Acute Pain¹

CELEBREX^® was comparable to diclofenac in relieving acute low back pain^1*

Adapted from Ralha L, et al. Revista Brasileira de Medicina. 2008.

Objective: To compare the efficacy of celecoxib 200 mg twice daily with diclofenac 75 mg twice daily in the treatment of acute low back pain (ALBP). Research design and methods: A non-inferiority multicenter, randomized, double-blind study. Patients with acute low back pain, Quebec Task Force grade 1 or 2, with a visual analog scale (VAS) score greater than 50 mm (range of 100 mm), and moderate to severe pain on a categorical scale were randomized to receive celecoxib 400 mg plus 200 mg on day 1 followed by 200 mg twice a day thereafter (N = 123) or diclofenac 75 mg twice daily (N = 121) for 7 days. Main outcome measurements: The primary endpoint was the change in pain intensity (PI) (VAS, mm) from baseline to day 3 for the population per-protocol. Secondary endpoints included pain and functional outcomes, and assessments of safety and tolerability.⁷

CI: Confidence Interval, VAS: Visual Analog Scale

*Based on data collected from MITT (modified-intent-to-treat) population.

†VAS ranging from 0 mm (no pain) to 100 mm (worst pain).

Sport Injury²

CELEBREX^® improved VAS scores in patients with acute pain due to ankle sprain, comparable to ns-NSAIDs^2†

Adapted from Cardenas-Estrada E. et al, J Int Med Res. 2009.

†ns-NSAIDs: Non-specific Nonsteroidal Anti-Inflammatory Drugs included diclofenac 100-200 mg, nimesulide 200 mg, ibuprofen 800-1600 mg, meloxicam 15 mg, piroxicam 20-40 mg, ketoprofen 100-200 mg, naproxen 1100 mg, cholestyramine diclofenac 150 mg, or tiaprofenic acid 600 mg.

LS= Least squares; VAS=Visual Analogue Scale.

7-day open-label, multicentre, randomized study compared the efficacy and safety of celecoxib with non-selective non-steroidal anti-inflammatory drugs (NSAIDs) in treating acute ankle sprain with moderate-to-severe ankle pain in 278 patients. Patients received either celecoxib (400 mg loading dose followed by 200 mg twice daily) or standard doses of non-selective NSAIDs. The primary endpoint was a change in the patient’s assessment of ankle pain on a 0 mm (no pain) - 100 mm (worst possible pain) visual analogue scale (VAS) at day 3 compared with baseline. From a baseline of 73 mm, mean VAS pain scores decreased to 29 and 32 mm in the celecoxib and non-selective NSAID groups, respectively. Difference between the 2 groups in the change from baseline in ankle pain VAS at day 3 was 3.39 mm (95% CI: -0.76, 7.55).²

Sport Injury³

CELEBREX^® provided sustained pain relief up to Day 14 in patients with acute shoulder tendinitis/bursitis, comparable to naproxen³

Adapted from Petri M, et al, J Rheumatol. 2009..

‡p<0.05 vs placebo. ¶p=not significant vs placebo

§ A statistically significant difference was not observed for naproxen vs placebo at Day 14.

OBJECTIVE: Shoulder tendinitis and subacromial bursitis are acute, painful inflammatory musculoskeletal conditions that may recur as a result of overuse. The study investigated the efficacy of celecoxib in managing patients with acute shoulder tendinitis/bursitis.³

METHODS: In this double blind, placebo controlled, parallel group study, patients with acute onset shoulder tendinitis and/or subacromial bursitis were randomized to receive one of: celecoxib 400 mg followed by 200 mg bid, naproxen 500 mg bid, or placebo bid for 14 days. The primary measure of efficacy was the mean reduction in Maximum Pain Intensity at Rest, measured using a 100 mm visual analog scale, from baseline to Days 7 and 14.³
bid: Twice daily

Sport Injury⁴

CELEBREX^® demonstrated a rapid return to normal functioning in patients with acute pain, similar to ibuprofen⁴

Median time to return to normal function (normal walking/activity or improved by ≥2 grades)

Adapted from Ekman E. F, et al, Am J Orthop. 2002.

*p=0.001, CELEBREX^® vs placebo.

†p=NS, CELEBREX^® vs ibuprofen.

