of diclofenac absorbed, although the onset and rate of absorption may be slightly delayed.

Bioavailability.

Approximately half of the administered diclofenac undergoes metabolism during the first pass through the liver (first-pass effect); the area under the concentration-time curve (AUC) after oral administration is approximately half of that obtained after administration of an equivalent parenteral dose.

The pharmacokinetic characteristics of the drug do not change with repeated administration. Accumulation does not occur when the recommended dosage regimen is followed.

Distribution.

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

Diclofenac penetrates into synovial fluid, where its maximum concentration is reached 2–4 hours after peak plasma levels are achieved. The apparent half-life in synovial fluid is 3–6 hours. Two hours after peak plasma concentrations are reached, the concentration of the active substance in synovial fluid becomes higher than in plasma and remains so for up to 12 hours.

Biotransformation.

Biotransformation of diclofenac occurs partially via glucuronidation of the intact molecule, but mainly through single and multiple hydroxylations and methoxylations, leading to the formation of several phenolic metabolites, most of which form conjugates with glucuronic acid. Two of these phenolic metabolites are biologically active, but significantly less so than diclofenac.

Elimination.

The total systemic clearance of diclofenac from plasma is 263±56 mL/min (mean value ± standard deviation). The terminal half-life in plasma is 1–2 hours. The half-life in plasma of four metabolites, including two pharmacologically active ones, is also short and ranges from 1–3 hours. One practically inactive metabolite has a much longer half-life.

Approximately 60% of the administered dose is excreted in urine as glucuronide conjugates of the intact molecule and as metabolites, most of which are also converted into glucuronide conjugates. Less than 1% of diclofenac is excreted unchanged. The remainder of the administered dose is excreted in bile and feces as metabolites.

Pharmacokinetics in specific patient groups.

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

Patients with renal impairment. The pharmacokinetics of a single dose in patients with impaired renal function do not indicate any accumulation of unchanged active substance under normal dosing regimens.

In patients with creatinine clearance less than 10 mL/min, theoretical steady-state plasma concentrations of hydroxylated metabolites were approximately four times higher than in healthy subjects. However, ultimately, these metabolites are excreted via bile.

Patients with liver disease. In patients with chronic hepatitis or compensated cirrhosis of the liver, pharmacokinetic parameters and diclofenac metabolism are similar to those in patients without liver disease.

Clinical characteristics.

Indications.

Inflammatory and degenerative forms of rheumatic diseases (rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, spondyloarthritides);
Pain syndromes of spinal origin;
Rheumatic diseases of periarticular soft 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 conditions of ENT organs accompanied by pain, e.g., pharyngotonsillitis, otitis.

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

Contraindications.

Hypersensitivity to the active substance or to any of the other components of the medicinal product;
Ortofen, like other nonsteroidal anti-inflammatory drugs (NSAIDs), is contraindicated in patients who experience attacks of bronchial asthma, angioedema, urticaria, or acute rhinitis, nasal polyps, or other allergic symptoms in response to ibuprofen, acetylsalicylic acid, or other NSAIDs;
Acute gastric or intestinal ulcer and/or duodenal ulcer, gastrointestinal bleeding or perforation;
Gastrointestinal disease; gastrointestinal hemorrhage or perforation;
History of gastrointestinal bleeding or perforation associated with prior treatment with nonsteroidal anti-inflammatory drugs (NSAIDs);
Active peptic ulcer disease/bleeding or recurrent peptic ulcer disease/bleeding (two or more separate episodes of confirmed ulcer or bleeding);
Inflammatory bowel diseases (e.g., Crohn’s disease or ulcerative colitis);
Hepatic insufficiency;
Renal insufficiency;
Congestive heart failure of functional class II–IV according to NYHA (New York Heart Association) classification;
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;
Not to be used for treatment of perioperative pain in coronary artery bypass grafting (or when using cardiopulmonary bypass);
Third trimester of pregnancy.

