A size #2 white color hard gelatin capsule with yellow stripe printed with "200" on cap and "YSP" on body, containing white to yellowish-white powder.
Active Ingredient: Each capsule contains 200 mg celecoxib.
Excipients/Inactive Ingredients: Magnesium stearate, lactose, sodium lauryl sulfate, polyvinylpyrrolidone, croscarmellose sodium, gelatin, titanium dioxide.
Source of capsule: Bovine.
Pharmacotherapeutic group: Non-steroidal anti-inflammatory and antirheumatic drugs, NSAIDs, Coxibs. ATC code: M01AH01.
Pharmacology: Pharmacodynamics: The mechanism of action of celecoxib is via inhibition of prostaglandin synthesis primarily by inhibition of cyclooxygenase 2 (COX-2). At therapeutic concentrations in humans, celecoxib does not inhibit cyclooxygenase 1 (COX-1). COX-2 is induced in response to inflammatory stimuli. This leads to the synthesis and accumulation of inflammatory prostanoids, in particular prostaglandin E2, causing inflammation, edema and pain. Celecoxib acts as an anti-inflammatory, analgesic, and antipyretic agent in animal models by blocking the production of inflammatory prostanoids via COX-2 inhibition. In animal colon tumor models, celecoxib reduced the incidence and multiplicity of tumors.
In vivo and ex vivo studies show that celecoxib has a very low affinity for the constitutively expressed COX-1 enzyme. Consequently at therapeutic doses, celecoxib has no effect on prostanoids synthesized by activation of COX-1, thereby not interfering with normal COX-1 related physiological processes in tissues, particularly the stomach, intestine and platelets.
Pharmacokinetics: Absorption: When given under fasting conditions, celecoxib is well absorbed reaching peak plasma concentrations after approximately 2-3 hours. Oral bioavailability from capsules is about 99% relative to administration in suspension (optimally available oral dosage form). Under fasting conditions, both peak plasma levels (Cmax) and area under the curve (AUC) are roughly dose proportional up to 200 mg twice daily; at higher doses there are less than proportional increases in Cmax and AUC.
Distribution: Plasma protein binding, which is concentration independent, is about 97% at therapeutic plasma concentrations and celecoxib is not preferentially bound to erythrocytes in the blood.
Metabolism: Celecoxib metabolism is primarily mediated via cytochrome P450 2C9. Three metabolites, inactive as COX-1 or COX-2 inhibitors, have been identified in human plasma: a primary alcohol, the corresponding carboxylic acid and its glucuronide conjugate.
Cytochrome P450 2C9 activity is reduced in individuals with genetic polymorphisms that lead to reduced enzyme activity, such as those homozygous for the CYP2C9*3 polymorphism.
In a pharmacokinetic study of celecoxib 200 mg administered once daily in healthy volunteers, genotyped as either CYP2C9*1/*1, CYP2C9*1/*3, or CYP2C9*3/*3, the median Cmax and AUC0-24 of celecoxib on day 7 were approximately 4-fold and 7-fold, respectively, in subjects genotyped as CYP2C9*3/*3 compared to other genotypes. In three separate single dose studies involving a total of 5 subjects genotyped as CYP2C9*3/*3, single-dose AUC0-24 increased by approximately 3-fold compared to normal metabolizers. It is estimated that the frequency of the homozygous *3/*3 genotype is 0.3-1.0% among different ethnic groups.
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.
Elimination: Elimination of celecoxib is mostly by hepatic metabolism with less than 1% of the dose excreted unchanged in urine. After multiple dosing, elimination half-life is 8 to 12 hours and the rate of clearance is about 500 mL/min. With multiple dosing, steady-state plasma concentrations are reached before day 5. The intersubject variability on the main pharmacokinetic parameters (AUC, Cmax, elimination half-life) is about 30%. The mean steady-state volume of distribution is about 500 L/70 kg in young healthy adults indicating wide distribution of celecoxib into the tissues. Preclinical studies indicate that the drug crosses the blood-brain barrier.
Food Effects: Dosing with food (high fat meal) delays absorption of celecoxib resulting in a Tmax of about 4 hours and increases bioavailability by about 20%.
