Celecoxib

381.37

381.37

200-001-8

JCX84Q7J1L

758624|719627

DTXSID0022777

C1728

Pale yellow solid

L01XX33|M01AH01|L - Antineoplastic and immunomodulating agents|M - Musculo-skeletal system

2935009090

86.4

3.4

white to off-white

1.4±0.1 g/cm3

157-159 °C

529.0±60.0

273.7±32.9 °C

1.606

DMSO: >20mg/mL

Store at RT

1.2X10-9 mm Hg at 25 deg C /Estimated/

11.1None

Henry's Law constant = 7.75X10-13 atm-cu m/mol at 25 °C (est)

11.1|pKa = 11.1 (sulfonamide moiety)

186.4 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|186.1 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Hydroxyl radical reaction rate constant = 1.45X10-11 cu cm/molec-sec at 25 °C (est)

IRRITANT

UN 3077 9 / PGIII

20/21/22-52-61-60

22-24/25-28-37/39

DB2944937

Xn

Stable under recommended storage conditions.

P201-P308 + P313

H360D

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging: Dispose of as unused product.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including celecoxib, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Danger|H360 (89.62%): May damage fertility or the unborn child [Danger Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 212 companies from 13 notifications to the ECHA C&L Inventory.|H360: May damage fertility or the unborn child [Danger Reproductive toxicity]|P201, P202, P273, P281, P308+P313, P391, P405, and P501

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).|Skin protection: Handle with gloves.|Body Protection: Impervious clothing. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.|Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.|Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Hazardous decomposition products formed under fire conditions: Carbon oxides, Nitrogen oxides (NOx), Sulfur oxides, Hydrogen fluoride.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided.|Precautions for safe handling: Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.|Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

The oral TDLo in humans 5.71 mg/kg. It is not advisable to administer celecoxib in patients with renal impairment or advanced hepatic impairment, as this may lead to increased serum concentrations, causing toxicity. Symptoms of overdose may include breathing difficulties, coma, drowsiness, gastrointestinal bleeding, high blood pressure, kidney failure, nausea, sluggishness, stomach pain, and vomiting. Because serious gastrointestinal tract ulceration and bleeding can occur without preceding symptoms, patients should be monitored for signs/symptoms of gastrointestinal bleeding. Symptomatic and supportive measures should be taken in a celecoxib overdose. The induction of emesis or administration of active charcoal should take place if the patient is seen within 4 hours of celecoxib ingestion. Diuresis, urinary alkalinization, hemodialysis, or hemoperfusion may not be useful in a celecoxib overdose due to its high level of protein binding.|IDENTIFICATION AND USE: Celecoxib is a pale yellow solid. It is a cyclooxygenase-2 (COX-2) inhibitor used in the management of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, pain, ankylosing spondylitis, and dysmenorrhea. HUMAN STUDIES: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. Allergic reactions, aggravated allergy, bronchospasm, or generalized or facial edema has been reported in 0.1-1.9% of patients receiving celecoxib. Anaphylactoid reactions and angioedema have occurred in patients receiving celecoxib. As with other NSAIDs, anaphylactic reactions have been reported rarely in patients with no previous exposure to the drug. Erythema multiforme, exfoliative dermatitis, Sweet's syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely in patients receiving celecoxib. Hepatitis, jaundice, or liver failure has been reported in patients receiving celecoxib during postmarketing surveillance. Celecoxib may cause premature closure of the ductus arteriosus. ANIMAL STUDIES: Celecoxib was not carcinogenic in rats given oral doses up to 200 mg/kg for males and 10 mg/kg for females, or in mice given oral doses up to 25 mg/kg for males and 50 mg/kg for females for two years. An increased incidence of fetuses with ventricular septal defects, sternebral fusion, rib fusion, and sternebrae abnormality was observed in reproduction studies in rabbits receiving oral celecoxib dosages of 150 mg/kg daily or more throughout organogenesis. A dose-dependent increase in diaphragmatic hernias was observed in rats receiving oral celecoxib dosages of 30 mg/kg or more daily throughout organogenesis. Celecoxib had no effect on male or female fertility or male reproductive function in rats at oral doses up to 600 mg/kg/day. Celecoxib was not mutagenic in an Ames test and a mutation assay in Chinese hamster ovary (CHO) cells, nor clastogenic in a chromosome aberration assay in CHO cells and an in vivo micronucleus test in rat bone marrow.

