Instructions for Etol Fort film-coated tablets 400 mg No. 28
Composition
active ingredient: etodolac;
1 tablet contains etodolac 400 mg;
excipients: anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silicon dioxide, magnesium stearate, povidone;
Opadry II pink coating (85F240035): polyvinyl alcohol, titanium dioxide (E 171), red iron oxide (E 172), polyethylene glycol 4000, talc.
Dosage form
Film-coated tablets.
Main physicochemical properties: oblong, pale pink, film-coated tablets with a breakline on one side and embossed with “NOBEL” on the other.
Pharmacotherapeutic group
Nonsteroidal anti-inflammatory and antirheumatic drugs. Acetic acid derivatives and related compounds. ATC code M01A B08.
Pharmacological properties
Pharmacodynamics
Etodolac is a nonsteroidal anti-inflammatory drug, a derivative of indoleacetic acid, which differs from other nonsteroidal anti-inflammatory drugs (NSAIDs) in the presence of a tetrahydropyranoindole nucleus. Etodolac has anti-inflammatory, analgesic and antipyretic properties. The drug reduces the synthesis of prostaglandins (PGs) from arachidonic acid by inhibiting the enzyme cyclooxygenase (COX), which reduces the sensitivity of receptors to pain mediators (histamine, bradykinin), reduces exudation, leukocyte migration, as well as the sensitivity of hypothalamic thermoregulation centers to the action of endogenous pyrogens (interleukin-1). Etodolac has moderate selectivity for COX-2, therefore it acts mainly in the focus of inflammation.
Pharmacokinetics
When administered orally, etodolac is rapidly absorbed from the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 1 hour and is 18 μg/ml. Binding to plasma proteins is 95%, the free fraction is 1.2-4.7%.
The plasma half-life is approximately 7 hours. Etodolac is metabolized in the liver and excreted mainly by the kidneys (up to 60% in the form of metabolites). The volume of distribution is 0.4 l/kg, plasma clearance is 41 ml/h/kg. The bioavailability of etodolac is at least 80%. Food and antacids do not affect bioavailability.
Indication
For urgent or long-term treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis.
Pain syndrome of various origins.
Contraindication
Hypersensitivity to any of the components of the drug; history of hypersensitivity reactions (e.g., attacks of bronchial asthma, urticaria, rhinitis, angioedema) due to taking acetylsalicylic acid, ibuprofen or other NSAIDs; active or recurrent peptic ulcer/bleeding in history (two or more separate confirmed cases of ulceration or bleeding); gastrointestinal bleeding or perforation associated with previous NSAID therapy in history; cytopenia, severe hepatic, renal, or cardiac failure.
Contraindicated for the treatment of pain during coronary artery bypass grafting.
Interaction with other medicinal products and other types of interactions
Because etodolac binds to blood proteins, dose adjustments of other drugs that are also highly bound to blood proteins may be necessary.
Other analgesics, including selective cyclooxygenase-2 inhibitors. Avoid the simultaneous use of two or more NSAIDs (including acetylsalicylic acid) as the risk of side effects increases (see section "Special instructions").
Antihypertensive drugs. Reduces the hypotensive effect.
Diuretics. Reduces diuretic effect. Diuretics increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase blood glycoside levels.
Lithium. Lithium excretion is reduced.
Methotrexate. Methotrexate excretion is reduced.
Cyclosporine: Cyclosporine-associated nephrotoxicity may be increased.
Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration, as NSAIDs may reduce the effect of mifepristone.
Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section "Special warnings and precautions for use").
Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as warfarin (see section 4.4). Prothrombin time may be prolonged when etodolac is used with other NSAIDs, therefore the risk of bleeding is increased when used with warfarin.
Quinolone antibiotics: Animal studies show that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients taking NSAIDs and quinolone antibiotics are at increased risk of developing seizures.
Antithrombotic drugs and selective serotonin reuptake inhibitors: Increased risk of gastrointestinal bleeding (see section "Special warnings and precautions for use").
Tacrolimus: Concomitant use of NSAIDs with tacrolimus increases the risk of nephrotoxicity.
Phenylbutazone: Concomitant use of phenylbutazone and etodolac is not recommended because phenylbutazone increases (up to approximately 80%) the free fraction of etodolac. In vivo studies have not been conducted.
