Etol fort

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ETOLFORT (ETOLFORT)

Composition:

Active substance: etodolac;

One tablet contains 400 mg of etodolac;

Excipients: anhydrous lactose, microcrystalline cellulose, sodium croscarmellose, colloidal anhydrous silicon dioxide, magnesium stearate, povidone;

Coating Opadry II pink (85F240035): polyvinyl alcohol, titanium dioxide (E 171), red iron oxide (E 72), polyethylene glycol 4000, talc.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: elongated, pale pink film-coated tablets, with a break line on one side and embossing "NOBEL" on the other.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Acetic acid derivatives and related compounds. ATC code M01AB08.

Pharmacological properties.

Pharmacodynamics.

Etodolac is a nonsteroidal anti-inflammatory drug (NSAID), a derivative of indoleacetic acid, differing from other nonsteroidal anti-inflammatory drugs (NSAIDs) by the presence of a tetrahydropyranoindole nucleus. Etodolac possesses anti-inflammatory, analgesic, and antipyretic properties. The drug reduces the synthesis of prostaglandins (PGs) from arachidonic acid by inhibiting the enzyme cyclooxygenase (COX), thereby decreasing the sensitivity of receptors to pain mediators (histamine, bradykinin), reducing exudation and leukocyte migration, as well as decreasing the sensitivity of hypothalamic thermoregulatory centers to the action of endogenous pyrogens (interleukin-1). Etodolac has moderate selectivity towards COX-2, thus acting predominantly at the site of inflammation.

Pharmacokinetics.

After oral administration, etodolac is rapidly absorbed from the gastrointestinal tract. Maximum plasma concentration is reached within 1 hour and amounts to 18 µg/mL. Plasma protein binding is 95%, with the free fraction accounting for 1.2–4.7%.

The elimination half-life from plasma is approximately 7 hours. Etodolac is metabolized in the liver and primarily excreted by the kidneys (up to 60% as metabolites). Volume of distribution is 0.4 L/kg; plasma clearance is 41 mL/h/kg. The bioavailability of etodolac is at least 80%. Food intake and antacids do not affect bioavailability.

Clinical characteristics.

Indications.

For emergency or long-term treatment of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis.

Pain syndrome of various origins.

Contraindications.

Hypersensitivity to any component of the drug; history of hypersensitivity reactions (e.g., bronchial asthma attacks, urticaria, rhinitis, angioedema) following intake of acetylsalicylic acid, ibuprofen, or other NSAIDs; active or recurrent peptic ulcer/bleeding history (two or more distinct confirmed episodes of ulcers or bleeding); gastrointestinal bleeding or perforation associated with previous NSAID therapy; cytopenia, severe hepatic, renal, or cardiac insufficiency.

Contraindicated for pain treatment associated with coronary artery bypass grafting.

Interaction with other medicinal products and other forms of interactions.

Since etodolac is protein-bound, dosage adjustment of other medicinal products that are also highly protein-bound may be required.

Other analgesics, including selective cyclooxygenase-2 inhibitors. Avoid concomitant use of two or more NSAIDs (including acetylsalicylic acid), as the risk of adverse effects increases (see section "Special precautions").

Antihypertensive medicinal products. Decreases hypotensive effect.

Diuretics. Decreases diuretic effect. Diuretics increase the risk of nephrotoxicity associated with NSAIDs.

Cardiac glycosides. NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase blood levels of glycosides.

Lithium. Lithium excretion is reduced.

Methotrexate. Methotrexate excretion is reduced.

Cyclosporine. May increase cyclosporine-related nephrotoxicity.

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

Corticosteroids. Increases the risk of gastrointestinal ulceration or bleeding (see section "Special precautions").

Anticoagulants. NSAIDs may potentiate the effect of anticoagulants such as warfarin (see section "Special precautions"). Prothrombin time may be prolonged when etodolac is used with other NSAIDs; therefore, when used with warfarin, the risk of bleeding increases.

Quinolone antibiotics. Animal studies show that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolone antibiotics have an increased risk of developing seizures.

Antiplatelet agents and selective serotonin reuptake inhibitors. Increases the risk of gastrointestinal bleeding (see section "Special precautions").

Tacrolimus. Concomitant use of NSAIDs with tacrolimus increases the risk of nephrotoxicity.

Zidovudine. Increased risk of hematotoxicity when NSAIDs are used concomitantly with zidovudine. Evidence suggests an increased risk of hemarthrosis and hematoma in HIV-positive patients with hemophilia who concurrently receive zidovudine and ibuprofen.

Phenylbutazone. Concomitant use of phenylbutazone and etodolac is not recommended, as phenylbutazone increases (by approximately 80%) the free fraction of etodolac. In vivo studies have not been conducted.

Antacids. When antacids are used concomitantly, there is no effect on the overall absorption of etodolac. Antacids may reduce the peak concentration of etodolac by 15–20%, but do not have a significant impact on peak concentration.

