ELYXYB (celecoxib)

There are 6 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Cerebrovascular accident
History of roux-en-Y gastric bypass
Post-operative from CABG surgery
Pregnancy
Renal transplant

There are 17 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
CYp2c9 intermediate metabolizer (activity score 1)
CYp2c9 poor metabolizer
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
History of kidney donation
Increased risk of bleeding
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Nephrectomy
Peptic ulcer
Systemic mastocytosis
Thrombotic disorder
Tobacco smoker

There are 7 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Anemia
Asthma
Chronic heart failure
Dehydration
Disease of liver
Edema
Hypertension

There are 75 severe adverse reactions.

More Frequent	Less Frequent
Abnormal hepatic function tests Accidental injury Increased alanine transaminase Increased aspartate transaminase	None.

Rare/Very Rare

Acute eruptions of skin Acute generalized exanthematous pustulosis Acute myocardial infarction Agranulocytosis Anaphylaxis Anemia Angina Angioedema Aplastic anemia Biliary calculus Bloody stools Bronchospastic pulmonary disease Bullous dermatitis Cellulitis Cerebrovascular accident Conjunctival hemorrhage Coronary artery disease Cystitis Deep venous thrombosis Diverticulitis of gastrointestinal tract DRESS syndrome Edema Erythema multiforme Esophageal perforation Esophagitis Exfoliative dermatitis Facial edema Gastroesophageal reflux disease Gastrointestinal hemorrhage Gastrointestinal obstruction Gastrointestinal perforation Gastrointestinal ulcer Heart failure Hematuria Hemorrhage Hepatic failure Hepatic necrosis Hepatitis Hiatal hernia Hypercholesterolemia Hyperglycemia Hyperkalemia Hypernatremia Hypertension Hypoglycemic disorder Hypokalemia Hyponatremia Interstitial nephritis Intracranial bleeding Jaundice Kidney stone Left ventricular hypertrophy Leukopenia Nephrotoxicity Non-infective meningitis Pancreatitis Pancytopenia Pneumonia Proteinuria Renal papillary necrosis Sepsis Sinus bradycardia Stevens-johnson syndrome Syncope Tendon rupture Thrombocytopenic disorder Thrombocytosis Thrombophlebitis Toxic epidermal necrolysis Vasculitis Vertigo

There are 78 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Diarrhea Dizziness Dysgeusia Dyspepsia Flatulence Peripheral edema Pharyngitis Rhinitis Skin rash Upper respiratory infection	Back pain Epicondylitis Headache disorder Insomnia Nausea Sinusitis

Rare/Very Rare

Allergic dermatitis Alopecia Anorexia Arthralgia Ataxia Body fluid retention Bronchitis Chest pain Constipation Contact dermatitis Cough Cramps in legs Depression Drowsy Dry skin Dysphagia Dyspnea Dysuria Ecchymosis Epistaxis Eructation Fatigue Fever Flu-like symptoms Flushing Gastritis Gastroenteritis General weakness Hearing loss Hemorrhoids Hyperhidrosis Hypertonia Hypoesthesia Increased appetite Increased urinary frequency Laryngitis Loss of sense of smell Loss of taste Maculopapular rash Medication overuse headache Migraine Myalgia Nervousness Ocular pain Ovarian cyst Pain Palpitations Paresthesia Pruritus of skin Skin irritation Skin photosensitivity Stomatitis Symptoms of anxiety Synovitis Tachycardia Tenesmus Tinnitus Urticaria Vomiting Weight gain Xerostomia

Use of NSAIAs during pregnancy at about 30 weeks of gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks of gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks of gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks of gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice.

Fetal renal dysfunction has been observed, on average, after days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible following discontinuance of NSAIA therapy. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation.

A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures, such as exchange transfusion or dialysis. Observational data regarding other embryofetal risks with NSAIAs during the first or second trimester of pregnancy are not conclusive.

An increased incidence of fetuses with ventricular septal defects, sternebral fusion or abnormality, and rib fusion was observed in reproduction studies in rabbits receiving oral celecoxib dosages >=150 mg/kg daily throughout organogenesis (exposure approximately twice the usual human dosage of 200 mg twice daily, expressed in terms of AUC (0-24 hours)). A dose-dependent increase in diaphragmatic hernias was observed in rats receiving oral celecoxib dosages >=30 mg/kg daily throughout organogenesis (exposure approximately 6-fold the usual human dosage of 200 mg twice daily, expressed in terms of AUC (0-24 hours)). Reproduction studies in rats using oral dosages up to 100 mg/kg daily (exposure approximately 7-fold the usual human dosage of 200 mg twice daily, expressed in terms of AUC (0-24 hours)) did not reveal evidence of delayed labor or parturition.

In rats receiving oral celecoxib dosages >=50 mg/kg daily (exposure approximately 6-fold the usual human dosage of 200 mg twice daily, expressed in terms of AUC (0-24 hours)), pre- and post-implantation losses and reduced embryonic/fetal survival were observed. Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as celecoxib, were associated with increased pre- and post-implantation losses.

Prostaglandins also have an important role in fetal kidney development. In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses. The effects of celecoxib on labor and delivery are unknown. In animal studies, drugs that inhibit prostaglandin synthesis, including NSAIAs, delayed parturition and increased stillbirth.

Celecoxib is distributed into milk in small amounts. Limited data obtained from nursing women receiving celecoxib indicate that the calculated average infant exposure to the drug is 10-40 mcg/kg daily, which is less than 1% of the weight-based therapeutic dosage for a 2-year-old child. Maternal use of celecoxib was not associated with adverse effects in 2 breast-fed infants 17 and 22 months of age.

It is not known whether celecoxib affects milk production. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for celecoxib and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Geriatric patients are at increased risk for NSAIA-associated serious adverse cardiovascular, GI, and renal effects. In clinical trials evaluating celecoxib for acute treatment of migraine attacks, approximately 70 patients were >=65 years of age, while in clinical trials evaluating celecoxib for other indications, more than 3300 patients were 65-74 years of age and about 1300 were >=75 years of age. No overall differences in efficacy of celecoxib were observed between geriatric and younger patients.

Although results from clinical studies indicated that renal function (measured by glomerular filtration rate, blood urea nitrogen, and creatinine) and platelet function (measured by bleeding time and platelet aggregation) in geriatric individuals receiving celecoxib did not differ from those in younger individuals, spontaneous postmarketing reports of fatal adverse GI effects and acute renal failure have occurred more often in geriatric individuals than in younger individuals. If it is determined that the anticipated benefits of celecoxib therapy outweigh the potential risks, celecoxib should be initiated at the lower end of the dosing range and patients should be monitored for adverse effects; if used for the acute treatment of migraine attacks, celecoxib should be used for the fewest possible number of days per month. Peak plasma concentration and AUC of celecoxib (as the oral capsules) were increased 40 and 50%, respectively, in geriatric individuals (i.e., >=65 years of age), but dosage adjustment in this age group based solely on age generally is not required.

Peak plasma celecoxib concentration and AUC values were higher in geriatric women than geriatric men, predominantly because of the lower body weight of these women. In geriatric patients weighing <50 kg, celecoxib therapy should be initiated at the lowest recommended dosage.