Comprehensive Monograph on Celecoxib (DrugBank ID: DB00482)

Executive Summary

Celecoxib is a potent non-steroidal anti-inflammatory drug (NSAID) that represents a distinct therapeutic class as the only orally available selective cyclooxygenase-2 (COX-2) inhibitor in the United States. Its primary mechanism involves the targeted inhibition of the COX-2 enzyme, which is induced during inflammation, thereby reducing the synthesis of pain- and inflammation-mediating prostaglandins. This selectivity allows it to spare the constitutively expressed COX-1 enzyme, which is responsible for gastrointestinal (GI) mucosal protection and platelet function. Consequently, celecoxib offers comparable analgesic and anti-inflammatory efficacy to traditional non-selective NSAIDs like ibuprofen and naproxen, but with a significantly lower risk of GI ulceration and bleeding.

The drug is approved for a range of conditions, including osteoarthritis, rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, acute pain, primary dysmenorrhea, and, in an oral solution formulation, acute migraine. It also holds a unique indication for reducing adenomatous colorectal polyps in patients with familial adenomatous polyposis (FAP). Pharmacokinetically, celecoxib is characterized by rapid absorption, extensive tissue distribution, and a half-life of approximately 11 hours. Its metabolism is critically dependent on the cytochrome P450 isoenzyme CYP2C9, a pathway subject to significant genetic polymorphism and drug-drug interactions, necessitating careful dose consideration in poor metabolizers and with co-administration of CYP2C9 inhibitors.