GMP Certified / Parecoxib Sodium for Injection 40mg

• Quality Standard: USP, Bp
• Packing: 1 Vial+1 AMP/Box
• Factory Certified: GMP
• Transport Package: Carton
• Specification: 40mg
• Trademark: Sinolead
• Model NO.: injection
• Origin: China
• Production Capacity: 100, 000, 000 Per Year

Product Description

Generic Name	Parecoxib Sodium For Injection
Strength	40mg
Packing	1 vial+1 amp / box
Origin	China

Value-added services:
 Packaging design by our team
 Registration service by our team
 Registration dossier available by our team
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Product name:
Parecoxib Sodium For Injection

Character:
 This product is white or white freeze-dried lump.

Indications:
Parecoxib sodium for injection, indicated for the short-term treatment of post-operative pain.

Taboo:
Patients with a history of allergy to any of the active ingredients or excipients of parecoxib sodium for injection.
A history of severe drug allergic reactions, especially skin reactions, such as cutaneous mucocutaneous syndrome (Stevens-Johnson syndrome), toxic epidermal necrolysis, erythema multiforme, etc., or known hypersensitivity to sulfonamides.
Patients with a history of gastrointestinal bleeding or perforation after nonsteroidal anti-inflammatory drugs.
Active digestive ulcer or gastrointestinal bleeding.
Patients who develop bronchospasm, acute rhinitis, nasal polyps, angioneurotic edema, urticaria, and other allergic reactions after taking aspirin or NSAIDs (including COX-2 inhibitors).
Patients who are in the last third of pregnancy or who are breastfeeding.
Severe liver function impairment (serum albumin [25 g/L or Child-Pugh score ≥10).
Inflammatory bowel disease.
Congestive heart failure (NYHA II-IV).
Contraindication for the treatment of postoperative pain after coronary artery bypass grafting (CABG).
Patients with established ischemic heart disease, peripheral arterial vascular and/or cerebrovascular disease.

Drug interaction:
Drug interaction studies have only been conducted in adults.
Pharmacodynamic interaction
The use of parecoxib in patients who are being treated with warfarin or other anticoagulants increases the risk of bleeding complications, especially in the first few days after treatment begins. The International Standardized ratio of prothrombin time (INR) in patients taking concurrent anticoagulants should be closely monitored, especially within a few days after initiation of parecoxib or dose adjustment of parecoxib.
Parecoxib had no effect on the effect of aspirin on platelet aggregation or bleeding time. Parecoxib can be used in combination with low-dose (≤325 mg) aspirin. Clinical studies suggest that, as with other NSaids, the combination of parecoxib and low-dose aspirin may increase the risk of developing digestive ulcers or other digestive complications.
Compared with heparin alone, the combination of parecoxib sodium and heparin did not affect the pharmacodynamic properties of heparin (activated partial thromboplastin time).
Nsaids can weaken the effects of diuretics and antihypertensive drugs. As with NSaids, parecoxib sodium increases the risk of acute renal insufficiency when used in combination with ACE inhibitors or diuretics.
The combination of NSAIDS (including selective COX-2 inhibitors) with ACE inhibitors may lead to deterioration of kidney function, including possible acute renal failure, in the elderly, those with insufficient volume (including diuretic therapy), or those with impaired renal function. These effects are usually reversible.
The combination of NSAIDS with cyclosporine or tacrolimus can enhance the renal toxicity of cyclosporine or tacrolimus. Renal function should be monitored if parecoxib sodium is used in combination with such drugs.
Parecoxib can be used in combination with opioid painkillers. In clinical studies, when administered in combination with parecoxib, the daily requirement for on-demand opioids can be significantly reduced.
Effects of other drugs on the pharmacokinetics of parecoxib (or its active metabolite vardecoxib)
Parecoxib can be rapidly hydrolyzed to the active metabolite vardecoxib. Clinical studies have confirmed that the metabolism of vardecxib is mainly mediated by cytochrome P450 (CYP) 3A4 and 2C9 isoenzymes.
In combination with fluconazole (primarily a CYP 2C9 inhibitor), plasma exposure to vardecoxib was increased (AUC by 62% and Cmax by 19%). Patients receiving fluconazole in combination with parecoxib should reduce the dose of parecoxib.
In combination with ketoconazole (primarily CYP 3A4 inhibitors), plasma exposure to vardecoxib increased (AUC increased by 38% and Cmax increased by 24%). However, patients treated with ketoconazole combined with parecoxib did not need to adjust the dose of parecoxib.
The induction of enzymes has not been studied. When combined with enzyme inducers such as rifampicin, phenytoin, carbamazepine or , the metabolic process of vardecoxib can be accelerated.
The pharmacokinetic effects of parecoxib (or its active metabolite vardecoxib) on other drugs
Treatment with vardecoxib (40 mg twice a day for 7 days) resulted in a three-fold increase in the plasma concentration of dextromethorphan (CYP 2D6 substrate). Parecoxib should be closely monitored when used in combination with drugs that are primarily metabolized by CYP 2D6 and treat dose-window stenosis, such as flucainide, propafenone, and metoprolol.
Vardecoxib treatment (40 mg each time, twice a day for 7 days) caused a 46% increase in plasma exposure to omeprazole (CYP 2C19 substrate, 40 mg each time, once a day), but vardecoxib plasma exposure was not affected. These results suggest that although vardecoxib is not metabolized by CYP 2C19 enzyme, it may still be an inhibitor of this enzyme. Therefore, careful attention should be paid when parecoxib is used in combination with a known CYP 2C19 substrate, such as phenytoin, diazepam or imipramine.
In drug interaction studies, the intramuscular injection of methotrexate once a week and the oral administration of vardecoxib (40 mg each time, twice a day) did not have clinically significant effects on plasma concentrations of methotrexate in patients with rheumatoid arthritis. However, when the two drugs are used in combination, adequate monitoring of the toxic effects associated with methotrexate should still be conducted.
The combination of valdecoxib with lithium resulted in a significant decrease in serum and renal clearance (25% and 30%, respectively), and the serum exposure level of lithium was higher than that of patients treated with lithium alone, and the serum lithium concentration should be closely monitored when starting parecoxib therapy or adjusting the dosage of parecoxib.
The pharmacokinetics (exposure level) and pharmacodynamics (glucose and insulin levels) of glibenuride were not affected by Vardecoxib when combined with glibenuride (CYP 3A4 substrate).
Injection anesthetic: Parecoxib sodium 40 mg is administered simultaneously with propofol (CYP 2C9 substrate) or midazolam (CYP 3A4 substrate). Parecoxib does not affect the pharmacokinetic (metabolic and exposure levels) and pharmacodynamic (electroencephalogram, psychomotor tests, and arousal to sedation) properties of propofol or midazolam. In addition, when administered in combination with midazolam, vardecoxib had no clinically significant effect on CYP 3A4-mediated metabolic processes in the liver and small intestine of oral midazolam. The pharmacokinetics of fentanyl or afentanil (CYP 3A4 substrate) were not significantly affected by intravenous administration of parecoxib sodium 40 mg.
Inhaled anesthetics: Drug interaction studies have not been formally conducted. Parecoxib sodium was administered preoperatively, and no pharmacodynamic interaction was observed between parecoxib sodium and inhaled anesthetics (nitric oxide and isoflurane).

