Drug Interaction Report

MONITOR: The coadministration of diuretics with tetracyclines may result in decreased renal function and abnormalities in electrolytes and acid-base balance. As a class, tetracyclines can cause anti-anabolic effects which have led to increased blood urea nitrogen (BUN), azotemia, acidosis, and hyperphosphatemia. Diuretics have the potential to cause electrolyte and metabolic abnormalities, as well as worsen renal function. When used together, it is possible that these two classes of medications could have additive adverse effects.

MANAGEMENT: Patients on concomitant therapy with tetracycline antibiotics and diuretics should have their renal function and electrolytes monitored closely. The risk of additive adverse effects on the patient's renal function, electrolytes, and acid-base balance differs depending on the type of diuretic being used, the specific tetracycline antibiotic, and the clinical status of the patient. The manufacturer's labeling should be consulted for more specific recommendations.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of eplerenone. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Inhibition of hepatic CYP450 3A4 may also contribute. In drug interaction studies, administration of a single 100 mg dose of eplerenone in combination with grapefruit juice resulted in a 25% increase in eplerenone systemic exposure (AUC). High blood levels of eplerenone can increase the risk of side effects including hyperkalemia. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with eplerenone.

ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, may reduce the absorption of omadacycline. The calcium content of these foods may form nonabsorbable chelates with omadacycline.

MANAGEMENT: Omadacycline should be administered at least 2 hours before (4 hours for dairy products) or 4 hours after meals.