Celecoxib (Page 3 of 11)
Hyperkalemia
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic- hypoadosteronism state.
5.7 Anaphylactic Reactions
Celecoxib has been associated with anaphylactic reactions in patients with and without known hypersensitivity to celecoxib and in patients with aspirin sensitive asthma. Celecoxib capsules is a sulfonamide and both NSAIDs and sulfonamides may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people [see CONTRAINDICATIONS (4) and WARNINGS AND PRECAUTIONS (5.8)].
Seek emergency help if any anaphylactic reaction occurs.
5.8 Exacerbation of Asthma Related to Aspirin Sensitivity
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, celecoxib is contraindicated in patients with this form of aspirin sensitivity [see CONTRAINDICATIONS (4)]. When celecoxib capsules are used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
5.9 Serious Skin Reactions
Serious skin reactions have occurred following treatment with celecoxib, including erythema multiforme, exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). These serious events may occur without warning and can be fatal.
Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of celecoxib at the first appearance of skin rash or any other sign of hypersensitivity. Celecoxib is contraindicated in patients with previous serious skin reactions to NSAIDs [see CONTRAINDICATIONS (4)].
5.10 Premature Closure of Fetal Ductus Arteriosus
Celecoxib may cause premature closure of the ductus arteriosus. Avoid use of NSAIDs, including celecoxib capsules, in pregnant women starting at 30 weeks of gestation (third trimester) [see USE IN SPECIFIC POPULATIONS (8.1)].
5.11 Hematological Toxicity
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with celecoxib has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
In controlled clinical trials the incidence of anemia was 0.6% with celecoxib and 0.4% with placebo. Patients on long-term treatment with celecoxib capsules should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia or blood loss.
NSAIDs, including celecoxib, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet drugs (e.g., aspirin), SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see DRUG INTERACTIONS (7)].
5.12 Masking of Inflammation and Fever
The pharmacological activity of celecoxib in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.
5.13 Laboratory Monitoring
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically [see WARNINGS AND PRECAUTIONS (5.2, 5.3, 5.6)].
In controlled clinical trials, elevated BUN occurred more frequently in patients receiving celecoxib capsules compared with patients on placebo. This laboratory abnormality was also seen in patients who received comparator NSAIDs in these studies. The clinical significance of this abnormality has not been established.
5.14 Disseminated Intravascular Coagulation (DIC)
Because of the risk of disseminated intravascular coagulation with use of celecoxib in pediatric patients with systemic onset JRA, monitor patients for signs and symptoms of abnormal clotting or bleeding, and inform patients and their caregivers to report symptoms as soon as possible.
6 ADVERSE REACTIONS
- Cardiovascular Thrombotic Events [see WARNINGS AND PRECAUTIONS (5.1)]
- GI Bleeding, Ulceration and Perforation [see WARNINGS AND PRECAUTIONS (5.2)]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS (5.3)]
- Hypertension [see WARNINGS AND PRECAUTIONS (5.4)]
- Heart Failure and Edema [see WARNINGS AND PRECAUTIONS (5.5)]
- Renal Toxicity and Hyperkalemia [see WARNINGS AND PRECAUTIONS (5.6)]
- Anaphylactic Reactions [see WARNINGS AND PRECAUTIONS (5.7)]
- Serious Skin Reactions [see WARNINGS AND PRECAUTIONS (5.9)]
- Hematologic Toxicity [see WARNINGS AND PRECAUTIONS (5.11)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
Of the celecoxib-treated patients in the pre-marketing controlled clinical trials, approximately 4,250 were patients with OA, approximately 2,100 were patients with RA, and approximately 1,050 were patients with post-surgical pain. More than 8,500 patients received a total daily dose of celecoxib capsules of 200 mg (100 mg twice daily or 200 mg once daily) or more, including more than 400 treated at 800 mg (400 mg twice daily). Approximately 3,900 patients received celecoxib capsules at these doses for 6 months or more; approximately 2,300 of these have received it for 1 year or more and 124 of these have received it for 2 years or more.
Pre-marketing Controlled Arthritis Trials
Table 1 lists all adverse events, regardless of causality, occurring in ≥ 2% of patients receiving celecoxib from 12 controlled studies conducted in patients with OA or RA that included a placebo and/or a positive control group. Since these 12 trials were of different durations, and patients in the trials may not have been exposed for the same duration of time, these percentages do not capture cumulative rates of occurrence.
