Drug Interaction Report

MONITOR: Vosoritide may cause transient decreases in blood pressure. Theoretically, coadministration with antihypertensives, organic nitrates, or agents with hypotensive properties may increase the potential for symptomatic hypotension. In clinical trials, 13% of patients treated with vosoritide experienced a transient decrease in blood pressure compared to 5% of patients on placebo. The median time to onset from injection was 31 (18 to 120) minutes with resolution within 31 (5 to 90) minutes. Two out of 60 (3%) vosoritide-treated patients each had one symptomatic episode of decreased blood pressure with vomiting and/or dizziness compared to 0 of 61 (0%) patients on placebo. Data on this interaction are lacking as patients with significant cardiac or vascular disease and patients on antihypertensive drugs were excluded from vosoritide clinical trials.

MANAGEMENT: Caution is advised during coadministration of vosoritide with blood pressure lowering agents or agents with hypotensive properties. To reduce the risk of low blood pressure and its associated signs and symptoms, patients should have adequate food intake before vosoritide administration and should drink approximately 240 to 300 mL of fluid within the hour prior to vosoritide administration. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience fatigue, nausea, dizziness, or lightheadedness. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.

MONITOR: Vosoritide may cause transient decreases in blood pressure. In clinical trials, 13% of patients treated with vosoritide experienced a transient decrease in blood pressure compared to 5% of patients on placebo. The median time to onset from injection was 31 (18 to 120) minutes with resolution within 31 (5 to 90) minutes. Two out of 60 (3%) vosoritide-treated patients each had one symptomatic episode of decreased blood pressure with vomiting and/or dizziness compared to 0 of 61 (0%) patients on placebo.

MANAGEMENT: To reduce the risk of low blood pressure and its associated signs and symptoms, patients should have adequate food intake before vosoritide administration and should drink approximately 240 to 300 mL of fluid within the hour prior to vosoritide administration. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their doctor if they experience fatigue, nausea, dizziness, or lightheadedness.

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.