vioxx and Alimta Interactions

Interactions between vioxx(rofecoxib) and Alimta (pemetrexed)

rofecoxib and pemetrexed (Moderate Drug-Drug)

ADJUST DOSING INTERVAL: Coadministration with nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the plasma concentrations of pemetrexed. The mechanism has not been described but may be related to NSAID inhibition of renal prostaglandins. Use of NSAIDs has been associated with nephropathy manifested as elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. Since pemetrexed is primarily eliminated unchanged by renal excretion, coadministration with NSAIDs may result in delayed and/or decreased clearance. Daily ibuprofen dosage of 400 mg four times a day has been shown to reduce pemetrexed clearance by about 20% in patients with normal renal function, whereas aspirin at 325 mg every 6 hours did not. The effect of higher dosages of ibuprofen or aspirin is unknown.

MANAGEMENT: Ibuprofen at 400 mg and aspirin at 325 mg four times a day, or less, may be used with pemetrexed in patients with normal renal function. However, caution is advised in patients with mild to moderate renal insufficiency (creatinine clearance 45 to 79 mL/min). These patients should avoid taking NSAIDs with short elimination half-lives (e.g., diclofenac, etodolac, fenoprofen, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, mefenamic acid, sulindac, tolmetin, low dosages of salicylates) 2 days before to 2 days after pemetrexed administration. If concomitant administration is necessary, patients should be monitored closely for toxicity, especially myelosuppression, nephrotoxicity, and gastrointestinal toxicity. In the absence of data regarding use with NSAIDs with longer half-lives, withholding NSAID dosing for at least 5 days before to 2 days after pemetrexed administration is recommended.