Celcoxx

Main information

  • Trade name:
  • Celcoxx 400mg Capsule
  • Dosage:
  • 400mg
  • Pharmaceutical form:
  • Capsule
  • Units in package:
  • Alu-Alu Blister Pack x 5's (Box of 20's)
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug
  • Manufactured by:
  • Getz Pharma (Private) Limited

Documents

Localization

  • Available in:
  • Celcoxx 400mg Capsule
    Philippines
  • Language:
  • English

Status

  • Source:
  • FDA - Food And Drug Administration - Philippines
  • Authorization number:
  • DR-XY36564
  • Authorization date:
  • 01-01-1970
  • Last update:
  • 09-07-2018

Summary of Product characteristics: dosage, interactions, side effects

WARNINGS

PRECAUTIONS

General:

Celecoxib cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency.

Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive

illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly

if a decision is made to discontinue corticosteroids.

Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation:

Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation of the stomach,

small intestine or large intestine, can occur at any time, with or without warning symptoms, in

patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal

problems, such as dyspepsia, are common and may also occur at any time during NSAID

therapy. With longer duration of use of NSAIDs, there is a trend for increasing the likelihood

of developing a serious GI event at some time during the course of the

rapy. However, even

short-term therapy is not without risk. Therefore, physicians and patients should remain alert

for ulceration and bleeding, even in the absence of previous GI tract symptoms.

NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer

disease or gastrointestinal bleeding. To minimize the potential risk for an adverse GI event, the

lowest effective dose should be used for the shortest possible duration.

Congestive Heart Failure and Edema:

Fluid retention and edema have been observed in some patients taking celecoxib. Therefore,

celecoxib should be used with caution in patients with fluid retention, hypertension, or heart

failure.

Hypertension:

As with all NSAIDs, celecoxib can lead to the onset of new hypertension or worsening of p

existing hypertension, either of which may contribute to the increased incidence of cardiovascular

events. Patients taking thiazides or loop diuretics may have impaired response to these therapies

when taking NSAIDs. NSAIDs, including celecoxib, should be used with caution in patients with

hypertension. Blood pressure should be monitored closely during the initiation of therapy with

celecoxib and throughout the course of therapy.

Hepatic Effects:

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal

liver test has occurred, should be monitored carefully for evidence of the development of a

more severe hepatic reaction while on therapy with celecoxib. If clinical signs and symptoms

consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia,

rash, etc.), celecoxib should be discontinued.

Renal Effects:

Long-term administration of NSAIDs has resulted in renal papillary necrosis a

nd other renal

injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a

compensatory role in the maintenance of renal perfusion. Patients at greatest risk of this reaction

are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics,

ACE-inhibitors, angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID

therapy is usually followed by recovery to the pre-treatment state.

Caution should be used when initiating treatment with celecoxib in patients with considerable

dehydration. It is advisable to rehydrate patients first and then start therapy with celecoxib.

Hematological Effects:

Anemia is sometimes seen in patients receiving celecoxib. Patients on long-term treatment with

celecoxib should have their hemoglobin or hematocrit checked if they exhibit any signs or

symptoms of anemia o

r blood loss. Celecoxib does not generally affect platelet counts,

prothrombin time (PT), or partial thromboplastin time (PTT), and does not inhibit platelet

aggregation at indicated dosages.

Serious Skin Reactions:

Patients appear to be at highest risk for serious skin reactions early in the course of therapy.

The onset of these events occurring in the majority of the cases within the first month of

treatment. Celecoxib should be discontinued at the first appearance of skin rash, mucosal

lesions, or any other sign of hypersensitivity.

Famalial Adenomatous Polyposis (FAP):

Treatment with celecoxib in FAP has not been shown to reduce the risk of gastrointestinal

cancer or the

need for prophylactic colectomy or other FAP-related surgeries. Therefore, the

usual care of FAP patients should not be altered because of the concurrent administration of

celecoxib.

Anaphylactic Reactions:

As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known

prior exposure to celecoxib. Celecoxib should not be given to patients with the aspirin triad.

This symptom complex typically occurs in asthmatic patients who experience rhinitis with or

without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin

or other NSAIDs.

Skin Reactions

Celecoxib is a sulfonamide and can cause serious skin adverse events such as exfoliative

dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), which can be

fatal. These serious events can occur without warning and in pa

tients without prior known sulfa

allergy. Patients should be informed about the signs and symptoms of serious skin manifestations

and use of the drug should be discontinued at the first appearance of skin rash or any other

sign of hypersensitivity.

Inflammation

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.

Concomitant NSAID Use

The concomitant use of celecoxib with any dose of a non-aspirin NSAID should be avoided due

to the potential for increased risk of adverse reactions.

Pregnancy:

Celecoxib should be used during pregnancy only if the potential benefit justifies the potential

risk to the fetus. In late pregnancy, starting at 30 weeks gestation, celecoxib should be avoided

because it may cause premature closure of the ductus arteriosus.