In clinical studies involving several thousand patients treated for at least 3 months, the rate of serum aminotransferase enzyme elevations above three times the upper limit of the normal range was 1.1% in celecoxib treated compared to 0.9% in placebo treated patients. The ALT elevations that occurred during celecoxib therapy were uncommon and usually benign, resolving even with continuation of the medication. It is unclear whether such elevations are due to the medication since similar rates of abnormalities are identified in patients with arthritis receiving placebo. In rare instances, celecoxib appears to be capable of causing clinical apparent, symptomatic and icteric drug induced liver injury. The pattern of liver enzyme elevations has ranged from hepatocellular (Case 1) to cholestatic (Case 2). Moreover, the resulting jaundice can be prolonged and accompanied by severe pruritus and chronic fatigue (Case 3). The latency to onset of liver injury is often short and the abruptness of onset resembles the hepatotoxicity caused by the sulfonamides. Indeed, in several instances, patients with celecoxib hepatotoxicity have a past history of sulfonamide hypersensitivity. Furthermore, celecoxib liver injury may occur in patients who have been treated with the drug without incident in the past, and reexposure after celecoxib liver injury usually results in reoccurrence with shortening of the latency period. Immunoallergic features are not uncommon in patients with clinically apparent liver injury due to celecoxib, but they are rarely prominent. Stevens Johnson syndrome has been described in patients on celecoxib. Autoimmune markers and features of autoimmunity are not common, although they may be present because of the underlying disease for which the celecoxib is prescribed.

Table: Clinically Significant Drug Interactions with Celecoxib [Table#6666]|Metabolism of celecoxib is mediated by the cytochrome P-450 (CYP) isoenzyme 2C9, and the possibility exists that drugs that inhibit this enzyme (e.g., fluconazole, fluvastatin, zafirlukast) may affect the pharmacokinetics of celecoxib. Therefore, celecoxib and drugs that inhibit the CYP2C9 isoenzyme should be administered concomitantly with caution. In addition, celecoxib inhibits CYP2D6, and the possibility exists that celecoxib may alter the pharmacokinetics of drugs metabolized by this isoenzyme, including various beta-adrenergic blocking agents, many tricyclic and other antidepressants, various antipsychotic agents, and some antiarrhythmics (e.g., encainide, flecainide). Results of in vitro studies indicate that celecoxib is not a substrate for CYP2D6, and the drug does not inhibit the CYP2C9, CYP2C19, or CYP3A4 isoenzymes.|Administration of an antacid containing magnesium or aluminum with celecoxib decreased peak plasma concentrations of celecoxib by 37% and the area under the plasma concentration-time curve (AUC) by 10% in clinical studies. However, the manufacturer makes no specific recommendation for administration of the drug with regard to antacids because these effects are not considered clinically important.|Results of clinical studies indicate that clinically important drug interactions may occur if celecoxib is administered with fluconazole. Concomitant administration of celecoxib with fluconazole can result in substantially increased plasma concentrations of celecoxib. This pharmacokinetic interaction appears to occur because fluconazole inhibits the CYP2C9 isoenzyme involved in celecoxib metabolism. In one study, concomitant administration of fluconazole (200 mg daily) and celecoxib (a single 200-mg dose) increased plasma concentrations of celecoxib twofold. The manufacturer of celecoxib states that celecoxib therapy should be initiated at the lowest recommended dosage in patients receiving fluconazole concomitantly.|For more Interactions (Complete) data for Celecoxib (12 total), please visit the HSDB record page.

Based on the mechanism of action, the use of prostaglandin-mediated nonsteroidal anti-inflammatory drugs (NSAIDs), including Celebrex, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including Celebrex, in women who have difficulties conceiving or who are undergoing investigation of infertility.|Patients with a prior history of peptic ulcer disease and/or GI bleeding who used nonsteroidal anti-inflammatory drugs (NSAIDs) had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; ... smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.|In patients with poor metabolizer phenotypes of the cytochrome P-450 (CYP) 2C9 isoenzyme, the metabolic clearance of celecoxib may be decreased and plasma concentrations may be increased. Therefore, the drug should be used with caution in patients who are known or suspected poor metabolizers of this isoenzyme, because higher than expected plasma concentrations of celecoxib may occur.|The daily recommended dose of Celebrex capsules in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by 50%. The use of Celebrex in patients with severe hepatic impairment is not recommended.|For more Populations at Special Risk (Complete) data for Celecoxib (12 total), please visit the HSDB record page.

