Drug Interactions between celecoxib / tramadol and netilmicin

MONITOR: The nephrotoxic effect of aminoglycosides may be potentiated by nonsteroidal anti-inflammatory drugs (NSAIDs), particularly if the latter had been given in high dosages for prolonged periods. Four children with cystic fibrosis who had been receiving chronic ibuprofen developed acute renal insufficiency shortly after initiation of IV aminoglycoside therapy for pulmonary exacerbations. An adolescent with CF who received intermittent, standard-dose ibuprofen during treatment with IV gentamicin also developed renal failure in addition to severe vestibular toxicity. Animal models suggest that renal prostaglandins may play a role in maintaining normal renal blood flow and glomerular filtration rate during the development of aminoglycoside nephrotoxicity, thus inhibition of their production by NSAIDs may worsen the renal damage.

MANAGEMENT: Whenever feasible, NSAID use should preferably be discontinued prior to initiating IV aminoglycoside therapy. If concomitant administration is necessary, hydration status as well as renal and vestibular functions should be closely monitored.

MONITOR: In premature infants, NSAIDs may increase the plasma concentrations of aminoglycosides. The proposed mechanism is decreased aminoglycoside clearance due to NSAID reduction of glomerular filtration rate, which is already low in premature infants. In a study of 20 preterm infants who had been given at least three days of amikacin or gentamicin therapy, mean peak plasma concentration increased by 17% and 33%, and mean trough concentration increased by 29% and 48%, respectively, on day 1 following administration of IV indomethacin for patent ductus arteriosus. Serum creatinine increased by 17%, while urine output and serum sodium decreased. Six patients developed hyponatremia.

MANAGEMENT: It may be advisable to consider reducing the dosage of aminoglycoside prior to initiation of NSAID therapy in infants. During coadministration, plasma antibiotic concentrations and renal function should be closely monitored, and the antibiotic dosage further adjusted as necessary.

MONITOR: Coadministration with celecoxib may increase the plasma concentrations of drugs that are substrates of the CYP450 2D6 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by celecoxib.

MANAGEMENT: Caution is advised if celecoxib must be used concurrently with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever celecoxib is added to or withdrawn from therapy.