In this multicenter, double-blind, randomized parallel-group study, 445 adult patients received celecoxib 400 mg/day, ibuprofen 2,400 mg/day, or placebo for 10 days. Patients had experienced grade 1 or 2 ankle sprains within 48 hours and had moderate to severe ankle pain. Adults 18 years or older were eligible for study participation. Inclusion criteria included a diagnosis of ankle sprain of grade 1 (microscopic tearing and inflammation of the ATFL or the CFL) with moderate to severe ankle pain. The injury had to have been sustained within 48 hours of the first dose of study medication. All women of childbearing potential had to be using adequate contraception and have a negative urine pregnancy test.⁴

Efficacy Endpoints: Primary measures of efficacy were patients VAS pain rating and Global assessment responses on day 4. Secondary measures of efficacy were patients’ VAS pain rating and Global assessment responses on days 8 and 11.⁴

ATFL: Anterior talofibular ligament; CFL: Calacneofibular ligament; NS: Not significant; VAS: Visual Analogue Scale.

Safety

Favorable Gastrointestinal Profile

In the CONDOR study, CELEBREX^® showed a 4x lower GI risk than diclofenac+omeprazole¹

Adapted from Chan, F.K, et al, Lancet. 2010.

A 6-month, double-blind, randomised trial in patients with osteoarthritis or rheumatoid arthritis at increased gastrointestinal risk at 196 centres in 32 countries or territories. Patients tested negative for Helicobacter pylori and were aged 60 years and older or 18 years and older with previous gastroduodenal ulceration. A computer-generated randomisation schedule was used to assign patients in a 1:1 ratio to receive celecoxib 200 mg twice a day or diclofenac slow release 75 mg twice a day plus omeprazole 20 mg once a day. Patients and investigators were masked to treatment allocation. The primary endpoint was a composite of clinically significant upper or lower gastrointestinal events adjudicated by an independent committee. 4484 patients were randomly allocated to treatment (2238 celecoxib; 2246 diclofenac plus omeprazole) and were included in intention-to-treat analyses. 20 (0·9%) patients receiving celecoxib and 81 (3·8%) receiving diclofenac plus omeprazole met criteria for the primary endpoint (hazard ratio 4·3, 95% CI 2·6–7·0; p<0·0001). 114 (6%) patients taking celecoxib versus 167 (8%) taking diclofenac plus omeprazole withdrew early because of gastrointestinal adverse events (p=0·0006).¹

GI: Gastrointestinal; ns-NSAID: Non-selective Non-steroidal anti-inflammatory drug; BID: twice daily; QD: once daily; SR: Slow Release.

CELEBREX^® demonstrated a lower incidence of both GI and treatment-related adverse events vs. diclofenac.^2®

Adapted from Ralha L, et al. Revista Brasileira de Medicina. 2008.

Objective: To compare the efficacy of celecoxib 200 mg twice daily with diclofenac 75 mg twice daily in the treatment of acute low back pain (ALBP). Research design and methods: A non-inferiority multicenter, randomized, double-blind study. Patients with acute low back pain, Quebec Task Force grade 1 or 2, with a visual analog scale (VAS) score greater than 50 mm (range of 100 mm), and moderate to severe pain on a categorical scale were randomized to receive celecoxib 400 mg plus 200 mg on day 1 followed by 200 mg twice a day thereafter (N = 123) or diclofenac 75 mg twice daily (N = 121) for 7 days. Main outcome measurements: The primary endpoint was the change in pain intensity (PI) (VAS, mm) from baseline to day 3 for the population per-protocol. Secondary endpoints included pain and functional outcomes, and assessments of safety and tolerability.²

With CELEBREX® all GI events were mild; with diclofenac 11 GI events were mild, 4 were moderate.²

GI: Gastrointestinal; VAS: Visual analogue scale; PI: Pain intensity; ALBP: Acute Low Back Pain.

Celecoxib was associated with a lower risk of clinically significant upper and / or lower GI events than ns-NSAIDs³

Adapted from Cryer, B. et al, Am J Gastroenterol. 2013.

