Etodolac

Etodolac (中文: 依托多拉克)is a nonsteroidal anti-inflammatory drug, an NSAID, with a preferential inhibitor of cyclo-oxygenase-2 (COX-2). As an NSAID, etodolac is an analgesic, anti-inflammatory and antipyretic. It has been used in musculoskeletal and joint disorders such as ankylosing spondylitis, osteoarthritis, rheumatoid arthritis including juvenile idiopathic arthritis, in soft-tissue disorders, in acute gout and in postoperative pain.

Drug Names

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Etodolac Capsule 200mg	n/a	P1S1S3

Mechanism of Action

Anti-inflammatory agent, Non-steroidal anti-inflammatory drug (NSAID) selective COX-2 inhibitor

Dosage

Treatment of rheumatoid arthritis and osteoarthritis	Oral: initially 600 to 1000 mg daily in divided doses adjusted to response to a maintenance dose of 300 to 600 mg daily. Modified-release preparations are available for once-daily use in stable conditions.
Treatment of acute pain	Oral: 200 to 400 mg every 6 to 8 hours, to a maximum of 1 g daily. Piroxicam has been given in similar doses as a rectal suppository or on a short-term basis by intramuscular injection. Piroxicam is one of the few NSAIDs that can be given parenteral routes.

Administration in children

Etodolac has been used in children with juvenile idiopathic arthritis according to body-weight. For children 6 years and above:

20-30kg	Oral : 400mg daily
31-45kg	Oral : 600mg daily
46-60kg	Oral : 800mg daily
over 60kg	Oral : 1000mg

Side Effects

As with other NSAIDs the principal side effects include:

• Digestive complaints like nausea, heartburn, diarrhoea and bleeds or ulceration of the stomach
• Headache, dizziness, depression, drowsiness, insomnia
• Hearing disturbances such as tinnitus
• High blood pressure, oedema
• Skin reactions (including, albeit rarely, Stevens-Johnson syndrome and toxic epidermal necrolysis)
• And rarely, kidney failure, pancreatitis and liver damage

Etodolac is a preferential inhibitor of cyclo-oxygenase-2 (COX-2) and consequently it has less gastric toxicity than the non-selective NSAIDs such as naproxen.

Pharmacokinetics

Peak plasma concentrations occur within about 2 hours of an oral dose. The plasma elimination half-life is about 7 hours.

Drug Management

Monitoring

• Regular physical examination to detect edema and signs of central nervous side effects.
• Blood pressure checks will reveal development of hypertension.
• Periodic serum electrolyte (sodium, potassium, chloride) measurements,
• complete blood counts
• assessment of liver enzymes as well as creatinine (renal function) should be performed.

This is particularly important if Indomethacin is given together with an ACE inhibitor or with potassium-sparing diuretic (e.g. spironolactone), because these combinations can lead to hyperkalemia and/or serious kidney failure.

Drug Interaction

• Increases the blood thinning effects of warfarin by displacing them from their plasma protein binding and increases their free concentrations in the bloodstream, so increases the risk of bleeding
• Increase the risk of adverse effects of lithium, methotrexate and cardiac glycosides by lowering their excretion via the kidneys.
• Risk of nephrotoxicity may be increased if given with ACE inhibitors, ciclosporin, tacrolimus or diuretics
• Combination with antihypertensive drugs such as ACE inhibitors, sartans and diuretics can decrease their effectiveness as well as increase the risk for kidney toxicity.
• Antihypertensive effects of ACEIs, beta blockers and diuretics may be reduced
• Use of more than one NSAID together (including aspirin) should be avoided because of the increased risk of adverse effects.
• It adds to the risk of gastrointestinal bleeding and ulceration when used with steroids, the SSRIs (such as sertraline or fluoxetine), the SNRI venlafaxaine, the antiplatelet clopidogrel, bisphosphonates or pentoxifylline.
• Concomitant use of ritonavir and piroxicam may result in increased plasma concentrations of piroxicam.

Many NSAIDs, but particularly indomethacin, cause lithium retention by reducing its excretion by the kidney. Thus, indomethacin users have an elevated risk of lithium toxicity. For patients taking lithium (e.g. for treatment of bipolar disorder), less toxic NSAIDs such as sulindac is preferred. All NSAIDs, including indomethacin, also increase plasma renin activity and aldosterone levels, and increase sodium and potassium retention. Vasopressin activity is also enhanced. Together these may lead to:

• Edema (swelling due to fluid retention
• Hyperkaelemia (high potassium levels)
• Hypernatremia (high sodium levels)
• Hypertension

Contraindication

• It should be avoided by children under 12
• People with liver problems
• Allergy to aspirin or other NSAIDs
• Avoided by patients with a history of asthma attacks
• Contraindicated during pregnancy and in lactating women
• Active stomach and/or duodenal ulceration or gastrointestinal bleeding, or history of peptic ulcer disease
• Inflammatory bowel disease such as Crohn’s disease or ulcerative colitis
• Severe congestive heart failure (NYHA III/IV)
• Severe chronic kidney disease (creatinine clearance <30 mi/min)
• Caution in patients with severe, active bleeding such as cerebral hemorrhage
• Caution in patients with fluid retention or heart failure
• Caution in patients with Parkinson’s disease, epilepsy, psychotic disorders (sulindac may worsen these conditions)
• Concurrent with potassium sparing diuretics
• Can lead to onset of new hypertension or worsening of pre-existing hypertension

Note

• Etodolac is best discontinued at least 4 days in advance of surgery because of a mild interference with clotting.
• The presence of phenolic metabolites of etodolac in the urine may give rise to a false-positive reaction for bilirubin.

FAQ

How should I take the tablet?

Should always be taken with food. Nearly all patients benefit from an ulcer protective drug (e.g. antacids, or famotidine 20mg or omeprazole 20 mg at bedtime).

What should I avoid while taking?

Avoid alcohol consumption.

What happen if I overdose?

Contact your primary care doctor. If emergency situation, call 999

What happen if I miss a dose?

Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.