Hypotension. Provided that hypovolemia as a cause has been ruled out, hypotension, i.e. MAP < 60 mmHg, may be treated with phenylephrine, ephedrine, norepinephrine or vasopressin according to investigator’s judgment. Hypertension Hypertension, i.e., systolic arterial pressure (SAP) > 160 mmHg may be treated with bolus doses, or an infusion, of nitroglycerin. Alternatively, sodium nitroprusside may be given. However, the concomitant use of nesiritide is not permitted due to its potentially excessive synergistic hypotensive effect with levosimendan. Low cardiac output To ensure sufficient cardiac output, the volume status, heart rate, blood pressure and cardiac rhythm of a patient should be optimized. The target is to maintain cardiac index > 2.2 L/min/m2. When a patient’s cardiac index falls below 2.0 L/min/m2, the first inotropic agent (dobutamine, milrinone, epinephrine, norepinephrine) should be administered. If this is not sufficient a second inotropic agent may be added. In case inotropic drugs cannot maintain cardiac index > 2.2 L/min/m2, mechanical assist device (IABP/LVAD) should be considered. Concomitant treatments from randomization until Day 5 or the end of initial hospitalization will be recorded on the eCRF for Concomitant Treatment. No other investigational drug or device should be used with the study drug. During the 30-day double-blind treatment and post-treatment phases, no use of commercial levosimendan is permitted unless the subject is rehospitalized for congestive heart failure, where approved for treatment of acute decompensated heart failure. Concomitant medications will be recorded in the source document and on eCRFs listing the common medications used in this subject population as per the list of specific medications identified in the study manual and CRF. These include secondary inotropes (dobutamine, milrinone, epinephrine, norepinephrine), pressors and anti-arrhythmics. Only medications on this list (prescriptions or over-the-counter medications) continued at the start of the study or started during the study and different from the study drug must be documented in the concomitant therapy section of the eCRF and in the source document. Record the time of each secondary inotrope’s dose (initiation and conclusion) and peak dose. The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in which prohibited therapies are administered.
Hypotension. Inform patients that APADAZ may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions (5.9)].
