Etol® [Etodolac]

Pharmacological properties

etodolac is an NSAID, a derivative of indoleacetic acid, which differs from other NSAIDs by the presence of a tetrahydropyranoindole core. etodolac has anti-inflammatory, analgesic and antipyretic properties. the drug reduces the synthesis of prostaglandins from arachidonic acid, inhibiting the enzyme cog, which reduces the sensitivity of receptors to pain mediators (histamine, bradykinin), exudation, migration of leukocytes, as well as the sensitivity of hypothalamic thermoregulation centers to the action of endogenous pyrogens (interleukin-1, etc.) . etodolac has moderate selectivity for cog-2, therefore, it acts mainly in the focus of inflammation.

Pharmacokinetics When used internally, etodolac is rapidly absorbed in the digestive tract. WITH_max in blood plasma is reached after 60 minutes and is 18 μg / ml. Binding to plasma proteins is 95%, the free fraction is 1.2–4.7%.

T_½ from blood plasma - about 7 hours. Etodolac is metabolized in the liver and excreted mainly by the kidneys (up to 60% in the form of metabolites). Distribution volume - 0.4 l / kg body weight and plasma clearance - 41 ml / h / kg. The bioavailability of etodolac is at least 80%, does not affect the intake of food and antacids.

Indications

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

Pain syndrome of any etiology.

Application

Adults: The recommended daily dose of Etol fort is 400 mg. the drug is taken 2 times a day, 1 tablet in the morning and evening after a meal. the maximum daily dose is 1000 mg.

In patients with a body weight of 60 kg, the maximum daily dose of the drug should not exceed 20 mg / kg of body weight.

In rheumatic diseases, the course of treatment depends on the effectiveness of therapy and the nature of the disease. Under the condition of a long course of treatment, the dose must be adjusted every 2-3 weeks.

In pain conditions due to acute inflammatory processes (for example, toothache, myositis, tendonitis), as well as postoperative pain syndromes, the course of treatment is 5 days. In case of headache and menstrual pain, Etol Fort is prescribed 1-2 tablets per day if necessary, but not more than 3 days.

Contraindications

Hypersensitivity to the components of the drug; the presence in the history of hypersensitivity reactions (for example, attacks of ba, urticaria, rhinitis, angioedema) due to the use of acetylsalicylic acid, ibuprofen or other NSAIDs; active or recurrent peptic ulcer / history of bleeding (two or more separate confirmed cases of ulcer or bleeding); gastrointestinal bleeding or perforation associated with previous history of NSAID therapy; cytopenia, severe hepatic, renal, heart failure.

Contraindicated to eliminate pain during coronary artery bypass grafting.

Side effects

The most common adverse reactions were gastrointestinal disturbances.

On the part of the blood and lymphatic system: thrombocytopenia, neutropenia, leukopenia, pancytopenia, agranulocytosis, anemia, aplastic anemia, hemolytic anemia, an increase in bleeding time, lymphadenopathy.

On the part of the immune system: when using NSAIDs, hypersensitivity reactions were noted: nonspecific allergic reactions and anaphylaxis; anaphylactoid reactions; airway reactivity, including asthma, exacerbation of asthma, bronchospasm and shortness of breath; mixed skin disorders, including various types of rash, itching, urticaria, purpura, angioedema, less often exfoliative and bullous dermatosis (including epidermal necrolysis and erythema polyforma).

From the side of the nervous system: depression, headache, dizziness, insomnia, confusion, impaired consciousness, hallucinations, disorientation (seeSPECIAL INSTRUCTIONS), paresthesia, tremor, weakness, nervousness, agitation, cramps, coma, drowsiness, taste change, aseptic meningitis (especially in patients with autoimmune diseases such as systemic lupus erythematosus, connective tissue diseases) with symptoms such as muscle rigidity nape, headache, nausea, vomiting.

From the side of the organ of vision: visual impairment, optic neuritis, blurred vision, photophobia, conjunctivitis.

From the side of the organ of hearing and the vestibular apparatus: tinnitus, vertigo, deafness.

From the cardiovascular system: edema, hypertension, arrhythmia, palpitations, heart failure, vasculitis, flushing of the face.

Studies and epidemiological data suggest that the use of certain NSAIDs (especially in high doses and with long-term treatment) is associated with an increased risk of developing vascular thrombotic events (e.g., myocardial infarction or stroke) (see SPECIAL INSTRUCTIONS).

