| Company Name |
| Memphis |
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| Therapeutic Group |
| COXIBS PLAIN |
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| Pharmaceutical form |
| Capsule |
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| Package |
| Carton box containing 5 Capsules & other of 10 Capsules in Al/PVC Strips with inner leaflet. |
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| Indications |
"Symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.
The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks ." |
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| Warning & Precautions |
| "Upper gastrointestinal complications [perforations, ulcers or bleedings (PUBs)], some of them resulting in fatal outcome, have occurred in patients treated with celecox. 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 acetylsalicylic acid concomitantly 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 celecox (gastrointestinal ulceration or other gastrointestinal complications), when celecox 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 long-term clinical trials The concomitant use of celecox and a non-aspirin NSAID should be avoided. Increased number of serious cardiovascular 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 200mg BID and 400mg BID compared to placebo . As the cardiovascular risks of celecox 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 . Patients with significant risk factors for cardiovascular events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with celecox after careful consideration .COX-2 selective inhibitors are not a substitute for acetylsalicylic acid for prophylaxis of cardiovascular thrombo-embolic diseases because of their lack of antiplatelet effects. Therefore, antiplatelet therapies should not be discontinued . As with other drugs known to inhibit prostaglandin synthesis, fluid retention and oedema have been observed in patients taking celecox. Therefore, celecox 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. As with all NSAIDS, celecox 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. Therefore blood pressure should be monitored closely during the initiation of therapy with celecox and throughout the course of therapy. 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 celecox, 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 celecox. 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 celecox treatment . If during treatment, patients deteriorate in any of the organ system functions described above, appropriate measures should be taken and discontinuation of celecox therapy should be considered. Celecox inhibits CYP2D6. Although it is not a strong inhibitor of this enzyme, a dose reduction may be necessary for individually dose-titrated drugs that are metabolised by CYP2D6 . Patients known to be CYP2C9 poor metabolisers should be treated with caution. 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 (anaphylaxis and angioedema) have been reported in patients receiving celecoxib . Patients with a history of sulphonamide allergy or any drug allergy may be at greater risk of serious skin reactions or hypersensitivity reactions. Celecox should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Celecox may mask fever and other signs of inflammation. In patients on concurrent therapy with warfarin, serious bleeding events have occurred. Caution should be exercised when combining celecox with warfarin and other oral anticoagulants . Celecox capsule contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. " |
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| Product Type |
| Human |
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| Dosage |
"Carefully consider the potential benefits and risks of celecox and other treatment options before deciding to use celecox. Use the lowest effective dose for the shortest duration consistant with individual patient treatment goals.
For osteoarthritis and rheumatoid arthritis, the lowest dose of celecox should be sought for each patient. These doses can be given without regard to timing of meals.
Osteoarthritis : For relief of the signs and symptoms of osteoarthritis the recommended oral dose is 200 mg per day administered as a single dose .
Rheumatoid arthritis : For relief of the signs and symptoms of rheumatoid arthritis the recommended oral dose is 200 mg twice per day.
Ankylosing spondylitis (AS) : For the management of the signs and symptoms of AS, the recommended dose of celecox is 200 mg daily single (once per day). If no effect is observed after 6 weeks , a trial on 400 mg daily may be worthwhile. If no effect is observed after 6 weeks on 400 mg daily, a response is not likely and consideration should be given to alternate treatment options.
Management of acute pain and treatment of primary dysmenorrhea:The recommended dose of celecox 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 populations
Hepatic insufficiency:
The daily recommended dose of celecox capsules in patients with moderate hepatic impairment (Child-Pugh Class B) should be reduced by approximately 50% . The use of celecox in patients with severe hepatic impairment is not recommended. " |
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| Adverse Reactions |
"Adverse reactions are listed by system organ class and ranked by frequency in Table 1.
Table 1. Adverse Drug Reactions in Celecoxib Clinical Trials and Surveillance Experience (MedDRA Preferred Terms)1,2
Adverse reaction Frequency Infections and infestations:Common ( 1/100 to <1/10):Sinusitis, upper respiratory tract infection, urinary tract infection.
