1. NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 100 mg capsule contains 100 mg celecoxib.
Each 200 mg capsule contains 200 mg celecoxib.
Each 400 mg capsule contains 400 mg celecoxib.
3. PHARMACEUTICAL FORM
Hard capsules for oral use.
100 mg Capsules: Opaque, white capsules with a blue band marked 7767 and
200 mg Capsules: Opaque, white capsules with a gold band marked 7767 and
400 mg Capsules: Hard Gelatin Capsule (containing white to off white
granulation. White opaque body with green ink band containing in white
"400". White opaque cap with green band containing in white "7767"
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
For the management of acute pain in adults and for the treatment of primary
Relief of the acute and chronic pain and inflammation of
rheumatoid arthritis and osteoarthritis.
Relief of signs and symptoms of ankylosing spondylitis.
4.2 Posology and method of administration
Carefully consider the potential benefits and risks of Celebrex and other
treatment options before deciding to use Celebrex. Use the lowest effective
dose for the shortest duration consistent with individual patient treatment
Management of acute pain and treatment of primary dysmenorrhoea: The
recommended dose of Celebrex is 400 mg, initially, followed by an additional
200 mg dose, if needed on the first day. On subsequent days, the recommended
dose is 200 mg twice daily, as needed. Doses up to 600 mg daily have been
studied for these indications. Celebrex has been administered up to 2 hours
prior to surgery.
Osteoarthritis: The recommended dose of Celebrex is 200 mg administered as a
single dose or as two divided doses. Doses up to 400 mg per day have been
Rheumatoid arthritis: The recommended dose of Celebrex is 100 or 200 mg
twice per day. Doses up to 800 mg per day have been studied.
Ankylosing Spondylitis (AS): The recommended dose of celecoxib is 200 mg
administered as a single dose. Some patients may benefit from a total daily
dose of 400 mg.
Elderly: No dosage adjustment is generally necessary. However, for elderly
patients with a lower than average body weight (< 50 kg), it is advisable to
initiate therapy at the lowest recommended dose.
Hepatic impairment: No dosage adjustment is necessary in patients with mild
hepatic impairment (Child-Pugh Class A). Introduce Celebrex at the lowest
recommended dose in arthritis patients with moderate hepatic impairment
(Child-Pugh Class B).
Patients with severe hepatic impairment have not been studied. The use of
Celebrex in patients with severe hepatic impairment is not recommended.
Renal impairment: No dosage adjustment is necessary in patients with mild or
moderate renal impairment. There is no clinical experience in patients with
severe renal impairment (See Section 4.4 Special Warnings and Special
Precautions for Use - Renal Effects and Section 5.2 Pharmacokinetics
Children: Celebrex has not been studied in subjects under 18
CYP2C9 Poor Metabolizers: Patients who are known, or suspected to be CYP2C9
poor metabolizers based on previous history/experience with other CYP2C9
substrates should be administered celecoxib with caution. Consider starting
treatment at half the lowest recommended dose. (See Section 4.5 Interaction
with other medicinal products and other forms of interaction and Section 5.2
Pharmacokinetic properties: Metabolism.)
Celecoxib is contraindicated in:
• Patients with known hypersensitivity to celecoxib or any other ingredient
of the product:
• Patients with known sulfonamide hypersensitivity;
• Patients who have experienced asthma, urticaria or allergic-type reactions
after taking acetylsalicylic acid (aspirin) or
nonsteroidal anti-inflammatory drugs (NSAIDs), including other
cyclooxygenase-2 (COX-2) specific inhibitors.
• Treatment of peri-operative pain in the setting of coronary artery bypass
graft (CABG) surgery. (See Section 4.4 Special
warnings and precautions for use.)
4.4 Special warnings and special precautions for use
RISK OF GI ULCERATION BLEEDING AND PERFORATION WITH NSAID
Serious GI toxicity such as bleeding, ulceration and perforation can occur
at any time, with or without warning symptoms, in patients treated with
NSAID therapy. Although minor upper GI problems (e.g. dyspepsia) are common,
usually developing early in therapy, prescribers should remain alert for
ulceration and bleeding in patients treated with NSAIDs even in the absence
of previous GI tract symptoms.
Studies to date have not identified any subset of patients not at risk of
developing peptic ulceration and bleeding. Patients with prior history of
serious GI events and other risk factors associated with peptic ulcer
disease (e.g. alcoholism, smoking, and corticosteroid therapy) are at
increased risk. elderly or debilitated patients seem tot tolerate ulceration
or bleeding less than other individuals and account for most spontaneous
reports for fatal GI events.
Cardiovascular Thrombotic Events: Celecoxib may cause an increased
risk of serious cardiovascular thrombotic events, myocardial infarction, and
stroke, which can be fatal. All NSAIDs may have a similar risk. This risk
may increase with dose, duration of use and baseline cardiovascular risk
factors. Patients with known cardiovascular disease may be at greater risk.