A prospective, randomized, open-label, blinded endpoint (PROBE) study may be an appropriate alternative, as the design allows the assessment of clinical outcomes in clinical practice settings. The Gastrointestinal (GI) Randomized Event and Safety Open-Label Nonsteroidal Anti-inflammatory Drug (NSAID) Study (GI-REASONS) was designed to reflect standard clinical practice while including endpoints rigorously evaluated by a blinded adjudication committee. The objective of this study was to assess if celecoxib is associated with a lower incidence of clinically significant upper and/or lower GI events than nonselective NSAIDs (nsNSAIDs) in standard clinical practice. This was a PROBE study carried out at 783 centers in the United States, where a total of 8,067 individuals aged ≥ 55 years, requiring daily NSAIDs to treat osteoarthritis, participated. The participants were randomized to celecoxib or nsNSAIDs (1:1) for 6 months and stratified by Helicobacter pylori status. Treatment doses could be adjusted as per the United States prescribing information; patients randomized to nsNSAIDs could switch between nsNSAIDs; crossover between treatment arms was not allowed, and patients requiring aspirin at baseline were excluded. The primary outcome was the incidence of clinically significant upper and/or lower GI events.³

ns-NSAID: Non-selective Non-steroidal anti-inflammatory drug; GI-REASONS: The Gastrointestinal (GI) Randomized Event and Safety Open-Label Nonsteroidal Anti-inflammatory Drug (NSAID) Study; PROBE: prospective, randomized, open-label, blinded endpoint. GI: Gastrointestinal; NSAID: Non-steroidal anti-inflammatory.

Acute Pain

Flexible dosing in acute pain management^1†

†As the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used for all indications.¹
CELEBREX^® is contraindicated for the treatment of perioperative pain in the setting of coronary bypass graft (CABG) surgery.¹
CELEBREX^® dosing in chronic pain management²

Chronic Pain

Osteoarthritis¹

CELEBREX^® demonstrated a significant improvement in patients’ global assessment of osteoarthritis pain compared to placebo¹

  

Adapted from Kivitz, A. J. et al, J Int Med Res. 2001. 

*p<0.001 vs placebo.

Data based on a scale ranging from 1 (very good) to 5 (very poor).
This was a randomized, double-blind, placebo-controlled, parallel-group trial, conducted over 12 months at 176 sites in the US and Canada, in accordance with the principles of good clinical practice and the Declaration of Helsinki. The protocol was approved by an institutional review board at each site, and all patients provided written, informed consent. Patients discontinued conventional NSAID therapy, and were screened at baseline after a washout period of 2 – 4 days (4 days for piroxicam and/or oxaprozin). Patients were assessed for enrollment at screening or baseline using the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis (OA) Index, the Arthritis Assessments for Verification of Flare Criteria, and the Patient’s Assessment of Arthritis Pain on a Visual Analog Scale (Arthritis Pain VAS). The Patient’s, and the Physician’s Global Assessments of Arthritis Condition, and the Osteoarthritis Severity Index (OSI) were also used.¹
BID: twice a day, NSAID: Non-steroidal anti-inflammatory drugs 

CELEBREX^® 200 mg once a day was as effective as ibuprofen 800 mg 3 times a day in the treatment of OA pain²

Adapted from Martin-Mola E, et al, Annals of the Rheumatic Diseases. 2005.

*p≤0.05 CELEBREX^® 200 mg QD vs placebo; ibuprofen 800 mg TID vs placebo.
Objectives: To determine whether celecoxib 200 mg QD is as effective as ibuprofen 800 mg TID in the treatment of the signs and symptoms associated with osteoarthritis (OA) of the knee. Methods: In this 6-week, multicentre, randomised, double-blind, placebo-controlled, parallel-group study, the efficacy and safety of celecoxib 200 mg QD was compared with ibuprofen 800 mg TID and placebo in patients with knee OA. Patients aged ≥40 years with active, symptomatic knee OA in a flare state were included. Patients included had a Patient's Assessment of Arthritis Pain on a 100-mm visual analogue scale (VAS) between 40 and 90 mm, and showed an increase of 1 or more grades in both Physician's and Patient's Global Assessments of Arthritis between screening and baseline visits.²
QD: once per day; TID: three times a day. WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index.

Osteoarthritis⁴

CELEBREX^® improved WOMAC scores in subjects unresponsive to naproxen or ibuprofen^3*

Adapted from Pressler, M. Arthritis Advisory Comittee. 2014.

*Subjects were unresponsive to treatment with prescription-strength naproxen (≥750 mg/day for 2 weeks) and ibuprofen (≥1200 mg/day for 2 weeks) or had failed a trial of naproxen and ibuprofen of any duration if failure was due to lack of tolerability.
QD: once per day; LS: Least Squares.

