CELEX (CAPSULES)
Celecoxib

Celecoxib is a nonsteroidal anti-inflammatory drug that exhibits analgesic, antipyretic, and
anti-inflammatory activities.
The mechanism of 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. COX-1 is a type of cyclooxygenase that is found in the stomach, that helps protect the stomach lining.
 

PHARMACOKINETICS:
Absorption:
Peak plasma levels of celecoxib occur approximately 3 hrs after an oral dose.
Food effects:
When Celecoxib capsules were taken with a high fat meal, peak plasma levels were delayed for about 1 to 2 hours.
Coadministration of Celecoxib with an aluminum- and magnesium-containing antacid resulted in a reduction in plasma celecoxib concentrations.
Celecoxib, at doses up to 200 mg BID can be administered without regard to timing of meals. Higher doses (400 mg BID) should be administered with food.
Distribution:
In healthy subjects, celecoxib is highly protein bound (97%) within the clinical dose range. Suggesting extensive distribution into the tissues. Celecoxib is not preferentially bound to red blood cells.
Metabolism:
Three metabolites, a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been identified in human plasma.
Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. These metabolites are inactive as COX-1 or COX-2 inhibitors. Patients who are known or suspected to be P450 2C9 poor metabolizers based on a previous history should be administered Celecoxib with caution as they may have abnormally high plasma levels due to reduced metabolic clearance.
Excretion:
Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug recovered in the urine and feces.
The effective half-life is approximately 11 hours under fasted conditions.
 

INDICATIONS:
Celecoxib is indicated:
1- For relief of the signs and symptoms of osteoarthritis.
2- For relief of the signs and symptoms of rheumatoid arthritis in adults.
 

CONTRAINDICATIONS:
- Celecoxib is contraindicated in patients with known hypersensitivity to Celecoxib.
- It should not be given to patients who have demonstrated allergic-type reactions to sulfonamides.
- It should not be given to patients who have experienced 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.
 

WARNINGS:
- Minor upper gastrointestinal problems, such as dyspepsia, are common.
Upper GI ulcers, gross bleeding or perforation are rarely to occur in approximately 1% of
patients treated for 3 to 6 months, and in about (2-4)% of patients treated for 1 year.
It should be prescribed with extreme caution in patients with a prior history of peptic ulcer or
gastrointestinal bleeding especially in elderly or debilitated patients.
To minimize the potential risk an adverse GI event, the lowest effective dose should be used
for the shortest possible duration.
- Anaphylactoid reactions were not reported in patients receiving Celecoxib in clinical trials.
- No information is available regarding the use of Celecoxib in patients with advanced kidney disease.
- Patients at greatest risk are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly.
- Caution should be used when initiating treatment with Celecoxib in patients with considerable dehydration.
- Pregnancy: In late pregnancy, Celecoxib should be avoided because it may cause premature closure of the ductus arteriosus. It is not advised to use it in breast feeding mothers.
- Pediatric use: Safety and effectiveness in pediatric patients below the age of 18 years have not been evaluated.
 

DRUG INTERACTIONS:
Severe significant interactions may occur when celecoxib is administered.
With drugs that inhibit P450 2C9.
- ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors. This interaction should be given consideration in patients taking Celecoxib concomitantly with ACE-inhibitors.
- Fluconazole: Concomitant administration of fluconazole at 200 mg QD resulted in a two-fold increase in Celecoxib plasma concentration.
- Lithium: Mean lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with Celecoxib 200 mg BID.
- Warfarin: Increase in protrhombin time occurs in patients receiving Celecoxib with Warfarin especially in elderly patients.
Glyburide, ketoconazole, methotrexate, phenytoin, and tolbutamide have been studied. In vivo and clinically no important interactions have been found.
 

SPECIAL POPULATIONS:
Geriatric: Dose adjustment in the elderly is not generally necessary. However, for patients of less than 50 Kg in body weight, initiate therapy at the lowest recommended dose.
Hepatic insufficiency: The daily recommended dose of Celecoxib capsules should be reduced by approximately 50% in patients with moderate (child-pugh class II) hepatic impairment.
The use of Celecoxib in patients with severe hepatic impairment is not recommended.
 

CLINICAL STUDIES:
- Celecoxib has demonstrated significant reduction in joint pain, stiffness, and functional
measures in OA.
Celecoxib doses of 100 mg BID and 200 mg BID provided significant reduction of pain within
24-48 hours of initiation of dosing.
At doses of 100 mg BID or 200 mg BID the effectiveness of Celecoxib was shown to be similar
to that of naproxen 500 mg BID.
- Celecoxib has demonstrated significant reduction in joint tenderness/pain and joint swelling in
rheumatoid arthritis.
Although Celecoxib 100 mg BID and 200 mg BID provided similar overall effectiveness,
some patients derived additional benefit from the 200 mg BID dose.
Doses of 400 mg BID provided no additional benefit above that seen with 100-200 mg BID.
Familial adenomatous polyposis (FAP): Celecoxib was evaluated to reduce the number of adenomatous colorectal polyps.
 

SIDE EFFECTS:
Celecoxib is generally well tolerated. It has lower incidence of stomach side effects irritation, ulcers, and even bleeding than other anti-inflammatory drugs.
 

DOSAGE:
1 cap of 100 mg twice daily in osteoarthritis.
1 cap of 100 mg } Twice daily in rheumatoid arthritis.
1 cap of 200 mg
Celecoxib is a break through drug therapy for the treatment of osteoarthritis and rheumatoid arthritis.
It relieves pain but what sets the drug apart from other pain killers is that it is much less likely to cause severe stomach problems such as bleeding ulcers.
 

STORAGE:
Keep out of the reach of children, and away from light and heat.