From the digestive system: peptic ulcer, perforation or gastrointestinal bleeding, sometimes fatal, especially in elderly patients (see SPECIAL INSTRUCTIONS), nausea, vomiting, diarrhea, dyspepsia, epigastric pain, abdominal pain, ulcerative stomatitis constipation, flatulence, vomiting of blood, melena, gastrointestinal ulcers, digestive disorders, heartburn, rectal bleeding, exacerbation of colitis and Crohns disease (see SPECIAL INSTRUCTIONS), gastritis, pancreatitis, glossitis, thirst, dry mouth, anorexia, belching, esophagitis with strictures and whether with or without cardiospasm.

From the hepatobiliary system: impaired liver function (bilirubinuria), increased activity of liver enzymes, hepatitis, cholestatic hepatitis, jaundice, cholestatic jaundice, liver failure, liver necrosis.

On the part of the skin and subcutaneous tissue: bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, photosensitivity, increased sweating, hyperpigmentation, alopecia, peeling of the skin, ecchymosis.

On the part of the kidneys and urinary tract: dysuria, increased urination, nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, renal failure, increased urea, increased creatinine, papillary necrosis of the kidneys, oliguria / polyuria, proteinuria, hematuria, cystitis, stones in the kidneys.

From the respiratory system: pulmonary infiltration with eosinophilia, bronchitis, pharyngitis, rhinitis, sinusitis, respiratory depression, pneumonia, nosebleeds.

Common disorders: increased fatigue, weakness, asthenia, chills, fever, impaired water-electrolyte balance, hypernatremia, hyperkalemia.

Others: leukorrhea, irregular uterine bleeding, hyperglycemia in patients with controlled glucose levels, in patients with diabetes mellitus, weight loss, infections, sepsis, deaths.

special instructions

Adverse reactions can be minimized by applying the smallest effective dose for the shortest treatment period necessary to control symptoms (see use and information on gastrointestinal and cardiovascular risks below).

The simultaneous use of etodolac with NSAIDs, including selective COX-2 inhibitors, should be avoided (see INTERACTIONS).

Violations of the respiratory system. Caution should be exercised when using etodolac in patients with AD, including a history, since NSAIDs can cause bronchospasm in such patients.

Cardiovascular, renal and liver failure. In patients with the use of NSAIDs, a dose-dependent decrease in the formation of prostaglandins can be noted and contribute to the development of renal decompensation.A high risk of developing these reactions is noted in patients with impaired renal function, heart failure, impaired liver function, patients who take diuretics and ACE inhibitors, and elderly people. It is necessary to reduce the dose of the drug and monitor renal function in these patients (see 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, peripheral blood.

Platelets. Although NSAIDs do not have a direct effect on platelets like acetylsalicylic acid, all of these drugs can inhibit the biosynthesis of prostaglandins, which can affect platelet function. It is necessary to observe patients who may have a negative effect on platelet function.

Elderly age. In general, there is no need for dose adjustment in elderly patients. However, caution should be exercised when selecting a dose, especially when increasing it. In elderly patients, the incidence of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforations, increases (see APPLICATION).

Cardiovascular and cerebrovascular disorders. Patients with hypertension and / or mild to moderate congestive heart failure should have a close observation in history, since fluid retention and edema are noted in the treatment of NSAIDs.

Studies and epidemiological data suggest that the use of certain NSAIDs (especially in high doses and with long-term treatment) is associated with an increased risk of developing vascular thrombotic events (for example, myocardial infarction or stroke). There is insufficient data to exclude such a risk when using etodolac.

In patients with uncontrolled hypertension, congestive heart failure, coronary heart disease, peripheral arterial and / or cerebrovascular disease, etodolac therapy should be carried out only after a thorough analysis.

Such an analysis is necessary at the beginning of long-term treatment of patients with risk factors for cardiovascular diseases (such as hypertension, hyperlipidemia, diabetes mellitus, smoking).

Gastrointestinal Disorders. As with other NSAIDs, potentially fatal gastrointestinal bleeding, ulcer, or perforation can occur at any time during treatment, regardless of the presence of preliminary symptoms or serious gastrointestinal diseases in the anamnesis.

The risk of gastrointestinal bleeding, ulcers or perforation is higher with an increase in the dose of NSAIDs in patients with a history of ulcer, especially complicated by bleeding or perforation (see CONTRAINDICATIONS), and in elderly patients. Such patients should begin treatment with a minimum effective dose. For such patients, as well as for patients requiring the simultaneous use of a low dose of acetylsalicylic acid or other drugs that increase gastrointestinal risks, combination therapy with protective drugs (such as misoprostol or proton pump inhibitors) should be considered (see INTERACTIONS).

Patients with a history of gastrointestinal toxicity, especially the elderly, should be advised of all unusual abdominal symptoms (especially gastrointestinal bleeding), mainly in the initial stages of treatment.

