COX B Capsule

Indications:

1. For the relief of the signs and symptoms of osteoarthritis.

2. For the relief of the signs and symptoms of rheumatoid arthritis.

3. For the regression and prevention of colorectal adenomatous polyps in patients with familial adenomatous polyposis (FAP).

Dosage:

Osteoarthritis: The recommended oral dose is 200 mg per day administered as a single dose or as 100 mg twice daily.

Rheumatoid arthritis: The recommended oral dose is 100 to 200 mg twice daily.

Familial adenomatous polyposis (FAP): Usual medical care for FAP patients should be continued while on Cox®B. To reduce the number of adenomatous colorectal polyps in patients with FAP, the recommended oral dose is 400 mg (2 X 200 mg capsules) twice daily to be taken with food.

Cox®B is contraindicated in patients with known hypersensitivity to Celecoxib.

Cox®B should not be given to patients who have demonstrated allergic-type reactions to sulfonamides (Celecoxib contains a sulfonamide side chain). Cox®B should not be given to patients who have demonstrated asthma, urticaria or allergic-type reactions after taking Aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients.

Adverse events occurring in ≥ 2 ≥ of Cox®B patients at recommended doses:

Abdominal pain 4.1%, diarrhoea 5.6%, dyspepsia 8.8%, flatulence 2.2%, nausea 3.5%, back pain 2.8%, peripheral edema 2.1%, injury-accidental 2.9%, dizziness 2.0%, headache 15.8%, insomnia 2.3%, pharyngitis 2.3%, rhinitis 2.0%, sinusitis 5.0%, upper respiratory tract infections 8.1%, rash 2.2%.

The following adverse events occurred in 0.1-1.9% of patients:

GI: Constipation, diverticulitis, dysphagia, eructation, esophagitis, gastritis, gastroenteritis, gastroesophageal reflux, hemorrhoids, hiatal hernia, melena, dry mouth, stomatitis, tenesmus, tooth disorder, vomiting.

Cardiovascular: Aggravated hypertension, angina pectoris, coronary artery disease, myocardial infarction.

General: Allergy aggravated, allergic reaction, asthenia, chest pain, cyst NOS, edema generalized, face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral pain.

Resistance mechanism disorders: Herpes simplex, herpes zoster, infection bacterial, infection fungal, infection soft tissue, infection viral, moniliasis, moniliasis genital, otitis media.

Nervous system: Leg cramps, hypertonia, hypoesthesia, migraine, neuralgia, neuropathy, paresthesia, vertigo.

Female reproductive system: Breast fibroadenosis, breast neoplasm, breast pain, dysmenorrhea, menstrual disorder, hemorrhagia, vaginitis.

Male reproductive system: Prostatic disorder.

Hearing and vestibular: Deafness, ear abnormality, earache, tinnitus.

Heart rate and rhythm: Palpitation, tachycardia.

Liver and biliary system: Peptic function abnormal, SGOT increased, SGPT increased.

Metabolic and nutritional: BUN increased, CPK increase, diabetes mellitus, hypercholesterolemia, hyperglycemia, hypokalemia, NPN increase, creatinine increased, alkaline phosphatase increase, weight increase.

Musculoskeletal: Arthralgia, arthrosis, fracture accidental, myalgia, neck stiffness, synovitis, tendinitis.

Platelets (bleeding or clotting): Ecchymosis, epistaxis, thrombocythemia.

Psychiatric: Anorexia, anxiety, appetite increase, depression, nervousness, somnolence.

Haemic: Anemia.

Respiratory: Bronchitis, bronchospasm, bronchospasm aggravated, coughing, dyspnea, laryngitis, pneumonia.

Skin and appendages: Alopecia, dermatitis, photosensitivity reaction, pruritus, rash erythematous, rash maculopapular, skin disorder, skin dry, sweating increase, urticaria.

Application site disorders: Cellulitis, contact dermatitis, skin nodule; Special senses: Taste perversion.

Urinary system: Albuminuria, cystitis, dysuria, hematuria, micturition frequency, renal calculus, urinary incontinence, urinary tract infection.

Vision: Blurred vision, cataract, conjunctivitis, eye pain, glaucoma.

Drug Interactions

General: Clinical studies with Celecoxib have identified potentially significant interactions with Fluconazole and Lithium. Experience with NSAIDs suggests the potential for interactions with Furosemide and ACE inhibitors.

ACE inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking Cox®B concomitantly with ACE inhibitors.

Furosemide: NSAIDs can reduce the natriuretic effect of Furosemide and Thiazides in some patients.

Aspirin: Cox®B can be used with low dose Aspirin. However, concomitant administration of Aspirin with Cox®B may result in an increased rate of GI ulceration or similar complications, compared to the use of Cox®B alone.

Fluconazole: Concomitant administration of Fluconazole at 200 mg QD resulted in a two-fold increase in Celecoxib plasma concentration. Cox®B should be introduced at the lowest recommended dose in patients receiving Fluconazole.

Lithium: Patients on Lithium treatment should be closely monitored when Cox®B is introduced or withdrawn.

Warfarin: Caution should be used when administering Cox®B with Warfarin since these patients are at increased risk of bleeding complications.

Cox®B, at doses upto 200 mg bid, can be administered without regard to timing of meal. Higher doses (400 mg bid) should be administered with food.

Co-administration of Cox®B with an aluminum and magnesium-containing antacid should be avoided, because they may reduce the absorbtion of Celecoxib.

NSAIDs inhibit both types of cyctooxygenases (COX-1 and COX- 2). With its polar sulfonamide side chain, Celecoxib binds tightly to a distinct hydrophilic side pocket region, which is close in proximity to the active COX-2 binding site. The COX-2 specificity is due to this ability of Celecoxib to occupy space within the active binding site that is not present on the COX-1 isoform. The enzymes cyclooxygenase-1 and cyclooxygenase-2 (COX-1and COX-2) catalyze the conversion of arachidonic acid to prostaglandin (PG) H2, the precursor of PGs and thromboxane. The inducible isoform, COX-2, is demonstrated to be important for the mediation of inflammation and pain. It is hypothesized that COX-1 produces prostaglandins that are beneficial to renal and gastric function. The in vitro IC50 selectivity ratio (50% inhibitory concentrations of COX-1 :COX-2) of Celecoxib is 375 versus 3 for Diclofenac; demonstrating markedly greater COX-2 selectivity for Celecoxib. At therapeutic concentrations in humans, Celecoxib does not significantly inhibit the COX-1 isoenzyme. In contrast to NSAIDs, Celecoxib does not inhibit platelet aggregation.