Olicoxib

White to off-white, lyophilised powder in a single use vial or white to off-white, lyophilised powder in a single use vial and clear colorless liquid free from visual particles in ampoule for reconstitution.
Each vial of OLICOXIB contains 40 mg parecoxib as 42.36 mg parecoxib sodium. When reconstituted in sodium chloride solution (0.9% w/v), OLICOXIB Injection contains approximately 0.44 mEq of sodium per 40 mg vial. The reconstituted solution is clear and colourless with the final concentration of 20 mg/mL parecoxib.
Chemical name: N-[[4-(5-methyl-3-phenyl-4 isoxazolyl) phenyl]sulfonyl] propanamide, sodium salt.
CAS Number: 198470-85-8.
Molecular formula: C₁₉H₁₇N₂O₄SNa.
Molecular weight: 392.40.
Excipients/Inactive Ingredients: Powder: Disodium phosphate anhydrous, O-phosphoric acid and/or sodium hydroxide (for pH adjustment).
Solvent (May not be applicable to all pack size): Sodium chloride, Water for injection.

Pharmacology: Pharmacodynamics: Mechanism of action: Following injection, parecoxib sodium is rapidly converted to valdecoxib: the in vivo pharmacology of parecoxib is therefore that of valdecoxib. The mechanism of action of valdecoxib is by inhibition of cyclooxygenase-2 (COX-2)-mediated prostaglandin synthesis. At therapeutic plasma concentrations in humans, valdecoxib does not inhibit cyclooxygenase-1 (COX-1).
In animal models, valdecoxib is anti-inflammatory, analgesic, and antipyretic.
By inhibition of both peripheral and central COX-2, valdecoxib reduces the production of prostaglandins that are important mediators of pain and inflammation. In animal models, the analgesic activity of valdecoxib is not reversible by naloxone. Therefore, OLICOXIB Injection is not expected to exhibit the potential for dependence, sedation or respiratory depression seen with opioid analgesic agents. When given at the recommended doses for management of acute pain, the onset of analgesia was 7-14 minutes and reached a peak effect within 2 hours. After a single dose, the duration of analgesia was dose and clinical pain model dependent, and ranged from 6 to greater than 24 hours.
Clinical trials: The analgesic efficacy and broad clinical utility of valdecoxib (delivered parenterally as the parecoxib sodium prodrug, Parecoxib sodium Injection) have been demonstrated in multiple clinical models of pain. The analgesic efficacy of Parecoxib sodium Injection was determined by various standard, primary and secondary measures, including absolute and differential pain relief scales and patient global evaluation. Comparisons were made to ketorolac (15 mg IV, 30 mg IV; 60 mg IM) and morphine (4 mg IV). Doses of parecoxib sodium are expressed in terms of parecoxib, not the sodium salt.
Analgesic response to Parecoxib sodium Injection was found to be independent of age, gender or severity of pain.
Use Beyond 3 Days (in the management of postoperative pain study): Most trial were designed for dosing up to 3 days. Data from 3 to 28 randomized placebo-controlled trials, where the protocols allowed treatment of parecoxib for >3 days was pooled and analyzed, 358 patients received parecoxib for >3 days and 318 patients received placebo for >3 days. Both groups had similar demographics. The mean (SD) duration of treatment was 4.1 (0.4) days for parecoxib and 4.2 (0.5) days for placebo, the range was 4 to 7 days for parecoxib and 4 to 9 days for placebo. The occurrence of AE in patients receiving parecoxib for 4 to 7 days (median duration 4 days) was low after treatment Day 3 and similar to placebo.
Opioid-sparing Effects: Parecoxib, at recommended doses, significantly reduced opioid consumption and patient-reported opioid-related adverse effects (fatigue, drowsiness, confusion, inability to concentrate, dizziness, nausea, constipation, difficult urination, itching, retching/vomiting), while providing improved pain relief compared to opioids alone. In a placebo-controlled, orthopedic and general surgery study (n=1050), patients received parecoxib at an initial parenteral dose of 40 mg IV followed by 20 mg twice daily for a minimum of 72 hours in addition to receiving standard care including supplemental patient controlled opioids (IV morphine sulfate). The reduction in opioid use with parecoxib treatment on Days 2 and 3 was 7.2 mg and 2.8 mg (37% and 28%, respectively). This reduction in opioid use was accompanied by significant reductions in patient-reported opioid symptom distress, as well as improved pain relief compared to opioids alone. Additional studies in other surgical setting provided similar observations.
Management of Pain: The perioperative efficacy of Parecoxib sodium Injection was established in studies of oral, gynaecologic, orthopaedic, and coronary artery bypass graft (CABG) surgical pain.
Post-oral Surgery: In single-dose post-oral surgery (extraction of ≥2 third molar teeth with bone removal) pain studies, patients were randomised to receive parecoxib sodium (1 to 100 mg), placebo, or an active control. The effective analgesic dose range for Parecoxib sodium Injection was 20 to 40 mg. Doses higher than 40 mg provided no additional analgesic efficacy. Onset of analgesia, following a single 20 or 40 mg dose of Parecoxib sodium Injection, was 11-14 minutes; magnitude of analgesic effect of the 40 mg dose was comparable with that of ketorolac 60 mg IM (see Table 1 for a representative study). In addition, the median duration of analgesia for the 40 mg dose was 15-22 hours, providing statistically significantly superior sustained pain relief over the 20 mg dose and comparators. (See Table 1.)

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Analgesic effectiveness of single and multiple doses of Parecoxib sodium Injection for post-surgical pain was evaluated in 819 patients following gynaecologic (abdominal hysterectomy) or orthopaedic (hip or knee joint replacement) surgery.
Post-gynaecologic Surgery: Parecoxib sodium Injection was evaluated in single and multiple dose regimens in women with moderate to severe pain following abdominal hysterectomy. Single doses of Parecoxib sodium Injection 20 and 40 mg IV were compared to placebo, morphine 4 mg IV, and ketorolac 30 mg IV. Onset of analgesia, following a single dose of 40 mg of Parecoxib sodium Injection, was 7-14 minutes and the magnitude of the analgesic effect was comparable to that of ketorolac (Table 2). Overall, a single dose of Parecoxib sodium Injection 40 mg was more efficacious than Parecoxib sodium Injection 20 mg. In the multiple dose treatment phase of the second study, 40 mg BD/PRN was comparable to 20 mg QID/PRN and both dose regimens were similar in effectiveness to ketorolac 30 mg QID/PRN. (See Table 2.)

