Drug Interaction Report

MONITOR: Coadministration with CYP450 3A4 inhibitors may increase the plasma concentrations of amlodipine, which is a substrate of the isoenzyme. In 8 elderly hypertensive patients, administration of a single 5 mg dose of amlodipine in combination with the moderate CYP450 3A4 inhibitor diltiazem (180 mg orally daily for 3 days) resulted in a nearly 60% increase in amlodipine peak plasma concentration (Cmax) and systemic exposure (AUC). Associated systolic, diastolic, and standing blood pressures decreased compared to those obtained with amlodipine alone. Erythromycin, another moderate inhibitor, did not significantly alter amlodipine systemic exposure in healthy volunteers. However, pharmacokinetic changes may be more pronounced in elderly patients.

MANAGEMENT: Close monitoring of clinical response and tolerance is recommended if amlodipine is prescribed with potent or moderate CYP450 3A4 inhibitors. Dosage reduction may be required for amlodipine. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.

ADJUST DOSING INTERVAL: Food enhances the absorption and oral bioavailability of darunavir administered in combination with low-dose ritonavir. The mechanism is unknown. When administered with food, the peak plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of darunavir were approximately 30% higher than when administered in the fasting state. Darunavir exposure was similar for the range of meals studied. The total caloric content of the various meals evaluated ranged from 240 Kcal (12 grams fat) to 928 Kcal (56 grams fat).

MANAGEMENT: To ensure maximal oral absorption, darunavir coadministered with ritonavir should be taken with food. The type of food is not important.