Celecoxib (Celebrex)

COX-2 inhibitor to prevent colorectal adenomas caused a dose-related increase in the risk of cardiovascular deaths, myocardial infarctions, strokes and heart failure.

Adenoma Prevention with Celecoxib (APC) (2004) trial stopped prematurely after 3 years because of increased thrombotic events, but a similar trial the Prevention of Spontaneous Adenomatous Polyps (PreSAP) showed no such difference.

PRECISION study evaluated celecoxib for safety in patients with rheumatoid arthritis or osteoarthritis involving more than 24,000 patients assigned to receive celecoxib hundred milligrams b.i.d., ibuprofen at 600 mg three times a day or naproxen 375 mg twice a day: after an average interval of 20 months celecoxib was found to be not inferior to naproxen or ibuprofen, with no increase in cardiovascular events.

Associated with a 1.8 fold increase in the relative risk of adverse GI events compared to non-selective NSAIDs.

Meta-analysis shows increased risk of cardiovascular events by roughly 1/3, and the risk is independent of baseline cardiovascular risk and is increased only when other risk factors are present.

Cox-2 selectivity is low compared to other COX2 inhibitors and similar to diclofenac, meloxicam, and etodolac.

Cardiovascular risk is associated with the degree of COX-2 selectivity.


Brand name Celebrex.

A COX-2 selective nonsteroidal anti-inflammatory drug (NSAID).

Used to treat the pain and inflammation of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute pain in adults, painful menstruation, and juvenile rheumatoid arthritis in people two years or older.

Pregnancy category C Risk not ruled out.

Routes of administration oral.

Protein binding 97%.

Hepatic metabolism, mainly CYP2C9

Biological half-life 7.8 hours, with 11 hours for mild hepatic impairment and 13 hours for moderate-severe hepatic impairment.

Excretion in feces (57%), and urine (27%).

Side effects include a 37% increase in incidence of major vascular events: including nonfatal myocardial infarction, nonfatal stroke, or death from a blood vessel-related cause.

An 81% increase in incidence of upper gastrointestinal complications occurs, which include perforations, obstructions, or gastrointestinal bleeding.

People at high risk for heart disease should only use this agent if there are not other possible treatments.

Costs about five times more than acetaminophen, ibuprofen, or naproxen, which are equally effective for pain relief.

Used to reduce the number of colon and rectal polyps in people with familial adenomatous polyposis.

It may also be used in children with juvenile rheumatoid arthritis who are older than two years of age and weigh more than 10 kg (22 lb).

NSAIDs are associated with an increased risk of serious adverse cardiovascular thrombotic events, including myocardial infarction and stroke.

NSAIDs risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease.

May exacerbate hypertension and may impair response to thiazide or loop diuretics.

May cause sodium and fluid retention.

Used with caution in patients with edema or heart failure.

The lowest effective dose for the shortest duration of time should be used to reduce risk of cardiovascular events.

May increase risk of serious GI ulceration, bleeding, and perforation.

Should be use caution with a history of GI disease, concurrent therapy with aspirin, anticoagulants, corticosteroids, smoking, use of alcohol, the elderly or debilitated.

When used with aspirin, a substantial increase in the risk of gastrointestinal complications occurs and concomitant proton pump inhibitor therapy is recommended.

Anemia may occur in patients on long-term treatment.

Does not usually affect prothrombin time, partial thromboplastin time or platelet counts, and does not inhibit platelet aggregation at approved doses.

Contains a sulfonamide moiety and may cause allergic reactions in those allergic to other sulfonamide-containing drugs.

May cause serious skin adverse events, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; events may occur without warning and in patients without prior known sulfa allergy.

Increases the risk of major cardiovascular problems by about 37%.

Other COX-2-selective inhibitors, such as rofecoxib, have significantly higher myocardial infarction rates than celecoxib.

In a meta-analysis of randomized control studies, the cerebrovascular events associated with COX-2 inhibitors were examined, but no significant risks were found when compared to nonselective NSAIDs or placebos.

A randomized trial found that celecoxib has noninferior cardiovascular safety to ibuprofen or naproxen.

Predominantly metabolized by cytochrome P450 2C9.

Caution with concomitant use of 2C9 inhibitor medications such as fluconazole, which can greatly elevate celecoxib serum levels.

Concomitant use with lithium, can increase lithium plasma levels.

Concomitant use with warfarin, may result in increased risk of bleeding complications.

It may increase the risk of kidney failure with angiotensin-converting enzyme-inhibitors, and diuretics, such as hydrochlorothiazide.

The drug is category C prior to 30 weeks gestation, and category D starting at 30 weeks gestation.

A highly selective reversible inhibitor of the COX-2 isoform of cyclooxygenase.

It inhibits the transformation of arachidonic acid to prostaglandin precursors.

Has antipyretic, analgesic and anti-inflammatory properties.

Nonselective NSAIDs, such as aspirin, naproxen, and ibuprofen, inhibit both COX-1 and COX-2.

Inhibition of COX-1inhibits the production of prostaglandins and the production of thromboxane A2, a platelet activator.

COX-1 plays a role in the protection of the gastrointestinal mucosa, kidney hemodynamics, and platelet thrombogenesis.

COX-2 is extensively expressed in cells involved in inflammation and is upregulated by bacterial lipopolysaccharides, cytokines, growth factors, and tumor promoters.

It is approximately 10-20 times more selective for COX-2 inhibition over COX-1.

This selectivity allows celecoxib and other COX-2 inhibitors to reduce inflammation while minimizing gastrointestinal adverse drug reactions that are more common with nonselective NSAIDs.

It reduces colon polyps, affects genes and pathways involved in inflammation and malignant transformation in tumors, but not normal tissues.

It binds to Cadherin-11.

Available as oral capsules containing 50, 100, 200 or 400 mg of celecoxib.

Studies show a 33 to 45% polyp recurrence reduction in people treated with celecoxib each day, but serious cardiovascular events were significantly more frequent.

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