In healthy adult volunteers, the overall systemic exposure (AUC) of celecoxib was equivalent when celecoxib was administered as intact capsule or capsule contents sprinkled on applesauce. There were no significant alterations in Cmax, Tmax or T½ after administration of capsule contents on applesauce.
Special Populations: Elderly: In the population >65 years, there is a one and a half to two-fold increase in mean Cmax and AUC for celecoxib. This is a predominantly weight-related rather than age-related change, celecoxib levels being higher in lower weight individuals and consequently higher in the elderly population who are generally of lower mean weight than the younger population. Therefore, elderly females tend to have higher drug plasma concentrations than elderly males. No dosage adjustment is generally necessary. However, for elderly patients with a lower than average body weight (<50 kg), initiate therapy at the lowest recommended dose.
Race: A meta-analysis of pharmacokinetic studies has suggested an approximately 40% higher AUC of celecoxib in the Black population compared to Caucasians. The cause and clinical significance of this finding is unknown.
Hepatic impairment: Plasma concentrations of celecoxib in patients with mild hepatic impairment (Child-Pugh Class A) are not significantly different from those of age and sex matched controls. In patients with moderate hepatic impairment (Child-Pugh Class B), celecoxib plasma concentrations are about twice those of matched controls.
Renal impairment: In elderly volunteers with age-related reductions in glomerular filtration rate (GFR) (mean GFR >65 mL/min/1.73 m2) and in patients with chronic stable renal insufficiency (GFR 35-60 mL/min/1.73 m2) celecoxib pharmacokinetics was comparable to those seen in patients with normal renal function. No significant relationship was found between serum creatinine (or creatinine clearance) and celecoxib clearance. Severe renal insufficiency would not be expected to alter clearance of celecoxib since the main route of elimination is via hepatic metabolism to inactive metabolites.
Renal effects: The relative roles of COX-1 and COX-2 in renal physiology are not completely understood. Celecoxib reduces the urinary excretion of PGE2 and 6-keto-PGF1α (a prostacyclin metabolite) but leaves serum thromboxane B2 (TXB2) and urinary excretion of 11-dehydro-TXB2, a thromboxane metabolite (both COX-1 products) unaffected. Specific studies have shown Celecoxib produces no decreases in GFR in the elderly or those with chronic renal insufficiency. These studies have also shown transient reductions in fractional excretion of sodium. In studies in patients with arthritis, a comparable incidence of peripheral edema has been observed to that seen with non-specific COX-inhibitors (which also possess COX-2 inhibitory activity). This was most evident in patients receiving concomitant diuretic therapy. However, increased incidences of hypertension and cardiac failure have not been observed and the peripheral edema has been mild and self-limiting.
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.
Relief of signs and symptoms of ankylosing spondylitis.
For the management of low back pain (100 mg and 200 mg only).
Celecoxib capsules can be taken with or without food.
Given the association between cardiovascular (CV) risk and exposure to COX-2 Inhibitors, doctors are advised to use the lowest effective dose for the shortest possible duration of treatment.
Adults: Symptomatic Treatment of Osteoarthritis (OA): The recommended dose of celecoxib is 200 mg administered as a single dose or as 100 mg twice per day.
Symptomatic Treatment of Rheumatoid Arthritis (RA): The recommended dose of celecoxib is 100 mg or 200 mg twice per day.
Ankylosing Spondylitis (AS): The recommended dose of celecoxib is 200 mg administered as a single dose or 100 mg twice per day. Some patients may benefit from a total daily dose of 400 mg.
Management of Acute Pain: The recommended dose of celecoxib 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.
Treatment of Primary Dysmenorrhea: The recommended dose of celecoxib 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.
Low Back Pain (LBP): Usual dosage for adults is 100 mg of celecoxib orally twice daily, morning and evening, or 200 mg once daily (100 mg and 200 mg only).
*Lexib Hard Capsule 200 mg is available at the strength of 200 mg only and may not be able to deliver all the dosing recommendations previously mentioned. In such cases, other approved strengths should be used.
Special Populations: 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 celecoxib at half the recommended dose in arthritis or pain patients with moderate hepatic impairment (Child-Pugh Class B). Patients with severe hepatic impairment (Child-Pugh Class C) have not been studied.