Nursing mothers:

Because many drugs are excreted in human milk and because of the potential for serio

adverse reactions in nursing infants from celecoxib, a decision should be made whether to

discontinue nursing or to discontinue the drug, taking into account the importance of the drug

to the mother.

Drug Interactions:

General: Celecoxib metabolism is predominantly mediated via cytochrome P450 2C9 in the

liver. Co-administration of celecoxib with drugs that are known to inhibit 2C9 should be done

with caution. 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 abnormall

high plasma levels due to reduced metabolic clearance.

ACE Inhibitors and Angiotensin II Antagonists: Reports suggest that NSAIDs may diminish the

antihypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors and angiotensin II

antagonists. This interaction should be given consideration

in patients taking celecoxib

concomitantly with ACE inhibitors and angiotensin II antagonists.

Furosemide: Clinical studies, as well as post marketing observations, have shown that NSAIDs

can reduce the natriuretic effect of furosemide and thiazides in some patients. This response

has been attributed to inhibition of renal prostaglandin synthesis.

Aspirin: Celecoxib can be used with low dose aspirin. However, concomitant administration of

aspirin with celecoxib may result in an increased rate of GI ulceration or other complications,

compared to use of celecoxib alone. Because of its lack of platelet effects, celecoxib is not a

substitute for aspirin for cardiovascular prophylaxis.

Fluconazole: Concomitant administration of fluconazole at 200mg q.d. resulted in a two-fold

increase in celecoxib plasma concentration. This increase is due to the inhibition of celecoxib

metabolism via P450 CYP2C9 by fluconazole. Celecoxib should be introd

uced at the lowest

recommended dose in patients receiving fluconazole.

Lithium: Clinical studies showed that the mean steady-state lithium plasma levels increased

approximately 17% in subjects receiving lithium 450mg b.i.d. with celecoxib 200mg b.i.d. as

compared to subjects receiving lithium alone. Patients on lithium treatment should be closely

monitored when celecoxib is introduced or withdrawn.

Warfarin: Anticoagulant activity should be monitored, particularly in the first few days, after

initiating or changing celecoxib therapy in patients receiving warfarin or similar agents, since

these patients are at an increased risk of bleeding complications.

Antacid: Co-administration of celecoxib with an aluminum and magnesium-containing antacid

resulted in a reduction in plasma celecoxib concentrations. No dose adjustment is required.

Glucocortico

ids: Oral glucocorticoids should be used with caution since they increase the risk

of GI side effects such as ulceration and bleeding. This is especially the case in older (>65

years of age) individuals.

OVER DOSAGE

Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea,

vomiting, and epigastric pain, which are generally reversible with supportive care. Anaphylactoid

reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following

an overdose. Patients should be managed by symptomatic and supportive care following an

NSAID overdose. Monitor patients for signs and symptoms of gastrointestinal ulceration and/or

haemorrhage. Monitor serum electrolytes, renal function and urinalysis after significant overdose.

STORAGE CONDITIONS

Store at temperatures not exceeding 30°C.

Protect from sunlight and moisture.

Expiration date refers to the product correctly stored at the required conditions.

AVAILABILITY

Celecoxib (CELCOXX ) Capsules 100mg are available in Alu-Alu blister packs of 10's and box

of 20’s.

Celecoxib (CELCOXX ) Capsules 200mg are available in Alu-Alu blister packs of 10's a

nd box

of 20’s.

Celecoxib (CELCOXX ) Capsules 400mg are available in Alu-Alu blister packs of 10's and box

of 20’s.

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.

Keep out of reach of children.

DESCRIPTION

Celecoxib (CELCOXX

) belongs to a new class of arthritis/analgesic medication called "COXIBS".

It is used in the treatment of rheumatoid arthritis, osteoarthritis, acute pain condition and in the

adjunctive treatment of adenomatous colorectal polyps. Celecoxib (CELCOXX

) is chemically

designated as 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1 H pyrazol-1-yl] benzenesulfonamide

and is a diaryl-substituted pyrazole. The molecular formula for celecoxib is C

S and

the structural formula is:

FORMULATION

Celecoxib (CELCOXX

) is available for oral administration as:

1. Celecoxib (CELCOXX

) Capsules 100mg

Each capsule contains:

Celecoxib...100mg

2. Celecoxib (CELCOXX

) Capsules 200mg

Each capsule contains:

Celecoxib...200mg

3. Celecoxib (CELCOXX

) Capsules 400mg

Each capsule contains:

Celecoxib...400mg

CLINICAL PHARMACOLOGY

Mechanism of Action

Celecoxib is a nonsteroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic,

and antipyretic 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.

Pharmacokinetics:

Absorption

Peak plasma levels of celecoxib occur approximately 3 hours after an oral dose. Under fasting

conditions, both peak plasma levels (C

) and area under the curve (AUC) are roughly dose

proportional up to 200mg b.i.d.; at higher doses there are less than proportional increases in

and AUC. With multiple dosing, steady state conditions are reached on or before day 5.