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Post-orthopaedic Surgery: Two double-blind, parallel group studies were conducted in adults with moderate to severe pain following knee or hip replacement surgery. Both studies included a single-dose phase comparing Parecoxib sodium Injection 20 and 40 mg IV to placebo, morphine 4 mg IV and ketorolac 30 mg IV (knee replacement study) or ketorolac 15 mg IV (hip replacement study). Onset of analgesia, following a single dose of 40 mg of Parecoxib sodium Injection, was 10-11 minutes (Table 3). Overall, a single dose of Parecoxib sodium Injection 40 mg was more efficacious than 20 mg. In the hip replacement study, 20 mg QID/PRN was comparable to 40 mg BD/PRN, and both dose regimens were similar in effectiveness to ketorolac 15 mg IV, QID/PRN. (See Table 3.)

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Patient who required any rescue medication in the gynaecologic and orthopaedic efficacy trials were withdrawn from the study (Table 4). As a result, experience is limited with parecoxib treatment for more than 2 days. (See Table 4.)

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Pre-operative Administration: Two clinical studies evaluating the pre-operative administration (i.e., pre-emptive dosing) of Parecoxib sodium Injection have demonstrated efficacy in reducing post-operative pain. Compared to placebo, administration of single doses of Parecoxib sodium Injection 30 to 45 minutes prior to surgery significantly delayed development of post-operative pain (as measured by the proportion of patients not requiring supplemental pain medication at 6, 12 and 24 hours post-surgery) in patients undergoing oral surgery, and orthopaedic (bunionectomy and total hip arthroplasty) surgery (Figure 1). The safety profile of Parecoxib sodium Injection administered pre-operatively was not different from that seen with post-operative administration. (See Figure 1.)

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Special Studies: CABG Post-operative Safety Studies: In addition to routine adverse event reporting, pre-specified event categories, adjudicated by an independent expert committee, were examined in two placebo-controlled safety studies in which patients received parecoxib sodium for at least 3 days and then were transitioned to oral valdecoxib for a total duration of 10-14 days. All patients received standard of care analgesia during treatment. Patients received low-dose acetylsalicylic acid prior to randomisation and throughout the two CABG surgery studies.
The first CABG surgery study evaluated patients treated with IV parecoxib sodium 40 mg BD for a minimum of 3 days, followed by treatment with valdecoxib 40 mg BD (parecoxib sodium/valdecoxib group) (n=311) or placebo/placebo (n=151) in a 14-day, double-blind placebo-controlled study. Nine pre-specified adverse event categories were evaluated (cardiovascular (CV) thromboembolic events, pericarditis, new onset or exacerbation of congestive heart failure, renal failure/dysfunction, upper gastrointestinal (GI) ulcer complications, major non-GI bleeds, infections, non-infectious pulmonary complications, and death). There was a significantly (p<0.05) greater incidence of CV/thromboembolic events (myocardial infarction, ischaemia, cerebrovascular accident, deep vein thrombosis and pulmonary embolism) detected in the parecoxib/valdecoxib treatment group compared to the placebo/placebo treatment group for the IV dosing period (2.2% and 0.0% respectively) and over the entire study period (4.8% and 1.3% respectively) (see Contraindications and Cardiovascular Adverse Effects under Precautions). Surgical wound complications (most involving the sternal wound) were observed at an increased rate with parecoxib/valdecoxib treatment.
In the second CABG surgery study, four pre-specified event categories were evaluated (cardiovascular/thromboembolic; renal dysfunction/renal failure; upper Gl ulcer/bleeding; surgical wound complication). Patients were randomised within 24-hours post-CABG surgery to: parecoxib initial dose of 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO (20 mg Q12H) (n=544) for the remainder of a 10 day treatment period; placebo IV followed by valdecoxib PO (n=544); or placebo IV followed by placebo PO (n=548). A significantly (p=0.033) greater incidence of events in the cardiovascular/thromboembolic category was detected in the parecoxib /valdecoxib treatment group (2.0%) compared to the placebo/placebo treatment group (0.5%). Placebo/valdecoxib treatment was also associated with a higher incidence of CV thromboembolic events versus placebo treatment, but this difference did not reach statistical significance. Three of the six cardiovascular thromboembolic events in the placebo/valdecoxib treatment group occurred during the placebo treatment period; these patients did not receive valdecoxib. Pre-specified events that occurred with the highest incidence in all three treatment groups involved the category of surgical wound complications, including deep surgical infections and sternal wound healing events.
There were no significant differences between active treatments and placebo for any of the other pre-specified event categories (renal dysfunction/failure, upper GI ulcer complications or surgical wound complications).
General Surgery: In a large (n=1,050) major orthopaedic/general surgery trial, patients received an initial dose of parecoxib 40 mg by IV, then 20 mg IV Q12H for a minimum of 3 days followed by valdecoxib PO (20 mg Q12H) (n=512) for the remainder of a 10-day treatment period, or placebo IV followed by placebo PO (n=525). There were no significant differences in the overall safety profile, including the four pre-specified event categories described as previously mentioned for the second CABG surgery study, for parecoxib sodium/valdecoxib compared to placebo treatment.
In an analysis of non-cardiac surgery controlled trials in which the majority of patients were treated for 2 days, patients treated with parecoxib did not experience an increased risk of CV adverse events compared to placebo. This included patients with none, one or two CV risk factors. This analysis was powered to detect a doubling in the background rate of CV adverse events in patients treated with parecoxib (see Cardiovascular Adverse Effects under Precautions).
Gastrointestinal: Endoscopy studies were conducted to evaluate the ulcerogenic effects of Parecoxib sodium Injection on the upper gastrointestinal (GI) mucosa. In short-term (7 day) studies involving healthy young or elderly subjects (≥65 years), Parecoxib sodium Injection treatment resulted in significantly fewer ulcers than either ketorolac or naproxen (Table 5). (See Table 5.)