Caution should be exercised in patients taking concomitant drugs that increase the risk of ulcers or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid (see INTERACTIONS).

If gastrointestinal bleeding or ulcers occur in patients using etodolac, treatment should be discontinued.

NSAIDs should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohns disease), as these conditions may worsen (see ADVERSE EFFECTS).

Systemic lupus erythematosus and connective tissue disease. In patients with systemic lupus erythematosus and connective tissue diseases, the risk of developing aseptic meningitis is increased (see ADVERSE EFFECTS).

Violations of the skin. When applying NSAIDs, severe skin reactions were very rarely observed, some of them were fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (see ADVERSE EFFECTS). The highest risk of such reactions is fixed at the beginning of treatment, while in most cases, such reactions appeared during the 1st month of treatment. At the first appearance of skin rashes, lesions of the mucous membranes or other signs of hypersensitivity, it is necessary to stop the use of etodolac.

Fertility. Etodolac may affect reproductive function. The drug is not recommended for women who want to become pregnant. For women who are planning a pregnancy or are being examined for infertility, consideration should be given to discontinuing etodolac.

The drug contains lactose, so it should not be used for hereditary galactose intolerance, Lapp lactase deficiency or impaired glucose-galactose malabsorption.

During pregnancy and breastfeeding. The drug is contraindicated during pregnancy or lactation.

Children. Do not use in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. The use of etodolac can cause dizziness, drowsiness, weakness, and visual impairment. This should be considered by patients when driving vehicles or other mechanisms. If such reactions occur, patients should avoid driving vehicles or other mechanisms.

Interactions

Since etodolac binds to blood proteins, it may be necessary to change the dose of other drugs that also bind well to blood proteins.

Other analgesics, including selective COX-2 inhibitors. Avoid the simultaneous use of two or more NSAIDs (including acetylsalicylic acid), as the risk of side effects increases (see SPECIAL INSTRUCTIONS).

Antihypertensive drugs. Reduces hypotensive effect.

Diuretics. Reduces diuretic effect. Diuretics increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides. NSAIDs can exacerbate heart failure, reduce glomerular filtration rate and increase blood glycosides.

Lithium. Lithium excretion is reduced.

Methotrexate. The excretion of methotrexate is reduced.

Cyclosporin. Nephrotoxicity associated with cyclosporine may increase.

Mifepristone NSAIDs should not be used within 8-12 days after the use of mifepristone, since NSAIDs can reduce the effect of mifepristone.

Corticosteroids. An increased risk of gastrointestinal ulcers or bleeding (see SPECIAL INSTRUCTIONS).

Anticoagulants. NSAIDs may enhance the effects of anticoagulants such as warfarin (see SPECIAL INSTRUCTIONS). 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 taking NSAIDs and quinolone antibiotics have an increased risk of developing seizures.

Antithrombotic drugs and serotonin selective uptake inhibitors. The risk of gastrointestinal bleeding increases (see SPECIAL INSTRUCTIONS).

Tacrolimus. With the simultaneous use of NSAIDs with tacrolimus, the risk of nephrotoxicity increases.

Zidovudine. The risk of hematotoxicity increases with the simultaneous use of NSAIDs with zidovudine. There is evidence of an increased risk of hemarthrosis and hematoma in HIV-positive hemophilia patients who take zidovudine and ibuprofen at the same time.

Phenylbutazone The simultaneous use of phenylbutazone and etodolac is not recommended, since phenylbutazone increases (up to about 80%) the free fraction of etodolac. No in vivo studies have been performed.

Antacids. With the simultaneous use of antacids, there is no effect on the overall absorption of etodolac. Antacids can reduce the peak concentration of etodolac by 15–20%, but the determining effect on C_max they do not render.

Laboratory data. When using etodolac, a false-positive test result for bilirubin is possible due to the presence of phenolic metabolites of etodolac in urine.

Overdose

Overdose symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhea, disorientation, agitation, coma, drowsiness, dizziness, tinnitus, fainting, and sometimes cramping. in the event of a significant overdose, arthritis and liver damage are possible.

The treatment is symptomatic. Activated charcoal must be taken within 1 hour after taking a potentially toxic amount of the drug. In adults, gastric lavage is necessary for 1 hour after taking the amount of a life-threatening drug. Adequate diuresis should be provided, and kidney and liver function should be monitored. It is necessary to observe patients for at least 4 hours after taking a potentially toxic amount of the drug. In case of frequent and prolonged seizures, diazepam is necessary. Other measures may be required depending on the patient’s clinical condition.

Storage conditions

In a dry, dark place at a temperature of no higher than 25 ° C.