Effect of Food and Antacid

When celecoxib was taken with a high fat meal, peak pla

sma levels were delayed for about 1

to 2 hours with an increase in total absorption (AUC) of 10% to 20%. Under fasting conditions,

at doses above 200mg, there is less than a proportional increase in C

and AUC, which is

thought to be due to the low solubility of the drug in aqueous media. Co-administration of celecoxib

with an aluminum- and magnesium-containing antacid resulted in a reduction in plasma celecoxib

concentrations with a decrease of 37% in C

and 10% in AUC.

Celecoxib, at doses up to 200mg b.i.d. can be administered without regard to timing of meals.

Higher doses (400mg b.i.d.) should be administered with food to improve absorption.

Distribution

In healthy subjects, celecoxib is highly protein bound (~97%) within the clinical dose range. The

apparent volume of distribution at stea

dy state (V

/F) is approximately 400L, suggesting extensive

distribution into the tissues. Celecoxib is not pref

erentially bound to red blood cells.

Metabolism

Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. 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.

Excretion

Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug

recovered in the urine and feces. The primary metabolite in both urine and feces was the

carboxylic acid metabolite (73% of dose) with low amounts of the glucuronide also appearing

in the urine. The effective half-life is approximately

11 hours under fasting conditions. The

apparent plasma clearance (CL/F) is about 500mL/min.

Special Populations

Geriatric: At steady state, elderly subjects (over 65 years old) had a 40% higher C

and a 50%

higher AUC compared to the young subjects. In elderly females, celecoxib C

and AUC are

higher than those for elderly males, but these increases are predominantly due to lower body

weight in elderly females. Dose adjustment in the elderly is not generally necessary. However,

for patients of less than 50kg in body weight, initiate therapy at the lowest recommended dose.

Pediatric: Celecoxib has not been investigated in JRA pediatric patients below 2 years of age,

in patients with body weight less than 10kg or beyond 24 weeks.

Hepatic Insufficiency: Steady state celecoxib AUC is increased about 40% and 180% in subjects

with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment respectively,

as compared to healthy control subjects.

Therefore, the daily-recommended dose of celecoxib

should be reduced by approximately 50% in patients with moderate (Child-Pugh Class B) hepatic

impairment. Patients with severe hepatic impairment (Child-Pugh Class C) have not been studied.

Renal Insufficiency: Studies indicate that celecoxib AUC was approximately 40% lower in patients

with chronic renal insufficiency (GFR 35-60mL/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.

THERAPEUTIC INDICATIONS

Celecoxib (CELCOXX

) 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.

3. For the symptomatic relief in the treatment of ankylosing spondylitis.

4. For relief of the signs and symptoms of juvenile rheumatoid arthritis (JRA) in patients 2 years

and older.

5. For the management of acute pain in adults especially in post operative pain.

6. For the treatment of primary dysmenorrhea.

7. To reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis

(FAP), as an adjunct to usual care (e.g., endoscopic surveillance, surgery).

DOSAGE AND ADMINISTRATION

For osteoarthritis and rheumatoid arthritis, the lowest dose of Celecoxib (CELCOXX

) should

be sought for each patient. These doses can be given without regard to timing of meals. Celecoxib

(CELCOXX

) can be taken with or without food.

Osteoarthritis: For relief of the signs and symptoms of osteoarthritis the recommended oral dose

is 200mg per day administered as a single dose or as 100mg twice daily. If necessary a dose

of 200mg twice daily may be used. In the absence of an increase in therapeutic benefit after two

weeks, other therapeutic options should be considered.

Rheumatoid arthri

tis: For relief of the signs and symptoms of rheumatoid arthritis the recommended

oral dose is 100 to 200mg twice daily. In the absence of an increase in therapeutic benefit after

two weeks, other therapeutic options should be considered.

Ankylosing spondylitis: The recommended daily dose is 200mg taken once daily or in two divided

doses. Dose can be increased to 400mg once daily or in two divided doses in patients with

insufficient relief of symptoms. In the absence of an increase in therapeutic benefit after two

weeks, other therapeutic options should be considered.

Juvenile rheumatoid arthritis: For the relief of the sign

s and symptoms of JRA the recommended

oral dose for pediatric patients (age 2 years and older) is based on weight. For patients >10kg

to <25kg the recommended dose is 50mg twice daily. For patients >25kg the recommended

dose is 100mg twice daily.

For patients who have difficulty swallowing capsules, the contents of a Celecoxib (CELCOXX

capsule can be added to applesauce. The entire capsule contents are carefully emptied onto a

level teaspoon of cool or room temperature applesauce and ingested immediately with water.

The sprinkled capsule contents on applesauce are stable for up to 6 hours under refrigerated

conditions (2-8°C).