Pharmacology and toxicology
1. Pharmacological effect
Parecoxib is a precursor to vardecoxib. Vadoxib is a selective cyclooxygenase-2 (COX-2) inhibitor in the clinical dose range, and cyclooxygenase is involved in prostaglandin synthesis. Two isomers, COX-1 and COX-2, exist. Studies have shown that COX-2, as an isomer of the cycoperoxidase, is induced by preinflammatory stimuli, which suggests that COX-2 plays a major role in the synthesis of prostaglandin-like transmitters associated with pain, inflammation, and fever. COX-2 has also been implicated in ovulation, implantation of fertilized eggs, closure of ductus arteriosus, regulation of renal function, and central nervous system function (induction of fever, pain, and cognitive function). COX-2 also helps ulcer healing. COX-2 has been found to be present in the periphery of human gastric ulcer tissue, but the association between COX-2 and ulcer healing has not been established.
There are clinically significant differences in antiplatelet activity between some COX-1-inhibiting NSaids and COX-2 selective inhibitors in patients at high risk for vascular embolism. COX-2 selective inhibitors reduce prostaglandin production in tissues, including endothelial tissue, but have no effect on thromboxanes in platelets. Clinical relevance of these observations has not been established.
2. Toxicological studies
Based on the results of preclinical routine safety pharmacological studies or multiple administration toxicity studies (doses equal to twice the maximum human exposure to parecoxib), parecoxib poses no particular risk to humans. However, toxicity studies with multiple doses in dogs and rats showed that systemic exposure levels to vardecoxib (the active metabolite of parexib) in both animals were about 0.8 times higher than systemic exposure levels in elderly humans receiving the maximum recommended dose (80 mg/ day). High doses of parecoxib aggravate skin infections and delay their healing, which is associated with COX-2 inhibition.
In the study of reproductive toxicity, the dose of parecoxib without toxic effect can also lead to the loss and absorption of fertilized eggs after implantation and the retarded growth of fetal weight. Parecoxib had no effect on fertility in male or female rats.
The effects of parecoxib on the third trimester and perinatal period have not been evaluated. The concentrations of parecoxib, vadoxib and vadoxib active metabolites in milk of lactating rats were similar to those in maternal plasma after single intravenous injection of parecoxib sodium.
The potential carcinogenic effect of parecoxib sodium has not been evaluated.

Storage:
Store tightly.
The prepared liquid medicine is for single use only and must not be frozen or refrigerated.