Etoricoxib

Etoricoxib (:中文 依托昔布) is a nonsteroidal anti-inflammatory drug, an NSAID, selectively inhibit cyclo- oxygenase-2 (COX-2). As an NSAID, celecoxib is an analgesic, anti-inflammatory and antipyretic.

Clinical indications for indomethacin include:

Musculoskeletal and joint disorders

• rheumatoid arthritis
• alkylosing spondylitis
• osteoarthritis
• gouty arthritis
• acute painful shoulder bursitis or tendinitis
• chronic low back pain

It is also used for the short-term treatment of moderate postoperative dental pain.

Drug name

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Etoricoxib tablet 120mg	ETOR06	P1S1S3

Mechanism of Action

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

Dosage

Osteoarthritis	Oral : 30 mg daily once daily, increased to 60 mg once daily if necessary.
Rheumatoid arthritis and ankylosing spondylitis	Oral: 60 mg once daily, increased to 90 mg once daily if necessary.
Gouty arthritis	Oral : 120 mg once daily. Such higher doses should only be used for acute symptomatic period and for a maximum of 8 days.
Postoperative dental pain	Oral : 90 mg once daily for a maximum of 3 days.
Administration in hepatic impairment	Mild hepatic impairment : 60 mg once daily Moderate hepatic impairment : 60 mg every other day or 30 mg once daily. Etoricoxib should not be given to patients with severe hepatic impairment.

Side Effects

Common side effects	Abdominal pain, nausea, diarrhea
Serious side effects	Heart attacks, strokes, gastrointestinal perforation, gastrointestinal bleeding, kidney failure

It is generally accepted that COX-2 inhibitor may cause less gastrotoxicity than that seen with the non-selective inhibition of the traditional NSAIDs. However, reports that upper gastrointestinal perforation, ulceration and bleeds have occurred with etoricoxib treatment and should not be used in patients with active gastrointestinal ulceration or bleeding.

Pharmacokinetics

Peak plasma concentrations occur in about 1 hour in fasted adults; food delays absorption by about 2 hours.

Plasma protein binding is about 92%. Celecoxib is metabolized in the liver mainly by the cytochrome P450 isoenzyme CYP3A4. It is eliminated mainly as metabolites in the urine (70%) and 20% in the faeces.

The plasma elimination half-life is about 22 hours.

Celecoxib is distributed into breast milk.

Drug Management

Monitoring

• Regular physical examination to detect edema and signs of central nervous side effects.
• High Blood pressure should be controlled before starting treatment and monitored for 2 weeks afterwards ten regularly thereafter.
• Periodic serum electrolyte (sodium, potassium, chloride) measurements
• complete blood counts and
• 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

• the metabolism of etoricoxib is mediated by the cytochrome P450 isoenzyme CYP3A4. Use of other drugs that inhibit or induce by this isoenzyme may result in changes in plasma concentration of etoricoxib. Rifampicin, a potent inducer of CYP isoenzymes, has decreased plasma concentrations of etoricoxib
• 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.
• Increase risk of kidney failure if given with ACE inhibitors such as lisinopril, ciclosporin, tacrolimus and diuretics, such as hydrochlorothiazide.
• Increase risk of hyperkalaemia with ACE inhibitors and potassium-sparing diuretics such as spironolactone.
• 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.

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

• Allergy to aspirin or other NSAIDs
• Avoided in patients with severer hepatic impairment
• Contraindicated during pregnancy and in breast-feeding 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 class II to 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
• Concurrent with potassium sparing diuretics
• Can lead to onset of new hypertension or worsening of pre-existing hypertension

Note

• Etoricoxib should not be used after coronary artery bypass surgery as there may be an increased risk of adverse effects such as myocardial infarction and stroke.
• It should be used with caution, if at all, in patients with a history of ischaemic heart disease, peripheral arterial disease, or cerebrovascular disease.

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.