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In a 12-week placebo-controlled study, scheduled endoscopies were conducted in 1150 patients with osteoarthritis. The gastroduodenal ulcer incidence rates with oral valdecoxib (active moiety of Parecoxib sodium Injection), diclofenac sodium, and ibuprofen were compared (Figure 2). Valdecoxib was associated with a statistically significantly lower incidence of endoscopic ulcers compared to ibuprofen and diclofenac over the study period. There was no difference in the incidence of ulcers between placebo and either of the two doses of valdecoxib. (See Figure 2.)

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In clinical trials studying young and elderly (≥65 years) adult subjects, single and multiple doses up to 7 days of Parecoxib sodium Injection 20 mg and 40 mg BD, had no effect on platelet aggregation or bleeding time. By comparison, ketorolac 15 mg and 30 mg as a single dose, or after 5 days treatment, significantly reduced platelet aggregation and significantly increased bleeding time (Figure 4). Full therapeutic doses of Parecoxib sodium Injection had no clinically significant effect on aspirin-mediated inhibition of platelet function compared to placebo (see Aspirin under Interactions). (See Figures 3 and 4.)

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Pharmacokinetics: The pharmacokinetics of the prodrug parecoxib sodium and its active moiety valdecoxib, have been evaluated in more than 1600 individuals, including patients with acute pain, hepatic disease, renal disease, and young and elderly healthy subjects.
Absorption: Following IV or IM injection, parecoxib sodium is rapidly and essentially completely converted to valdecoxib. Exposure [plasma concentration vs. time curve (AUC) and peak concentration (C_max)] of valdecoxib following injection of parecoxib sodium is approximately linear in the dosage range of 1 mg to 100 mg IV and 1 mg to 40 mg IM given as a single dose, or 5 to 50 mg IV and 5 to 20 mg IM given repeatedly twice a day (BD). Steady state was reached within 4 days with BD dosing.
The pharmacokinetics of parecoxib and valdecoxib following single IV and IM doses of parecoxib sodium are shown in Table 6. (See Table 6.)

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Distribution: The volume of distribution of valdecoxib after its IV administration is approximately 55 L. Plasma protein binding is about 98% over the concentration range (0.21-2.38 mcg/mL) achieved with the highest recommended dose. Valdecoxib, but not parecoxib, is extensively partitioned into erythrocytes with an RBC to plasma concentration ratio of about 4:1 and a blood to plasma ratio of about 2.5:1. This ratio remains approximately constant with time and therapeutic blood concentrations, and therefore measurement of plasma concentrations of valdecoxib in pharmacokinetics studies is appropriate.
Metabolism: Parecoxib is rapidly and almost completely converted to valdecoxib in vivo with a plasma half-life of <60 minutes. The rate of conversion of parecoxib to valdecoxib is not affected in patients with mild to moderate hepatic impairment. Elimination of valdecoxib is by extensive hepatic metabolism involving multiple pathways. The cytochrome P-450 (CYP-450) dependent pathway involves predominantly 3A4 and 2C9 isozymes while the CYP-450 independent pathway leads to glucuronide conjugates of the sulfonamide moiety.
One active minor metabolite (a hydroxylated form via the CYP-450 pathway) of valdecoxib has been identified in human plasma at approximately 10% the concentration of valdecoxib. It also undergoes extensive metabolism, with <5% of the dose excreted in the urine and faeces. Because of its minor presence, this metabolite is not expected to contribute a significant clinical effect after administration of therapeutic doses of parecoxib sodium.
Excretion: Following conversion from parecoxib, valdecoxib is eliminated via hepatic metabolism with <5% of the dose excreted unchanged in the urine. No unchanged parecoxib is detected in urine and only a trace amount in faeces. About 70% of the dose is excreted in the urine as inactive metabolites. The elimination half-life (T½) of valdecoxib after IV or IM dosing of parecoxib sodium is about 8 hours. Plasma clearance (CLp) for valdecoxib is about 6 L/hr. In patients undergoing haemodialysis the CLp of valdecoxib was similar to the CLp found in healthy subjects.
Special Populations: Elderly (>65 years): Parecoxib sodium Injection has been administered to 335 elderly patients (65-96 years of age) in pharmacokinetic and therapeutic trials. Valdecoxib steady state plasma exposures in elderly female subjects, when adjusted for body weight, are about 40% higher than those in young male subjects. Dose adjustment in the elderly is not generally necessary; however for elderly female patients weighing <50 kg, initiate treatment with half the usual recommended dose of OLICOXIB Injection (see Dosage & Administration).
Children and Adolescents: Parecoxib sodium Injection has not been investigated in paediatric patients under 18 years of age.
Race: Pharmacokinetic differences due to race have not been identified in clinical and pharmacokinetic studies conducted to date.
Renal Impairment: Valdecoxib pharmacokinetics has been studied in patients with varying degrees of renal impairment. Because renal elimination of valdecoxib is not important to its disposition, no changes in valdecoxib clearance were found even in patients with severe renal impairment or in patients undergoing renal dialysis (see Dosage & Administration).
Hepatic Impairment: In patients with moderate (Child-Pugh score 7-9) hepatic impairment, treatment should be initiated with half the usual recommended dose of Parecoxib sodium Injection since valdecoxib exposures were more than doubled (130%) in these patients. However, moderate hepatic impairment did not result in reduced rate or extent of parecoxib conversion to valdecoxib. There is no clinical experience in patients with severe hepatic impairment (Child-Pugh score ≥10); therefore, the use of OLICOXIB Injection is contraindicated in these patients (see Contraindications and Dosage & Administration).
Toxicology: Preclinical safety data: Genotoxicity: Parecoxib sodium was not mutagenic in bacterial cells and the Hypoxanthine-Guanine Phosphoribosyl Transferase (HGPRT) mutation assay in Chinese hamster ovary (CHO) cells. Parecoxib increased the incidence of chromosomal aberrations in an in vitro CHO cell assay, however, it was negative in an in vivo micronucleus and chromosomal aberration test in rat bone marrow. Valdecoxib was negative in assays for gene mutations and clastogenicity.
Carcinogenicity: Long-term animal studies to evaluate the carcinogenic potential of parecoxib sodium have not been conducted.

