Drug Interactions between amoxicillin / clarithromycin / omeprazole and amphotericin b lipid complex

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.

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Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.

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Clarithromycin may increase and prolong the omeprazole plasma concentration. The mechanism may be related to clarithromycin inhibition of hepatic cytochrome P450 enzymes responsible for omeprazole metabolism. Coadministration of omeprazole may result in an increase in clarithromycin and 14-(R)-hydroxyclarithromycin plasma concentrations. These increases may be due to the effect of omeprazole on gastric pH.

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