Etodolac 2care4

Etodolac.

Light brown, oblong, biconvex film-coated tablets.
Each tablet: Drug substance: Etodolac 200 mg.
Excipients/Inactive Ingredients: Microcrystalline cellulose MC-102, lactose monohydrate 200, povidone K30, sodium starch glycolate type A, magnesium stearate, opadry II 85F38197.

Pharmacotherapeutic group: Nonsteroidal anti-inflammatory drug. ATC code: M01AB08.
Pharmacology: Pharmacodynamics: Anti-inflammatory activity, analgesic activity, antipyretic activity.
Inhibitory activity on the synthesis of prostaglandins.
Inhibitory activity on platelet aggregation.
Pharmacokinetics: Absorption: Etodolac is rapidly absorbed orally: The serum peak is reached approximately 1 hour after administration. Bioavailability is high (close to 100 percent). Taking etodolac with meals does not affect the amount of drug absorbed but does delay the onset of peak plasma levels.
Distribution: Etodolac is extensively bound to plasma proteins (greater than or equal to 99 percent). The volume of distribution is 0.4 1/kg. The elimination half-life is approximately 7 hours. In plasma, etodolac is found primarily in the unconjugated and glucuronide form.
Elimination: Etodolac is eliminated mainly via the urine (75 percent) in the hydroxylated and glucuronide form and via the faeces (25 percent).
The pharmacokinetic parameters of bioavailability and the elimination half-life are identical in young subjects and subjects over 65 years of age.
Renal impairment appears to have little effect on the pharmacokinetics of etodolac.

Long-term symptomatic treatment: Chronic inflammatory rheumatism, in particular rheumatoid arthritis, ankylosing spondylitis; certain painful and disabling osteoarthritis.
Short-term symptomatic treatment of acute flare-ups of osteoarthritis (coxarthrosis, gonarthrosis).
Short-term symptomatic treatment of: Acute attacks of abarticular rheumatism (acute painful shoulder, tendonitis, bursitis); severe lumbo radiculalgia.

Posology: The occurrence of adverse reactions may be minimized by using the lowest possible dose for the shortest treatment duration necessary to relieve symptoms.
Average dose: 400 mg/day; one 200 mg tablet in the morning and one 200 mg tablet in the evening, preferably between meals.
The dosage can be adapted in certain patients depending on the acute or chronic nature of the condition and increased, for example, to 200 mg or 600 mg/day.
Usual dosage for short-term attack treatment of: Acute attacks of abarticular rheumatism (acute painful shoulder, tendonitis, bursitis); low back pain, severe radiculalgia: 600 mg/day in 3 intakes morning-midday and evening preferably in the middle of meals.
Method of administration: Oral route.
Reserved for adults and children over 15 years old.
The tablets are to be swallowed whole, without chewing them with a glass of water, preferably during meals.

In case of overdose, symptomatic treatment will be instituted.

This drug is contraindicated in the following situations: Hypersensitivity to the active substance or to any of the excipients; history of allergy or asthma triggered by taking this medicine or substances with close activity such as other NSAIDs, acetylsalicylic acid; pregnancy, from the beginning of the 6th month (beyond 24 weeks of amenorrhea); history of gastrointestinal bleeding or perforation during previous treatment with NSAIDs; active peptic ulcer, history of peptic ulcer or recurrent bleeding (2 or more distinct episodes of bleeding or ulceration objectified); severe hepatocellular insufficiency; severe kidney failure; severe heart failure; child under 15 years old.
This medicine should generally not be used in combination with: Oral anticoagulants, other NSAIDs (including salicylates from 3 g/day in adults); heparin; lithium; methotrexate from 20 mg/week, pemetrexed.

