Parestat Drug Interactions

General: The drug interaction studies were performed with either parecoxib or the active moiety (valdecoxib).
In humans, parecoxib undergoes extensive hepatic metabolism involving P450 isoenzymes 3A4 and 2C9 and non-P450 dependent pathways (i.e., glucuronidation). Concomitant administration of parecoxib with known CYP3A4 and 2C9 inhibitors can result in increased AUC of parecoxib.
Drug-specific: Interaction of parecoxib with warfarin or similar agents: see Precautions.
Fluconazole and ketoconazole: Co-administration of fluconazole, a CYP2C9 inhibitor, and ketoconazole, a CYP3A4 inhibitor, enhanced the AUC of valdecoxib by 62% and 38%, respectively. When parecoxib is co-administered with fluconazole, the lowest recommended dose of parecoxib should be used. No dosage adjustment is necessary when parecoxib is co-administered with ketoconazole.
Anti-hypertensives including ACE inhibitors, angiotensin II antagonists, beta-blockers and diuretics: Inhibition of prostaglandins may diminish the effect of angiotensin converting enzyme (ACE) inhibitors, angiotensin II antagonists, beta-blockers and diuretics. This interaction should be given consideration in patients receiving parecoxib concomitantly with ACE inhibitors, angiotensin II 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 II antagonists, 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 need to monitor the renal function should be assessed at the beginning of the concomitant treatment and periodically thereafter.
Diuretics: Clinical studies have shown that NSAIDs, in some patients, can reduce the natriuretic effect of furosemide and thiazides by inhibition of renal prostaglandin synthesis.
Cyclosporine: Because of their effect on renal prostaglandins, NSAIDs may increase the risk of nephrotoxicity with cyclosporine.
Methotrexate: A pharmacokinetic interaction study was conducted using valdecoxib and methotrexate and no clinically important interactions were seen. However, caution is advised when methotrexate is administered concurrently with NSAIDs because NSAID administration may result in increased plasma levels of methotrexate.
Lithium: Valdecoxib produced significant decreases in lithium serum clearance (25%) and renal clearance (30%), resulting in a 34% higher serum AUC compared to lithium alone. Lithium serum concentrations should be monitored closely when initiating or changing parecoxib therapy in patients receiving lithium.
Other: Interaction studies were conducted between parecoxib and IV or oral midazolam, heparin, propofol, fentanyl, and alfentanil. Interaction studies were also conducted between valdecoxib and glibenclamide (glyburide), oral contraceptives (ethinylestradiol/norethindrone), phenytoin, omeprazole and diazepam. No clinically important interactions were seen in these studies.
Parecoxib may be co-administered with opioid analgesics. In clinical trials, the daily requirement for PRN opioids was significantly reduced when co-administered with parecoxib.
No formal interaction studies were performed with parecoxib and inhalation anesthetic agents, such as nitrous oxide and isoflurane; however, no evidence of a drug interaction was observed in clinical studies.
Parecoxib does not interfere with the anti-platelet effect of low-dose aspirin. Because of its lack of platelet effects, parecoxib is not a replacement for aspirin in the prophylactic treatment of cardiovascular disease.