Parecoxib is indicated for management of acute pain and for the short-term treatment of post-operative pain.
Parecoxib is indicated only in patients with a need for parenteral therapy and for whom a similar benefit could not be obtained from alternative oral therapy. Do not use parecoxib in acute traumatic pain patients with unstable hemodynamic condition.
Parecoxib should not be used for non-severe pain.

Parecoxib may be administered as single or multiple IV or IM doses on a regular or as needed schedule. After initiation of therapy, dosage should be adjusted based on patient response.
Parecoxib is a prodrug of valdecoxib, which is a non-steroidal anti-inflammatory drug (NSAID).
The mechanism of action is believed to be due to inhibition of prostaglandin synthesis primarily through inhibition of selective cyclooxygenase-2 (COX-2). Parecoxib is only indicated for patients with a need for parenteral therapy and for whom a similar benefit could not be obtained from alternative oral therapy. It is recommended that patients be transitioned to alternative oral therapy as soon as clinically indicated.
As the cardiovascular (CV) risk of COX-2 specific inhibitors and non-specific NSAIDs may increase with dose and duration of exposure, the shortest duration possible, not to exceed 3 days, and the lowest effective daily dose should be used. However, the relevance of these findings for the short-term use of parecoxib in the post-operative setting has not been evaluated.
Clinical studies with parecoxib were conducted using up to 7 days of treatment.
Management of Acute Pain and Treatment of Post-operative Pain: The recommended single or initial dose is 40 mg, administered either IV or IM, followed by 20 mg or 40 mg every 6 to 12 hours, as required, up to a maximum daily dosage of 80 mg. The IV bolus injection may be given directly into a vein or into an existing IV line. The IM injection should be given slowly and deeply into the muscle.
Elderly: No dosage adjustment is generally necessary. However, for elderly patients weighing less than 50 kg, it is advisable to reduce the initial dose of parecoxib by 50%. The maximum daily dose should be reduced to 40 mg in elderly patients weighing less than 50 kg. Caution should be used when treating elderly patients as they have cardiovascular risk factors (see Precautions and Pharmacology: Pharmacokinetics: Special Populations: Elderly (>65 years) under Actions).
Hepatic Impairment: No dosage adjustment is necessary in patients with mild hepatic impairment (Child-Pugh Class A). Treatment with parecoxib should be initiated at the lowest recommended dose in patients with moderate hepatic impairment (Child-Pugh Class B).
Patients with severe hepatic impairment (Child-Pugh Class C) have not been studied. The use of parecoxib in these patients is not recommended (see Contraindications and Pharmacology: Pharmacokinetics: Hepatic Impairment under Actions).
Renal Impairment: In patients with severe renal impairment (creatinine clearance <30 mL/minute), or patients who may be predisposed to fluid retention, parecoxib should be initiated at the lowest recommended dose and the patient's kidney function closely monitored (see Precautions and Pharmacology: Pharmacokinetics: Renal Impairment under Actions).
Co-administration with Fluconazole: When parecoxib is co-administered with fluconazole, the lowest recommended dose of parecoxib should be used (see Interactions).
Children: Safety and efficacy have not been established in children under 18 years of age.

Signs and Symptoms: Clinical experience of overdose is limited and a minimum human toxic dose has not been established. No symptoms of overdose have been observed with single IV doses of up to 200 mg of parecoxib sodium or oral doses up to 400 mg of valdecoxib in healthy subjects. Parecoxib sodium doses of 50 mg BD IV for 7 days did not result in any signs of toxicity.
Symptoms following acute NSAID overdoses are usually limited to lethargy, drowsiness, nausea, vomiting, epigastric pain, and other gastrointestinal effects, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Hypertension, acute renal failure, respiratory depression and coma may occur, but are rare. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.
Treatment of Overdosage: There are no specific antidotes. Patients should be managed by symptomatic and supportive care following an overdose. Monitor patients for signs and symptoms of gastrointestinal ulceration and/or haemorrhage. Monitor serum electrolytes, renal function and urinalysis after significant overdose.
Valdecoxib is not removed by haemodialysis. Forced diuresis or alkalinisation of urine may not be useful due to high protein binding of valdecoxib.

Parecoxib is contraindicated in: Patients with known hypersensitivity to parecoxib to any other ingredient of the product.
Patients who have demonstrated serious allergic-type reactions of any type, especially cutaneous reactions such as Steven-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme or patients with known hypersensitivity to sulfonamides.
Patients with active peptic ulceration or gastrointestinal (GI) bleeding.
Patients who have experienced asthma, urticaria, or allergic-type reactions after taking acetylsalicylic acid (aspirin) or non-steroidal anti-inflammatory drugs (NSAIDs), including other COX-2 specific inhibitors.
The third trimester of pregnancy and breast-feeding.
Severe hepatic dysfunction (serum albumin <25 g/L or Child-Pugh score ≥10).
Inflammatory bowel disease.
Congestive heart failure (NYHA II-IV).
Parecoxib is contraindicated for the treatment of post-operative pain immediately following coronary artery bypass graft (CABG) surgery and should not be used in this setting.
Established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease.