Special safety precautions.

General warnings.

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

Concomitant use of Ortofen and other systemically acting NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, should be avoided, as there is no evidence of synergistic benefit and an increased risk of additional adverse effects.

Caution is required when administering to patients over 65 years of age. In particular, the lowest effective doses are recommended for physically frail elderly patients or patients with below-normal body weight.

To reduce the risk of gastrointestinal ulceration, bleeding, or perforation—which may occur at any time during NSAID therapy, regardless of COX-2 selectivity and even in the absence of prior warning symptoms or predisposing factors—the lowest effective dose should be used for the shortest possible duration.

Ortofen should be used only under strict medical supervision and only if absolutely indicated in patients with gastrointestinal disorders, impaired liver function, or suspected history of gastric or intestinal ulcer.

The effect of NSAIDs on the kidneys may lead to fluid retention and edema and/or arterial hypertension. Therefore, diclofenac should be used with caution in patients with cardiac disorders or other conditions predisposing to fluid retention. Caution is also advised in patients concurrently using diuretics or angiotensin-converting enzyme (ACE) inhibitors or those at increased risk of hypovolemia.

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

Like other NSAIDs, Ortofen, due to its pharmacodynamic properties, may mask signs and symptoms of infection.

According to standard approaches to the treatment of infectious-inflammatory diseases, etiologic agents should also be used. Isolated elevation of body temperature is not an indication for use of this medicinal product.

Ortofen tablets contain lactose. Therefore, they should not be administered to patients with rare hereditary forms of galactose intolerance, glucose-galactose malabsorption syndrome, or severe lactase deficiency.

The medicinal product contains sugar, which should be considered in patients with diabetes mellitus.

Gastrointestinal effects.

For all NSAIDs, including diclofenac, gastrointestinal bleeding (hematemesis, melena), ulceration, or perforation—potentially fatal—may occur at any time during treatment, with or without preceding symptoms, or in patients with a history of serious gastrointestinal events. These events are generally most dangerous in elderly patients. If such complications develop in patients receiving Ortofen, the drug should be discontinued.

As with other NSAIDs, including diclofenac, careful medical monitoring and special caution are required when prescribing Ortofen to patients with symptoms suggesting gastrointestinal disorders or a history of gastric or intestinal ulcer, bleeding, or perforation.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, including diclofenac, and in patients with a history of peptic ulcer (especially if complicated by bleeding or perforation) and in elderly patients (cases may be fatal).

To reduce the risk of gastrointestinal toxicity, treatment in such patients should be initiated and maintained at the lowest effective dose. For such patients, and for those requiring concomitant use of acetylsalicylic acid or other drugs increasing 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 inform their physician of any unusual abdominal symptoms (particularly gastrointestinal bleeding). Caution is advised when prescribing to patients concurrently using drugs that may increase the risk of ulceration or bleeding, such as systemic corticosteroids, anticoagulants (e.g., warfarin), antiplatelet agents (e.g., acetylsalicylic acid), or selective serotonin reuptake inhibitors (SSRIs).

NSAIDs, including diclofenac, may be associated with an increased risk of gastrointestinal anastomotic insufficiency. Careful medical monitoring and caution are recommended when using diclofenac after gastrointestinal surgery.

Hepatic effects.

Ortofen should be prescribed under continuous medical supervision in patients with impaired liver function, as their condition may worsen.

As with other NSAIDs, including diclofenac, elevations in one or more liver enzymes may occur. This has been observed very frequently with diclofenac, but rarely with clinical symptoms. In most cases, enzyme levels rise to borderline values. Elevations are often mild, while marked increases occur in approximately 1% of cases. Elevation of liver enzymes is associated with clinical signs of liver injury in 0.5% of cases. Enzyme elevations are usually reversible upon discontinuation of the drug.