Special warnings: Concomitant use of etodolac 200 mg with other NSAIDs, including selective cyclooxygenase 2 (cox-2) selective inhibitors, should be avoided.
The occurrence of undesirable effects can be minimized by using the lowest possible dose for the shortest treatment duration necessary to relieve symptoms.
Patients with asthma associated with chronic rhinitis, chronic sinusitis and/or nasal polyposis have a higher risk of allergic manifestation when taking acetylsalicylic acid and/or non-steroidal anti-inflammatory drugs than the rest of the population. Administration of etodolac may lead to an asthma attack, particularly in certain subjects allergic to acetylsalicylic acid or to an NSAID.
Gastrointestinal effects: Gastrointestinal bleeding, ulceration or perforation, sometimes fatal, have been reported with all NSAIDs at any time during treatment, without necessarily having any warning signs or a history of adverse effects, serious gastrointestinal illnesses.
The risk of gastrointestinal haemorrhage, ulceration or perforation increases with the dose used in patients with a history of ulcer, particularly in the event of complications such as haemorrhage or perforation as well as than in the elderly. In these patients, treatment should be started at the lowest posology possible. Mucosal protective therapy (e.g. misoprostol or proton pump inhibitor) should be considered for these patients, as for patients requiring treatment with low dose acetylsalicylic acid or treated with other drugs likely to increase gastrointestinal risk. Patients with a gastrointestinal history, especially elderly patients, should report any unusual abdominal symptoms (especially gastrointestinal bleeding), especially at the start of treatment. Particular attention should be paid to patients receiving concomitant treatments which may increase the risk of ulceration or bleeding, such as corticosteroids administered orally, oral anticoagulants such as warfarin, selective inhibitors of the reuptake of serotonin (SSRI) and antiplatelet agents such as acetylsalicylic acid.
In the event of onset of haemorrhage or ulceration occurring in a patient receiving etodolac 200 mg treatment must be stopped.
NSAIDs should be administered with caution and under close monitoring in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease), due to a risk of aggravation of the pathology.
Cardiovascular and cerebrovascular effects: Adequate monitoring and recommendations are required in patients with a history of hypertension and/or mild to moderate heart failure, cases of fluid retention and edema having been reported in association with NSAID treatment.
Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially when used at high doses and over a long period) may be associated with a small increased risk of arterial thrombotic events (eg, heart attack myocardium or stroke). There are currently insufficient data to rule out this increased risk for etodolac.
Patients with uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or a history of stroke (including transient ischemic attack) should not be treated with etodolac only after a careful assessment of the benefit/risk ratio.
Similar attention should be paid before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as hypertension, hyperlipidaemia, diabetes or smoking).
Skin effects: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndromes and Lyell's syndromes have been reported very rarely during treatment with NSAIDs.
The incidence of these adverse effects seems to be greater at the start of treatment, the time to onset being, in the majority of cases, during the first month of treatment. Etodolac 200 mg should be discontinued as soon as a skin rash, mucosal lesions or any other sign of hypersensitivity appear.
Functional renal failure: NSAIDs, by inhibiting the vasodilating action of renal prostaglandins, are liable to cause (functional renal failure by reduction in glomerular filtration. This side effect is dose dependent.
At the start of treatment or after a dose increase, monitoring of diuresis and renal function is recommended in patients with the following risk factors: Elderly subjects; associated medications such as: ACE inhibitors, sartans, diuretics; hypovolaemia whatever the cause; heart failure; chronic renal failure; nephrotic syndrome; lupus nephropathy; decompensated hepatic cirrhosis.
Water and sodium retention: Water and sodium retention with possibility of oedema, hypertension or increase in hypertension, worsening of heart failure. Clinical monitoring is necessary from the start of treatment in the event of hypertension or heart failure. A decrease in the effect of antihypertensives is possible.
Hyperkalemia: Hyperkalaemia favored by diabetes or concomitant treatment with hyperkalaemic medicinal products.
Regular monitoring of serum potassium should be performed in these circumstances.
Cardiovascular thromboembolic risk: Systemic non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur as early as the first few weeks of treatment and may increase with duration of use. The risk of cardiovascular thromboembolic events has been observed mainly at high doses.
Physicians should periodically evaluate patients for the occurrence of cardiovascular events, even if they have no previous cardiovascular symptoms. Patients should be warned about the symptoms of serious cardiovascular events and should seek medical attention immediately if these symptoms occur.
To minimize the risk of adverse events, use the lowest effective daily dose for the shortest possible duration.
This medicine contains lactose. Its use is not recommended in patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases).
This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially 'sodium free'.
Effects on Ability to Drive and Use Machines: The drug has minor or moderate influence on the ability to drive and use machines because it can cause headaches, slight feelings of dizziness and fatigue.
Use in Pregnancy & Lactation: Precautions for use: Etodolac, like any drug that inhibits the synthesis of cyclooxygenases and prostaglandins, can impair fertility. Its use is not recommended in women who wish to conceive a child.
Use in the Elderly: Elderly are at increased risk of adverse reactions to NSAIDs, in particular gastrointestinal bleeding and perforation which may be fatal.

