Celecoxib
Cebex ®
Category
Analgesic; Antidysmenorrheal; Antirheumatic( nonsteroidal anti-inflammatory).
(USP DI)
Chemistry
P-[5-p-tolyl-3-(trifluromethyl) pyrazol-1-yl] benzenesulfonamide. (Martindale)
Mechanism of action / pharmacokinetics
Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory analgesic, and antipyretic affects. It has been proposed that celecoxib inhibits the activity of the enzyme cyclooxygenase-2 (COX-2), resulting in a decreased formation of precursors of prostaglandins. However, unlike most NSAIDs, celecoxib does not inhibit cyclooxygenase-1(COX-1) isoenzyme in humans at therapeutic concentrations.
Pharmacokinetic Properties
Absorption Rapid, celecoxib may be co-administered with meals.
Protein binding Very high (97%)
Biotransformation Hepatic via cytochrome P450 C9 enzymes to inactive metabolites.
Time to peak concentration Approximately 3 Hours
Half life Approximately 11 Hours
Peak plasma Concentration Approximately 3 hours
Elimination 57% in the feces and 27% in the urine
Hemodialysis Is not effective
( USP DI)
Indications
Arthritis rheumatoid (treatment): or Osteoarthritis, Dysmenorrhea, Familial adenomatous polyposis( FAP), pain, acute( treatment) such as pain following dental or orthopedic surgery. (USP DI)
Contraindications
Allergic reactions, such as anaphylaxis or angioedema, induced by aspirin, other NSAIDs or sulfonamide-derivatives. Nasal polyps associated with bronchospasm. Also risk- benefit should be considered when the following medical problems exist: Anemia, Asthma, Alcoholism, Gastrointestinal bleeding, peptic ulcer, active or pre- existing or tobacco use, congestive heart failure, edema, Hypertension, Hepatic function impairment, renal function impairment. (USP DI)
Warnings and precautions
Celecoxib may cause an increased risk of serious cardiovascular (CV) trombotic events, myocardial infarction (MI) and stroke, which can be fatal. All NSAIDs may have a similar risk.
Celecoxib may cause bronchoconstriction or anaphylaxis in aspirin-sensitive asthmatics, especially those with aspirin-induced nasal polyps, asthma and other allergic reactions.
Celecoxib is contraindicated for treatment of prioperative pain in the setting of coronary artery bypass graft (CABG) surgery.
NSAIDs including celecoxib, caused an increased risk of serious GI adverse reactions, including bleeding, ulceration, and perforation of the stomach or intestines which can be fatal. These reactions can occur at anytime during use and without warning symptoms. Elderly patients are at higher risk for serious GI events. (USP DI)
Pregnancy
Adequate and well-controlled studies in humans have not been done. Celecoxib may cause premature closure of the ductus arterious. Therefore, use of celecoxib is not recommended during late pregnancy. FDA pregnancy category C. (USP DI)
Breast-feeding
It is not known whether celecoxib is distributed into human breast milk. However,
Celecoxib may potentially cause serious adverse effects in the nursing infant.
(USP DI)
Drug interactions
Celecoxib should be administered with caution in patients receiving: Angiotensin-converting enzyme (ACE) inhibitors, as concurrent use of celecoxib may decrease the effects of these drugs.
Antiacids, containing aluminum or magnesium interfere with celecoxib absorption.
Other possible interactions are with: Aspirin, Diuretics, Thiazide or Furosemide, Fluconazole, Lithium and Warfarin. (USP DI)
Adverse reactions
Edema (swelling of face, fingers, feet, lower legs), skin rash, upper respiratory tract infection (cough, fever, sneezing, sore throat), and also bronchitis, dyspnea, gastritis, gastroenteritis, gastrointestinal bleeding or ulceration, influenza-like symptoms, tachycardia which all need medical attention.
Other side effects as below, only need medical attention if they continue or are bothersome: Back pain, diarrhea, dizziness, dyspepsia, flatulence, headache, insomnia, blurred vision, constipation, depression, dry mouth, dysphagia, esophagitis, fatigue, fever, hot flashes, increased sweating, nervousness, poupitations, parasthesias, somnolence, taste perversion, tendonitis, tinnitus, vertigo, vomiting. (USP DI)
Overdosage
Acute renal failure, drowsiness, epigastric pain, gastrointestinal bleeding, hypertension, lethargy, nausea and - or vomiting, respiratory depression.
For treatment of overdosage: Decreased absorption by emptying the stomach via induction of emesis and administering activated carol.
And for enhancing elimination: Administering and osmotic cathartic. (PDR)
Dosage and administration
-Usual adult dosage
• Arthritis rheumatoid - oral, 100 to 200 mg twice daily
• Dysmenorrhea – oral, 400 mg initially, followed by a 200 mg if needed on the first day, then 200 mg twice a day as needed.
• FAP (familial adenomatous polyposis) – oral, 400 mg twice daily to be taken with food.
• Osteoarthritis – oral, 200 mg daily as single dose or 100 mg twice a day.
• Pain – oral, 400 mg initially, followed by 200 mg if needed on the first day, then 200 mg twice a day as needed.
-For geriatric dose: see usual adult dose. It is recommended that therapy with celecoxib be initiated at the lowest dosage in patients less than 50 kg of body weight.
-Safety and efficacy have not been established in pediatric use. (USP DI)
Storage
Store below 30º c and protect from humidity & direct light. (PDR)
How supplied
Cebex® 200 is supplied as white opaque capsules in transparent blisters of 10`s in boxes of 30`s.
Cebex® 100 is supplied as white opaque capsules with blue ring in transparent blisters of 10`s in boxes of 30`s.
References
1- PDR 2006 2- USP DI 2006 3- USP DI 2004
4- Martindale 2007 5- Drug facts 2004