Etopan

/ Taro

Antirheumatic – Management of signs and symptoms: Initially 800-1,200mg/ day in divided doses: 400mg t.i.d or b.i.d, 300mg q.i.d or t.i.d or 600mg b.i.d, followed by dosage adjustment within the range of 600-1,200mg/ day in divided doses (600mg b.i.d or 400mg t.i.d or b.i.d; 300mg q.i.d, t.i.d or b.i.d, 200mg q.i.d or t.i.d). Note: administration on a three-dose a day schedule may provide greater benefit than two divided doses.
The total daily dose of etodolac should not exceed 1,200mg. For patients weighing 60 kg or less – not to exceed a total daily dose of 20mg/kg. As with other NSAIDs, the lowest dose and longest interval should be sought for each patient. Therefore, after observing the response to initial therapy with etodolac, the dose and frequency should be adjusted to suit individual patient’s needs (tolerance and response). In responsive patients, partial symptomatic relief of symptoms usually occurs within 1 or 2 weeks, although maximum effectiveness may occur only after several weeks of therapy.
Analgesia (acute pain) – Initially 400mg followed by 200-400mg every 6-8 hours or 600mg twice daily followed by 600mg once-twice daily, as needed. Not to exceed a total daily dose of 1,200mg. For patients weighing 60 kg or less – not to exceed a total daily dose of 20mg/kg. Onset of action – 30 minutes. Time to peak effect: 1-2 hours. Symptom relief last approximately 5-6 hours following single 400mg doses and up to 8-12 hours in some patients. If a patient taking 400mg doses has adequate pain relief that does not last 8 hours, then 300mg every 6 hours (q.i.d) is a reasonable schedule to try.
During long-term administration the dose of Etopan may be adjusted, up or down, depending on the patient’s clinical response (maximum dose of 1200 mg/day).
As with other NSAIDs, Etopan is preferably taken after meals or with food or antacids to reduce gastrointestinal irritation, especially during chronic use. However, for faster absorption when a rapid initial effect is required, the first 1 or 2 doses may be taken 30 minutes before meals or at least 2 hours after meals. If an antacid is taken concurrently, an aluminum and magnesium-containing formulation may be preferred. It is recommended to take etodolac tablets/ capsules with a full glass of water and that the patient remain in an upright position for 15-30 minutes after administration.
In the treatment of primary dysmenorrhea, maximum benefit is achieved by initiating etodolac therapy as rapidly as possible after the onset of menses. Patients should be advised to avoid alcoholic beverages while under treatment with this medicine.

Treatment of osteoarthritis and rheumatoid arthritis ‐ acute and long term use in the management of signs and symptoms.
Management of pain‐relief of mild to moderate pain, especially when anti‐
inflammatory actions may also be desired, e.g., following dental, obstetric or
orthopedic surgery, and for the relief of musculoskeletal pain due to soft tissue
athletic injuries. Relief of mild to moderate bone pain caused by metastatic
neoplastic disease.
Treatment of acute gouty arthritis or calcium pyrophosphate deposition disease
‐ uricosuric activity, relief of acute attacks, long‐term prophylactic use may decrease the incidence or severity of recurrent acute gout attacks, especially during the early months of antihyperuricemic therapy and in patients unable to tolerate even prophylactic doses of colchicine.
Treatment of nonrheumatic inflammation ‐ e.g. athletic injuries, bursitis, capsulitis, synovitis, tendinitis, tenosynovitis.
Treatment of vascular headache ‐ relieve (when taken at the first sign of onset)
migraine headache or other vascular headaches.
Treatment of dysmenorrhea ‐ relief of the pain and other symptoms of primary
dysmenorrhea.

– Hypersensitivity to etodolac or to any of the excipients.
– NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.
– History of gastrointestinal bleeding or perforation, related to previous NSAID’s therapy.
– Active or history of recurrent peptic ulcer/haemorrhage (two or more distinctepisodes of proven ulceration or bleeding).
– Severe heart failure, hepatic failure and renal failure.
– During the last trimester of pregnancy.