Management of acute pain and treatment of primary dysmenorrhea: The recommended dose

of Celecoxib (CELCOXX

) is 400mg initially, followed by an additional 200mg dose if needed

on the first day. On subsequent days, the recommended dose is 200mg twice daily as needed

or 400mg once daily.

Familial adenomatous, polyposis (FAP): Usual medical care for FAP patients should be continued

while on Celecoxib (CELCOXX

). To reduce the number of adenomatous colorectal polyps in

patients with FAP, the recommended oral dose is 400mg twice per day to be taken with food.

Elderly patients: (>65 years) As in younger adults, 200mg per day should be used initially. The

dose may, if needed, later be increased to 200mg twice daily. Particular caution should be

exercised in elderly with a body weight less than 50kg.

Hepatic insufficient patients: The daily recommended dose of Celecoxib (CELCOXX

) capsules

in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by

approximately 50%.

Poor Metabolizers of CYP2C9 Substrates: Consideration should be given to starting treatment

at half the lowest recommended dose in these patients. Consideration should also be given to

using alternative management in JRA patients who are poor metabolizers.

ADVERSE REACTIONS

The following adverse drug reactions have been reported during therapy of celecoxib:

Most common

Gastrointestinal: Abdominal pain, diarrhea, dyspepsia, flatulence, nausea.

Central and peripheral nervous system: Dizziness, headache, hypertonia.

Respiratory: Pharyngitis, rhinitis, sinusitis, upper respiratory tract infection.

Others: Back pain

, insomnia, rash.

Less common

Gastrointestinal: Constipation, dysphagia, esophagitis, gastritis, gastroenteritis, gastroesophageal

reflux, hemorrhoids, melena, dry mouth, stomatitis, vomiting.

Cardiovascular: Aggravated hypertension, angina pectoris, coronary artery disorder, myocardial

infarction, palpitation, tachycardia.

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

pneumonia.

Central, peripheral nervous system: Leg cramps, hypertonia, hypoesthesia, migraine, neuralgia,

neuropathy, paresthesia, vertigo. Psychiatric: Anorexia, anxiety, appetite increased, depression,

nervousness, somnolence, tiredness.

Reproductive: Breast fibroadenosis, breast neoplasm, breast pain, dysmenorrhea, menstrual

disorder, vaginal hemorrhage, vaginitis, prostatic disorder.

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

Musculoskeletal: Arthralgia, bone disorder, myalgia, neck stiffness, tendonitis.

Metabolic and nutritional: BUN increased, CPK increased, diabetes mellitus, hypercholesterolemia,

hyperglycemia, hypokalemi

a, NPN incre

ase, creatinine increased, alkaline phosphatase increased,

weight increase.

General: Allergy aggravated, allergic reaction, asthenia, chest pain, cyst NOS, edema generalized,

face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral pain, anemia,

ear abnormality, earache, photosensitivity reaction, pruritus, dermatitis, taste perversion, otitis

media, blurred vision, eye pain, glaucoma, urinary tract infection.

Very rare:

Congestive heart failure,

pulmonary embolism, vasculitis cerebrovascular accident, gastrointestina

bleeding, colitis with bleeding, esophageal perforation, pancreatitis, hepatitis, thrombocytopenia,

agranulocytosis, aplastic anemia, pancytopenia, leukopenia, hypoglycemia, hyponatremia,

aseptic meningitis, ataxia, acute renal failure, interstitial nephritis erythema multiforme, exfoliative

dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylactoid reaction,

angioedema.

CONTRAINDICATIONS

Celecoxib is contraindicated in:

Patients with known hypersensitivity to celecoxib.

Patients who have demonstrated allergic-type reactions to sulfonamid

Patients who have experienced asthma, urticaria, or allergic-type reactions after taking acetyl

salicylic acid (ASA) or other NSAIDs including other COX-2 specific

inhibitors. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in

such patients.

Patients with renal impairment associated with creatinine clearance of <30mL/min.

Patients with severe hepatic impairment (Child-Pugh Class C).

Patients who have previously had a myocardial infarction or stroke.

Patients for the treatment of peri-operative pain in the setting of coronary artery bypass graft

(CABG) surgery.

Patients with active peptic ulceration or gastrointestinal bleeding and inflammatory bowel

disease.

Patients with established ischaemic heart disease (congestive heart failure), peripheral arterial

disease and/or cerebrovascular disease.

Celecoxib

200008005

100mg, 200mg, 400mg Capsules

Celecoxib

Celcoxx

Selective COX-2 Inhibitor

WARNINGS

PRECAUTIONS

General:

Celecoxib cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency.

Abrupt discontinuation of corticosteroids may lead to exacerbation of corticosteroid-responsive

illness. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly

if a decision is made to discontinue corticosteroids.

Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation:

Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation of the stomach,

small intestine or large intestine, can occur at any time, with or without warning symptoms, in

patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal

problems, such as dyspepsia, are common and may also occur at any time during NSAID

therapy. With longer duration of use of NSAIDs, there is a trend for increasing the likelihood

of developing a serious GI event at some time during the course of the

rapy. However, even

short-term therapy is not without risk. Therefore, physicians and patients should remain alert

for ulceration and bleeding, even in the absence of previous GI tract symptoms.

NSAIDs should be prescribed with extreme caution in patients with a prior history of ulcer

disease or gastrointestinal bleeding. To minimize the potential risk for an adverse GI event, the

lowest effective dose should be used for the shortest possible duration.

Congestive Heart Failure and Edema:

Fluid retention and edema have been observed in some patients taking celecoxib. Therefore,

celecoxib should be used with caution in patients with fluid retention, hypertension, or heart

failure.

Hypertension:

As with all NSAIDs, celecoxib can lead to the onset of new hypertension or worsening of p

existing hypertension, either of which may contribute to the increased incidence of cardiovascular

events. Patients taking thiazides or loop diuretics may have impaired response to these therapies

when taking NSAIDs. NSAIDs, including celecoxib, should be used with caution in patients with

hypertension. Blood pressure should be monitored closely during the initiation of therapy with

celecoxib and throughout the course of therapy.

Hepatic Effects:

A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal

liver test has occurred, should be monitored carefully for evidence of the development of a

more severe hepatic reaction while on therapy with celecoxib. If clinical signs and symptoms

consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia,

rash, etc.), celecoxib should be discontinued.

Renal Effects:

Long-term administration of NSAIDs has resulted in renal papillary necrosis a

nd other renal

injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a

compensatory role in the maintenance of renal perfusion. Patients at greatest risk of this reaction

are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics,

ACE-inhibitors, angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID

therapy is usually followed by recovery to the pre-treatment state.

Caution should be used when initiating treatment with celecoxib in patients with considerable

dehydration. It is advisable to rehydrate patients first and then start therapy with celecoxib.

Hematological Effects:

Anemia is sometimes seen in patients receiving celecoxib. Patients on long-term treatment with

celecoxib should have their hemoglobin or hematocrit checked if they exhibit any signs or

symptoms of anemia o

r blood loss. Celecoxib does not generally affect platelet counts,

prothrombin time (PT), or partial thromboplastin time (PTT), and does not inhibit platelet

aggregation at indicated dosages.

Serious Skin Reactions:

Patients appear to be at highest risk for serious skin reactions early in the course of therapy.

The onset of these events occurring in the majority of the cases within the first month of

treatment. Celecoxib should be discontinued at the first appearance of skin rash, mucosal

lesions, or any other sign of hypersensitivity.

Famalial Adenomatous Polyposis (FAP):

Treatment with celecoxib in FAP has not been shown to reduce the risk of gastrointestinal

cancer or the

need for prophylactic colectomy or other FAP-related surgeries. Therefore, the

usual care of FAP patients should not be altered because of the concurrent administration of

celecoxib.

Anaphylactic Reactions:

As with NSAIDs in general, anaphylactoid reactions have occurred in patients without known

prior exposure to celecoxib. Celecoxib should not be given to patients with the aspirin triad.

This symptom complex typically occurs in asthmatic patients who experience rhinitis with or

without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin

or other NSAIDs.

Skin Reactions

Celecoxib is a sulfonamide and can cause serious skin adverse events such as exfoliative

dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN), which can be

fatal. These serious events can occur without warning and in pa

tients without prior known sulfa

allergy. Patients should be informed about the signs and symptoms of serious skin manifestations

and use of the drug should be discontinued at the first appearance of skin rash or any other

sign of hypersensitivity.

Inflammation

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.

Concomitant NSAID Use

The concomitant use of celecoxib with any dose of a non-aspirin NSAID should be avoided due

to the potential for increased risk of adverse reactions.

Pregnancy:

Celecoxib should be used during pregnancy only if the potential benefit justifies the potential

risk to the fetus. In late pregnancy, starting at 30 weeks gestation, celecoxib should be avoided

because it may cause premature closure of the ductus arteriosus.

Nursing mothers:

Because many drugs are excreted in human milk and because of the potential for serio

adverse reactions in nursing infants from celecoxib, a decision should be made whether to

discontinue nursing or to discontinue the drug, taking into account the importance of the drug

to the mother.

Drug Interactions:

General: Celecoxib metabolism is predominantly mediated via cytochrome P450 2C9 in the

liver. Co-administration of celecoxib with drugs that are known to inhibit 2C9 should be done

with caution. 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 abnormall

high plasma levels due to reduced metabolic clearance.

ACE Inhibitors and Angiotensin II Antagonists: Reports suggest that NSAIDs may diminish the

antihypertensive effect of Angiotensin Converting Enzyme (ACE) inhibitors and angiotensin II

antagonists. This interaction should be given consideration

in patients taking celecoxib

concomitantly with ACE inhibitors and angiotensin II antagonists.

