Drug Interaction Report

ADJUST DOSING INTERVAL: Administration of enteric-coated, gastro-resistant formulations of peppermint oil (e.g., delayed or sustained release capsules) with food may cause premature dissolution of the enteric coating and early release of the peppermint oil, which could lead to gastrointestinal irritation and reduced therapeutic effects.

MANAGEMENT: Enteric-coated, gastro-resistant formulations of peppermint oil should not be taken immediately after eating. These products should preferably be taken 30 to 90 minutes before a meal with water. The labeling for the specific product should be consulted for administration recommendations and other guidance.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.