Antacids: Concomitant administration of antacids has no effect on the overall absorption of etodolac. Antacids may reduce the peak concentration of etodolac by 15-20%, but they do not have a significant effect on the peak concentration.
Laboratory data: When using etodolac, a false positive result for bilirubin may occur due to the presence of phenolic metabolites of etodolac in the urine.
Application features
Adverse reactions can be minimised 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).
The concomitant use of etodolac with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided (see section "Interaction with other medicinal products and other types of interactions").
Respiratory disorders.
Caution should be exercised when administering etodolac to patients with bronchial asthma, including a history of it, since NSAIDs may cause bronchospasm in such patients.
Cardiovascular, renal and hepatic failure.
In patients taking NSAIDs, a dose-dependent decrease in prostaglandin formation may occur and contribute to the development of renal decompensation. Patients with impaired renal function, heart failure, impaired liver function, patients taking diuretics and ACE inhibitors, and elderly patients are at high risk of developing these reactions. It is necessary to reduce the dose of the drug and monitor renal function in these patients (see section "Contraindications").
Etodolac should be used with caution in patients with fluid retention, hypertension, or heart failure.
With prolonged use of etodolac, it is necessary to regularly monitor the function of the liver, kidneys, and peripheral blood.
Platelets.
Although NSAIDs do not have a direct effect on platelets, as aspirin does, all of these drugs can inhibit prostaglandin biosynthesis, which can affect platelet function. Patients who may have a negative effect on platelet function should be monitored.
Old age.
In general, no dose adjustment is necessary in elderly patients. However, caution should be exercised when selecting the dose, especially when increasing the dose. Elderly patients are more likely to experience adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation (see section 4.2).
Cardiovascular and cerebrovascular disorders.
Close observation is recommended in patients with hypertension and/or a history of mild to moderate congestive heart failure, as fluid retention and edema have been reported with NSAID therapy.
Clinical and epidemiological data suggest that the use of some NSAIDs (especially at high doses and in long-term treatment) is associated with an increased risk of vascular thrombotic events (e.g. myocardial infarction or stroke). There is insufficient evidence to exclude such a risk with etodolac.
Patients with uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with etodolac only after careful consideration.
Such analysis is necessary before starting long-term treatment of patients with risk factors for cardiovascular disease (such as 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 previous symptoms or a history of serious gastrointestinal disease.
The risk of gastrointestinal bleeding, ulceration or perforation is higher with increasing NSAID doses in patients with a history of ulcer, particularly complicated by bleeding or perforation (see section 4.3), and in the elderly. In such patients, treatment should be initiated at the lowest effective dose. For such patients, as well as for patients requiring concomitant low-dose acetylsalicylic acid or other medicinal products that increase gastrointestinal risks, combination therapy with protective medicinal products (such as misoprostol or proton pump inhibitors) should be considered (see information below and section 4.5).
Caution should be exercised in patients taking concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or antiplatelet agents such as acetylsalicylic acid (see section 4.5).
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 diseases (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 are at increased risk of developing aseptic meningitis (see section "Adverse reactions").
Skin disorders.
Serious skin reactions, some of which were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely with NSAIDs (see section 4.8). The risk of these reactions is highest at the beginning of treatment, with most occurring within the first month of treatment. 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 attempting to conceive. For women attempting to conceive or undergoing investigation of infertility, discontinuation of etodolac should be considered.
The drug contains lactose, so it should not be used in cases of hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
Ability to influence reaction speed when driving vehicles or other mechanisms
Etodolac may cause dizziness, drowsiness, weakness, and visual disturbances (visual impairment). This should be taken into account by patients when driving or operating machinery. If such reactions occur, patients should avoid driving or operating machinery.
Use during pregnancy or breastfeeding
The drug is contraindicated for use during pregnancy or breastfeeding.
Method of administration and doses
Adults: the recommended single dose of Etol Fort is 400 mg. The drug is used 2 times a day: 1 tablet in the morning and evening after meals.
The maximum daily dose is 1000 mg.
In rheumatic diseases, the course of treatment depends on the effectiveness of therapy and the nature of the disease. In the case of a long course of therapy, the dose must be adjusted every 2-3 weeks of use of the drug.