Osteoarthritis⁴

CELEBREX^® significantly reduced osteoarthritis flares with continuous use over 22 weeks^4†

Adapted from Strand, V et al, J Rheumatol. 2011.
†Flares over 22 weeks.
‡p<0.0001

Objective. To determine whether “continuous” celecoxib is more efficacious than “intermittent” use in preventing osteoarthritis (OA) flares of the knee and/or hip. Methods. A double-blind, randomized, multicenter international study comparing efficacy and safety of continuous (daily) versus intermittent (as required during predefined OA flare) celecoxib 200 mg/day in 858 subjects, aged 18–80 years. The study consisted of 3 periods: (I) screening/washout visit; (II) open-label run-in with celecoxib; and (III) 22-week blinded treatment. Only subjects whose OA flares resolved in Period 2 (without subsequent flare) were randomized. The primary endpoint, number of flares per time of exposure during Period III (number of flares per month), was compared using analysis of variance with treatment as the independent variable. Acetaminophen was available as rescue medication.⁴
QD: once per day

[Celebrex] ^® abbreviated prescribing information

Presentation: 100, 200, 400 mg, Hard capsules for oral use, Celecoxib. 100 mg capsules; Blister pack containing 20 capsules, 200 mg capsules; Blister pack containing 10 or 20 capsules, 400 mg capsules; Blister pack containing 10 capsules.

Indication(s): Celebrex is indicated in adults for the symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Juvenile Idiopathic Arthritis (JIA) For the management of the signs and symptoms of JIA in patients 2 years and older, Acute Pain For the management of acute pain in adults, Primary Dysmenorrhea For the management of primary dysmenorrhea. The decision to prescribe a selective cyclooxygenase-2 (COX-2) inhibitor should be based on an assessment of the individual patient's overall risks.

Dosage and Administration: Oral use: Celecoxib may be taken with or without food. For patients who have difficulty swallowing capsules, the contents of a celecoxib capsule can be added to applesauce, rice gruel, yogurt or mashed banana. To do so, the entire capsule contents must be carefully emptied onto a level teaspoon of cool or room temperature applesauce, rice gruel, yogurt or mashed banana and should be ingested immediately with 240 ml of water. The sprinkled capsule contents on applesauce, rice gruel or yogurt are stable for up to 6 hours under refrigerated conditions (2°C-8°C). The sprinkled capsule contents on mashed banana should not be stored under refrigerated conditions and should be ingested immediately. Posology: As the cardiovascular (CV) risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis. Osteoarthritis: The usual recommended daily dose is 200 mg taken once daily or in two divided doses. In some patients, with insufficient relief from symptoms, an increased dose of 200 mg twice daily may increase efficacy. In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered. Rheumatoid arthritis: The initial recommended daily dose is 200 mg taken in two divided doses. The dose may, if needed, later be increased to 200 mg 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 200 mg taken once daily or in two divided doses. In a few patients, with insufficient relief from symptoms, an increased dose of 400 mg once daily or in two divided doses may increase efficacy. In the absence of an increase in therapeutic benefit after two weeks, other therapeutic options should be considered. Juvenile Idiopathic Arthritis: For JIA, the dosage for pediatric patients (age 2 years and older) is based on weight. For patients >10 kg to <25 kg the recommended dose is 50 mg twice daily. For patients >25 kg the recommended dose is 100 mg twice daily. For patients who have difficulty swallowing capsules, the contents of a CELEBREX 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°C -8°C). Management of Acute Pain and Treatment of Primary Dysmenorrhea: For management of Acute Pain and Treatment of Primary Dysmenorrhea, the dosage 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. Special Population: Elderly: As in younger adults, 200 mg per day should be used initially. The dose may, if needed, later be increased to 200 mg twice daily. Particular caution should be exercised in elderly with a body weight less than 50 kg. CYP2C9 poor metabolisers: Patients who are known or suspected to be CYP2C9 poor metabolisers based on genotyping or previous history/experience with other CYP2C9 substrates should be administered celecoxib with caution as the risk of dosedependent adverse effects is increased. Consider reducing the dose to half the lowest recommended dose. Hepatic impairment: Treatment should be initiated at half the recommended dose in patients with established moderate liver impairment with a serum albumin of 25-35 g/l. Experience in such patients is limited to cirrhotic patients. Renal impairment: Experience with celecoxib in patients with mild or moderate renal impairment is limited, therefore such patients should be treated with caution. Pregnancy: Studies in animals (rats and rabbits) have shown reproductive toxicity, including malformations. Inhibition of prostaglandin synthesis might adversely affect pregnancy. Data from epidemiological studies suggest an increased risk of spontaneous abortion after use of prostaglandin synthesis inhibitors in early pregnancy. The potential for human risk in pregnancy is unknown but cannot be excluded. Celecoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus during the last trimester. During the second or third trimester of pregnancy, NSAIDs including celecoxib may cause fetal renal dysfunction which may result in reduction of amniotic fluid volume or oligohydramnios in severe cases. Such effects may occur shortly after treatment initiation and are usually reversible. If a woman becomes pregnant during treatment, celecoxib should be discontinued. Breast-feeding: Celecoxib is excreted in the milk of lactating rats at concentrations similar to those in plasma. Administration of celecoxib to a limited number of lactating women has shown a very low transfer of celecoxib into breast milk. Women who take celecoxib should not breastfeed. Fertility: Based

