Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin.
OBJECTIVE
Data on file with the US FDA, and other published studies, suggest that the selective cyclo-oxygenase (COX)-2 inhibitor NSAID rofecoxib has a greater hypertensive adverse effect than other NSAIDs, including celecoxib. In this study we describe a pharmacoepidemiologic analysis of spontaneous adverse event reports of acute, clinically serious hypertension (as defined by hospitalisation) reported in association with rofecoxib, celecoxib, nabumetone and oxaprozin. The objective of this analysis is to assess whether postmarketing data are consistent with results of clinical trials. We also collapse cases into series for the identification of possible risk factors for clinically severe, NSAID-associated hypertension.


METHODS
Domestic (US) cases of apparently unconfounded, acute hypertension leading to hospitalisation were collected and reviewed from the spontaneous adverse events database of the FDA for rofecoxib, celecoxib, nabumetone and oxaprozin for the initial 3 years of marketing. Drug use data for the same intervals enabled calculation of reporting rates.


RESULTS
In an analysis of reporting rates, hospitalisation for acute blood pressure (BP) elevation was reported more frequently (3.8-fold) for rofecoxib compared with celecoxib. A total of 34 cases are collapsed into case series. No cases were identified for either nabumetone or oxaprozin. Inspection of reviewed cases for celecoxib and rofecoxib suggest that these patients (average age 72 years) were potentially high-risk candidates for NSAID therapy.


CONCLUSIONS
During early marketing, hospitalisation for acute BP elevation appears to have been reported more frequently for rofecoxib compared with celecoxib. This is consistent with clinical trial data on file with the FDA, and other published studies that found rofecoxib to have a greater effect on BP than other NSAIDs, including celecoxib. This finding may be particularly relevant in older patients given the prevalence of hypertension and cardiovascular disease in this age group.
Brinker
Allen
A
Division of Drug Risk Evaluation, Office of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20875, USA. brinkera@cder.fda.gov
Goldkind
Lawrence
L
Bonnel
Renan
R
Beitz
Julie
J
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002074:Butanones / Q000009:adverse effects*; D000068579:Celecoxib; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D000077430:Nabumetone; D000077431:Oxaprozin; D011422:Propionates / Q000009:adverse effects*; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000009:adverse effects*; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D011422:Propionates; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D000077430:Nabumetone; D000077431:Oxaprozin