Parenteral esmolol formulation

Abstract

A parenteral formulation of esmolol hydrochloride for use in the treatment of a patient suffering from tachycardia comprising a lyophilized powder consisting of pure esmolol hydrochloride, wherein said powder is reconstituted to obtain a ready-to-use i.v. solution of esmolol hydrochloride at a concentration of 20-100 mg/mL, and said i.v. solution is directly administered to the patient, and further a method of producing a ready-to-use i.v. solution of esmolol hydrochloride by reconstituting a lyophilized powder consisting of pure esmolol hydrochloride with a solvent, characterized in that said solvent is an i.v. solvent devoid of alcohol or a buffer excipient, in an amount necessary to obtain a ready-to-use i.v. solution at a concentration of 20-100 mg/mL, and the ready-to-use i.v. solution containing a parenteral formulation of 20-100 mg/mL pure esmolol hydrochloride in an infusion device or consisting of a parenteral formulation of 20-100 mg/mL pure esmolol hydrochloride, WFI and/or saline solution, devoid of any alcohol or buffer excipients.

1 . A method of treating a patient suffering from tachycardia comprising the steps of:
 reconstituting a lyophilized powder consisting of pure esmolol hydrochloride with an aqueous solution to obtain a ready-to-use intravenous (i.v.) solution of esmolol hydrochloride at a concentration of 20-100 mg/mL, and   administering said i.v. solution to the patient.   
     
     
         2 . The method of  claim 1 , wherein said powder is reconstituted in an i.v. solvent devoid of alcohol or a buffer excipient, and wherein the solvent is selected from the group consisting of water for injection (WFI), a glucose solution, a glucose and Ringer solution, a glucose and saline solution, a saline solution, a Ringer Lactate solution, and a Ringer Lactate and saline solution. 
     
     
         3 . The method of  claim 1 , wherein said i.v. solution has a pH of 4.5 to 5.0. 
     
     
         4 . The method of  claim 1 , wherein said esmolol hydrochloride concentration is at least 50 mg/mL. 
     
     
         5 . The method of  claim 1  Formulation according to any of  claims 1  to  3 , wherein said i.v. solution is administered as a continuous infusion. 
     
     
         6 . The method of  claim 1 , wherein said i.v. solution is administered as a maintenance infusion at a dose of at least 25 μg/kg/min. 
     
     
         7 . The method of  claim 1 , wherein said i.v. solution is local tissue tolerant at the infusion site, thereby preventing local venous irritation or skin necrosis at the infusion site. 
     
     
         8 . The method of  claim 1 , wherein said patient is:
 a. suffering from a condition selected from the group consisting of supraventricular tachycardia, ventricular tachycardia, non-compensatory sinus tachycardia, atrial fibrillation, and atrial flutter, or   b. in need of blood pressure lowering during aortic dissection or for controlled hypotension to avoid blood loss in ear/nose/throat surgery or for diagnostic purposes.   
     
     
         9 . The method of  claim 1 , wherein said patient is experiencing one or more conditions selected from the group consisting of cardiac decompensation, hyperhydratation, renal decompensation, hypernatremia, hyperchloramic acidosis, hyperhydratation. 
     
     
         10 . A method of producing a ready-to-use i.v. solution of esmolol hydrochloride, comprising the step of reconstituting a lyophilized powder consisting of pure esmolol hydrochloride with an amount of a solvent necessary to obtain a solution having a concentration of esmolol hydrochloride of 20-100 mg/mL, wherein said solvent is an i.v. solvent devoid of alcohol or a buffer excipient, thereby producing a ready-to-use i.v. solution of esmolol. 
     
     
         11 . (canceled) 
     
     
         12 . A ready-to-use i.v. solution comprising a parenteral formulation of 20-100 mg/mL pure reconstituted lyophilized esmolol hydrochloride and water for injection (WFI), devoid of any alcohol or buffer excipients. 
     
     
         13 . (canceled) 
     
     
         14 . A kit for preparing the ready-to-use i.v. solution of  claim 12 , comprising the following components:
 a) a lyophilized powder consisting of pure esmolol hydrochloride, and   b) WFI or saline solution.   
     
     
         15 . The kit of  claim 14 , wherein 2500 mg of the powder is contained in a 50 mL vial. 
     
     
         16 . The method of  claim 6 , wherein the i.v. solution is administered following an initial infusion of the i.v. solution at a dose of at least 300 μg/kg/min. 
     
     
         17 . The ready-to-use i.v. solution of  claim 12 , wherein the i.v. solution is a saline solution. 
     
     
         18 . The ready-to-use i.v. solution of  claim 12 , wherein the i.v. solution is stored in an infusion device. 
     
     
         19 . The kit of  claim 14 , further comprising an infusion device suitable for i.v. administration.