It should be noted that Ortofen is recommended only for short-term treatment (not more than 2 weeks). In cases of prolonged diclofenac use, precautionary measures include regular monitoring of liver function and liver enzyme levels. The drug should be discontinued if liver dysfunction or worsening occurs, if clinical signs or symptoms suggest liver disease, or if other symptoms (e.g., eosinophilia, rash) appear. Liver disease such as hepatitis may develop without prodromal symptoms.

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

Diclofenac should be used with caution in patients with hepatic porphyria due to the risk of provoking an attack.

Renal effects.

Prolonged use of high doses of NSAIDs, including diclofenac, frequently (1–10%) leads to edema and arterial hypertension.

Particular caution is required in patients with impaired cardiac or renal function, history of arterial hypertension, elderly patients, patients concurrently using diuretics or drugs significantly affecting renal function, and patients with marked reduction in extracellular fluid volume (e.g., pre-/post-surgery). Renal function should be monitored when prescribing Ortofen in such cases. Patient status usually normalizes after discontinuation of therapy.

Skin effects.

Very rarely, serious skin reactions (in some cases fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported with NSAIDs, including Ortofen. The highest risk occurs early in treatment, usually within the first month. Ortofen should be discontinued at the first signs of rash, mucosal lesions, or any other signs of hypersensitivity.

SLE and mixed connective tissue diseases.

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

Cardiovascular and cerebrovascular effects.

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

An increased risk of thrombotic and cerebrovascular complications has been observed with selective COX-2 inhibitors. It is currently unclear whether this risk directly correlates with COX-1/COX-2 selectivity of individual NSAIDs. As there are no long-term data on high-dose diclofenac treatment for comparison, such an increased risk cannot be excluded. Until such data are available, the risk-benefit ratio should be carefully assessed before prescribing diclofenac to patients with clinically confirmed ischemic heart disease, cerebrovascular disorders, peripheral arterial occlusive disease, or significant risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Diclofenac may be prescribed to patients with significant cardiovascular risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes mellitus, smoking) only after careful clinical evaluation. As cardiovascular risks of diclofenac may increase with dose and duration of treatment, it should be used for the shortest possible duration and at the lowest effective dose. The need for diclofenac and response to therapy should be periodically reviewed.

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

Patients should be informed about the possibility of serious thrombotic events (chest pain, dyspnea, weakness, speech disturbances) that may occur at any time. In such cases, immediate medical attention is required.

Hematological effects.

Ortofen is recommended only for short-term treatment. If prolonged use is required, regular monitoring of the hemogram is recommended, as with other NSAIDs.

Like other NSAIDs, diclofenac may transiently inhibit platelet aggregation; therefore, patients with coagulation disorders, hemorrhagic diathesis, or hematological disorders should be carefully monitored.

History of bronchial asthma.

In patients with bronchial asthma, seasonal allergic rhinitis, nasal mucosal swelling (e.g., nasal polyps), chronic obstructive pulmonary disease (COPD), or chronic respiratory infections (especially with symptoms resembling allergic rhinitis), adverse effects such as exacerbation of bronchial asthma (so-called analgesic intolerance or analgesic-induced asthma), Quincke’s edema, or urticaria occur more frequently with NSAIDs than in other patients. Therefore, special precautions (readiness for emergency intervention) are recommended for such patients. This also applies to patients with allergic reactions to other drugs, e.g., rash, pruritus, urticaria.

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

Fertility.

Like other NSAIDs, Ortofen may affect female fertility and is therefore not recommended for women planning pregnancy. Use of this drug should be discontinued in women who are infertile or undergoing infertility investigations.

Interaction with other medicinal products and other types of interactions.

The following interactions have been observed with Ortofen and/or other doses and formulations of diclofenac.

Lithium. Diclofenac may increase plasma lithium concentrations when used concomitantly. Monitoring of serum lithium levels is recommended.

Digoxin. Diclofenac may increase plasma digoxin concentrations when used concomitantly. Monitoring of serum digoxin levels is recommended.