Undesirable effects may be minimized by using the lowest effective dose for the shortest duration necessary to controlsymptoms.
The use of etodolac with concomitant NSAIDs including cyclooxygenase‐2 selective inhibitors should be avoided.
Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation, which may be fatal.
Platelets: Although non‐steroidal anti‐inflammatory drugs do not have the same direct effects on platelets as does aspirin, all drugs which inhibitthe biosynthesis of prostaglandins may interfere, to some extent, with platelet function. Patients receiving etodolac who may be adversely affected by such actions should be carefully observed.
Cardiovascular, Renal and Hepatic Impairment: In patients with renal, cardiac or hepatic impairment especially those taking diuretics and the elderly, renal function should be monitored in these patients. Caution is required since the use of NSAIDs may result in a dose dependent reduction in prostaglandin formation and precipitate renal failure. The dose should be kept as low as possible. However, impairment of renal or hepatic functions due to other causes may alter drug metabolism; patients receiving concomitant long term therapy, especially the elderly, should be observed for potential side effects and their drug doses adjusted as needed, or the drug discontinued.
Patients on long‐term treatment with etodolac should be regularly reviewed as
a precautionary measure e.g.for changes in renal function, haematological
parameters, or hepatic function.
Cardiovascular and cerebrovascular effects: Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestiveheart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for etodolac.
Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with etodolac after careful consideration. Similar consideration should be made before initiating long‐term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).
Dermatological: Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens‐Johnson syndrome, and toxic epidermal necrolysis have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk of these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Etodolac should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
Respiratory disorders: Caution is required if etodolac is administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
SLE and mixed connective tissue disease: In patients with systemic lupus erythematous (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
Impaired female fertility: The use of etodolac may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of etodolac should be considered.
Gastrointestinal bleeding, ulceration and perforation: Serious gastrointestinal adverse effects such as bleeding, ulceration and perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events. If any sign of gastrointestinal bleeding occurs, etodolac should be stopped immediately.
The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID
doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation, and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin or other drugs likely to increase gastrointestinal risk.
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin‐reuptake inhibitors or anti‐
platelet agents such as aspirin.
When GI bleeding or ulceration occurs in patients receiving etodolac, the treatment should be withdrawn.
NSAIDs should be given with care to patients with a history of gastrointestinal
disease (ulcerative colitis, Crohn’s disease) as these conditions may be exacerbated.
Patients with rare hereditary problems or galactose intolerance, the Lap lactase
deficiency or glucose‐galactose malabsorption should not take this medicine.

Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.
Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Cardiovascular and cerebrovascular: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Clinical trial and epidemiological data suggests that use of some NSAID’s (particularly at high doses and in long term treatment)may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction of stroke). Other adverse reactions reported less commonly include:
Endocrine disorders: Oedema, pyrexia.
Musculoskeletal connective tissue and bone disorders: Weakness/malaise
Respiratory thoracic and mediastinal disorders: Dyspnoea.
Neurological and special senses: Visual disturbances, optic neuritis, headaches, paraesthesia, reports of aseptic meningitis (especially in patients with existingauto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiffneck, headache, nausea, vomiting, fever or disorientation, depression, confusion, hallucinations, tinnitus,vertigo, dizziness, malaise, fatigue, tremor, insomnia, and drowsiness.
Dermatological: Bullous reactions including Stevens-Johnson syndrome, and Toxic Epidermal Necrolysis (very rare). Photosensitivity.
Haematological: Thrombocytopenia, neutropenia, agranulocytosis, aplastic anaemia and haemolyticanaemia.
Hepatic: Abnormal liver function, hepatitis and jaundice.
Renal: Bilirubinuria, urinary frequency, dysuria, Nephrotoxicity in various forms including interstitial nephritis, nephrotic syndrome, renal failure.

Corticosteroids: increased risk of gastrointestinal ulceration or bleeding.
Anti‐coagulants: NSAIDs may enhance the effects of anti‐coagulants, such as
warfarin.
Since etodolac is extensively protein ‐ bound, it may be necessary to modify the dosage of other highly protein‐bound drugs.
Bilirubin tests can give a false positive result due to the presence of phenolic metabolites of etodolac in the urine.
Anti‐hypertensives: Reduced anti‐hypertensive effect.
Mifepristone: NSAIDs should not be used for 8 – 12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.
Other analgesics including cyclooxygenase‐2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase
the risk of adverse effects.
Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.
Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and
increase plasma glycoside levels.
Lithium: Decreased elimination of lithium.
Methotrexate: Decreased elimination of methotrexate.
Cyclosporin: Increased risk of nephrotoxicity.
Anti‐platelet agents and selective serotonin reuptake inhibitors (SSRIs):
Increased risk of gastrointestinal bleeding.
Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given
with tacrolimus.
Zidovudine: Increased risk of haematological toxicity when NSAIDs are given
with zidovudine. There is evidence of an increased risk of haemarthroses and
haematoma in HIV(+) haemophiliacs receiving concurrent treatment with
zidovudine and ibuprofen.

Pregnancy: Drugs which inhibit prostaglandin biosynthesis may cause dystocia and delayed parturition as evidenced by studies in pregnantanimals. Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low infrequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child. NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to thepatient outweighs the potential risk to the foetus.
Lactation: In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding.
For full details see prescribing information.

Symptoms: Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, and occasionally convulsions. In cases of significant poisoning acuterenal failure and liver damage are possible.
Therapeutic measure: Patients should be treated symptomatically as required. Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults,gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose. Good urine output should be ensured. Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient’s clinical condition.
The standard practices of gastric lavage, activated charcoal administration and
general supportive therapy should be undertaken.