Furosemide: Clinical studies, as well as post marketing observations, have shown that NSAIDs

can reduce the natriuretic effect of furosemide and thiazides in some patients. This response

has been attributed to inhibition of renal prostaglandin synthesis.

Aspirin: Celecoxib can be used with low dose aspirin. However, concomitant administration of

aspirin with celecoxib may result in an increased rate of GI ulceration or other complications,

compared to use of celecoxib alone. Because of its lack of platelet effects, celecoxib is not a

substitute for aspirin for cardiovascular prophylaxis.

Fluconazole: Concomitant administration of fluconazole at 200mg q.d. resulted in a two-fold

increase in celecoxib plasma concentration. This increase is due to the inhibition of celecoxib

metabolism via P450 CYP2C9 by fluconazole. Celecoxib should be introduc

ed at the lowest

recommended dose in patients receiving fluconazole.

Lithium: Clinical studies showed that the mean steady-state lithium plasma levels increased

approximately 17% in subjects receiving lithium 450mg b.i.d. with celecoxib 200mg b.i.d. as

compared to subjects receiving lithium alone. Patients on lithium treatment should be closely

monitored when celecoxib is introduced or withdrawn.

Warfarin: Anticoagulant activity should be monitored, particularly in the first few days, after

initiating or changing celecoxib therapy in patients receiving warfarin or similar agents, since

these patients are at an increased risk of bleeding complications.

Antacid: Co-administration of celecoxib with an aluminum and magnesium-containing antacid

resulted in a reduction in plasma celecoxib concentrations. No dose adjustment is required.

Glucocorticoids:

Oral glucocorticoids should be used with caution since they increase the risk

of GI side effects such as ulceration and bleeding. This is especially the case in older (>65

years of age) individuals.

OVER DOSAGE

Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea,

vomiting, and epigastric pain, which are generally reversible with supportive care. Anaphylactoid

reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following

an overdose. Patients should be managed by symptomatic and supportive care following an

NSAID overdose. Monitor patients for signs and symptoms of gastrointestinal ulceration and/or

haemorrhage. Monitor serum electrolytes, renal function and urinalysis after significant overdose.

STORAGE CONDITIONS

Store at temperatures not exceeding 30°C.

Protect from sunlight and moisture.

Expiration date refers to the product correctly stored at the required conditions.

AVAILABILITY

Celecoxib (CELCOXX

) Capsules 100mg are available in Alu-Alu blister packs of 10's and box

of 20’s.

Celecoxib (CELCOXX

) Capsules 200mg are available in Alu-Alu blister packs of 10's and box

of 20’s.

Celecoxib (CELCOXX

) Capsules 400mg are available in Alu-Alu blister packs of 10's and box

of 20’s.

CAUTION

Foods, Drugs, Devices and Cosmetics Act prohibits dispensing without prescription.

Keep out of reach of children.

DESCRIPTION

Celecoxib (CELCOXX ) belongs to a new class of arthritis/analgesic medication called "COXIBS".

It is used in the treatment of rheumatoid arthritis, osteoarthritis, acute pain condition and in the

adjunctive treatment of adenomatous colorectal polyps. Celecoxib (CELCOXX ) is chemically

designated as 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1 H pyrazol-1-yl] benzenesulfonamide

and is a diaryl-substituted pyrazole. The molecular formula for celecoxib is C

S and

the structural formula is:

FORMULATION

Celecoxib (CELCOXX ) is available for oral administration as:

1. Celecoxib

(CELCOXX ) Capsules 100mg

Each capsule contains:

Celecoxib...100mg

2. Celecoxib (CELCOXX ) Capsules 200mg

Each capsule contains:

Celecoxib...200mg

3. Celecoxib (CELCOXX ) Capsules 400mg

Each capsule contains:

Celecoxib...400mg

CLINICAL PHARMACOLOGY

Mechanism of Action

Celecoxib is a nonsteroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic,

and antipyretic 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 therapeuti

concentrations in humans, celecoxib does not inhibit the cyclooxygenase-1 (COX-1) isoenzyme.

Pharmacokinetics:

Absorption

Peak plasma levels of celecoxib occur approximately 3 hours after an oral dose. Under fasting

conditions, both peak plasma levels (C

) and area under the curve (AUC) are roughly dose

proportional up to 200mg b.i.d.; at higher doses there are less than proportional increases in

and AUC. With multiple dosing, steady state conditions are reached on or before day 5.

Effect of Food and Antacid

When celecoxib was taken with a high fat meal, peak plasma levels were delayed for about 1

to 2 hours with an increase in total absorption (AUC) of 10% to 20%. Under fasting conditions,

at doses above 200mg, there is less th

an a proportional increase in C

and AUC, which is

thought to be due to the low solubility of the drug in aqueous media. Co-administration of celecoxib

with an aluminum- and magnesium-containing antacid resulted in a reduction in plasma celecoxib

concentrations with a decrease of 37% in C

and 10% in AUC.

