Drugs and medications

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 100.
200 mg Capsules: Opaque, white capsules with a gold band marked 7767 and 200.
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 dysmenorrhoea.

Relief of the acute and chronic pain and inflammation of rheumatoid arthritis and osteoarthritis.

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 goals.

Adults
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 studied.
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 Properties).

Children: Celebrex has not been studied in subjects under 18 years old.
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.)

4.3 Contra-indications
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.)

WARNING

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 Effects
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 discontinued.

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 therapy.

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.

Gastrointestinal Effects
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.

Renal Effects
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 celecoxib.

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 of administration.)

Anaphylactoid Reactions
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 hypersensitivity.

Hepatic Effects
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.

General
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.