Liquid pharmaceutical formulations containing 3.7-diazabicyclo[3,3,1]nonane compounds and methods of treatment relating to arrhythmic events

Abstract

A method of using 3,7-diazabicyclo[3,3,1]nonane compounds, preferably of 9,9-alkylene-3,7-diazabicyclo[3,3,1]nonane compounds, and most preferably to the use of tedisamil, and the physiologically acceptable acid addition salts and/or solvates thereof, in the form of a liquid pharmaceutical preparation for the treatment and/or inhibition of arrhythmic events in human patients, preferably in conversion of recent onset of atrial fibrillation or flutter to normal sinus rhythm in humans, as well as related methods and pharmaceutical products or packages.

1 . A method of treating or inhibiting arrhythmic events in a human comprising administering to said human a liquid pharmaceutical composition comprising a therapeutically effective amount of at least one 3,7-diazabicyclo[3,3,1]nonane compound, or a physiologically acceptable acid addition salt thereof, in a plurality of successive phases.  
   
   
       2 . The method of  claim 1 , wherein said compound is administered in a non-continuous administration.  
   
   
       3 . The method of  claim 1 , wherein said compound is administered in a partially continuous administration.  
   
   
       4 . The method of  claim 1 , wherein said compound is administered by stepwise infusion.  
   
   
       5 . The method of  claim 4 , wherein in at least one step, said compound is administered as a partially continuous infusion.  
   
   
       6 . A pharmaceutical product or package comprising: 
 a liquid pharmaceutical composition with a therapeutically effective amount of at least one 3,7-diazabicyclo[3,3,1]nonane compound or a physiologically acceptable acid addition salt thereof, wherein said compound corresponds to Formula I:                          wherein    R1 represents an alkyl group containing from 1 to 6 carbon atoms; an alkylene group containing from 3 to 6 carbon atoms having a double bond which is not linked directly to the nitrogen atom; a cycloalkylalkyl group containing from 4 to 9 carbon atoms or a benzyl group;    R2 represents a lower alkyl group;    R3 represents a lower alkyl group or    R2 and R3 together form an alkylene chain containing from 3 to 6 carbon atoms; and    R4 represents an alkyl group containing from 1 to 6 carbon atoms; an alkenyl group containing from 3 to 6 carbon atoms having a double bond which is not linked directly to the nitrogen atom; a cycloalkylalkyl group containing from 4 to 9 carbon atoms; a group corresponding to Formula a:                        wherein    R5 represents hydrogen, halogen, lower alkyl or lower alkoxy, and    Z represents an alkylene chain containing from 1 to 3 carbon atoms; 
 a propenylene chain having a double bond which is conjugated with the phenyl group; or  
     a group corresponding to Formula b:                          CH b 
 wherein  
 R6 represents hydrogen, halogen, lower alkyl or lower alkoxy and  
 R7 represents hydrogen, halogen, lower alkyl or lower alkoxy and  
   a label or package insert indicating that said 3,7-diazabicyclo[3,3,1]nonane compound may be administered in a multiphase administration.    
   
   
       7 . The pharmaceutical product or package of  claim 6 , wherein said label or package insert indicates that said 3,7-diazabicyclo[3,3,1]nonane compound may be administered non-continuously.  
   
   
       8 . The pharmaceutical product or package of  claim 6 , wherein said label or package insert indicates that said 3,7-diazabicyclo[3,3,1]nonane compound may be administered partially continuously.  
   
   
       9 . The pharmaceutical product or package of  claim 6 , wherein said label or package insert indicates that said 3,7-diazabicyclo[3,3,1]nonane compound may be administered in a two-step administration of two continuous administration phases.  
   
   
       10 . The pharmaceutical product or package of  claim 6 , wherein said compound is present as a solvate or as a prodrug.  
   
   
       11 . The pharmaceutical product or package of  claim 6 , wherein said label or package insert indicates that said 3,7-diazabicyclo[3,3,1]nonane compound may be administered as an infusion.  
   
   
       12 . The pharmaceutical product or package of  claim 6 , wherein said label or package insert indicates that said 3,7-diazabicyclo[3,3,1]nonane compound may be administered by stepwise infusion.  
   
   
       13 . The pharmaceutical product or package of  claim 12 , wherein said label or package insert indicates that in at least one step, said 3,7-diazabicyclo[3,3,1]-nonane compound may be administered as a partially continuous infusion.  
   
   
       14 . The pharmaceutical product or package of  claim 6 , wherein said label or package insert indicates that said 3,7-diazabicyclo[3,3,1]nonane compound may be administered as a two-step infusion of two continuous administration phases.  
   
   
       15 . The pharmaceutical product or package of  claim 6 , wherein said label or package insert indicates that a first therapeutically effective amount of said 3,7-diazabicyclo[3,3,1]nonane compound may be administered over a first time period of from about 8 to about 12 minutes and a second therapeutically effective amount of said 3,7-diazabicyclo[3,3,1]nonane compound may be administered over a second time period of from about 15 to about 25 minutes.  
   
   
       16 . The pharmaceutical product or package of  claim 15 , wherein said first time period is from about 9 to about 11 minutes.  
   
   
       17 . The pharmaceutical product or package of  claim 15 , wherein said first time period is from about 9.5 to about 10.5 minutes.  
   
   
       18 . The pharmaceutical product or package of  claim 15 , wherein said second time period is from about 17 to about 23 minutes.  
   
   
       19 . The pharmaceutical product or package of  claim 15 , wherein said second time period is from about 19 to about 21 minutes.