Diuretics and antihypertensive agents. Concomitant use of NSAIDs, including diclofenac, with diuretics or antihypertensive agents (e.g., beta-blockers, ACE inhibitors) may reduce their antihypertensive effect by inhibiting vasodilatory prostaglandin synthesis. Therefore, such combinations should be used with caution, and blood pressure should be periodically monitored, especially in elderly patients. Adequate fluid intake should be ensured, and renal function should be monitored after initiation of combination therapy and regularly thereafter, particularly when diuretics and ACE inhibitors are used due to increased risk of nephrotoxicity.

Agents causing hyperkalemia. Concomitant use with potassium-sparing diuretics, cyclosporine, tacrolimus, or trimethoprim may increase serum potassium levels; therefore, potassium levels should be monitored more frequently.

Other NSAIDs, including selective cyclooxygenase-2 inhibitors and corticosteroids. Concomitant use of diclofenac with other systemically acting NSAIDs or corticosteroids may increase the frequency of gastrointestinal adverse reactions and the risk of gastrointestinal bleeding or ulceration. Concomitant use of two or more NSAIDs should be avoided.

Anticoagulants and antiplatelet agents. Use with caution, as concomitant use with diclofenac may increase the risk of bleeding. There are isolated reports of increased bleeding risk in patients receiving diclofenac and anticoagulants. Therefore, continuous monitoring is recommended to ensure no dosage adjustments of anticoagulants are needed. Like other NSAIDs, diclofenac at high doses may transiently inhibit platelet aggregation.

Selective serotonin reuptake inhibitors (SSRIs). Concomitant use of systemically acting NSAIDs, including diclofenac, with SSRIs increases the risk of gastrointestinal bleeding.

Antidiabetic agents. Diclofenac may be used concomitantly with oral antidiabetic agents without affecting their clinical efficacy. However, isolated reports of hyperglycemia and hypoglycemia requiring dose adjustment of antidiabetic agents have occurred. Therefore, as a precaution, blood glucose levels should be monitored during combination therapy.

Methotrexate. Diclofenac may inhibit renal tubular clearance of methotrexate, leading to increased methotrexate levels. NSAIDs, including diclofenac, should be used with caution and not less than 24 hours before or after methotrexate therapy, as methotrexate concentrations may increase, enhancing its toxicity.

Cyclosporine. Diclofenac, like other NSAIDs, may increase cyclosporine nephrotoxicity due to effects on renal prostaglandin synthesis. Therefore, diclofenac should be used at lower doses than in patients not receiving cyclosporine.

Quinolone antibiotics. Isolated reports of convulsions have been associated with concomitant use of quinolones and NSAIDs. This may occur in patients with or without a history of epilepsy or seizures. Therefore, caution is advised when considering quinolone use in patients already receiving NSAIDs.

Potent CYP2C9 inhibitors. Use diclofenac with caution when combined with CYP2C9 inhibitors (e.g., sulfaphenazole, voriconazole), as this may lead to a significant increase in plasma concentration and effect of diclofenac due to inhibition of its metabolism.

Phenytoin. Monitoring of plasma phenytoin concentrations is recommended when used concomitantly with diclofenac due to possible increased phenytoin effects.

Tacrolimus. Concomitant use of NSAIDs with tacrolimus may increase the risk of nephrotoxicity.

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 cholestyramine/colestipol.

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

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

Special precautions for use.

Use during pregnancy or breastfeeding.

Pregnancy

Studies on the use of diclofenac in pregnant women have not been conducted.

Starting from the 20th week of pregnancy, use of Ortofen may cause oligohydramnios due to fetal renal dysfunction. Impairment of kidney function may occur soon after initiation of treatment and is usually reversible upon discontinuation of therapy. Starting from the 20th week of pregnancy, prenatal monitoring for oligohydramnios may be advisable after taking Ortofen for several days. Treatment with Ortofen should be discontinued if oligohydramnios is detected.