The protein binding of celecoxib is 97%, and it is primarily bound to albumin.

Celecobix's production and administration as a medication(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 9.7X10+4(SRC), determined from a structure estimation method(2), indicates that celecoxib is expected to be immobile in soil(SRC). Volatilization of celecoxib from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.8X10-13 atm-cu m/mole(SRC), estimated using a fragment constant estimation method(3). Celecoxib is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-9 mm Hg(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2005).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 9.7X10+4(SRC), determined from a structure estimation method(2), indicates that celecoxib is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.8X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 90(SRC), from an estimated log Kow of 3.47(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Biodegradation data in water were not available(SRC, 2018).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), celecoxib, which has an estimated vapor pressure of 1.2X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase celecoxib may be removed from the air by wet and dry deposition(SRC). Celecoxib contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Celecoxib is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Celecoxib contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 90 was calculated for celecoxib(SRC), using an estimated log Kow of 3.47(1) and a regression-derived equation(1). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for celecoxib can be estimated to be 9.7X10+4(SRC). According to a classification scheme(2), this estimated Koc value suggests that celecoxib is expected to be immobile in soil.

The Henry's Law constant for celecoxib is estimated as 7.8X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that celecoxib is expected to be essentially nonvolatile from water surfaces(2). Celecoxib's Henry's Law constant indicates that volatilization from moist soil surfaces is not expected(SRC). Celecoxib is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.2X10-9 mm Hg(SRC), determined from a fragment constant method(1).

Occupational exposure to celecoxib may occur through inhalation and dermal contact with this compound at workplaces where celecoxib is produced or used. The general public is not likely to be exposed to celecoxib unless by direct medical treatment. (SRC)

Celecoxib is indicated for symptomatic treatment of adult osteoarthritis (OA) and adult rheumatoid arthritis (RA). Celecoxib is not a substitute for aspirin for cardiovascular event prophylaxis. It may be also be used to treat acute pain from various sources, juvenile rheumatoid arthritis in children over 2, ankylosing spondylitis, and primary dysmenorrhea.|Onsenal is indicated for the reduction of the number of adenomatous intestinal polyps in familial adenomatous polyposis (FAP), as an adjunct to surgery and further endoscopic surveillance (see section 4.4).The effect of Onsenal-induced reduction of polyp burden on the risk of intestinal cancer has not been demonstrated (see sections 4.4 and 5.1)|Treatment of pain

Celecoxib is a nonsteroidal antiinflammatory drug (NSAID) with selectively for inhibition of cycloxgenase-2 (Cox-2), which is widely used in the therapy of arthritis. Celecoxib has been linked to rare instances of idiosyncratic drug induced liver disease.

Nonsteroidal Antiinflammatory Drugs

Cyclooxygenase 2 Inhibitors|/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Celecoxib is included in the database.|/Celebrex is indicated/ for the management of the signs and symptoms of osteoarthritis. /Included in US product labeling/|/Celebrex is indicated/ for the management of the signs and symptoms of rheumatoid arthritis. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for Celecoxib (14 total), please visit the HSDB record page.

/BOXED WARNING/ WARNING: RISK OF SERIOUS CARDIOVASCULAR EVENTS. Cardiovascular Thrombotic Events: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in the treatment and may increase with duration of use. Celebrex is contraindicated in the setting of coronary artery bypass graft (CABG) surgery.|/BOXED WARNING/ WARNING: RISK OF SERIOUS GASTROINTESTINAL EVENTS. Gastrointestinal Bleeding, Ulceration, and Perforation: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.|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 nonsteroidal anti-inflammatory drugs (NSAIDs). Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, celebrex is contraindicated in patients with this form of aspirin sensitivity. When celebrex is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.|Celebrex is contraindicated in patients with previous serious skin reactions to nonsteroidal anti-inflammatory drugs (NSAIDs).|For more Drug Warnings (Complete) data for Celecoxib (33 total), please visit the HSDB record page.