The decision to prescribe a selective COX-2 inhibitor should be based on an assessment of the individual patient's overall risks (see Contraindications).
Administration Other Than IV or IM: Modes of administration other than IV or IM (e.g. intra-articular, intrathecal) have not been studied and should not be used.
Cardiovascular Adverse Effects: All NSAIDs, including COX-2 inhibitors, of which parecoxib is one, have been associated with an increased risk of cardiovascular and thrombotic adverse events when taken long term. 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 known cardiovascular disease or CV risk factors may be at greater risk in terms of absolute incidence, due to their increased rate at baseline.
Patients treated with Parecoxib sodium for pain immediately following CABG surgery have a higher risk for CV/thromboembolic events, deep surgical infections or sternal wound healing complications. This was seen more often in elderly patients (>65 years old) or patients with a history of peripheral vascular or cerebrovascular disease or poor post-surgical renal function (see Pharmacology: Pharmacodynamics: Special Studies: CABG Post-operative Safety Studies under Actions).
OLICOXIB is therefore contraindicated for the treatment of post-operative pain following CABG surgery (see Contraindications).
Parecoxib sodium has not been studied in other cardiovascular surgical procedures.
In an analysis of non-cardiac surgery controlled trials, patients treated with parecoxib did not experience an increased risk of CV adverse events compared with placebo.
However, patients with significant and multiple risk factors for CV events (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking) should only be treated with parecoxib sodium after careful consideration (see Pharmacology: Pharmacodynamics: Special Studies: General Surgery under Actions).
All patients should receive the lowest dose effective in relieving symptoms. The dose should not exceed 40 mg.
Serious Skin Reactions: Serious skin reactions including erythema multiforme and Stevens-Johnson syndrome have been reported through post-marketing surveillance in patients receiving parecoxib. In addition to erythema multiforme and Stevens-Johnson syndrome, exfoliative dermatitis and toxic epidermal necrolysis have been reported through post-marketing surveillance in patients receiving valdecoxib. Fatalities due to Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with valdecoxib and the potential cannot be ruled out for parecoxib (the prodrug of valdecoxib). Generalised bullous fixed drug eruption (GBFDE) may occur with parecoxib exposure based on a reaction with etoricoxib exposure. Drug reaction with eosinophilia and systemic symptoms syndrome (DRESS syndrome) may occur with parecoxib exposure based on other serious skin reactions reported with celecoxib and valdecoxib exposure (see Post-Marketing Experience under Adverse Reactions). Patients appear to be at highest risk for these events early in the course of therapy; with the onset of the event occurring in the majority of cases in the first two weeks of treatment. OLICOXIB Injection should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. Serious skin reactions have been reported with other COX-2 inhibitors during post-marketing experience.
Valdecoxib, the active moiety of parecoxib, contains a sulfonamide moiety. Patients with a history of sulfonamide allergy may be at a greater risk for skin reactions, however, patients without a history of sulfonamide allergy may also be at risk.
Anaphylactoid Reactions: Anaphylactoid reactions were not reported in patients receiving Parecoxib sodium Injection in clinical trials. However, as with NSAIDs in general, anaphylactoid reactions may occur in patients without known prior exposure to Parecoxib sodium Injection. OLICOXIB Injection should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see Contraindications and Pre-existing Asthma as follows). Emergency help should be sought in cases where an anaphylactoid reaction occurs.
Hypersensitivity reactions (anaphylactic reactions and angioedema) have been reported in post-marketing experience with valdecoxib and parecoxib (see Post-Marketing Experience under Adverse Reactions). These reactions have occurred in patients with and without a history of allergic-type reactions to sulfonamides (see Contraindications). Parecoxib should be discontinued at the first sign of hypersensitivity.
General: OLICOXIB Injection may mask fever. The concomitant use of parecoxib with other non-specific NSAIDs should be avoided.
In addition, caution should be exercised with respect to monitoring the incision for signs of infection in patients receiving OLICOXIB Injection. When used in post-CABG patients at a dose of 80 mg/day over 14 days, no increase in overall infection rate was seen. However, sternal wound infections occurred at a somewhat higher rate in patients receiving Parecoxib sodium compared to placebo (Parecoxib sodium 2.6%, placebo 2.0%, p=NS).
In the repeated dose toxicity studies in dogs and rats, the systemic exposures to valdecoxib (the active metabolite of parecoxib) were approximately 0.8-fold the systemic exposure in elderly human subjects at the maximum recommended therapeutic dose of 80 mg daily. Higher doses were associated with aggravation and delayed healing of skin infections, an effect probably associated with COX-2 inhibition.
Gastrointestinal Effects - Risk of GI Ulceration, Bleeding, and Perforation: It is unclear, at the present time, how the rates of serious GI toxicity associated with NSAIDs that inhibit both COX-1 and COX-2, apply to OLICOXIB Injection. Parecoxib sodium Injection, a COX-2 specific inhibitor, does not affect COX-1 function as demonstrated by relevant clinical results.
Serious Gl toxicity such as bleeding, ulceration, and perforation of the stomach, small intestine or large intestine, can occur at any time, with or without warning symptoms, in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs), including OLICOXIB Injection. Minor upper Gl problems, such as dyspepsia, are common and may also occur at any time during NSAID therapy. Therefore, physicians and patients should remain alert for ulceration and bleeding, even in the absence of previous GI tract symptoms. Patients should be informed about the signs and/or symptoms of serious Gl toxicity and the steps to take if they occur. The utility of periodic laboratory monitoring has not been demonstrated, nor has it been adequately assessed. Only one in five patients who develop a serious upper Gl adverse event on NSAID therapy is symptomatic. It has been demonstrated that upper Gl ulcers, gross bleeding or perforation, caused by NSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. These trends continue thus, increasing the likelihood of developing a serious Gl event at some time during the course of therapy. However, even short-term therapy is not without risk.
The ulcerogenic effects of Parecoxib sodium Injection and oral valdecoxib on the upper GI tract were examined in short-term (7 day) studies in young and elderly healthy subjects, and a 12-week study in OA patients, respectively. Significantly fewer endoscopically detected ulcers were seen with Parecoxib sodium Injection compared to ketorolac and naproxen, and with valdecoxib compared to ibuprofen and naproxen (see Pharmacology: Pharmacodynamics: Clinical Trials and Special Studies under Actions).
Patients most at risk of developing Gl complications with NSAIDs are elderly patients; patients with cardiovascular disease; patients using concomitant aspirin, corticosteroids, selective serotonin reuptake inhibitors (SSRIs) or other NSAIDs; patients ingesting alcohol; and patients with a history of, or active, GI disease (such as ulceration, bleeding or inflammatory conditions). In addition, pharmaco-epidemiological studies have identified several other co-therapies or co-morbid conditions that may increase the risk for GI bleeding such as: treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism, and poor general health status. OLICOXIB Injection should be prescribed with caution in these patients. Physicians and patients should remain alert for ulceration and bleeding even in the absence of symptoms.
Most spontaneous reports of fatal Gl events are in elderly or debilitated patients and therefore special care should be taken in treating this population. To minimise the potential risk for an adverse GI event, the lowest effective dose should be used for the shortest possible duration. For high-risk patients, alternate therapies that do not involve NSAIDs should be considered. Studies have shown that patients with a prior history of peptic ulcer disease and/or GI bleeding and who use NSAIDs, have a greater than 10-fold higher risk for developing a GI bleed than patients with neither of these risk factors.
Use in hepatic impairment: Borderline elevations of one or more liver function tests were observed in 3.4% of surgical patients receiving Parecoxib sodium Injection and 5.8% of placebo patients. Notable elevations (greater than three or more times the Upper Limit of Normal) were seen in 0.7% of patients treated with Parecoxib sodium Injection and 0.8% of placebo patients.
Rare cases of severe hepatic reactions, including jaundice, fatal fulminant hepatitis, liver necrosis, hepatic failure (some with fatal outcome), and liver transplant have been reported with NSAIDs. In post-marketing experience, rare cases of jaundice, hepatomegaly, and hepatic failure have been reported with Parecoxib sodium Injection (see Post-Marketing Experience under Adverse Reactions).
A patient with symptoms and/or signs suggesting hepatic dysfunction, or in whom an abnormal liver function test has occurred, should be evaluated for evidence of the development of a hepatic reaction while on therapy with OLICOXIB Injection. If clinical signs and symptoms consistent with hepatic disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), OLICOXIB Injection should be discontinued.
Use in renal impairment: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a non-steroidal anti-inflammatory drug may cause a dose-dependent reduction in renal prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, ACE inhibitors, or angiotensin receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state. Clinical trials with valdecoxib have shown renal effects similar to those observed with comparator NSAIDs.
Caution should be used when initiating treatment with OLICOXIB Injection in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with OLICOXIB Injection.
Caution is also recommended in patients with pre-existing renal disease. Even though, pharmacokinetically, there was no difference in excretion, in patients with severe renal disease treatment with OLICOXIB Injection should be initiated with caution. Close monitoring of the patient's renal function is advisable.
Acute renal failure has been reported through post-marketing surveillance in patients receiving parecoxib (see Adverse Reactions).
Concomitant Use of ACE inhibitors or Angiotensin Receptor Antagonists and Anti-inflammatory Drugs and Thiazide Diuretics: The use of an ACE inhibiting medicine (ACE-inhibitor or angiotensin receptor antagonist), and an anti-inflammatory drug (NSAID or COX-2 inhibitor) and a thiazide diuretic at the same time, increases the risk of renal impairment. This includes use in fixed-combination products containing more than one class of medicine. Concomitant use of all three classes of these medications should be accompanied by increased monitoring of serum creatinine, particularly at the institution of the treatment. The concomitant use of medicines from these three classes should be used with caution particularly in elderly patients or those with pre-existing renal impairment (see Anti-hypertensives including ACE-inhibitors, Angiotensin Receptor Antagonists, Beta Blockers and Diuretics under Interactions).
Concomitant Use of Oral Anticoagulants: The concomitant use of NSAIDs with oral anticoagulants increases the risk of bleeding (see Anticoagulants under Interactions). Oral anticoagulants include warfarin/coumarin-type and novel oral anticoagulants (e.g. apixaban, dabigatran, and rivaroxaban).
Hypertension: As with all NSAIDs, parecoxib 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. NSAIDs, including parecoxib, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of therapy with parecoxib and throughout the course of therapy.
Severe Hypotension: Cases of severe hypotension shortly following parecoxib administration have been reported in postmarketing experience with parecoxib. Some of these cases have occurred without other signs of anaphylaxis. The practitioner should be prepared to treat severe hypotension.
Fluid Retention and Oedema: Fluid retention and oedema have been observed in <1.0% of patients undergoing general surgery who received Parecoxib sodium Injection, similar to placebo. OLICOXIB Injection should be used with caution in patients with compromised cardiac function, pre-existing oedema, or other conditions predisposing to, or worsened by, fluid retention including those taking diuretic treatment or otherwise at risk of hypovolaemia.
Pre-existing Asthma: Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm, which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other non-steroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, OLICOXIB should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma (see Contraindications and Anaphylactoid Reactions as previously mentioned).
Effects on laboratory tests: Isolated laboratory abnormalities following surgery were seen in patients taking Parecoxib sodium Injection, placebo and comparators. No particular testing, other than appropriate post-operative laboratory monitoring, is indicated in patients receiving OLICOXIB Injection.
Effects on Ability to Drive and Use Machines: The effect of Parecoxib sodium Injection on ability to drive or use machinery has not been studied. However, patients who experience dizziness, vertigo or somnolence after receiving OLICOXIB Injection should refrain from driving or operating machinery.
Use in Children: Safety and effectiveness in paediatric patients below the age of 18 have not been evaluated.
Use in the Elderly: Of the total number of patients who received Parecoxib sodium Injection in clinical trials, more than 250 were 65-74 years of age, while approximately 70 additional patients were 75 years and over. No overall differences in safety and effectiveness between these patients and younger patients have been identified, but greater sensitivity of some older individuals cannot be ruled out.