Blood and lymphatic system disorders:Uncommon ( 1/1000 to <1/100) : Anemia -Rare ( 1/10,000 to <1/1000) :Leucopenia, thrombocytopenia:Frequency Not Known - (Post-marketing experience)3:Pancytopenia.
Immune system disorders :Common ( 1/100 to <1/10):Allergy aggravated-Frequency Not Known - (Post-marketing experience)3:Serious allergic reactions, anaphylactic shock, anaphylaxis.
Metabolism and nutrition disorders:Uncommon ( 1/1000 to <1/100) :Hyperkaelemia Psychiatric disorders:Common ( 1/100 to <1/10):Insomnia-Uncommon ( 1/1000 to <1/100) :Anxiety, depression, tiredness-Rare ( 1/10,000 to <1/1000):Confusion-Frequency Not Known - (Post-marketing experience)3:Hallucinations.
Nervous system disorders:Common ( 1/100 to <1/10):Dizziness, hypertonia -Uncommon ( 1/1000 to <1/100) :Paraesthesia, somnolence, cerebral infarction1- Rare ( 1/10,000 to <1/1000):Ataxia, taste alteration- Frequency Not Known - (Post-marketing experience)3:Headache, aggravated epilepsy, meningitis aseptic, ageusia, anosmia, fatal intracranial haemorrhage. Eye disorders: Uncommon ( 1/1000 to <1/100) :Blurred vision-Frequency Not Known - (Post-marketing experience)3:Conjunctivitis, ocular haemorrhage, retinal artery or vein occlusion. Ear and labyrinth disorders:Uncommon ( 1/1000 to <1/100) :Tinnitus, hypoacusis1 Cardiac disorders:Common ( 1/100 to <1/10):Myocardial infarction1- Uncommon ( 1/1000 to <1/100) : Heart failure, palpitations, tachycardia-Frequency Not Known - (Post-marketing experience)3:Arrhythmia. Vascular disorders :Very Common ( 1/10):Hypertension1-Uncommon ( 1/1000 to <1/100) :Hypertension aggravated-Frequency Not Known - (Post-marketing experience)3:Flushing, vasculitis, pulmonary embolism.
Respiratory, thoracic, and mediastinal disorders : Common ( 1/100 to <1/10):Pharyngitis, rhinitis, cough, dyspnoea1-Frequency Not Known - (Post-marketing experience)3:Bronchospasm. Gastrointestinal disorders:Common ( 1/100 to <1/10):Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting1, dysphagia1- Uncommon ( 1/1000 to <1/100) :Constipation, eructation, gastritis, stomatitis, aggravation of gastrointestinal inflammation-Rare ( 1/10,000 to <1/1000):Duodenal, gastric, oesophageal, intestinal, and colonic ulceration, intestinal perforation, oesophagitis, melaena, pancreatitis- Frequency Not Known - (Post-marketing experience)3:Nausea, gastrointestinal haemorrhage, colitis/colitis aggravated. Hepatobiliary disorders :Uncommon ( 1/1000 to <1/100) :Abnormal hepatic function, increased SGOT and SGPT-Rare ( 1/10,000 to <1/1000):Elevation of hepatic enzymes- Frequency Not Known - (Post-marketing experience)3:Hepatic failure (sometimes fatal or requiring liver transplant), fulminant hepatitis (some with fatal outcome), liver necrosis, hepatitis, jaundice. Skin and subcutaneous tissue disorders:Common ( 1/100 to <1/10):Rash, pruritus- Uncommon ( 1/1000 to <1/100) : Urticaria- Rare ( 1/10,000 to <1/1000): Alopecia, photosensitivity-Frequency Not Known - (Post-marketing experience)3: Ecchymosis, bullous eruption, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, acute generalised exanthematous pustulosis. Musculoskeletal and connective tissue disorders:Uncommon ( 1/1000 to <1/100) : Leg cramps- Frequency Not Known - (Post-marketing experience)3: Arthralgia, myositis. Renal and urinary disorders:Uncommon ( 1/1000 to <1/100) :Increased creatinine, BUN increased- Frequency Not Known - (Post-marketing experience)3: Acute renal failure, interstitial nephritis, hyponatraemia . Reproductive system and breast disorders :Frequency Not Known - (Post-marketing experience)3:Menstrual disorder NOS. General disorders and administrative site conditions : Common ( 1/100 to <1/10):Flu-like symptoms, peripheral oedema/ fluid retention- Frequency Not Known - (Post-marketing experience)3: Chest pain. .
