Drug Interaction Report

MONITOR: Concomitant use with antihypertensive agents or drugs with hypotensive effects may increase the risk and severity of hypotension associated with amifostine. Hypotension has been reported frequently in patients treated with amifostine. It is usually transient (lasting from 5 to 15 minutes) and closely associated with amifostine administration, but may persist or become evident hours after administration. Moreover, hypotension can occur despite adequate hydration and positioning of the patient. Significant drops in systolic blood pressure have been reported, in some cases resulting in premature termination of amifostine infusion. In rare cases, sometimes during or after hypotension, patients have experienced tachycardia, bradycardia, dyspnea, apnea, hypoxia, chest pain, myocardial ischemia, renal failure, myocardial infarction, convulsions, unconsciousness, respiratory arrest, and cardiac arrest.

MANAGEMENT: If medically feasible, antihypertensive medications should be interrupted 24 hours prior to amifostine administration. Blood pressure should be closely monitored during and after treatment. In addition to hypotension, transient hypertension or exacerbation of preexisting hypertension may occur from intravenous hydration, discontinuation of antihypertensive medications, or other causes. Patients who continue their hypotensive medication(s) during amifostine therapy should be carefully monitored for the development of hypotension. Clinical symptoms of hypotension are usually quickly reversed by fluid infusion and postural management.

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.