Contraindications: Hypersensitivity to the active substance or to any of the excipients. Known hypersensitivity to sulfonamides. Active peptic ulceration or gastrointestinal (GI) bleeding. Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid (aspirin) or other non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors. Breast-feeding. Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10). Patients with estimated creatinine clearance <30 ml/min. Inflammatory bowel disease. Congestive heart failure (NYHA II-IV). Established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

Warning and Precautions: Gastrointestinal (GI) effects: Upper and lower gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them resulting in fatal outcome, have occurred in patients treated with celecoxib. Caution is advised with treatment of patients most at risk of developing a gastrointestinal complication with NSAIDs; the elderly, patients using any other NSAID or antiplatelet drugs (such as acetylsalicylic acid or glucocorticoids concomitantly, patients using alcohol, or patients with a prior history of gastrointestinal disease, such as ulceration and GI bleeding. There is further increase in the risk of gastrointestinal adverse effects for celecoxib (gastrointestinal ulceration or other gastrointestinal complications), when celecoxib is taken concomitantly with acetylsalicylic acid (even at low doses). A significant difference in GI safety between selective COX-2 inhibitors + acetylsalicylic acid vs. NSAIDs + acetylsalicylic acid has not been demonstrated in longterm clinical trials. Concomitant NSAID use: The concomitant use of celecoxib and a non-aspirin NSAID should be avoided. Cardiovascular effects: Increased number of serious cardiovascular (CV) events, mainly myocardial infarction, has been found in a long-term placebo-controlled study in subjects with sporadic adenomatous polyps treated with celecoxib at doses of 200 mg bis in die (BID) and 400 mg BID compared to placebo. As the cardiovascular risks of celecoxib may increase with dose and duration of exposure, the shortest duration possible and the lowest effective daily dose should be used. NSAIDs, including COX-2 selective inhibitors, have been associated with increased risk of cardiovascular and thrombotic adverse events when taken long term. The exact magnitude of the risk associated with a single dose has not been determined, nor has the exact duration of therapy associated with increased risk. The patient's need for symptomatic relief and response to therapy should be re-evaluated periodically, especially in patients with osteoarthritis. Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with celecoxib after careful consideration. COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thromboembolic diseases because of their lack of antiplatelet effects. Therefore, antiplatelet therapies should not be discontinued. Fluid retention and oedema: As with other medicinal products known to inhibit prostaglandin synthesis, fluid retention and oedema have been observed in patients taking celecoxib. Therefore, celecoxib should be used with caution in patients with history of cardiac failure, left ventricular dysfunction or hypertension, and in patients with pre-existing oedema from any other reason, since prostaglandin inhibition may result in deterioration of renal function and fluid retention. Caution is also required in patients taking diuretic treatment or otherwise at risk of hypovolaemia. Hypertension: As with all NSAIDS, celecoxib can lead to the onset of new hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of cardiovascular events. Therefore, blood pressure should be monitored closely during the initiation of therapy with celecoxib and throughout the course of therapy. Hepatic and renal effects: Compromised renal or hepatic function and especially cardiac dysfunction are more likely in the elderly and therefore medically appropriate supervision should be maintained. 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, those taking diuretics, angiotensin converting enzyme (ACE)-inhibitors, angiotensin II receptor antagonists, and the elderly. Such patients should be carefully monitored while receiving treatment with celecoxib. Some cases of severe hepatic reactions, including fulminant hepatitis (some with fatal outcome), liver necrosis and, hepatic failure (some with fatal outcome or requiring liver transplant), have been reported with celecoxib. Among the cases that reported time to onset, most of the severe adverse hepatic events developed within one month after initiation of celecoxib treatment. If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken, and discontinuation of celecoxib therapy should be considered. CYP2D6 inhibition: Celecoxib inhibits CYP2D6. Although it is not a strong inhibitor of this enzyme, a dose reduction may be necessary for individually dose-titrated medicinal products that are metabolised by CYP2D6. CYP2C9 poor metabolisers: Patients known to be CYP2C9 poor metabolisers should be treated with caution. Skin and systemic hypersensitivity 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. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Serious hypersensitivity reactions (including anaphylaxis, angioedema and drug rash with eosinophilia and systemic symptoms (DRESS), or hypersensitivity syndrome), have been reported in patients receiving celecoxib. Patients with a history of sulfonamide allergy or any drug allergy may be at greater risk of serious skin reactions or hypersensitivity reactions. Celecoxib should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Premature closure of the ductus arteriosus: Celecoxib, as with other medicinal products inhibiting prostaglandin synthesis, may cause premature closure of the ductus arteriosus during the last trimester. General: Celecoxib may mask fever and other signs of inflammation. Use with oral anticoagulants: In patients on concurrent therapy with warfarin, serious bleeding events, some of them fatal, have been reported. Increased prothrombin time (INR) with concurrent therapy has been reported. Therefore, this should be closely monitored in patients receiving warfarin/coumarin-type oral anticoagulants, particularly when therapy with celecoxib is initiated or celecoxib dose is changed. Concomitant use of anticoagulants with NSAIDS may increase the risk of bleeding. Caution should be exercised when combining celecoxib with warfarin or other oral anticoagulants, including novel anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban). Excipients: Celebrex 100 mg, 200 mg and 400 mg capsules contain lactose (149.7 mg, 49.8 mg and 99.6 mg respectively). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. Celebrex contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’