Effects on fertility: Parecoxib sodium did not impair rat fertility at intravenous doses of 25 mg/kg/day (males) or 12.5 mg/kg/day (females). These doses resulted in systemic exposures (plasma AUC) that were 1.4-fold human exposure for valdecoxib, at the maximum recommended therapeutic dose (40 mg BD). Based on the mechanism of action, the use of NSAIDs 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 OLICOXIB, should be considered.
Use in pregnancy: Category C.
Teratogenic Effects: Embryo-fetal development studies conducted with intravenous parecoxib sodium in rats and rabbits have not shown any evidence of developmental malformations. Doses used (respectively up to 25 and 40 mg/kg/day) resulted in systemic exposures (plasma AUC) to valdecoxib that were 4.3-fold and 2.2-fold human exposure at the maximum recommended therapeutic dose, respectively. Animal reproduction studies are not always predictive of human responses, and there are no adequate and well-controlled studies in pregnant women. Use of OLICOXIB Injection during pregnancy is not recommended.
Non-Teratogenic Effects: Parecoxib sodium increased post-implantation losses in rats and rabbits at doses that resulted in systemic exposures (plasma AUC) to valdecoxib that were similar to the human exposure at the maximum recommended therapeutic dose. This effect is thought to be a consequence of the inhibition of prostaglandin synthesis, and has been reported to occur with other NSAIDs. No studies have been conducted to evaluate the effect of valdecoxib on the closure of the ductus arteriosus in humans or animals. The use of cyclooxygenase inhibitors may result in premature closure of the ductus arteriosus or uterine inertia. Therefore, the use of OLICOXIB Injection during the third trimester should be avoided.
Inhibition of prostaglandin synthesis might adversely affect pregnancy. 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. Pregnant women on parecoxib should be closely monitored for amniotic fluid volume.
Labour and Delivery: Parecoxib sodium has not been studied in late pregnancy and parturition in either animals or humans. In animal studies, both COX-1 and COX-2 have been shown to be present in the ductus arteriosus of fetal lambs and to contribute to the maintenance of patency and the fetal ductus arteriosus was constricted significantly in near-term rats.
Use in lactation: Parecoxib, valdecoxib and an active metabolite of valdecoxib, are excreted in the milk of lactating rats. Parecoxib and valdecoxib are also reported to be transferred into the breast milk of lactating women. Because of the potential for adverse effects in nursing infants from OLICOXIB Injection, breast-feeding should be discontinued during treatment.