1 Adverse drug reactions that occurred in polyp prevention trials, representing subjects treated with celecoxib 400 mg daily in 2 clinical trials of duration up to 3 years (the APC and PreSAP trials). The adverse drug reactions listed above for the polyp prevention trials are only those that have been previously recognized in the post-marketing surveillance experience, or have occurred more frequently than in the arthritis trials.
2 Furthermore, the following previously unknown adverse reactions occurred in polyp prevention trials, representing subjects treated with celecoxib 400 mg daily in 2 clinical trials of duration up to 3 years (the APC and PreSAP trials): Common: angina pectoris, irritable bowel syndrome, nephrolithiasis, blood creatinine increased, benign prostatic hyperplasia, weight increased. Uncommon: helicobacter infection, herpes zoster, erysipelas, bronchopneumonia, labyrinthitis, gingival infection, lipoma, vitreous floaters, conjunctival haemorrhage, deep vein thrombosis, dysphonia, haemorrhoidal haemorrhage, frequent bowel movements, mouth ulceration, allergic dermatitis, ganglion, nocturia, vaginal haemorrhage, breast tenderness, lower limb fracture, blood sodium increased.
3 Adverse drug reactions spontaneously reported to the safety surveillance database over a period in which an estimated>70 million patients were treated with celecoxib (various doses, durations, and indications). As a result, the frequencies of these adverse drug reactions cannot be reliably determined. Adverse drug reactions listed for the post-marketing population are only those that are not already listed for the arthritis trials or the polyp prevention trials.
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| Contra Indications |
" Celecox is contraindicated in patients with known hypersensitivity to celecoxib.
- Celecox should not be given to patients who have demonstrated allergic-type reactions to sulphonamides.
- Celecox should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal anaphylactic-like reactions to NSAIDs have been reported in such patients.
- Celecox is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft( CABG) surgery. " |
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| Drug Interactions |
"General :
Celecoxib metabolism is predominantly mediated via cytochrome P450 2C9 in the liver. Co-administration of celecox with drugs that are known to inhibit 2C9 should be done with caution. In vitro studies indicate that celecoxib although not a substrate, is an inhibitor of cytochrome P450 2D6.
Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by P450 2D6.
ACE inhibitors:
Reports suggest that NSAIDs may diminish the antihypertensive effect of angiotensin converting enzyme(ACE) inhibitors. This interaction should be given consideration in patients taking celecox concomitantly with ACE inhibitors.
Aspirin :
Celecox can be used with low-dose, however, concomitant administration of aspirin with celecox increases the rate of GI ulceration or other complications compared to use of celecox alone.
Because of its lack of platelet effects, celecox is not a substitute for aspirin for cardiovascular prophylaxis.
Fluconazole:
Concomitant administration of fluconazole at 200 mg QD resulted in a two-fold increase in celecox plasma concentration. This increase is due to the inhibition of celecoxib metabolism via P450 2C9 by fluconazole. Celecox should be introduced at the lowest recommended dose in patients receiving fluconazole.
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.
Lithium:
In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjecys receiving lithium 450 mg BID with celecox 200 mg BID as compared to subjects receiving lithium alone. Patients on lithium treatment should be closely monitored when celecox is introduced or withdrawn.
Methotrexate:
In an interaction study of rheumatoid arthritis patients taking methotrexate, celecox did not have a significant effect on the pharmacokinetics of methotrexate.
Warfarin:
Anticoagulant activity should be monitored, particularly in the first few days, after initiating or changing celecox therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding complications. The effect of celecoxib on the anticoagulant effect of warfarin was studied in a group of healthy subjects receiving daily doses of 2-5 mg of warfarin. In these subjects, celecoxib did not alter the anticoagulant effect of warfarin as determined by prothrombin time. However, in post-marketing experience, serious bleeding events, some of which were fatal, have been reported, predominantly in the elderly, in association with increases in prothrombin time in patients receiving celecox concurrently with warfarin." |
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