Interactions: Pharmacodynamic interactions: (1) Anticoagulants. (2) Anti-hypertensives: NSAIDs may reduce the effect of anti-hypertensive medicinal products including ACE-inhibitors, angiotensin II receptor antagonists, diuretics and beta-blockers. (3) Ciclosporin and tacrolimus. (4) Acetylsalicylic acid: Celecoxib can be used with low-dose acetylsalicylic acid but is not a substitute for acetylsalicylic acid for CV prophylaxis. Pharmacokinetic interactions: Effects of celecoxib on other medicinal products: (1) CYP2D6 inhibition: Examples of medicinal products which are metabolised by CYP2D6 are antidepressants (tricyclics and SSRIs), neuroleptics, anti-arrhythmic medicinal products, etc. (2) CYP2C19 inhibition: Examples of medicinal products which are metabolised by CYP2C19 are diazepam, citalopram and imipramine. (3) Methotrexate. (4) Lithium. (5) Oral contraceptives. (6) Glibenclamide/tolbutamide. Effects of other medicinal products on celecoxib: (1) CYP2C9 poor metabolisers. (2) CYP2C9 inhibitors and inducers. (3) Ketoconazole and antacids. Paediatric population: Interaction studies have only been performed in adults.

Overdosing: There is no clinical experience of overdose. Single doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy subjects for nine days without clinically significant adverse effects. In the event of suspected overdose, appropriate supportive medical care should be provided e.g. by eliminating the gastric contents, clinical supervision and, if necessary, the institution of symptomatic treatment. Dialysis is unlikely to be an efficient method of medicinal product removal due to high protein binding.

Adverse Reaction: Adverse drug reactions in celecoxib clinical trials and surveillance Experience: Very Common (≥1/10): Hypertension (including aggravated hypertension) while Common (≥1/100 to <1/10): Sinusitis, upper respiratory tract infection, pharyngitis, urinary tract infection, Hypersensitivity, Insomnia, Dizziness, hypertonia, headache, Myocardial infarction, Rhinitis, cough, dyspnea, Nausea, abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting, dysphagia, Rash, pruritus (includes pruritus generalised), Arthralgia, Influenza like illness, oedema peripheral/fluid retention, Injury (accidental injury).

Pharmaceutical Precautions: Shelf life: Do not use Celebrex after the expiry date which is stated on the carton / Blister after EXP:. The expiry date refers to the last day of that month. Store below 30oC. The sprinkled capsule contents on applesauce, rice gruel or yogurt are stable for up to 6 hours under refrigerated conditions (2° C -8° C/ 35-45° F). The sprinkled capsule contents on mashed banana should not be stored under refrigerated conditions.

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