Celecoxib inhibits cyclooxygenase 2 (COX-2) enzyme, reducing pain and inflammation. It is important to note that though the risk of bleeding with celecoxib is lower than with certain other NSAIDS, it exists nonetheless and caution must be observed when it is administered to those with a high risk of gastrointestinal bleeding. **A note on the risk of cardiovascular events** Significant concerns regarding the safety of COX-2 selective NSAIDs emerged in the early 2000s. [Rofecoxib], another member of the COX-2 inhibitor drug class, also known as Vioxx, was withdrawn from the market due to prothrombotic cardiovascular risks. Following an FDA Advisory Committee meeting in 2005, in which data from large clinical outcome trials were evaluated, the FDA concluded that the risk for cardiovascular thrombotic events for both COX-2 selective NSAIDs and nonselective NSAIDs was evident. It was determined that the benefits of celecoxib treatment, however, outweighed the risks. Postmarketing cardiovascular outcomes trial (PRECISION) revealed that the lowest possible dose of celecoxib was similar in cardiovascular safety to moderate strength doses of both naproxen and ibuprofen. Patients who had previous cardiovascular events including acute MI, coronary revascularization, or coronary stent insertion were not evaluated in the trial. It is not advisable to administer NSAIDS to these groups of patients.

A subclass of cyclooxygenase inhibitors with specificity for CYCLOOXYGENASE-2. (See all compounds classified as Cyclooxygenase 2 Inhibitors.)|Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)

Celecoxib is absorbed rapidly in the gastrointestinal tract. When a single oral dose of 200 mg was given to healthy research subjects, the peak plasma levels of celecoxib occurred within 3 hours. The Cmax is 705 ng/mL. When multiple doses are given, steady-state concentrations are reached on or before day 5. When taken with a high-fat meal, peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. The AUC of celecoxib has been shown to be significantly lower in patients with chronic renal impairment. A meta-analysis of pharmacokinetic studies has suggested an approximately 40% higher AUC (area under the curve) of celecoxib in black patients compared to Caucasians for unknown reasons.|Celecoxib is primarily eliminated by hepatic metabolism with small amounts (<3%) of the unchanged drug found in both the urine and feces. About 57% of an oral dose of celecoxib is excreted in the feces and 27% is found to be excreted into the urine in the form of metabolites. The main metabolite in urine and feces is identified as the carboxylic acid metabolite (73%). The amount of glucuronide in the urine is reported to be low.|The apparent volume of distribution of celecoxib at steady state (Vss/F) is about 429 L, which suggests wide distribution into various tissues. Celecoxib is not preferentially bound to red blood cells. Another resource reports a volume of distribution of 455 ± 166L.|Apparent clearance (CL/F), single oral 200 mg dose, healthy subjects = 27.7 L/hr. Clearance may be decreased by about 47% in patients with chronic renal insufficiency, according to a pharmacokinetic study. Studies have not been performed in patients with severe renal impairment.|/MILK/ Limited data from 3 published reports that included a total of 12 breastfeeding women showed low levels of Celebrex in breast milk. The calculated average daily infant dose was 10-40 ug/kg/day, less than 1% of the weight-based therapeutic dose for a two-year old-child.|/MILK/ The aim of this study was to investigate the transfer of celecoxib into human milk. In one group of 3 breastfeeding patients on celecoxib at steady state, milk levels were determined at set intervals over 24 hours. Plasma levels were determined in 2 of their infants, age 17 and 22 months. In a second group of 2 subjects, intravenous lines were placed and a single 200-mg dose of celecoxib was followed by multiple paired plasma and milk samples over 8 hours. The mean milk-to-plasma ratio for celecoxib was 0.23 (95% confidence interval [CI]: 0.15-0.31). The average concentration of celecoxib in milk during the 8-hour dosing interval was 66 ug/L (95% CI: 41-89). The absolute infant dose averaged 9.8 ug/kg/d (95% CI: 6.2-13.4); the mean relative infant dose was 0.30%. Therefore, the average clinical dose transferred to the infant daily would be approximately 0.3% of the weight-adjusted maternal dose. ...|/MILK/ A 40 year old woman who was breastfeeding her 5 month old daughter was admitted to the hospital for surgery. In the postoperative period, she received four doses of celecoxib (100 mg twice/day) in addition to other medications. Starting about 5 hours after her last dose, four milk samples were obtained by hand expression over a 24 hour interval. The elimination half life range was 4.0-6.5 hours. These data suggest that celecoxib would be eliminated from breast milk about 24 hours after the last dose. Although maternal plasma was not obtained, the estimated milk:plasma ratios (based on reported adult plasma levels) were 0.27-0.59. the infant did not resume breastfeeding until 48 hours after the last dose. If she had nursed, the estimated maximum infant dose would have have been about 40 ug/kg/day.|/MILK/ /The aim of this study was/ to determine the milk-to-plasma (M/P) concentration ratio of celecoxib, and estimate likely infant exposure. Blood and milk were sampled for 48 hr after oral administration of celecoxib 200 mg to six lactating volunteers. The M/P ratio was derived from the area under the concentration-time curves (0-infinity) and the infant 'dose' estimated from celecoxib concentrations in milk. The median (range) M/P ratio was 0.18 (0.15-0.26). The median (range) infant 'dose' was 0.23% (0.17-0.30%) of the maternal dose, adjusted for weight. ...|For more Absorption, Distribution and Excretion (Complete) data for Celecoxib (11 total), please visit the HSDB record page.