Pregnancy: Inhibition of prostaglandin synthesis by NSAIDs may affect the course of pregnancy and/or the development of the embryo or foetus.
Risks associated with use during the 1st trimester: Data from epidemiological studies suggest an increased risk of miscarriage, heart defects and gastroschisis after treatment with a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of cardiovascular malformation has increased from less than 1% in the general population to approximately 1.5% in people exposed to NSAIDs. The risk appears to increase with dose and duration of treatment. In animals, administration of a prostaglandin synthesis inhibitor has been shown to cause increased pre- and post-implantation loss and increased embryo-foetal lethality. In addition, a higher incidence of certain malformations, including cardiovascular, has been reported in animals given a prostaglandin synthesis inhibitor during the organogenesis phase of gestation.
Risks associated with use from the 12th week of amenorrhea until birth: From the 12th week of amenorrhea and until birth, all NSAIDs, by inhibiting the synthesis of prostaglandins, can expose the fetus to renal functional impairment: In utero which can be observed from 12 weeks of amenorrhea (initiation of fetal diuresis): Oligohydramnios (most often reversible when treatment is stopped), or even anamnios in particular during prolonged exposure.
At birth, renal failure (reversible or not) may persist, particularly in the event of late and prolonged exposure (with a risk of severe delayed hyperkalaemia).
Risks associated with use beyond the 24th week of amenorrhea and until birth: Beyond the 24th week of amenorrhea, NSAIDs can expose the fetus to cardiopulmonary toxicity (premature closure of the arterial duct and pulmonary arterial hypertension). Constriction of the arterial duct can occur from the beginning of the 6th month (beyond the 24th week of amenorrhea) and can lead to fetal or neonatal right heart failure or even fetal death in utero. This risk is all the more important as the catch is close to the end (less reversibility). This effect exists even for a onetime shot.
At the end of pregnancy, the mother and the newborn may present: A prolongation of the bleeding time due to an anti-aggregating action which may occur even after administration of very low doses of medicinal product; inhibition of uterine contractions leading to delayed delivery or prolonged labour.
Consequently: Unless absolutely necessary, this medicine should not be prescribed to a woman planning a pregnancy or during the first 5 months of pregnancy (first 24 weeks of amenorrhea). If this medicine is administered to a woman wishing to become pregnant or less than 6 months pregnant, the dose should be as low as possible and the duration of treatment as short as possible. Prolonged intake is strongly discouraged.
From the beginning of the 6th month (beyond 24 weeks of amenorrhea): any intake of this medicine, even occasionally, is contraindicated. Inadvertent use from this date justifies cardiac and renal, fetal and/or neonatal monitoring depending on the term of exposure. The duration of this monitoring will be adapted to the elimination half-life of the molecule.
Breastfeeding: As NSAIDs pass into breast milk, this medication is not recommended for breastfeeding women.

Clinical studies and epidemiological data suggest that the use of certain NSAIDs (especially when used at high doses and over a long period) may be associated with a small increased risk of an arterial thrombotic event (e.g. heart attack myocardium or cerebrovascular accident).
Gastrointestinal effects: The most frequently observed side effects are of a gastrointestinal nature. Peptic ulcers, perforations or gastrointestinal bleeding, sometimes fatal, may occur, particularly in the elderly.
Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, ulcerative stomatitis, abdominal pain, melaena, haematemesis, exacerbation of recto-colitis or Crohn's disease have been reported following administration of NSAIDs. Less frequently, gastritis has been observed.
Cardiovascular effects: Edema, hypertension and heart failure have been reported in association with NSAID treatment.
Rarely have been reported: Increased blood pressure, tachycardia, chest pain, arrhythmia, palpitations, hypotension, congestive heart failure.
Hypersensitivity reactions: Respiratory: possibility of occurrence of an asthma attack, in particular in subjects allergic to aspirin and other non-steroidal anti-inflammatory drugs.
Skin reactions: Very rarely bullous reactions (including Stevens-Johnson syndrome and Lyell's syndrome) have been observed.
Also reported: Rash, urticaria and aggravation of chronic urticaria, pruritus, purpura.
Cases of photosensitization have been exceptionally reported.
Biological changes: Liver: Transient and minimal elevation of serum transaminases.
Central Nervous System Effects: Headaches, slight feelings of dizziness and fatigue have been reported.
Kidney effects: Water and sodium retention, hyperkalaemia.
Functional acute renal failure (ARF) in patients with risk factors.
Organic kidney damage that may result in an ARF: Isolated cases of interstitial nephritis, acute tubular necrosis, nephrotic syndrome, papillary necrosis have been reported.
Cardiovascular thromboembolic risk (see also Precautions).
"Any adverse drug reactions should be immediately reported to the physician".

