Monograph: |
CELECOXIB
(Celecoxib capsules)
COLCIBRA 100 mg capsules COLCIBRA 200 mg capsules
Each capsule contains : Each capsule contains :
Celecoxib lOOmg Celecoxib 200 mg
DESCRIPTION
Celecoxib is chemically designated as 4-(5-(4-methylphenyl)-3-(tfifluoroniethyl)-1H-pyrazol-1-yl
benzenesulfonamide and is a diaryl-substituted pyrazole.The empirical formula for celecoxib is C,,H,,F,N,O,S
CELECOXIB
PHARMACOLOGY' STRUCTURAL FORMULA
Mechanism of Action
Celecoxib is a nonsleroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic
activities in animal models. The mechanism ol action of celecoxib is believed to be due to inhibition of
prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2), and at therapeutic concentrations
in humans, celecoxib does not inhibit the cyclooxygenase-1 (COX-1) isoenzyme.
Pharmacokinetics
Peak plasma louals of celecoxib occur approxbaalaly 3 hrs after an oral dose. Both peak plasma levels (Cw«)
and area under the curve (AUC) are roughly dose proportional across the clinical dose range of 100-200 mg
studied. With multiple dosing, steady state conditions are reached on or before day 5. When celecoxib is taken
with a high fat meal, peak plasma levels have been reported to be delayed for about 1 to 2 hours with an
increase in total absorption (AUC) of 10% to 20%. COLCIBRA can be administered without regard to the
timing of meals.
Celecoxib is highly protein bound (-97%) within the clinical dose range. The apparent volume of distribution at
steady state is approximately 400 L, suggesting extensive distribution into the tissues. Celecoxib is primarily
metabolised to three inactive metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide
conjugate. Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug
appearing in the urine and fe'ces. Following a single oral administration, approximately 57% of the dose is
excreted in the feces and 27% in the urine.The primary metabolite in both urine and feces is the carboxylic acid
metabolite (73% of dose) with low amounts of the glucuronide also appearing in the urine.The effective hall-life
is approximately 11 hours under fasted conditions. The apparent plasma clearance is about 500 mL/min.
INDICATIONS'
COLCIBRA is indicated
• For relief of the signs and symptoms of osteoarthritis.
• For relief of the signs and symptoms of rheumatoid arthritis in adults.
DOSAGE AND ADMINISTRATION'
Osteoarthritis : For relief of the signs and symptoms of osteoarthritis the recommended oral dose is 200 mg
per day administered as a single dose or as 100 mg twice per day.
Rheumatoid arthritis : For relief of the signs and symptoms of rheumatoid arthritis the recommended oral dose is
100 to 200 mg twice per day.
Dosage in Renal Insufficiency : In a cross-study comparison, celecoxib AUC was approximately 40% lower
in patients with chronic renal insufficiency (GFR 35-60 mL/min) than that seen in subjects with normal renal
function. No significant relationship was found between GFR and celecoxib clearance. Patients with severe
renal insufficiency have not been studied.
No information is available regarding the use of celecoxib in patients with advanced kidney disease. Therefore,
treatment with celecoxib is not recommended in these patients. If celecoxib therapy must be initiated, close
monitoring of the patient's kidney function is advisable
Dosage in Hepatic Insufficiency: Celecoxib should be introduced at a reduced dose in patients with moderate
hepatic impairment. Patients with severe hepatic impairment have not been studied. Therefore, the use of
celecoxib in such patients is not recommended.
PRECAUTIONS'
General : Celecoxib cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency.
The pharmacological activity of celecoxib in reducing inflammation, and possibly fever, may diminish the utility
of these diagnostic signs in detecting infectious complications of presumed noninfectious, painful conditions.
Borderline elevations ~fli~aLOaW9JiXStstsma~cpc-uf in up to 15% of patients taking NSAlUs, and notable
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