NSAIDs Parecoxib

The interaction between aspirin and omeprazole is not established. The balance of evidence suggests that omeprazole is unlikely to have an important effect on the pharmacokinetics and efficacy of aspirin. However, because of the uncertainty generated by the animal and preliminary clinical data, " it would be of benefit to confirm this in further studies. No clinically significant pharmacokinetic interactions have been identified between any of the other NSAIDs and PPIs cited here, and no special precautions are needed during concurrent use. For mention that valdecox-ib raises plasma levels of omeprazole see NSAIDs Parecoxib + Miscellaneous , p.l60. Note that omeprazole and other proton pump inhibitors are widely used in the management of the gastrointestinal complications of aspirin and NSAIDs. 

Although information is limited, these pharmacokinetic interactions appear to be established. Their clinical relevance remains to be determine, but it seems likely that the efficacy of these NSAIDs will be reduced by rifampicin. Combined use should be well monitored, and the NSAID dosage increased if necessary. See also NSAIDs Parecoxib -i- Miscellane-ous%p.l60. The clinical relevance ofthe increase in rifampicin maximum levels with metamizole is uncertain. 

For the interactions of parecoxib with midazolam see NSAIDs Parecoxib + Miscellaneous , p.l60. 

It follows that drugs that selectively inhibit COX-2 should cause fewer side effects than those that inhibit both COX-1 and COX-2. At therapeutic doses, all currently available NSAIDs, with the excqrtion of celecoxib, etoricoxib, lumiracoxib and parecoxib (the prodrug of valdecoxib), are non-selective and inhibit both COX isoforms. 

FLECAINIDE NS AIDS Parecoxib may t flecainide levels Parecoxib weakly inhibits CYP2D6-mediated metabolism of flecainide Monitor PR and BP closely. If possible, use only short courses of NSAID... 

CORTICOSTEROIDS ANALGESICS-NSAIDs 1. T risk of gastrointestinal ulceration and bleeding 2. Parecoxib levels may be 1 by dexamethasone 1. Additive effect 2. Dexamethasone induces CYP3A4-mediated metabolism of parecoxib 1. Watch for early signs of gastrointestinal upset remember that corticosteroids may mask these features 2. Watch for poor response to parecoxib... 

NS AIDs RIFAMPICIN Rifampicin L diclofenac, celecoxib, etoricoxib and parecoxib levels Rifampicin T CYP2C9-mediated metabolism of these NSAIDs Monitor analgesic effects consider using alternative NSAIDs... 

FLUCONAZOLE NSAIDs Fluconazole T celecoxib and possibly parecoxib levels Fluconazole inhibits CYP2C9-mediated metabolism of celecoxib and parecoxib Halve the dose of celecoxib, and start parecoxib at the lowest dose... 

Parecoxib sodium is an injectable COX-2 inhibitor developed for the treatment of acnte pain. It is a prodrug of a sulfonamide-based COX-2 inhibitor, valdecoxib, a potent anti-inflammatory and analgesic dmg. The published information on this componnd is inadequate to draw any conclusion about its tolerability. Single-dose and mnlti-ple-dose studies have not shown any safety problems compared with placebo (1 ). In small short-term endoscopic studies parecoxib was much better tolerated than the non-selective NSAID ketorolac (5,6). However, it shonld be noted that valdecoxib was withdrawn in 2005 (7). 

NSAIDs ANTIEPILEPTICS 1. Parecoxib levels may be i by carbamazepine and phenytoin 2. Report of T phenytoin levels when celecoxib added 1. Carbamazepine and phenytoin induce CYP3A4-mediated metabolism of parecoxib 2. Uncertain possibly competitive inhibition of CYP2C9-mediated metabolism of phenytoin 1. Watch for poor response to parecoxib 2. Monitor phenytoin levels... 

A number of pharmacodynamic studies have investigated whether or not NSAIDs affect the antiplatelet effects of aspirin. Celecoxib 200 mg twice daily, diclofenac 75 mg twice dailyetoricoxib 120 mg daily, lumira-coxib 400 mg daily, meloxicam 15 mg dailynaproxen 500 mg twice daily, parecoxib 40 mg twice dailyand rofecoxib 25 mg daily have all been shown not to alter the antiplatelet effects of aspirin in doses of 75 to 325 mg daily. The effects of ibuprofen ate less elear, and may be related to the order of drug administration. 

Etoricoxib, lumiracoxib and rofecoxib caused a slight 8% to 15% increase in the INR in response to warfarin, whereas celecoxib and parecoxib had no effect. However, raised INRs accompanied by bleeding, particularly in the elderly, have been attributed to the use of waHarin and celecoxib or rofecoxib in other reports. In addition, in a case-control study in patients taking warfarin, the use of celecoxib or rofecoxib was associated with an increased risk of hospitalisation for upper gastrointestinal haemorrhage, which was of a similar magnitude to that seen with non-selective NSAIDs. 

Studies in patients with rheumatoid arthritis found that oral valdecoxib 40 mg twice daily had no clinically significant effect on the plasma levels of methotrexate given weekly by the intramuscular route [dose not stated]. Even so the manufacturers suggest that careful monitoring should be considered, probably because of the problems seen with other NSAIDs. Note that valdecoxib is the main metabolite of parecoxib. 

Tilmacoxib is a COX-2 inhibiting, oxazole-containing, nonsteroidal anti-inflammatory agent, and valdecoxib is an isoxazole NSAID. Formation of the sodium salt of an A -acylated derivative of valdecoxib affords parecoxib, a water-soluble valdecoxib prodrug amenable to injectable formulations. Valdecoxib was withdrawn from the US market in 2005 due to concern of increased risk of heart attack or stroke. While parecoxib is approved for use in the EU, the US FDA issued a letter of nonapproval for the drug, also in 2005. While no documentation for the nonapproval was made public, proximity to the 2004 withdrawal of rofecoxib (Vioxx) cannot be overlooked. 

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