Ortofen may be used during the first and second trimesters of pregnancy only if the potential benefit to the mother outweighs the possible risk to the fetus, and only at the lowest effective dose. The duration of treatment should be as short as possible. As with other NSAIDs, use of Ortofen during the third trimester of pregnancy is contraindicated due to the risk of inhibition of uterine contractions and premature closure of the ductus arteriosus in the fetus.

Inhibition of prostaglandin synthesis may have adverse effects on pregnancy and/or embryonic/fetal development.

If Ortofen is used by women attempting to conceive or during the first trimester of pregnancy, the dose should be kept as low as possible and the duration of treatment as short as possible.

During the third trimester of pregnancy, all inhibitors of prostaglandin synthesis may affect:

the fetus:

cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
renal dysfunction, which may progress to renal failure with oligohydramnios (see above);

the mother towards the end of pregnancy and the newborn:

prolonged bleeding time, anti-aggregatory effect, which may occur even at very low doses;
inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, Ortofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding

Like other NSAIDs, diclofenac passes into breast milk in small amounts. Therefore, Ortofen should not be administered during breastfeeding to avoid the risk of adverse effects in the infant.

Ability to influence reaction rate when driving or operating machinery.

Generally, when the drug is taken at the recommended dose and for a short-term course of treatment, no effect on reaction speed is observed. However, patients who experience visual disturbances, dizziness, vertigo, drowsiness, lethargy, fatigue, or other central nervous system (CNS) disorders while taking Ortofen should refrain from driving or operating complex machinery.

Dosage and Administration

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

The tablets should be swallowed whole, without chewing, with water, preferably before meals.

For adults, the recommended initial dose is 100–150 mg per day. In cases of mild to moderate symptoms and during long-term therapy, a daily dose of 75–100 mg is generally sufficient. The daily dose should be divided into 2–3 administrations.

For primary dysmenorrhea, the daily dose of Ortofen should be individually adjusted. The usual daily dose is 50–100 mg. If necessary, the dose may be increased over the following menstrual cycles up to the maximum dose of 200 mg per day. Treatment with Ortofen tablets should be initiated at the onset of the first pain symptoms and continued for several days, depending on the patient's response and symptomatology.

The recommended maximum daily dose of Ortofen is 150 mg.

Elderly patients

Although the pharmacokinetics of Ortofen in elderly patients is not significantly impaired to a clinically relevant extent, nonsteroidal anti-inflammatory drugs (NSAIDs) should be used with particular caution in this population, as they are generally more susceptible to adverse reactions. Especially in 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.

Children (aged 1–14 years)

The 25 mg tablets may be administered to children from the age of 1 year, as prescribed by a physician, at a daily dose of 0.5–2 mg/kg body weight, depending on symptom severity; this dose should be divided into 2–3 administrations. In the treatment of juvenile rheumatoid arthritis, the daily dose may be increased up to 3 mg/kg body weight in several divided doses.

For example, for a child weighing 30 kg, the daily dose may range from 15 to 60 mg. Based on this range, the child may be prescribed 2 tablets—1 tablet of 25 mg twice daily.

If the prescribed dose cannot be achieved with these tablets, alternative dosage forms of diclofenac with appropriate strengths should be used.

Children aged 14 years and older should receive a daily dose of 75–150 mg, divided into 2–3 doses. The maximum daily dose of 150 mg should not be exceeded.

Children

The 25 mg tablets may be used in children aged 1 year and older with juvenile chronic arthritis, provided that the weight-based dosing can be achieved.

Overdose

Symptoms

There is no typical clinical picture of diclofenac overdose. Symptoms may include headache, nausea, vomiting, epigastric pain, gastrointestinal hemorrhage, diarrhea, dizziness, tinnitus, seizures, disorientation, agitation, coma, and somnolence. In severe cases, acute renal failure and hepatic injury may occur.