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.
Paediatric population: Celecoxib is not indicated for use in children.
CYP2C9 Poor Metabolizers: Patients who are known or suspected to be CYP2C9 poor metabolizers based on genotyping or previous history/experience with other CYP2C9 substrates should be administered celecoxib with caution as the risk of dose-dependent adverse effects is increased. Consider reducing the dose to half the lowest recommended dose.
Route of Administration: Oral.
Clinical experience of overdose is limited. Single doses up to 1200 mg and multiple doses up to 1200 mg twice daily have been administered to healthy subjects without clinically significant adverse effects.
In the event of suspected overdose, appropriate supportive medical care should be provided.
Dialysis is unlikely to be an efficient method of drug removal because of high protein binding of the drug.
Celecoxib is contraindicated in: Patients with known hypersensitivity to celecoxib or any other ingredient of the product listed.
Patients with known sulfonamide hypersensitivity.
Patients who have experienced asthma, urticaria or allergic-type reactions after taking acetylsalicylic acid (ASA [aspirin]) or other 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.
Patients who have established CV disease (ischaemic heart disease and stroke).
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 to tolerate ulceration or bleeding less than other individuals and account for most spontaneous reports for fatal GI events.
Patients with risk factors of heart disease, hypertension, hyperlipidaemia, diabetes mellitus, smoking patients and patients with peripheral arterial disease should only be treated with celecoxib after careful consideration.
Cardiovascular Effects: Cardiovascular Thrombotic Events: Celecoxib may cause an increased risk of serious CV thrombotic events, myocardial infarction (MI), and stroke, which can be fatal. All NSAIDs may have a similar risk. This risk may increase with dose and duration of use. The relative increase of this risk appears to be similar in those with or without known CV disease or CV risk factors. However, patients with CV disease or CV risk factors may be at greater risk in terms of absolute incidence due to their increased rate at baseline. To minimize the potential risk for an adverse CV 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 CV symptoms. Patients should be informed about the signs and symptoms of serious CV toxicity and the steps to take if they occur.
Two large, controlled, clinical trials of a different COX-2 selective NSAID for the treatment of pain in the first 10 to 14 days following CABG surgery found an increased incidence of myocardial infarction and stroke.
Celecoxib is not a substitute for acetylsalicylic acid for prophylaxis of CV thromboembolic diseases because of the lack of effect on platelet function. Because celecoxib does not inhibit platelet aggregation, anti-platelet 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 CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics or loop diuretics may have impaired response to these therapies when taking NSAIDs. 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 (CHF) 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 (GI) Effects: Upper and lower GI perforations, ulcers or bleeds have occurred in patients treated with celecoxib. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with Celecoxib. Patients most at risk of developing these types of GI complications with NSAIDs are the elderly, patients with CV disease, patients using concomitant glucocorticoids, antiplatelet drugs (such as aspirin), or other NSAIDs, patients using alcohol or patients with a prior history of, or active, GI disease, such as ulceration, GI bleeding or inflammatory conditions. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, antiplatelet drugs (such as aspirin), anticoagulants; or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most spontaneous reports of fatal GI events have been in elderly or debilitated patients.
Strategies to Minimize the GI Risks in NSAID-treated Patients: Use the lowest effective dosage for the shortest possible duration.
Avoid administration of more than one NSAID at a time.
Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs.
Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Celecoxib until a serious GI adverse event is ruled out.
In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding.
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.
Anaphylactoid Reactions: As with NSAIDs in general, anaphylactoid reactions have occurred in patients exposed to celecoxib.
Serious Skin Reactions: Serious skin reactions, some of them fatal, including drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), 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 events early in the course of therapy, the onset of the event occurring in the majority of cases within the first month of treatment. 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 half the recommended dose.
Rare 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.
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 Oral Anticoagulants: The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding and should be given with caution. Oral anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban). 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, anticoagulation/INR should be monitored in patients taking a warfarin/coumarin-type anticoagulant 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.
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.
Effects on ability to drive and use machines: The effect of celecoxib on ability to drive or use machinery has not been studied, but based on its pharmacodynamic properties and overall safety profile, it is unlikely to have an effect.