Laboratory data. False-positive results in bilirubin testing may occur during etodolac use due to the presence of phenolic metabolites of etodolac in urine.

Special precautions for use.

Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration" and information on gastrointestinal and cardiovascular risks below).

Concomitant use of etodolac with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided (see section "Interaction with other medicinal products and other forms of interaction").

Respiratory disorders.

Caution should be exercised when administering etodolac to patients with bronchial asthma, including those with a history of bronchial asthma, as NSAIDs may induce bronchospasm in such patients.

Cardiovascular, renal, and hepatic impairment.

In patients receiving NSAIDs, dose-dependent reduction in prostaglandin formation may occur, potentially leading to renal decompensation. Patients at higher risk of such reactions include those with impaired renal function, heart failure, hepatic dysfunction, patients taking diuretics and ACE inhibitors, and elderly patients. The dosage of the drug should be reduced and renal function monitored in these patients (see section "Contraindications").

Etodolac should be used with caution in patients with fluid retention, arterial hypertension, or heart failure.

During prolonged treatment with etodolac, regular monitoring of liver and kidney function and peripheral blood counts is required.

Platelets.

Although NSAIDs do not have a direct effect on platelets, as does aspirin, all these medicinal products may inhibit prostaglandin biosynthesis, which can affect platelet function. Patients in whom a negative impact on platelet function is possible should be monitored.

Elderly.

Generally, no dose adjustment is required for elderly patients. However, caution should be exercised when selecting the dose, especially when increasing the dose. The frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, is increased in elderly patients (see section "Dosage and administration").

Cardiovascular and cerebrovascular disorders.

Careful monitoring is recommended for patients with arterial hypertension and/or a history of mild to moderate congestive heart failure, as fluid retention and edema have been observed during NSAID therapy.

Clinical studies and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and during long-term treatment) is associated with an increased risk of vascular thrombotic events (e.g., myocardial infarction or stroke). There is insufficient data to exclude such a risk with etodolac.

Therapy with etodolac should be initiated only after careful consideration in patients with uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.

A similar risk-benefit assessment is required before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Gastrointestinal disorders.

As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulceration, or perforation may occur at any time during treatment, regardless of the presence of previous symptoms or serious gastrointestinal disorders in the patient's history.

The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially complicated by bleeding or perforation (see section "Contraindications"), and in elderly patients. Such patients should start treatment with the lowest effective dose. For these patients, as well as for those requiring concomitant use of low-dose acetylsalicylic acid or other medicinal products that increase gastrointestinal risks, combination therapy with protective agents (such as misoprostol or proton pump inhibitors) should be considered (see information below and section "Interaction with other medicinal products and other forms of interaction").

Patients with a history of gastrointestinal toxicity, particularly elderly patients, should be informed about any unusual abdominal symptoms (especially gastrointestinal bleeding), particularly during the initial stages of treatment.

Caution should be exercised in patients who are concurrently using medicinal products that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid (see section "Interaction with other medicinal products and other forms of interaction").

If gastrointestinal bleeding or ulceration occurs in patients taking etodolac, treatment should be discontinued.

NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as these conditions may be exacerbated (see section "Adverse reactions").

Systemic lupus erythematosus and connective tissue diseases.

Patients with systemic lupus erythematosus and connective tissue diseases have an increased risk of developing aseptic meningitis (see section "Adverse reactions").

Skin disorders.

Serious skin reactions, some of which have been fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been very rarely observed with NSAIDs (see section "Adverse reactions"). The highest risk of such reactions occurs early in treatment, with most cases appearing within the first month of therapy. Etodolac should be discontinued at the first appearance of skin rash, mucosal lesions, or other signs of hypersensitivity.

Fertility.

Etodolac may affect reproductive function. The drug is not recommended for women who are trying to conceive. For women planning pregnancy or undergoing infertility evaluation, discontinuation of etodolac should be considered.

The product contains lactose and therefore should not be used in patients with hereditary galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy and breastfeeding.

Ability to influence reaction rate when driving or operating machinery.

Etodolac may cause dizziness, drowsiness, weakness, and visual disturbances (visual impairment). These effects should be taken into account by patients when driving or operating machinery. If such reactions occur, patients should avoid driving or operating machinery.

Method of Administration and Dosage.

Adults: the recommended single dose of Etol Fort is 400 mg. The drug is administered twice daily: 1 tablet in the morning and evening, taken after meals.

Maximum daily dose – 1000 mg.

For rheumatic diseases, the treatment course depends on the therapeutic efficacy and the nature of the disease. In prolonged treatment courses, the dose should be adjusted every 2–3 weeks of drug use.

For the treatment of pain due to acute inflammatory conditions (such as dental pain, myositis, tendinitis), as well as postoperative pain syndromes, the treatment course lasts 5 days. For headache and menstrual pain, Etol Fort is taken at a dose of 1–2 tablets per day, as needed, for no more than 3 days.