A large part of celecoxib metabolism is mediated by cytochrome P450 2C9 in the liver with some contribution from CYP3A4 and CYP2C8 and possible contributions from CYP2D6. It is metabolized by biotransformation to carboxylic acid and glucuronide metabolites. Three metabolites, a primary alcohol, a carboxylic acid, and a glucuronide conjugate, have been found in human plasma after celecoxib administration. These are considered inactive metabolites in regards to COX enzyme inhibition. Patients who are known or suspected to have decreased cytochrome P450 2C9 activity or function, based on their previous history, should be administered celecoxib with caution as they may have abnormally high serum concentrations resulting from decreased metabolism celecoxib.|Celecoxib metabolism is primarily mediated via CYP2C9. Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma. These metabolites are inactive as COX-1 or COX-2 inhibitors.|Celecoxib has known human metabolites that include Hydroxy celecoxib.

The effective half-life of celecoxib is approximately 11 hours when a single 200 mg dose is given to healthy subjects. The terminal half-life of celecoxib varies because of its low solubility, which prolongs absorption.|A 40 year old woman who was breastfeeding her 5 month old daughter was admitted to the hospital for surgery. In the postoperative period, she received four doses of celecoxib (100 mg twice/day) in addition to other medications. Starting about 5 hours after her last dose, four milk samples were obtained by hand expression over a 24 hour interval. The elimination half life range was 4.0-6.5 hours. ...|The plasma elimination half-life of celecoxib following oral administration of a single 200-mg dose under fasting conditions is about 11 hours, and the apparent plasma clearance of the drug is about 500 mL/minute; these parameters exhibit wide intraindividual variability, presumably because the low aqueous solubility of celecoxib prolongs absorption. The half-life of celecoxib is prolonged in patients with renal or hepatic impairment and has been reported to be 13.1 hours in patients with chronic renal insufficiency and 11 or 13.1 hours in patients with mild or moderate hepatic impairment, respectively.