Fertility: Based on the mechanism of action, the use of NSAIDs, including celecoxib, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of NSAIDs, including celecoxib, should be considered.
Pregnancy: There are no studies in pregnant women. Studies in animals have shown reproductive toxicity. The relevance of these data for humans is unknown.
Celecoxib, as with other drugs inhibiting prostaglandin synthesis, may cause uterine inertia and premature closure of the ductus arteriosus and should be avoided during the third trimester of pregnancy.
Celecoxib should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
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. In animals, administration of prostaglandin synthesis inhibitors has been shown to result in increased pre- and post-implantation loss.
If used during second or third trimester of pregnancy, NSAIDs 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 upon discontinuation. Pregnant women on celecoxib should be closely monitored for amniotic fluid volume.
Lactation: Studies in rats show that celecoxib is excreted in milk at concentrations similar to those in plasma. Administration of celecoxib to lactating women has shown very low transfer of celecoxib into breast milk. Because of the potential for adverse reactions in nursing infants from celecoxib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the expected benefit of the drug to the mother.
Clinical Trials Experience: The following adverse drug reactions (ADRs) in Table 1 were identified with incidence rates greater than 0.01% in celecoxib group and greater than those reported in placebo group, during 12 placebo- and/or active-controlled clinical trials of treatment duration up to 12 weeks at daily doses from 100 mg up to 800 mg in adults.
The frequencies on the ADRs in Table 1 are updated based on a more recent pooling of 89 randomized, controlled clinical trial data representing clinical exposure in 38,102 patients taking celecoxib. ADR frequencies are defined as: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%), rare (≥0.01% and <0.1%), very rare (<0.01%). The ADRs in Table 1 are listed by system organ class and ranked by frequency in descending order. (See Table 1.)
Click on icon to see table/diagram/image
The following additional adverse drug reactions in Table 2 were identified with incidence rates greater than placebo in long-term polyp prevention studies of duration up to 3 years at daily doses from 400 mg up to 800 mg.
Frequencies of ADRs in Table 2 were determined based on these long-term polyp prevention studies and defined as: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%). The ADRs in Table 2 are listed by system organ class and ranked by frequency in descending order. (See Table 2.)
Click on icon to see table/diagram/image
Post-marketing Experience: Adverse reactions identified from post-marketing experience are provided as follows. Even though these were identified as reactions from post-marketing reports, trial data was consulted to estimate frequency. As previously mentioned, frequencies are based on a pooling of trials representing exposure in 38,102 patients. Frequencies are defined as: very common (≥10%), common (≥1% and <10%), uncommon (≥0.1% and <1%), rare (≥0.01% and <0.1%), very rare (<0.01%), not known (cannot be estimated from the available data):
Immune system disorders: Very rare: anaphylactic reaction.
Psychiatric disorders: Rare: hallucination.
Nervous system disorders: Very rare: cerebral haemorrhage, meningitis aseptic, ageusia, anosmia.
Eye disorders: Uncommon: conjunctivitis.
Vascular disorders: Very rare: vasculitis.
Respiratory, thoracic and mediastinal disorders: Rare: pulmonary embolism, pneumonitis.
Gastrointestinal disorders: Rare: gastrointestinal haemorrhage.
Hepatobiliary disorders: Rare: hepatitis. Very rare: hepatic failure, hepatitis fulminant, hepatic necrosis, cholestasis, hepatitis cholestatic, jaundice.
Skin and subcutaneous tissue disorders: Rare: photosensitivity reaction. Very rare: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalised exanthematous pustulosis (AGEP), dermatitis exfoliative.
Renal and urinary disorders: Rare: renal failure acute, hyponatremia. Very rare: tubulointerstitial nephritis, nephrotic syndrome, glomerulonephritis minimal lesion.
Reproductive system and breast disorders: Rare: menstrual disorder. Not known: infertility female (female fertility decreased).
General disorders and administration site conditions: Uncommon: chest pain.
General: Celecoxib metabolism is predominantly mediated via cytochrome P450 (CYP) 2C9 in the liver. Patients who are known or suspected to be poor CYP2C9 metabolizers based on previous history/experience with other CYP2C9 substrates should be administered celecoxib with caution as they may have abnormally high plasma levels due to reduced metabolic clearance. Consider starting treatment at half the lowest recommended dose.
