Celecoxib is metabolised by CYP2C9 enzyme into hydroxycelecoxib. Genetic polymorphism of CYP2C9 may have direct impact on the pharmacokinetics of celecoxib and variability in drug responses. CYP2C9 genotyping test may be considered prior to initiation of therapy in order to select the dose of celecoxib and to avoid possible side effects.
CYP2C9 poor metabolisers (carriers of allele *3/*3)
Patient may have reduced metabolism of celecoxib and may have higher risk of adverse effects, particularly gastrointestinal bleeding. Reduce initial dose by 50% of the lowest recommended dose in adults and alternative treatments may be considered in children with juvenile idiopathic arthritis. Shortest possible duration of treatment is recommended.
Moderate (Child-Pugh class B): Reduce dose by 50%. Severe (Child-Pugh class C or ≥10 score): Contraindicated.
May be taken with or without food.
Hypersensitivity (including urticaria, asthma, angioneurotic edema) to celecoxib and other NSAIDs, aspirin or sulfonamides. Active peptic ulceration or gastrointestinal bleeding, inflammatory bowel disease, CHF (NYHA II-IV), established ischaemic heart disease, cerebrovascular disease or peripheral arterial disease. Treatment of postoperative pain in the setting of CABG surgery. Severe renal (CrCl <30 mL/min) and hepatic (Child-Pugh class C or ≥10 score) impairment. Pregnancy (3rd trimester) and lactation.
Patient with history of gastrointestinal complications (e.g. ulceration and bleeding), hypertension, diabetes mellitus, hyperlipidaemia, recent MI, and other CV disease risk factors (e.g. smoking, alcoholism); pre-existing asthma (without known aspirin sensitivity), pre-existing oedema, hypovolaemia. Dehydrated patient. May mask underlying fever and other signs of inflammation. CYP2C9 poor metabolisers. Moderate hepatic impairment. Children and elderly. Pregnancy (1st-2nd trimester).
Significant: Fluid retention, oedema, hypertension, renal papillary necrosis (prolonged use). Blood and lymphatic system disorders: Anaemia. Cardiac disorders: Angina pectoris. Gastrointestinal disorders: Nausea, abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting, dysphagia, GERD, irritable bowel syndrome. General disorders and administration site conditions: Influenza-like symptoms. Injury, poisoning and procedural complications: Accidental injury. Investigations: Increased blood creatinine, weight increased, elevated ALT or AST. Musculoskeletal and connective tissue disorders: Arthralgia. Nervous system disorders: Headache, hypertonia. Psychiatric disorders: Insomnia. Renal and urinary disorders: Nephrolithiasis, UTI. Reproductive system and breast disorders: Benign prostatic hyperplasia. Respiratory, thoracic and mediastinal disorders: Sinusitis, upper respiratory tract infection, pharyngitis, dyspnea, rhinitis, cough. Skin and subcutaneous tissue disorders: Rash, pruritus. Potentially Fatal: Gastrointestinal perforation, ulceration, or bleeding; CV thrombotic events including MI and stroke, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis, anaphylaxis, severe hepatic reactions (e.g. fulminant hepatitis, hepatic necrosis, hepatic failure).
PO: C (prior to 30 weeks gestation), D (starting at 30 weeks gestation), Z (NSAIDs use in >20 weeks gestation may cause oligohydramnios and foetal renal impairment. Foetal ductus arteriosus premature closure and persistent pulmonary hypertension may occur >30 weeks gestation. Avoid NSAIDs 30 weeks and later. If an NSAID is needed during 20-30 weeks, use lowest effective dose for shortest duration.)
Patient Counseling Information
This drug may cause dizziness, vertigo or somnolence, if affected, do not drive or operate machinery.
Monitor blood pressure during initial treatment and throughout therapy, CBC and chemistry profile periodically (prolonged use), liver and renal functions. Monitor for signs and symptoms of abnormal bleeding or clotting in children with juvenile idiopathic arthritis. Correct volume depletion in dehydrated or hypovolaemic patients prior to treatment.
Increased risk of gastrointestinal ulceration or bleeding with anticoagulants (e.g. warfarin, apixaban), antiplatelet agents (e.g. aspirin), SSRIs, corticosteroids (e.g. glucocorticoids), other NSAIDs. May reduce the antihypertensive effect of ACE inhibitors, angiotensin II receptor antagonists, diuretics, β-blockers and other antihypertensive agents. May increase the nephrotoxic effect of ciclosporin and tacrolimus. Increases the serum concentration of lithium, digoxin and methotrexate. Increased plasma concentration with CYP2C9 inhibitors (e.g. fluconazole). Decreased plasma concentrations with CYP2C9 inducers (e.g. rifampicin, carbamazepine, barbiturates). May increase serum concentration and toxicity of CYP2D6 substrates (e.g. aripiprazole, perhexiline, atomoxetine).
Description: Celecoxib, an NSAID, is a selective cyclooxygenase-2 (COX-2) inhibitor primarily responsible for inhibition of prostaglandin synthesis. It exhibits anti-inflammatory, analgesic and antipyretic activities. Pharmacokinetics: Absorption: Well absorbed from the gastrointestinal tract. High fat meal may delay absorption time. Time to peak plasma concentration: Approx 2-3 hours. Distribution: Extensively distributed in tissues and present in breastmilk. Volume of distribution: Approx 400 L. Plasma protein binding: Approx 97%, mainly to albumin. Metabolism: Metabolised in the liver by CYP2C9 to form inactive metabolites such as a primary alcohol, corresponding carboxylic acid and its glucuronide conjugate. Excretion: Via urine (27% as metabolites, <3% as unchanged drug), faeces (approx 57% as metabolites, <3% as unchanged drug). Elimination half-life: Approx 11 hours.
M01AH01 - celecoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.
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