Treatment

Management of acute poisoning with nonsteroidal anti-inflammatory drugs (NSAIDs), including diclofenac, generally involves supportive care and symptomatic treatment of complications such as arterial hypotension, renal failure, seizures, gastrointestinal disturbances, and respiratory depression.

Specific interventions such as forced diuresis, dialysis, or hemoperfusion do not significantly enhance the elimination of NSAIDs, including diclofenac, due to the high degree of plasma protein binding and extensive metabolism of these drugs.

In cases of potentially toxic overdose, activated charcoal should be administered.

In cases of potentially life-threatening overdose, evacuation of gastric contents (induction of emesis or gastric lavage) should be performed.

Adverse Reactions

Adverse effects are classified according to their frequency of occurrence: very common (>1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare (<1/10,000), including isolated cases.

The following adverse reactions have been reported during short-term or long-term treatment with the medicinal product Orthofen and/or other diclofenac formulations:

Blood and lymphatic system disorders: very rare – thrombocytopenia, leukopenia, anemia (including hemolytic and aplastic anemia), agranulocytosis;
Immune system disorders: rare – hypersensitivity, anaphylactic and anaphylactoid reactions (including arterial hypotension and shock); very rare – angioedema (including facial swelling);
Psychiatric disorders: very rare – confusion, depression, insomnia, nightmares, irritability, psychotic disorders;
Central nervous system disorders: common – headache, dizziness;
rare – somnolence, fatigue; very rare – paresthesia, memory impairment, anxiety, seizures, tremor, aseptic meningitis, taste disturbances, stroke; frequency not known – confusion, hallucinations, sensory disturbances, general 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;
Cardiac and vascular disorders: very rare – palpitations, chest pain, heart failure, myocardial infarction, arterial hypertension, arterial hypotension, vasculitis; frequency not known – Kounis syndrome;
Respiratory, thoracic and mediastinal disorders: rare – asthma (including dyspnea); very rare – pneumonitis;
Gastrointestinal disorders: common – nausea, vomiting, diarrhea, dyspepsia, abdominal pain, flatulence, loss of appetite; rare – gastritis, gastrointestinal hemorrhage (vomiting blood, hemorrhagic diarrhea, melena), gastric and intestinal ulcers with or without bleeding or perforation (sometimes fatal, especially in elderly patients); very rare – colitis (including hemorrhagic colitis and exacerbation of ulcerative colitis or Crohn’s disease), constipation, stomatitis (including ulcerative stomatitis), glossitis, esophageal dysfunction, diaphragm-like intestinal stricture, pancreatitis; frequency not known – ischemic colitis;
Hepatobiliary disorders: common – increased transaminase levels; rare – hepatitis, jaundice, liver dysfunction; very rare – fulminant hepatitis, liver necrosis, liver failure;
Skin and subcutaneous tissue disorders: common – rash; rare – urticaria; very rare – bullous rash (blister-like eruptions), eczema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exfoliative dermatitis, alopecia, photosensitivity, purpura (including allergic purpura), pruritus;
Renal and urinary disorders: very rare – acute renal failure, hematuria, proteinuria, nephrotic syndrome, interstitial nephritis, renal papillary necrosis; common – fluid retention, edema, arterial hypertension;
General disorders: rare – edema;
Reproductive system and breast disorders: very rare – impotence.

Diclofenac, particularly at high doses (150 mg per day) and with prolonged use, increases the risk of arterial thromboembolic complications (e.g., myocardial infarction or stroke).

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

Packaging.

10 tablets per blister, 1 or 3 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

JSC "VITAMINS".

Manufacturer's location and address of business activity.

31 Uspenska Street, Uman, Cherkasy region, 20300, Ukraine.

Marketing Authorization Holder.

JSC "VITAMINS".

Address of the Marketing Authorization Holder.

31 Uspenska Street, Uman, Cherkasy region, 20300, Ukraine.