Concomitant administration of celecoxib with inhibitors of CYP2C9 can lead to increases in plasma concentrations of celecoxib. Therefore, a dose reduction of celecoxib may be necessary when celecoxib is co-administered with CYP2C9 inhibitors.
Concomitant administration of celecoxib with inducers of CYP2C9, such as rifampicin, carbamazepine and barbiturates can lead to decreases in plasma concentrations of celecoxib. Therefore, a dose increase of celecoxib may be necessary when celecoxib is co-administered with CYP2C9 inducers.
Clinical pharmacokinetics study and in vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of CYP2D6. Therefore, there is a potential for an in vivo drug interaction with drugs that are metabolized by CYP2D6.
Drug-specific: Interaction of celecoxib with warfarin or similar agents: (See Use with Oral Anticoagulants under Precautions).
Lithium: In healthy subjects, lithium plasma levels increased approximately 17% in subjects receiving lithium together with celecoxib. Patients on lithium treatment should be closely monitored when celecoxib is introduced or withdrawn.
Aspirin: Celecoxib does not interfere with the anti-platelet effect of low-dose aspirin. Because of its lack of platelet effects, celecoxib is not a substitute for aspirin in the prophylactic treatment of CV disease.
Anti-hypertensives including Angiotensin-converting enzyme inhibitors (ACEIs), Angiotensin II antagonists (also known as angiotensin receptor blockers, [ARBs]), diuretics and beta-blockers: Inhibition of prostaglandins may diminish the effect of anti-hypertensives including ACEIs and/or ARBs, diuretics and beta-blockers. This interaction should be given consideration in patients taking celecoxib concomitantly with ACEIs and/or ARBs, diuretics and beta-blockers.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors, angiotensin II antagonists or diuretics, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the concomitant administration of these drugs should be done with caution. Patients should be adequately hydrated and the clinical need to monitor the renal function should be assessed at the beginning of the concomitant treatment and periodically thereafter.
Cyclosporine: Because of their effect on renal prostaglandins, NSAIDs may increase the risk of nephrotoxicity with cyclosporine.
Fluconazole and ketoconazole: Since celecoxib is predominantly metabolised by CYP2C9, it should be used at half the recommended dose in patients receiving fluconazole. Concomitant use of 200 mg single dose of celecoxib and 200 mg once daily of fluconazole, a potent CYP2C9 inhibitor, resulted in a mean increase in celecoxib Cmax of 60% and in AUC of 130%. Ketoconazole, a CYP3A4 inhibitor, showed no clinically relevant inhibition in the metabolism of celecoxib.
Dextromethorphan and metoprolol: Concomitant administration of celecoxib 200 mg twice daily resulted in a 2.6-fold and a 1.5-fold increase in plasma concentrations of dextromethorphan and metoprolol (CYP2D6 substrates), respectively. These increases are due to celecoxib inhibition of the CYP2D6 substrate metabolism via CYP2D6. Therefore, the dose of drugs as CYP2D6 substrate may need to be reduced when treatment with celecoxib is initiated or increased when treatment with celecoxib is terminated.
Diuretics: NSAIDs, in some patients, can reduce the natriuretic effect of furosemide and thiazides by inhibition of renal prostaglandin synthesis.
Methotrexate: No pharmacokinetic and clinically important interactions have been observed in a clinical study between celecoxib and methotrexate.
Oral contraceptives: No clinically relevant effects on the pharmacokinetics of a prototype combination oral contraceptive (1 mg norethindrone/0.035 mg ethinylestradiol).
Other drugs: No clinically important interactions between celecoxib and antacids (aluminium and magnesium), omeprazole, glibenclamide (glyburide), phenytoin, or tolbutamide.
Incompatibilities: No incompatibilities are known.
Special precautions for disposal: Not applicable.
Store below 30°C. Protect from light and moisture.
Shelf life: 3 years.
M01AH01 - celecoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.
Lexib hard cap 200 mg
10 × 10's;3 × 10's
Sign Out
Click on icon to see table/diagram/image
Click on icon to see table/diagram/image