To minimize the potential risk for an adverse cardiovascular event in
patients treated with celecoxib, the lowest effective dose should be used
for the shortest duration possible. Physicians and patients should remain
alert for the development of such events, even in the absence of previous
cardiovascular symptoms. Patients should be informed about the signs and/or
symptoms of serious cardiovascular toxicity and the steps to take if they
occur. (See Section 5.1 Pharmacodynamic properties.)
Two large, controlled, clinical trials of a different COX-2 selective NSAID
for the treatment of pain in the first 10-14 days following CABG surgery
found an increased incidence of myocardial infarction and stroke (See
Section 4.3 Contraindications).
Celecoxib is not a substitute for acetylsalicylic acid for prophylaxis of
cardiovascular thrombo-embolic diseases because of the lack of effect on
platelet function. Because celecoxib does not inhibit platelet aggregation,
antiplatelet therapies (e.g., acetylsalicylic acid) should not be
Hypertension: As with all NSAIDS, celecoxib can lead to the onset of
new hypertension or worsening of pre-existing hypertension, either of which
may contribute to the increased incidence of cardiovascular events. Patients
taking antihypertensives with NSAIDs may have an impaired anti-hypertensive
response. 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
Fluid Retention and Edema: As with other drugs known to inhibit
prostaglandin synthesis, fluid retention and edema have been observed in
some patients taking celecoxib. Therefore, patients with pre-existing
congestive heart failure or hypertension should be closely monitored.
Celecoxib should be used with caution in patients with compromised cardiac
function, pre-existing edema, or other conditions predisposing to, or
worsened by, fluid retention including those taking diuretic treatment or
otherwise at risk of hypovolemia.
Upper gastrointestinal (GI) perforations, ulcers or bleeds have occurred in
patients treated with celecoxib. These conditions can occur at any time
without warning and may increase with dose or duration of use. Patients most
at risk of developing these types of GI complications with NSAIDs are the
elderly, patients with cardiovascular disease, patients using concomitant
aspirin, patients with a prior history of smoking and alcoholism or patients
with a prior history of, or active, gastrointestinal disease, such as
ulceration, GI bleeding or inflammatory conditions. Therefore, caution is
advised in these patients. Most spontaneous reports of fatal
gastrointestinal events have been in elderly or debilitated patients. When
gastrointestinal bleeding or ulceration occur in patients receiving NSAIDs,
the drug should be withdrawn immediately. Doctors should warn patients about
signs and symptoms of serious gastrointestinal toxicity.
The concurrent use of aspirin and NSAIDs also increases the risk of serious
gastrointestinal adverse events.
NSAIDs, including celecoxib may cause renal toxicity. Clinical trials with
celecoxib have shown renal effects similar to those observed with comparator
NSAIDs. Patients at greatest risk for renal toxicity are those with impaired
renal function, heart failure, liver dysfunction, and the elderly. Such
patients should be carefully monitored while receiving treatment with
Caution should be used when initiating treatment in patients with
dehydration. It is advisable to rehydrate patients first and then start
therapy with celecoxib.
Advanced Renal Disease
Renal function should be closely monitored in patients with advanced renal
disease who are administered celecoxib. (See Section 4.2 Posology and method
As with NSAIDs in general, anaphylactoid reactions have occurred in patients
exposed to celecoxib. (See Section 4.3 Contraindications.)
Serious Skin Reactions
Serious skin reactions, some of them fatal, including exfoliative
dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have
been reported very rarely in association with the use of celecoxib and can
occur without warning. These serious adverse events are idiosyncratic and
are independent of dose or duration of use. Patients appear to be at highest
risk for these events early in the course of therapy: the onset of the event
occurring in the majority of cases within the first month of treatment.
Patients should be advised of the signs and symptoms of serious skin
reactions and to consult their doctor at the first appearance of skin rash
or any other sign of hypersensitivity. Celecoxib should be discontinued at
the first appearance of skin rash, mucosal lesions, or any other sign of
Patients with severe hepatic impairment (Child-Pugh Class C) have not been
studied. The use of celecoxib in patients with severe hepatic impairment is
not recommended. Celecoxib should be used with caution when treating
patients with moderate hepatic impairment (Child-Pugh Class B), and
initiated at the lowest recommended dose. (See Section 4.2 Posology and
method of administration.)
Rare cases of severe hepatic reactions, including fulminant hepatitis (some
with fatal outcome), liver necrosis, hepatic failure (some with fatal
outcome or requiring liver transplant), have been reported with celecoxib.
A patient with symptoms and/or signs of liver dysfunction, or in whom an
abnormal liver function test has occurred, should be monitored carefully for
evidence of the development of a more severe hepatic reaction while on
therapy with celecoxib.
Use with Warfarin or Similar Agents
In patients on concurrent therapy with warfarin or similar agents, serious
bleeding events, some of them fatal, have been reported. Because increases
in prothrombin time (INR) have been reported, anticoagulant activity should
be monitored after initiating treatment with celecoxib or changing the dose.
By reducing inflammation, celecoxib may diminish the utility of diagnostic
signs, such as fever, in detecting infections. The concomitant use of
celecoxib and a non-aspirin NSAID should be avoided.