Clinical Trial Experience: The following adverse reactions were reported in patients who received parecoxib (N=5,402) in 28 placebo-controlled clinical trials.
Very common (Events occurring ≥10%): Gastrointestinal disorders: Nausea.
Common (Events occurring ≥1% and <10%): Gastrointestinal disorders: Abdominal pain, constipation, dyspepsia, vomiting.
General disorders and administration site conditions: Edema peripheral.
Infections and infestations: Alveolar osteitis (dry socket).
Nervous system disorders: Dizziness.
Psychiatric disorders: Insomnia.
Renal and urinary disorders: Oliguria.
Skin and subcutaneous tissue disorders: Sweating increased, pruritus.
Vascular disorders: Hypotension.
Uncommon (Events occurring ≥0.5% and <1%): Gastrointestinal disorders: Mouth dry, flatulence.
Musculoskeletal and connective tissue disorders: Back pain.
Cardiac disorders: Bradycardia.
Infections and infestations: Pharyngitis.
Skin and subcutaneous tissue disorders: Rash.
Vascular disorders: Hypertension.
Uncommon to rare (Events occurring <0.5%): Cardiac disorders: Myocardial infarction.
Ear and labyrinth disorders: Earache.
Gastrointestinal disorders: Esophagitis, gastroesophageal reflux, hypoactive bowel sounds, pancreatitis, perioral swelling.
General disorders and administration site conditions: Injection site pain, injection site reaction, asthenia.
Immune system disorders: Anaphylactoid reaction.
Investigations: BUN increased, creatine phosphokinase increased, creatinine increased, LDH increased.
Injury, poisoning and procedural complications: Skin post-operative complications.
Metabolism and nutrition disorders: Anorexia, hyperglycemia.
Musculoskeletal and connective tissue disorders: Arthralgia.
Nervous system disorders: Cerebrovascular disorder.
Psychiatric disorders: Agitation.
Renal and urinary disorders: Renal failure acute.
Respiratory, thoracic and mediastinal disorders: Embolism pulmonary.
Skin and subcutaneous tissue disorders: Ecchymosis, urticaria.
Vascular disorders: Hypertension aggravated, hypotension postural.
Following coronary artery bypass graft surgery, patients administered parecoxib have a higher risk of adverse events, such as cardiovascular thromboembolic events (e.g., myocardial infarction and cerebrovascular accident), deep surgical infections or sternal wound healing complications.
Post-Marketing Experience: In post-marketing experience, the following rare, serious adverse events have been reported in association with the use of parecoxib: Renal failure, acute renal failure, aseptic meningitis, congestive heart failure, circulatory collapse, erythema multiforme, hepatic failure, hepatomegaly, jaundice, Stevens-Johnson syndrome and hypersensitivity reactions including anaphylaxis and angioedema (see Precautions). In post-marketing experience, in addition to the severe cutaneous adverse reaction erythema multiforme and Stevens-Johnson syndrome, the following events have been reported in association with the use of valdecoxib and cannot be ruled out for OLICOXIB Injection: Myocardial infarction (very rare), exfoliative dermatitis and toxic epidermal necrolysis (see Precautions). The reported rate of serious skin events appears to be greater for valdecoxib as compared to other COX-2 selective inhibitors.