Unlike most NSAIDs, which inhibit both types of cyclooxygenases (COX-1 and COX-2), celecoxib is a selective noncompetitive inhibitor of cyclooxygenase-2 (COX-2) enzyme. COX-2 is expressed heavily in inflamed tissues where it is induced by inflammatory mediators. The inhibition of this enzyme reduces the synthesis of metabolites that include prostaglandin E2 (PGE2), prostacyclin (PGI2), thromboxane (TXA2), prostaglandin D2 (PGD2), and prostaglandin F2 (PGF2). Resultant inhibition of these mediators leads to the alleviation of pain and inflammation. By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract. Celecoxib poses less of an ulceration risk than other NSAIDS, owing to its decreased effect on gastric mucosal prostaglandin synthesis when compared to placebo. Celecoxib exerts anticancer effects by binding to the cadherin-11 (CDH11)protein, which is thought to be involved in the progression of tumors, and inhibiting the 3-phosphoinositide-dependent kinase-1 (PDK-1) signaling mechanism. In addition, celecoxib has been found to inhibit carbonic anhydrase enzymes 2 and 3, further enhancing its anticancer effects. As mentioned in the pharmacodynamics section of this drug entry, celecoxib may cause an increased risk of thrombotic events. The risk of thrombosis resulting from COX-2 inhibition is caused by the vasoconstricting actions of thromboxane A2, leading to enhanced platelet aggregation, which is uncontrolled when the actions of prostacyclin, a platelet aggregation inhibitor, are suppressed through the inhibition of COX-2.|Nonsteroidal anti-inflammatory drugs (NSAIDs) are well-known causes of acute renal insufficiency and gastropathy in patients with chronic inflammatory diseases. This action is presumed to result from nonselective inhibition of both constitutive and inducible forms of prostaglandin H synthases, also known as the cyclooxygenase enzymes (i.e., COX-1 amd COX-2). Celecoxib (Celebrex) is a COX-2 enzyme inhibitor and has emerged as a preferred therapeutic agent for the treatment of rheumatoid arthritis as compared to other NSAIDs. Celecoxib has recently been the subject of criticism for its side effects, mainly arterial thrombosis and renal hemorrhage, although it is considered a superior drug in protecting the gastrointestinal tract. In the present study, we report that celecoxib not only inhibited COX-2, but also exhibited the property of inhibiting adenylyl cyclase, an important enzyme forming the intracellular second messenger 3',5'-adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Celecoxib also inhibited cholera toxin-stimulated cAMP formation, which indicated its ability to permeate cell membranes in order to reach intracellular adenylyl cyclase. It inhibited in vitro adenylyl cyclase activity in both human colonic epithelial cells and purified adenylyl cyclase from Bordetella pertussis. The IC50 of celecoxib for B. pertussis adenylyl cyclase was calculated to be 0.375 mM. Lineweaver-Burk analysis showed that the type of enzyme inhibition was competitive. The apparent Km and Vm of adenylyl cyclase was calculated as 25.0 nM and 7.14 nmol/min/mg, respectively. Celecoxib changed the Km value to 66.6 nM without affecting the Vmax. The current study suggests that apart from inflammation, celecoxib therapy could be further extended to diseases involving cAMP upregulation either by endogenous reactions or exogenous agents. These new data showing inhibition of adenylyl cyclase should be considered in light of the drug's pathological effects or in patients specifically excluded from treatment (e.g., asthmatics).|Cardiovascular disease is one of the leading causes of death worldwide, and evidence indicates a correlation between the inflammatory process and cardiac dysfunction. Selective inhibitors of cyclooxygenase-2 (COX-2) enzyme are not recommended for long-term use because of potentially severe side effects to the heart. Considering this and the frequent prescribing of commercial celecoxib, the present study analyzed cellular and molecular effects of 1 and 10 uM celecoxib in a cell culture model. After a 24-hr incubation, celecoxib reduced cell viability in a dose-dependent manner as also demonstrated in MTT assays. Furthermore, reverse transcription-polymerase chain reaction analysis showed that the drug modulated the expression level of genes related to death pathways, and Western blot analyses demonstrated a modulatory effect of the drug on COX-2 protein levels in cardiac cells. In addition, the results demonstrated a downregulation of prostaglandin E2 production by the cardiac cells incubated with celecoxib, in a dose-specific manner. These results are consistent with the decrease in cell viability and the presence of necrotic processes shown by Fourier transform infrared analysis, suggesting a direct correlation of prostanoids in cellular homeostasis and survival.|Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has recently been shown to affect the development of different types of cancer. The present study utilized a murine H22 hepatocarcinoma model to investigate the molecular mechanisms involved in celecoxib-induced inhibition of tumor angiogenesis. Tumor-bearing mice were randomly divided into five groups: i) control; ii) low-dose celecoxib (50 mg/kg); iii) high-dose celecoxib (200 mg/kg); iv) 5-fluorouracil (5-FU), (20 mg/kg) and v) combination of 5-FU and celecoxib (50 mg/kg). The antitumor effect of celecoxib was determined by measuring tumor volume. Tumor angiogenesis was evaluated by microvessel density (MVD). Tumor histology and immunostaining for CD34 in endothelial cells were performed to detect MVD. The expression levels of phosphatase and tensin homologue deleted from chromosome 10 (PTEN), phosphatidylinositol 3-kinase (PI3K), phospho-Akt (P-Akt), COX-2, hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor-A (VEGF-A) were detected by ELISA, immunohistochemistry and western blotting, respectively. We discovered substantial growth delay in murine H22 hepatoma as a result of celecoxib treatment. The inhibition rate of tumor growth induced by high-dose and low-dose celecoxib was 49.3 and 37.0%, respectively (P<0.05). The expression of PI3K, P-Akt, COX-2, HIF-1a, VEGF-A and PTEN in tumor tissues treated with celecoxib was demonstrated by immunohistochemistry, and the MVD was decreased in a dose-dependent manner (P<0.05). Reduced PI3K and P-Akt was particularly apparent in the high-dose celecoxib group (P<0.05). ELISA and western blotting data showed that the expression of PI3K, P-Akt, COX-2, HIF-1a and VEGF-A were reduced and PTEN was increased after treatment with celecoxib. In conclusion, the impact of celecoxib-induced tumor growth delay of murine H22 hepatocarcinoma may correlate with the inhibition of angiogenesis by reducing PI3K, P-Akt, COX-2, HIF-1a and VEGF-A expression and increasing PTEN expression in tumor tissue.|The mechanism of action of Celebrex is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2).