Celecoxib, at doses up to 200mg b.i.d. can be administered without regard to timing of meals.

Highe r dose s (400 mg b.i.d.) shou ld be administered with food to improve

absorption .

Distribution

In healthy subjects, celecoxib is highly protein bound (~97%) within the clinical dose range. The

appa

rent volume of distribution at steady state (V

/F) is approximately 400L, suggesting extensive

distribu tion into the tis sues. Celecoxib is not prefere ntially

bound to red blood cells.

Metabolism

Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, a

primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate, have been

identified in human plasma. These m etabolites are ina ctive as COX-1 or C OX-2 inhibitors.

Excretion

Celecoxib is eliminated predominantly by hepatic metabolism with little (<3%) unchanged drug

recovered in the urine and feces. The primary metabolite in both urine and feces was the

carboxylic acid metabolite (73% of dose) with low amounts of the glucuronide also appearing

in the urine. The effective half -life i

s approximately 11 hours under fasting condi tions. The

apparent plasma clearance (CL/F) is about 500mL/min.

Special Populations

Geriatric: At steady state, elderly subjects (over 65 years old) had a 40% higher C

and a 50%

higher AUC compared to the young subjects. In elderly females, celecoxib C

and AUC are

higher than those for elderly males, but these increases are predominantly due to lower body

weight in elderly females. Dose adjustment in the elderly is not generally necessary. However,

for patients of less than 50kg in body weight, initiate therapy at the lowest recommended dose.

Pediatric: Celecoxib has not been investigated in JRA pediatric patients below 2 yea

rs of age,

in patients with body weight less than 10kg or beyond 24 weeks.

Hepatic Insufficiency: Steady state celecoxib AUC is increased about 40% and 180% in subjects

with mild (Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment respectively,

as compared to healthy control subjects. Therefore, the daily-recommended dose of celecoxib

should be reduced by approximately 50% in patients with moderate (Child-Pugh Class B) hepatic

impairment. Patients with severe hepatic impairment (Child-Pug

h Class C) have not been studied.

Renal Insufficiency: Studies indicate that celecoxib AUC was approximately 40% lower in patients

with chronic renal insufficiency (GFR 35-60mL/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.

THERAPEUTIC INDICATIONS

Celecoxib (CELCOXX ) is indicated:

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

2. For relief of the signs and symptoms of rheumat

oid arthritis in adults.

3. For the symptomatic relief in the treatment of ankylosing spondylitis.

4. For relief of the signs and symptoms of juvenile rheumatoid arthritis (JRA) in patients 2 years

and older.

5. For the management of acute pain in adults especially in post operative pain.

6. For the treatment of primary dysmenorrhea.

7. To reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis

(FAP), as an adjunct to usual care (e.g., endoscopic surveillance, surgery).

DOSAGE AND ADMINISTRATION

For osteoarthritis and rheumatoid arthritis, the lowest dose of Celec

oxib (CELCOXX ) should

be sought for each patient. These doses can be given without regard to timing of meals. Celecoxib

(CELCOXX ) can be taken with or without food.

Osteoarthritis: For relief of the signs and symptoms of osteoarthritis the recommended oral dose

is 200mg per day administered as a single dose or as 100mg twice daily. If necessary a dose

of 200mg twice daily may be used. In the absence of an increase in therapeutic benefit after two

weeks, other therapeutic options should be considered.

Rheumatoid arthritis: For relief of the sig

ns and symptoms of rheumatoid arthritis the recommended

oral dose is 100 to 200mg twice daily. In the absence of an increase in therapeutic benefit after

two weeks, other therapeutic options should be considered.

Ankylosing spondylitis: The recommended daily dose is 200mg taken once daily or in two divided

doses. Dose can be increased to 400mg once daily or in two divided doses in patients with

insufficient relief of symptoms. In the absence of an increase in therapeutic benefit after two

weeks, other therapeutic options should be considered.

Juvenile rheumatoid arthritis: For the relief of the signs and symptoms of JRA

the recommended

oral dose for pediatric patients (age 2 years and older) is based on weight. For patients >10kg

to <25kg the recommended dose is 50mg twice daily. For patients >25kg the recommended

dose is 100mg twice daily.

For patients who have difficulty swallowing capsules, the contents of a Celecoxib (CELCOXX )

capsule can be added to applesauce. The entire capsule contents are carefully emptied onto a

level teaspoon of cool or room temperature applesauce and ingested immediately with water.

The sprinkled capsule contents on applesauce are stable for up to 6 hours under refrigerated

conditions (2-8°C).

Management of acute pain and treatment of primary dysmenorrhea: The recommended dose

of Celecoxib (CEL

COXX ) is 400mg initially, followed by an additional 200mg dose if needed

on the first day. On subsequent days, the recommended dose is 200mg twice daily as needed

or 400mg once daily.

Familial adenomatous, polyposis (FAP): Usual medical care for FAP patients should be continued

while on Celecoxib (CELCOXX ). To reduce the number of adenomatous colorectal polyps in

patients with FAP, the recommended oral dose is 400mg twice per day to be taken with food.

