Drug Interactions between amikacin and lansoprazole / naproxen

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.

GENERALLY AVOID: Theoretically, proton pump inhibitors may decrease the gastrointestinal absorption of enteric-coated naproxen, which requires an acidic environment for dissolution. The proposed mechanism is an increase in gastric pH (i.e. decreased gastric acidity) induced by proton pump inhibitors. In patients treated with proton pump inhibitors, the possibility of a reduced or subtherapeutic response to enteric-coated naproxen should be considered.

MANAGEMENT: Concomitant use of these drugs is generally not recommended.

MONITOR: Chronic use of proton pump inhibitors (PPIs) may induce hypomagnesemia, and the risk may be increased during concomitant use of diuretics or other agents that can cause magnesium loss. The mechanism via which hypomagnesemia may occur during long-term PPI use is unknown, although changes in intestinal absorption of magnesium may be involved. Hypomagnesemia has been reported rarely in patients treated with PPIs for at least three months, but in most cases, after a year or more. Serious adverse events include tetany, seizures, tremor, carpopedal spasm, atrial fibrillation, supraventricular tachycardia, and abnormal QT interval; however, patients do not always exhibit these symptoms. Hypomagnesemia can also cause impaired parathyroid hormone secretion, which may lead to hypocalcemia. In approximately 25% of the cases of PPI-associated hypomagnesemia reviewed by the FDA, the condition did not resolve with magnesium supplementation alone but also required discontinuation of the PPI. Both positive dechallenge as well as positive rechallenge (i.e., resolution of hypomagnesemia with PPI cessation and recurrence with PPI resumption) were reported in some cases. After discontinuing the PPI, the median time required for magnesium levels to normalize was one week. After restarting the PPI, the median time for hypomagnesemia to recur was two weeks.

MANAGEMENT: Monitoring of serum magnesium levels is recommended prior to initiation of therapy and periodically thereafter if prolonged treatment with a proton pump inhibitor is anticipated or when combined with other agents that can cause hypomagnesemia such as diuretics, aminoglycosides, cation exchange resins, amphotericin B, cetuximab, cisplatin, cyclosporine, foscarnet, panitumumab, pentamidine, and tacrolimus. Patients should be advised to seek immediate medical attention if they develop potential signs and symptoms of hypomagnesemia such as palpitations, arrhythmia, muscle spasm, tremor, or convulsions. In children, abnormal heart rates may cause fatigue, upset stomach, dizziness, and lightheadedness. Magnesium replacement as well as discontinuation of the PPI may be required in some patients.