Risk related to hyperkalemia: Certain drugs or therapeutic classes are likely to promote the occurrence of hyperkalaemia: Potassium salts, hyperkalaemic diuretics, converting enzyme inhibitors, angiotensin II antagonists, non-steroidal anti-inflammatory drugs, heparins (low molecular weight or unfractionated), immunosuppressants such as ciclosporin or tacrolimus, trimethoprim. The combination of these drugs increases the risk of hyperkalaemia. This risk is particularly high with potassium-sparing diuretics, especially when they are combined with each other or with potassium salts, while the combination of an ACE inhibitor and an NSAID has a lower risk.
To know the risks and levels of constraints specific to hyperkalaemic drugs, it is advisable to refer to the interactions specific to each substance.
However, some medications such as trimethoprim, are not the subject of specific interactions with regard to this risk. Nevertheless, they can act as contributing factors when combined with other drugs such as those mentioned previously.
Simultaneous administration of etodolac with the following products requires careful monitoring of the patient's clinical and biological status.
Combinations not recommended: Oral anticoagulants: Increased risk of bleeding from oral anticoagulant (aggression of the gastroduodenal mucosa by NSAIDs). NSAIDs may potentiate the effects of anticoagulants, such as warfarin.
If the association cannot be avoided, close clinical and biological monitoring.
Other NSAIDs: Increased risk of ulcerogenic and gastrointestinal bleeding.
Acetylsalicylic acid at anti-inflammatory doses (≥1 g per dose and/or ≥3 g per day), and at analgesic or antipyretic doses (≥500 mg per dose and/or <3 g per day): Increased risk of ulceration and gastrointestinal bleeding.
Unfractionated heparins, low molecular weight heparins and related (at curative doses and/or in the elderly): Increased risk of bleeding (inhibition of platelet function and aggression of the gastroduodenal mucosa by NSAIDs).
If the association cannot be avoided, close clinical (and biological for unfractionated heparins) monitoring.
Lithium: Increase in lithium which can reach toxic values (decrease in renal excretion of lithium). If the combination cannot be avoided, closely monitor the lithium and adapt the lithium dosage during the combination and after stopping the nonsteroidal anti-inflammatory drug.
Methotrexate used at doses greater than or equal to 20 mg/week: Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory drugs).
Pemetrexed (patients with low to moderate renal function, creatinine clearance between 45 mL/min and 80 mL/min): Risk of increased toxicity of pemetrexed (decreased renal clearance by NSAIDs).
Combinations subject to precautions for use: Ciclosporin, tacrolimus: Risk of addition of nephrotoxic effects, especially in the elderly.
Monitor renal function at the start of treatment with NSAIDs.
Diuretics, ACE inhibitors, angiotensin II receptor antagonists: Acute renal failure in patients at risk (elderly and/or dehydrated subject) by reduction in glomerular filtration (inhibition of vasodilator prostaglandins by NSAIDs).
Moreover, reduction of the antihypertensive effect.
Hydrate the patient; Look at the kidney function at the start of the treatment.
Methotrexate used at doses less than or equal to 20 mg/week: Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory drugs).
Weekly control of the blood count during the first weeks of the association.
Increased monitoring in the event of impairment (even slight) of renal function, as well as in the elderly.
Pemetrexed (patients with normal kidney function): Risk of increased toxicity of pemetrexed (decreased renal clearance by NSAIDs).
Biological monitoring of the renal function.
Associations to consider: Acetylsalicylic acid at anti-aggregation doses (from 50 mg to 375 mg per day in 1 or more doses): Increased risk of ulceration and gastrointestinal bleeding.
Glucocorticoids (except hydrocortisone in replacement therapy): Increased risk of gastrointestinal ulceration and bleeding.
Antiplatelet drugs and serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding.
Unfractionated heparins, low molecular weight heparins (preventive doses): Increased risk of bleeding.
Beta-blockers (except esmolol): Reduction of the antihypertensive effect (inhibition of vasodilating prostaglandins by NSAIDs and water and sodium retention with pyrazole NSAIDs).
Deferasirox: Increased risk of ulcerogenic and digestive bleeding.

Store below 30°C.
Shelf-Life: 36 months from date of manufacture.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AB08 - etodolac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.