Parecoxib sodium

The main ingredient is parecoxib sodium (ParecoxibNa), and the main excipients are: disodium hydrogen phosphate heptahydrate, phosphoric acid and/or sodium hydroxide (used to adjust the pH value).

Pharmacodynamic interactions: The use of parecoxib in patients receiving warfarin or other anticoagulants will increase the risk of bleeding complications, especially within a few days after the start of treatment. The international normalized ratio (INR) of the prothrombin time in patients taking anticoagulants should be closely monitored, especially within a few days after starting parecoxib or adjusting the dose of parecoxib. Parecoxib has no effect on the inhibitory effect of aspirin on platelet aggregation or bleeding time. Parecoxib can be used in combination with low-dose (≤325mg) aspirin. Clinical studies have shown that, like other nonsteroidal anti-inflammatory drugs, the combination of parecoxib and low-dose aspirin will increase the risk of peptic ulcers or other gastrointestinal complications. Compared with heparin alone, the combination of parecoxib sodium and heparin does not affect the pharmacodynamic properties of heparin (activated partial thromboplastin time). Nonsteroidal anti-inflammatory drugs can weaken the effects of diuretics and antihypertensive drugs. As with NSAIDs, the risk of acute renal insufficiency increases when parecoxib sodium is used in combination with ACE inhibitors or diuretics. The combination of NSAIDs with cyclosporine or tacrolimus can enhance the nephrotoxicity of cyclosporine or tacrolimus. If parecoxib sodium is used in combination with such drugs, renal function should be monitored. Parecoxib can be used in combination with opioid analgesics. When parecoxib is used in combination with morphine, the latter only requires a smaller dose (28-36% of the conventional dose) to achieve the same clinical analgesic effect. Effects of other drugs on the pharmacokinetics of parecoxib (or its active metabolite valdecoxib): Parecoxib can be rapidly hydrolyzed into the active metabolite valdecoxib. Clinical studies have confirmed that the metabolism of valdecoxib is mainly mediated by cytochrome P450 (CYP) 3A4 and 2C9 isozymes. When co-administered with fluconazole (mainly a CYP2C9 inhibitor), the plasma exposure level of valdecoxib increased (AUC increased by 62%, Cmax increased by 19%). When parecoxib is used in combination with patients receiving fluconazole, the parecoxib dose should be reduced. When co-administered with ketoconazole (mainly a CYP3A4 inhibitor), the plasma exposure level of valdecoxib increased (AUC increased by 38%, Cmax increased by 24%). However, no parecoxib dose adjustment is required for patients receiving ketoconazole. Enzyme induction has not been studied. When co-administered with enzyme inducers (such as rifampicin, phenytoin, carbamazepine or dexamethasone, etc.), the metabolism of valdecoxib can be accelerated. Effects of parecoxib (or its active metabolite valdecoxib) on the pharmacokinetics of other drugs: Treatment with valdecoxib (40 mg each time, twice a day for a total of 7 days) can lead to a 3-fold increase in the plasma concentration of dextromethorphan (CYP2D6 substrate). Close monitoring is required when parecoxib is co-administered with drugs that are primarily metabolized by CYP2D6 and have a narrow therapeutic dose window (e.g., flecainide, propafenone, and metoprolol). Valdecoxib treatment (40 mg twice a day for 7 days) caused a 46% increase in plasma exposure to omeprazole (CYP2C19 substrate, 40 mg once a day), but the plasma exposure to valdecoxib was not affected. These results suggest that although valdecoxib is not metabolized by the CYP2C19 enzyme, it may still be an inhibitor of the enzyme. Therefore, close attention should be paid when parecoxib is co-administered with known CYP2C19 substrates (e.g., phenytoin, diazepam, or imipramine). In drug interaction studies, oral valdecoxib (40 mg twice a day) did not produce clinically significant effects on the plasma concentration of methotrexate in patients with rheumatoid arthritis who received intramuscular methotrexate once a week. However, when the two drugs are used together, methotrexate-related toxic reactions should still be adequately monitored. The co-administration of valdecoxib with lithium can lead to a significant decrease in lithium serum clearance and renal clearance (25% and 30%, respectively). At the same time, the serum exposure level of lithium is higher than that of patients treated with lithium alone. When patients start parecoxib treatment or adjust the parecoxib dose, their serum lithium concentration should be closely monitored. When valdecoxib is co-administered with glyburide (CYP3A4 substrate), the former does not affect the pharmacokinetics (exposure level) and pharmacodynamics (blood glucose and insulin levels) of glyburide. Injectable anesthetics: Parecoxib sodium 40 mg is injected intravenously with propofol (CYP2C9 substrate) or midazolam (CYP3A4 substrate). Parecoxib does not affect the pharmacokinetics (metabolism and exposure level) and pharmacodynamics (EEG, psychomotor testing, and awakening from sedation) of intravenous propofol or midazolam. In addition, valdecoxib had no clinically significant effect on the CYP3A4-mediated metabolism of oral midazolam in the liver and small intestine when valdecoxib was coadministered with midazolam. Parecoxib sodium 40 mg intravenously had no significant effect on the pharmacokinetics of intravenously administered fentanyl or alfentanil (CYP3A4 substrates). Inhalational anesthetics: No formal drug interaction studies have been conducted. No pharmacodynamic interactions between parecoxib sodium and inhalational anesthetics (nitric oxide and isoflurane) have been found in patients receiving parecoxib sodium preoperatively.