Clinical Trials Experience: The following adverse drugs reactions (ADRs) in Table 6 were identified with incidence rates greater than 0.01% in celecoxib group and greater than those reported in placebo group, during 12 placebo- and/or active-controlled clinical trials of treatment duration up to 12 weeks at daily doses from 100 mg up to 800 mg in adults.
The frequencies on the ADRs in Table 6 are based on a more recent pooling of 89 randomized, controlled clinical trials data representing clinical exposure in 38,102 patients taking celecoxib. ADR frequencies are defined as: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%), rare (≥0.01% and <0.1%), very rare (<0.01%). The ADRs in Table 6 are listed by system organ class and ranked by frequency in descending order. (See Table 6.)
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The following additional adverse drug reactions in Table 7 were identified with incidence rates greater than placebo in long-term polyp prevention studies of duration up to 3 years at daily doses from 400 mg up to 800 mg. (see Pharmacology: Clinical Studies: CV Safety: Long-Term Studies Involving Patients with Sporadic Adenomatous Polyps under Actions).
Frequencies of ADRs in Table 7 were determined based on these long-term polyp prevention studies and defined as: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%). The ADRs in Table 7 are listed by system organ class and ranked by frequency in descending order. (See Table 7.)
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Post-marketing Experience: Adverse reactions identified from post-marketing experience are provided as follows. Even though these were identified as reactions from post-marketing reports, trial data was consulted to estimate frequency. As above, frequencies are based on a pooling of trials representing exposure in 38,102 patients. Frequencies are defined as: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%), rare (≥0.01% and <0.1%), very rare (<0.01%), not known (cannot be estimated from the available data).
Immune system disorders: Very rare: anaphylactic reaction.
Psychiatric disorders: Rare: hallucination.
Nervous system disorders: Very rare: cerebral haemorrhage, meningitis aseptic, ageusia, anosmia.
Eye disorders: Uncommon: conjunctivitis.
Vascular disorders: Very rare: vasculitis.
Respiratory, thoracic and mediastinal disorders: Rare: pulmonary embolism, pneumonitis.
Gastrointestinal disorders: Rare: gastrointestinal haemorrhage.
Hepato-biliary disorders: Rare: hepatitis; Very rare: hepatic failure, hepatitis fulminant, hepatic necrosis, cholestasis, hepatitis cholestatic, jaundice.
Skin and subcutaneous tissue disorders: Rare: photosensitivity reaction; Very rare: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), dermatitis exfoliative.
Renal and urinary disorders: Rare: renal failure acute, hyponatraemia; Very rare: tubulointerstitial nephritis, nephrotic syndrome, glomerulonephritis minimal lesion.
Reproductive system and breast disorders: Rare: menstrual disorder; Not known: infertility female (female fertility decreased).†
General disorders and administration site conditions: Uncommon: chest pain.
† Women intending to become pregnant are excluded from all trials, thus consultation of the trial database for the frequency of this event was not reasonable.
Safety Data from CLASS Study: Hematological Events: During this study (see Pharmacology: Clinical Studies: Special Studies: Celecoxib Long-term Arthritis Safety Study under Actions), the incidence of clinically significant decreases in hemoglobin (>2 g/dL) confirmed by repeat testing was lower in patients on CELEBREX 400 mg BID (4-fold and 2-fold the recommended OA and RA doses, respectively, and the approved dose for FAP) compared to patients on either diclofenac 75 mg BID or ibuprofen 800 mg TID: 0.5%, 1.3% and 1.9%, respectively. The lower incidence of events with CELEBREX was maintained with or without ASA use (see PHARMACOLOGY: Platelets under Actions).
Withdrawals/Serious Adverse Events: Kaplan-Meier cumulative rates at 9 months for withdrawals due to adverse events for CELEBREX, diclofenac and ibuprofen were 24%, 29%, and 26%, respectively. Rates for serious adverse events (i.e., those causing hospitalization or felt to be life-threatening or otherwise medically significant) regardless of causality were not different across treatment groups, respectively, 8%, 7%, and 8%.
Adverse events from ankylosing spondylitis studies: A total of 378 patients were treated with CELEBREX in placebo- and active-controlled ankylosing spondylitis studies. Doses up to 400 mg QD were studied. The types of adverse events reported in the ankylosing spondylitis studies were similar to those reported in the arthritis studies.
Adverse events from analgesia and dysmenorrhea studies: Approximately 1,700 patients were treated with CELEBREX in analgesia and dysmenorrhea studies. All patients in post-oral surgery pain studies received a single dose of study medication. Doses up to 600 mg/day of CELEBREX were studied in primary dysmenorrhea and post-orthopedic surgery pain studies. The types of adverse events in the analgesia and dysmenorrhea studies were similar to those reported in arthritis studies. The only additional adverse event reported was post-dental extraction alveolar osteitis (dry socket) in the post-oral surgery pain studies.
Adverse events from the controlled trial in familial adenomatous polyposis: The adverse event profile reported for the 83 patients with familial adenomatous polyposis enrolled in the randomized, controlled clinical trial was similar to that reported for patients in the arthritis controlled trials. Intestinal anastomotic ulceration was the only new adverse event reported in the FAP trial, regardless of causality, and was observed in 3 of 58 patients (one at 100 mg BID, and two at 400 mg BID) who had prior intestinal surgery.