Children.

The safety and efficacy of etodolac have not been evaluated in children; therefore, it is not used in pediatric practice.

Overdose.

Symptoms.

Symptoms of overdose include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhea, disorientation, excitement, coma, drowsiness, dizziness, tinnitus, fainting, and occasionally seizures. In cases of significant overdose, acute renal failure and liver damage are possible.

Treatment.

Symptomatic treatment. Activated charcoal should be administered within 1 hour after ingestion of a potentially toxic amount of the drug. In adults, gastric lavage should be performed within 1 hour after ingestion of a life-threatening amount of the drug. Adequate diuresis must be maintained. Renal and hepatic functions must be monitored. Patients must be observed for at least 4 hours after ingestion of a potentially toxic amount of the drug. In the event of frequent and prolonged seizures, intravenous diazepam should be administered. Depending on the patient's clinical condition, other interventions may be required.

Side effects.

The most common adverse reactions were gastrointestinal disorders.

Blood and lymphatic system disorders: thrombocytopenia, neutropenia, leukopenia, pancytopenia, agranulocytosis, anemia, aplastic anemia, hemolytic anemia, prolonged bleeding time, lymphadenopathy.

Immune system disorders: hypersensitivity reactions have been reported with the use of NSAIDs: non-specific allergic reactions and anaphylaxis; anaphylactoid reactions; respiratory tract reactivity, including bronchial asthma, exacerbation of bronchial asthma, bronchospasm, and dyspnea; various skin disorders, including different types of rashes, pruritus, urticaria, purpura, angioneurotic edema, and less frequently exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Nervous system disorders: depression, headache, dizziness, insomnia, confusion, disturbance of consciousness, hallucinations, disorientation (see section "Special precautions"), paresthesia, tremor, weakness, nervousness, excitement, seizures, coma, somnolence, taste disturbances, aseptic meningitis (especially in patients with autoimmune diseases such as systemic lupus erythematosus or connective tissue diseases), with symptoms such as nuchal rigidity, headache, nausea, vomiting.

Eye disorders: eye disorders (visual disturbances), optic neuritis, blurred vision, photophobia, conjunctivitis.

Ear and labyrinth disorders: tinnitus, vertigo, deafness.

Cardiovascular system disorders: edema, arterial hypertension, arrhythmia, palpitations, heart failure, vasculitis, flushing.

Data from clinical trials and epidemiological studies suggest that the use of certain NSAIDs (particularly at high doses and during long-term treatment) may be associated with an increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special precautions").

Gastrointestinal disorders: peptic ulcer, gastrointestinal perforation or gastrointestinal hemorrhage, sometimes fatal, especially in elderly patients (see section "Special precautions"), nausea, vomiting, diarrhea, dyspepsia, epigastric pain, abdominal pain, ulcerative stomatitis, constipation, flatulence, vomiting of blood, melena, gastrointestinal ulcers, digestive disturbances, heartburn, rectal bleeding, exacerbation of colitis and Crohn’s disease (see section "Special precautions"), gastritis, pancreatitis, glossitis, thirst, dry mouth, anorexia, belching, duodenitis, esophagitis with or without strictures or cardiospasm.

Hepatobiliary disorders: liver function abnormalities (bilirubinuria), increased liver enzyme activity, hepatitis, cholestatic hepatitis, jaundice, cholestatic jaundice, liver failure, hepatic necrosis.

Skin and subcutaneous tissue disorders: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, photosensitivity, increased sweating, hyperpigmentation, alopecia, skin desquamation, ecchymoses.

Renal and urinary disorders: dysuria, increased frequency of urination, nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, renal failure, increased blood urea levels, increased creatinine levels, renal papillary necrosis, oliguria/polyuria, proteinuria, hematuria, cystitis, kidney stones.

Respiratory system disorders: pulmonary infiltration with eosinophilia, bronchitis, pharyngitis, rhinitis, sinusitis, respiratory depression, pneumonia, epistaxis.

General disorders: increased fatigue, weakness, asthenia, chills, elevated body temperature, disturbances in water-electrolyte balance, hypernatremia, hyperkalemia.

Other: leukorrhea, irregular uterine bleeding, hyperglycemia in patients with controlled blood glucose levels in diabetes, changes in body weight, infections, sepsis, fatal cases.

Shelf life. 4 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Packaging.

14 tablets in a blister. 1 or 2 blisters per cardboard package.

4 tablets in a blister. 1 blister per cardboard package.

Prescription status. Prescription only.

Manufacturer.

NOBEL ILAC SANAYI VE TICARET A.S.

Manufacturer’s address and place of business.

Sankaklar District, Eskisehir Yolu Akcakoca Highway, No: 299, 81100 Duzce, Turkey.