Celebrex Clinical Pharmacology

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Celebrex - Clinical Pharmacology [celecoxib]

Use with Aspirin:

The Celecoxib Long-Term Arthritis Safety Study (CLASS) was a prospective long-term safety outcome study conducted postmarketing in approximately 5,800 OA patients and 2,200 RA patients. Patients received CELEBREX 400 mg BID (4-fold and 2-fold the recommended OA and RA doses, respectively, and the approved dose for FAP), ibuprofen 800 mg TID or diclofenac 75 mg BID (common therapeutic doses).

Median exposures for CELEBREX (n = 3,987) and diclofenac (n = 1,996) were 9 months while ibuprofen (n = 1,985) was 6 months. The Kaplan-Meier cumulative rates at 9 months are provided for all analyses. The primary endpoint of this outcome study was the incidence of complicated ulcers (gastrointestinal bleeding, perforation or obstruction). Patients were allowed to take concomitant low-dose ( 325 mg/day) aspirin (ASA) for cardiovascular prophylaxis (ASA subgroups: CELEBREX, n = 882; diclofenac, n = 445; ibuprofen, n = 412).

Differences in the incidence of complicated ulcers between CELEBREX and the combined group of ibuprofen and diclofenac were not statistically significant. Those patients on CELEBREX and concomitant low-dose ASA experienced 4-fold higher rates of complicated ulcers compared to those not on ASA (see WARNINGS - Gastrointestinal (GI) Effects). The results for CELEBREX are displayed in Table 4. For complicated and symptomatic ulcer rates, see WARNINGS - Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation.

Table 4
Effects of Co-Administration of Low-Dose Aspirin on Complicated Ulcer Rates with
CELEBREX 400 mg BID (Kaplan-Meier Rates at 9 months [%])
Non-Aspirin Users Aspirin Users
n=3105 n=882
Complicated Ulcers 0.32 1.12
Platelets:

In clinical trials, CELEBREX at single doses up to 800 mg and multiple doses of 600 mg BID for up to 7 days duration (higher than recommended therapeutic doses) had no effect on platelet aggregation and bleeding time. Comparators (naproxen 500 mg BID, ibuprofen 800 mg TID, diclofenac 75 mg BID) significantly reduced platelet aggregation and prolonged bleeding time.

Because of its lack of platelet effects, CELEBREX is not a substitute for aspirin for cardiovascular prophylaxis.