Elderly patients: (>65 years) As in younger adults, 200mg per day should be used initially. The

dose may, if needed, lat er be increased to 200mg twice dai ly. Particular caut ion should be

exercised in elderly with a body weigh

t less than 50kg.

Hepatic insufficient patients: The daily recommended dose of Celecoxib (CELCOXX ) capsules

in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by

approximately 50%.

Poor Metabolizers of CYP2C9 Substrates: Consideration should be given to starting treatment

at half the lowest recommended dose in these patients. Consideration should also be given to

using alternative management in JRA patients who are poor metabolizers.

ADVERSE REACTIONS

The follow ing adverse drug reactions

have been reported during therapy

of celecoxib:

Most common

Gastrointe stinal: A bdominal pain , diarrhea , dysp epsia, flatu lence , nausea.

Central and peripheral nervous system: Dizziness, headache, hypertonia.

Respir

atory: Pharyngitis, rhinitis, sinusitis, upper respiratory tract infection.

Others: Back pain, insomnia, rash.

Less common

Gastrointestinal: Constipation, dysphagia, esophagitis, gastritis, gastroenteritis, gastroesophageal

reflux, hemorrhoids, melena, dry mouth, stomatitis, vomiting.

Cardiovascular: Aggravated hypertension, angina pectoris, coronary artery disorder, myocardial

infarction, palpitation, tachycardia.

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

pneumonia.

Central, peri

pheral nervous system: Leg cramps, hypertonia, hypoesthesia, migraine, neuralgia,

neuropathy, paresthesia, vertigo. Psychiatric: Anorexia, anxiety, appetite increased, depression,

nervousness, somnolence, tiredness.

Reproductive: Breast fibroadenosis, breast neoplasm, breast pain, dysmenorrhea, menstrual

disorder, vaginal hemorrhage, vaginitis, prostatic disorder.

Liver and biliary system : Hepatic function abnorm al, SGOT increased , SGPT increased .

Musculoskeletal: Arthralgia, bone disorder, myalgia, neck stiffness, tendonitis.

Metabolic and nutritional: BUN increased, CPK increased, diabetes mellitus, hypercholester

olemia,

hyperglycemia, hypokalemia, NPN increase, creatinine increased, alkaline phosphatase increased,

weight increase.

General: Allergy aggravated, allergic reaction, asthenia, chest pain, cyst NOS, edema generalized,

face edema, fatigue, fever, hot flushes, influenza-like symptoms, pain, peripheral pain, anemia,

ear abnormality, earache, photosensitivity reaction, pruritus, dermatitis, taste perversion, otitis

media, blurred vision, eye pain, glaucoma, urinary tract infection.

Very rare:

Congestive heart failure, pulmonary embol

ism, vasculitis cerebrovascular accident, gastrointestinal

bleeding, colitis with bleeding, esophageal perforation, pancreatitis, hepatitis, thrombocytopenia,

agranulocytosis, apla stic anemia, pancytopenia, leukopenia, hypoglycemia, hyponatremia,

aseptic meningitis, ataxia, acute renal failure, interstitial nephritis erythema multiforme, exfoliative

dermatitis, Stevens-Johnson syndrome, tox ic epidermal necrolysis, anaphylactoid rea ction,

angioedema.

CONTRAINDICATIONS

Celecoxib is contraindicated in:

Patients with known hypersensitivity to celecoxib.

Patients who have demonstrated allergic-type reactions to

sulfonamides.

Patients who have experienced asthma, urticaria, or allergic-type reactions after taking acetyl

salicylic acid (ASA) or other NSAIDs including other COX-2 specific

inhibitors. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in

such patients.

Patients

with rena l impairm ent assoc iate d with creatinine

cleara nce of <30mL/min.

Patients with severe hepatic impairment (Child-Pugh Class C).

Patients who have previously had a myocardial infarction or stroke.

Patients for the treatment of peri-operative pain in the setting of coronary artery bypass graft

(CABG) surgery.

atients with active peptic ulceration or gastrointestinal bleeding and inflammatory bowel

disease.

Patients with established ischaemic heart disease (congestive heart failure), peripheral arterial

disease and/or cerebrovascular disease.

Not to be given to those patients who have history of:

- Stroke: Cerebrovascular accident. CVA

Heart attack: Myocardial infarction. MI

Coronary artery bypass graft: CABG

Uncontrolled hypertension

Congestive heart failure (CHF) NYHA II-IV

Please read the contents carefully before use.

This package insert is continually updated from time to time.

Manufactured by: Getz Pharma (Pvt.) Ltd., 29-30/27, K.I.A., Karachi - 74900, Pakistan.

Imported by: Getz Pharma (Phils.) Inc., 2/F Tower 1, The Rockwell Business Center,

Ortigas Ave., Pasig City, Philippines.

200008005