| CBX = Celecoxib 100 mg to 200 mg twice daily or 200 mg once daily; | |||||
| NAP = Naproxen 500 mg twice daily; | |||||
| DCF = Diclofenac 75 mg twice daily; | |||||
| IBU = Ibuprofen 800 mg three times daily. | |||||
| CBX | Placebo | NAP | DCF | IBU | |
| N=4146 | N=1864 | N=1366 | N=387 | N=345 | |
| Gastrointestinal | |||||
| Abdominal Pain | 4.1% | 2.8% | 7.7% | 9.0% | 9.0% |
| Diarrhea | 5.6% | 3.8% | 5.3% | 9.3% | 5.8% |
| Dyspepsia | 8.8% | 6.2% | 12.2% | 10.9% | 12.8% |
| Flatulence | 2.2% | 1.0% | 3.6% | 4.1% | 3.5% |
| Nausea | 3.5% | 4.2% | 6% | 3.4% | 6.7% |
| Body as a whole | |||||
| Back Pain | 2.8% | 3.6% | 2.2% | 2.6% | 0.9% |
| Peripheral Edema | 2.1% | 1.1% | 2.1% | 1.0% | 3.5% |
| Injury-Accidental | 2.9% | 2.3% | 3.0% | 2.6% | 3.2% |
| Central, Peripheral Nervous system | |||||
| Dizziness | 2.0% | 1.7% | 2.6% | 1.3% | 2.3% |
| Headache | 15.8% | 20.2% | 14.5% | 15.5% | 15.4% |
| Psychiatric | |||||
| Insomnia | 2.3% | 2.3% | 2.9% | 1.3% | 1.4% |
| Respiratory | |||||
| Pharyngitis | 2.3% | 1.1% | 1.7% | 1.6% | 2.6% |
| Rhinitis | 2.0% | 1.3% | 2.4% | 2.3% | 0.6% |
| Sinusitis | 5.0% | 4.3% | 4.0% | 5.4% | 5.8% |
| Upper Respiratory Infection | 8.1% | 6.7% | 9.9% | 9.8% | 9.9% |
| Skin | |||||
| Rash | 2.2% | 2.1% | 2.1% | 1.3% | 1.2% |
In placebo- or active-controlled clinical trials, the discontinuation rate due to adverse events was 7.1% for patients receiving celecoxib capsules and 6.1% for patients receiving placebo. Among the most common reasons for discontinuation due to adverse events in the celecoxib treatment groups were dyspepsia and abdominal pain (cited as reasons for discontinuation in 0.8% and 0.7% of celecoxib patients, respectively). Among patients receiving placebo, 0.6% discontinued due to dyspepsia and 0.6% withdrew due to abdominal pain.
| Gastrointestinal: | Constipation, diverticulitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, hemorrhoids, hiatal hernia, melena, dry mouth, stomatitis, tenesmus, vomiting |
| Cardiovascular: | Aggravated hypertension, angina pectoris, coronary artery disorder, myocardial infarction |
| General: | Hypersensitivity, allergic reaction, chest pain, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral pain |
| Central, peripheral nervous system: | Leg cramps, hypertonia, hypoesthesia, migraine, paresthesia, vertigo |
| Hearing and vestibular: | Deafness, tinnitus |
| Heart rate and rhythm: | Palpitation, tachycardia |
| Liver and biliary: | Hepatic enzyme increased (including SGOT increased, SGPT increased) |
| Metabolic and nutritional: | Blood urea nitrogen (BUN) increased, creatine phosphokinase (CPK) increased, hypercholesterolemia, hyperglycemia, hypokalemia, NPN increased, creatinine increased, alkaline phosphatase increased, weight increased |
| Musculoskeletal: | Arthralgia, arthrosis, myalgia, synovitis, tendinitis |
| Platelets (bleeding or clotting): | Ecchymosis, epistaxis, thrombocythemia |
| Psychiatric: | Anorexia, anxiety, appetite increased, depression, nervousness, somnolence |
| Hemic: | Anemia |
| Respiratory: | Bronchitis, bronchospasm, bronchospasm aggravated, cough, dyspnea, laryngitis, pneumonia |
| Skin and appendages: | Alopecia, dermatitis, photosensitivity reaction, pruritus, rash erythematous, rash maculopapular, skin disorder, skin dry, sweating increased, urticaria |
| Application site disorders: | Cellulitis, dermatitis contact |
| Urinary: | Albuminuria, cystitis, dysuria, hematuria, micturition frequency, renal calculus |
| The following serious adverse events (causality not evaluated) occurred in <0.1% of patients | |
| Cardiovascular: | Syncope, congestive heart failure, ventricular fibrillation, pulmonary embolism, cerebrovascular accident, peripheral gangrene, thrombophlebitis |
| Gastrointestinal: | Intestinal obstruction, intestinal perforation, gastrointestinal bleeding, colitis with bleeding, esophageal perforation, pancreatitis, ileus |
| General: | Sepsis, sudden death |
| Liver and biliary: | Cholelithiasis |
| Hemic and lymphatic: | Thrombocytopenia |
| Nervous: | Ataxia, suicide [see DRUG INTERACTIONS (7.1)] |
| Renal: | Acute renal failure |
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