General: In vitro studies with human hepatic microsomal systems showed no significant inhibitory effects on CYP3A4, 2D6, 2E1, and 1A2 isoforms by parecoxib and Valdecoxib (active moiety). Weak inhibitory activity was found for 2C9 and 2C19 isozymes.
In humans, studies have demonstrated that valdecoxib metabolism is predominantly mediated via CYP450 3A4 and 2C9 isozymes.
Glucuronidation is a further route of metabolism. Due to CYP450-mediated and non-CYP450-mediated metabolic pathways, genetic polymorphisms leading to substantially higher plasma concentrations resulting from impaired metabolism are not expected.
Aspirin: Parecoxib sodium Injection had no effect on aspirin-mediated inhibition of platelet aggregation or bleeding times. Clinical trials indicate that Parecoxib sodium Injection can be given with low dose aspirin. Because of its lack of platelet effects, OLICOXIB Injection is not a substitute for aspirin for cardiovascular prophylaxis.
Methotrexate: In interaction studies in rheumatoid arthritis patients receiving weekly methotrexate (5-20 mg IM), valdecoxib (10 mg BD and 40 mg BD) did not have a clinically significant effect on the plasma exposure to methotrexate. However, caution is advised when methotrexate is administered concurrently with NSAIDs, because NSAID administration may result in increased plasma levels of methotrexate.
Anti-hypertensives including ACE-inhibitors, Angiotensin Receptor Antagonists, Beta Blockers and Diuretics: Reports suggest that NSAIDs may diminish the antihypertensive effects of angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, beta blockers and diuretics. It is unclear, at the present time, how this may apply to OLICOXIB Injection. This potential interaction should be given consideration in patients taking OLICOXIB Injection concomitantly with ACE-inhibitors, angiotensin receptor antagonists, beta blockers and diuretics.
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with ACE inhibitors and/or angiotensin receptor antagonists, may result in deterioration of renal function, including possible acute renal failure.
Therefore, the concomitant administration of these drugs should be done with caution. Patients should be adequately hydrated and the need to monitor the renal function should be assessed at the beginning of the concomitant treatment and periodically thereafter.
Cyclosporin: Because of their effect on renal prostaglandins, NSAIDs may increase the risk of nephrotoxicity with cyclosporin.
Injectable Anaesthetics: Propofol is metabolised by CYP2C9. Coadministration of parecoxib sodium with propofol did not affect either the pharmacokinetics (metabolism and exposure) or the pharmacodynamics of IV propofol.
Midazolam is metabolised primarily by CYP3A4. Coadministration of parecoxib sodium IV, or valdecoxib orally, with IV midazolam did not affect the pharmacokinetics (metabolism and exposure) or the pharmacodynamics of midazolam.
Fentanyl and Alfentanil are extensively metabolised by CYP3A4. Coadministration with parecoxib sodium had no significant effect on the pharmacokinetics of either IV fentanyl or IV alfentanil.
Inhalation Anaesthetics: No formal interaction studies have been conducted. In the general surgery studies, no evidence of pharmacodynamic medicine interaction was observed between parecoxib sodium administered preoperatively and the inhalation anaesthetic agents; nitrous oxide and isoflurane.
Glibenclamide: Glibenclamide is a CYP3A4 substrate. Coadministration of valdecoxib (10 mg BD for 7 days) with glibenclamide (5 mg or 10 mg OD) did not affect the pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of glibenclamide.
Anticonvulsants: Potential interactions with phenytoin (2C9/19 substrate) and carbamazepine (3A4 substrate) have not been studied. However, as mentioned previously (see General), no interactions were noted using prototype 3A4 and 2C9 substrates of these isozymes.
Ketoconazole and Fluconazole: AUC and C_max of valdecoxib was increased (62%) when coadministered with fluconazole, indicating that the dose of parecoxib sodium should be reduced in those patients who are receiving fluconazole therapy. AUC and C_max of valdecoxib was increased (38%) when coadministered with ketoconazole.
Dextromethorphan: Valdecoxib 40 mg BD for 7 days did not produce clinically relevant inhibition in the metabolism by the CYP 2D6-mediated pathway involved in the conversion of dextromethorphan to dextrorphan.
Lithium: Valdecoxib 40 mg BD for 7 days produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone. Lithium serum concentrations should be monitored closely when initiating or changing parecoxib sodium therapy in patients receiving lithium.
Anticoagulants: The effect of valdecoxib on the anticoagulant effect of warfarin (1-8 mg/day) was studied in healthy subjects by IV coadministration of 10 mg parecoxib sodium BD for 7 days. There was a slight increase in the plasma concentration of R-warfarin, but not S-warfarin, as a result of parecoxib sodium coadministration. The effect of oral valdecoxib (40 mg BD) on the anticoagulant effect of warfarin (1-8 mg/day) was studied in healthy subjects by coadministration for 7 days. Valdecoxib caused a statistically significant increase in plasma exposure of R-warfarin and S-warfarin (12% and 15% respectively), and in the pharmacodynamic effects (prothrombin time, measured as INR of warfarin). While mean INR values were only slightly increased (≤8%) with coadministration of valdecoxib, the day-to-day variability in individual INR values was increased.
Anticoagulant therapy should be monitored, particularly during the first few days, after initiating OLICOXIB Injection therapy in patients receiving warfarin or similar agents, since these patients are at increased risk of bleeding complications.

Instructions for Use and Handling and Disposal: Reconstitute OLICOXIB Injection with 2 mL sodium chloride solution (0.9% w/v) using aseptic technique. The only other acceptable diluents for reconstitution are: 5% Glucose Intravenous Infusion; 0.45% Sodium Chloride and 5% Glucose Injection.
Use of Sterile Water for Injections is not recommended, as the resulting solution is not isotonic.
Use of Lactated Ringers or 5% Glucose in Lactated Ringer's for reconstitution will cause the medicine to precipitate from solution and therefore is not recommended.
After reconstitution, OLICOXIB Injection should be inspected visually for particulate matter and discolouration prior to administration. The solution should not be used if discoloured or cloudy or if particulate matter is observed.
To reduce microbiological hazard, use as soon as practicable after reconstitution.
The reconstituted product should not be stored in a refrigerator or freezer. Store the reconstituted product for not more than 24 hours at 20-25°C.
After reconstitution with acceptable diluents, OLICOXIB Injection may only be injected IV or IM, or into IV lines delivering: Sodium Chloride Solution (0.9% w/v); 5% Glucose Intravenous Infusion; 0.45% Sodium Chloride and 5% Glucose Injection; Lactated Ringer's.
Injection into IV lines delivering 5% Glucose in Lactated Ringer's, or other IV diluents not listed here, is not recommended as this may cause precipitation from solution, Parecoxib sodium should not be admixed for injection with any other drug, Do not inject parecoxib into an IV line delivering any other drug. The IV line must be adequately flushed prior to, and after parecoxib injection with a solution of known compatibility (see Incompatibilities as follows).
This product contains no antimicrobial agent. OLICOXIB Injection is for single use in one patient only. Discard any residue. Any unused product, diluent or waste material should be disposed of according to local requirements.
Incompatibilities: This medicinal product must not be mixed with other medicinal products and should be reconstituted only with sodium chloride solution (0.9% w/v) (provided in some packs) or the diluents mentioned in Dosage & Administration and Instructions for Use and Handling and Disposal as previously mentioned.
Use of Lactated Ringer's or 5% Glucose in Lactated Ringer's for reconstitution will cause the medicine to precipitate from solution and therefore is not recommended.
Use of Sterile Water for Injections is not recommended, as the resulting solution is not isotonic.
Injection into an IV line delivering 5% Glucose in Lactated Ringer's, or other IV fluids not listed in Dosage & Administration and Instructions for Use and Handling and Disposal as previously mentioned, is not recommended as this may cause precipitation from solution.
Special Precautions For Disposal: This product contains no antimicrobial agent. OLICOXIB Injection is for single use in one patient only. Discard any residue.

Store below 30°C.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

M01AH04 - parecoxib ; Belongs to the class of non-steroidal antiinflammatory and antirheumatic products, coxibs.

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