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen. 2. Treat seizures, coma, and hypotension, if they occur. 3. Antacids may be used for mild GI upset. Replace fluid losses with IV crystalloid solutions. /Nonsteroidal anti-inflammatory drugs/|Specific drugs and antidotes. There is no antidote. Vitamin K may be used for patients with elevated prothrombin time caused by hypoprothrombinemia. /Nonsteroidal anti-inflammatory drugs/|Decontamination. Administer activated charcoal orally if conditions are appropriate. Gastric lavage is not necessary after small-to-moderate ingestion if activated charcoal can be given promptly. /Nonsteroidal anti-inflammatory drugs/|Nonsteroidal anti-inflammatory drugs are highly protein bound and extensively metabolized. Thus, hemodialysis, peritoneal dialysis, and forced diuresis are not like to be effective. ... /Nonsteroidal anti-inflammatory drugs/|For more Antidote and Emergency Treatment (Complete) data for Celecoxib (10 total), please visit the HSDB record page.

/SIGNS AND SYMPTOMS/ Celecoxib may cause premature closure of the ductus arteriosus. Avoid use of nonsteroidal anti-inflammatory drugs (NSAIDs), including Celebrex, in pregnant women starting at 30 weeks of gestation (third trimester).|/SIGNS AND SYMPTOMS/ 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 nonsteroidal anti-inflammatory drugs (NSAIDs). Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, celebrex is contraindicated in patients with this form of aspirin sensitivity. When celebrex is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.|/SIGNS AND SYMPTOMS/ Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.|/SIGNS AND SYMPTOMS/ Allergic reactions, aggravated allergy, bronchospasm, or generalized or facial edema has been reported in 0.1-1.9% of patients receiving celecoxib. Anaphylactoid reactions and angioedema have occurred in patients receiving celecoxib. As with other nonsteroidal anti-inflammatory drugs (NSAIDs), anaphylactic reactions have been reported rarely in patients with no previous exposure to the drug. Erythema multiforme, exfoliative dermatitis, Sweet's syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely in patients receiving celecoxib.|For more Human Toxicity Excerpts (Complete) data for Celecoxib (36 total), please visit the HSDB record page.

4-(5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide

Table: Celecoxib Preparations [Table#6665]

Information available in 2005 indicated that Celecoxib was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Australia, Austria, Bahrain, Belgium, Brazil, Canada, Chile, Colombia, Costa Rica, Croatia, Cyprus, Czech Republic, Denmark, Egypt, El Salvador, Finland, France, Germany, Guatemala, Honduras, Hong Kong, Hungary, India, Indonesia, Ireland, Israel, Italy, Jordan, Kuwait, Lebanon, Malaysia, Mexico, Netherlands, New Zealand, Nicaragua, Norway, Oman, Panama, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Singapore, Slovenia, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, United Arab Emirates, United Kingdom, United States, Yugoslavia (1,2)

We report on a ratiometric fluorescent sensor based on dual-emission molecularly imprinted mesoporous silica embedded with carbon dots and CdTe quantum dots (mMIP@CDs/QDs) for celecoxib (CLX) as target molecule. The fluorescence of the embedded CDs is insensitive to the analyte while the green emissive QDs are selectively quenched by it. This effect is much stronger for the MIP than for the non-imprinted polymer, which indicates a good recognition ability of the mesoporous MIP. The hybrid sensor also exhibited good selectivity to CLX over other substances. The ratio of the intensity at two wavelengths (F550/F440) proportionally decreased with the increasing of CLX concentration in the range of 0.08-0.90 uM. A detection limit as low as 57 nM was achieved. Experimental results testified that this sensor was highly sensitive and selective for the detection of CLX in human serum samples.

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