In the treatment of pain conditions due to acute inflammatory processes (such as toothache, myositis, tendinitis), as well as after surgical pain syndromes, the course of treatment is 5 days. For headaches and menstrual pain, Etol Fort is taken 1-2 tablets per day, if necessary, for no more than 3 days.
Children
The safety and efficacy of etodolac have not been evaluated in children, so it is not used in pediatric practice.
Overdose
Symptoms.
Symptoms of overdose include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhea, disorientation, agitation, coma, drowsiness, dizziness, tinnitus, fainting, sometimes convulsions. In case of significant overdose, acute renal failure and liver damage are possible.
Treatment.
Symptomatic treatment. Activated charcoal should be administered within 1 hour of ingestion of a potentially toxic amount of the drug. In adults, gastric lavage should be performed within 1 hour of ingestion of a life-threatening amount of the drug. Adequate diuresis should be ensured. Renal and hepatic function should be monitored. Patients should be observed for at least 4 hours after ingestion of a potentially toxic amount of the drug. In the event of frequent and prolonged convulsions, intravenous diazepam should be administered. Other measures may be necessary depending on the clinical condition of the patient.
Adverse reactions
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.
Nervous system: depression, headache, dizziness, insomnia, confusion, impaired consciousness, hallucinations, disorientation (see section "Special warnings and precautions for use"), paresthesia, tremor, weakness, nervousness, agitation, convulsions, coma, drowsiness, taste changes, aseptic meningitis (especially in patients with autoimmune diseases such as systemic lupus erythematosus, connective tissue diseases) with symptoms such as stiffness of the muscles of the back of the head, headache, nausea, vomiting.
On the part of the organs of vision: eye disorders (visual impairment), optic neuritis, blurred vision, photophobia, conjunctivitis.
From the side of the organs of hearing and vestibular apparatus: tinnitus, vertigo, deafness.
Cardiovascular system: edema, hypertension, arrhythmia, palpitations, heart failure, vasculitis, flushing.
Research and epidemiological data suggest that the use of some NSAIDs (especially at high doses and with long-term treatment) is associated with an increased risk of vascular thrombotic events (e.g. myocardial infarction or stroke) (see section "Special warnings and precautions for use").
On the part of the digestive tract: peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients (see section "Special warnings and precautions for use"), nausea, vomiting, diarrhea, dyspepsia, epigastric pain, abdominal pain, ulcerative stomatitis, constipation, flatulence, haematemesis, melena, gastrointestinal ulcers, indigestion, heartburn, rectal bleeding, exacerbation of colitis and Crohn's disease (see section "Special warnings and precautions for use"), gastritis, pancreatitis, glossitis, thirst, dry mouth, anorexia, eructation, duodenitis, esophagitis with or without strictures or cardiospasm.
From the hepatobiliary system: impaired liver function (bilirubinuria), increased liver enzyme activity, hepatitis, cholestatic hepatitis, jaundice, cholestatic jaundice, hepatic failure, liver necrosis.
Skin and subcutaneous tissue disorders: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, photosensitivity, increased sweating, hyperpigmentation, alopecia, skin peeling, ecchymoses.
Renal and urinary disorders: dysuria, increased urination, nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, renal failure, increased urea levels, increased creatinine levels, renal papillary necrosis, oliguria/polyuria, proteinuria, hematuria, cystitis, kidney stones.
Respiratory system: pulmonary infiltration with eosinophilia, bronchitis, pharyngitis, rhinitis, sinusitis, respiratory depression, pneumonia, epistaxis.
General disorders: increased fatigue, weakness, asthenia, chills, increased body temperature, impaired water and electrolyte balance, hypernatremia, hyperkalemia.
Others: leukorrhea, irregular uterine bleeding, hyperglycemia in patients with controlled sugar levels in patients with diabetes mellitus, weight change, infections, sepsis, fatalities.
Expiration date
4 years.
Storage conditions
Store at a temperature not exceeding 25 ºС in the original packaging.
Keep out of reach of children.
Packaging
14 tablets in a blister. 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
NOBEL ILACH SANAI VE TJARET A.Sh.
Location of the manufacturer and its business address
Sankaklar Quarter, Eski Akcakoca Ave., No. 299, 81100 Duzce, Turkey.
