Intranasal Pharmaceutical Dosage Forms Comprising Naloxone

Abstract

The present invention relates to an intranasal pharmaceutical dosage form comprising a dosing unit comprising naloxone or a pharmaceutically acceptable salt thereof in an amount of equivalent to ≧0.5 mg naloxone HCl dissolved in an application fluid of a volume of ≦250 μl. Furthermore, the present invention relates to such an intranasal pharmaceutical dosage form for use in the treatment of opioid overdosing and/or at least one symptom thereof.

What is claimed: 
     
         1 . An intranasal pharmaceutical dosage form comprising a dosing unit, the dosing unit containing 100 μl of an application fluid comprising naloxone or a pharmaceutically acceptable salt thereof in a final concentration equivalent to between 5 mg naloxone HCl per ml application fluid and 100 mg naloxone HCl per ml application fluid. 
     
     
         2 . The dosage form according to  claim 1 , wherein the final concentration of naloxone or the pharmaceutically acceptable salt thereof in the application fluid is equivalent to between 5 mg naloxone HCl and 70 mg naloxone HCl per ml application fluid. 
     
     
         3 . The dosage form according to  claim 1 , wherein the final concentration of naloxone or the pharmaceutically acceptable salt thereof in the application fluid is equivalent to between 8.5 mg naloxone HCl and 44 mg naloxone HCl per ml application fluid. 
     
     
         4 . The dosage form according to  claim 1 , wherein the final concentration of naloxone or the pharmaceutically acceptable salt thereof in the application fluid is equivalent to 40 mg naloxone HCl per ml application fluid. 
     
     
         5 . The dosage form according to  claim 1 , wherein the application fluid is water or an aqueous saline solution. 
     
     
         6 . The dosage form according to  claim 5 , wherein the application fluid is a 0.9% (weight/volume) saline solution. 
     
     
         7 . The dosage form according to  claim 1 , wherein the dosage form is a nasal spray. 
     
     
         8 . A method of treating a subject suffering from an opioid overdose and/or at least one symptom thereof, comprising intranasally administering to said subject, the dosage form of  claim 1 . 
     
     
         9 . The method of  claim 8 , wherein the final concentration of naloxone or the pharmaceutically acceptable salt thereof in the application fluid is equivalent to between 5 mg naloxone HCl and 70 mg naloxone HCl per ml application fluid. 
     
     
         10 . The method of  claim 8 , wherein the final concentration of naloxone or the pharmaceutically acceptable salt thereof in the application fluid is equivalent to between 8.5 mg naloxone HCl and 44 mg naloxone HCl per ml application fluid. 
     
     
         11 . The method of  claim 8 , wherein the final concentration of naloxone or the pharmaceutically acceptable salt thereof in the application fluid is equivalent to 40 mg naloxone HCl per ml application fluid. 
     
     
         12 . The method of  claim 8 , wherein the application fluid is water or an aqueous saline solution. 
     
     
         13 . The method of  claim 12 , wherein the application fluid is a 0.9% (weight/volume) saline solution. 
     
     
         14 . The method of  claim 11 , wherein intranasally administering the dosage form comprises intranasally administering the dosing unit into a first nostril of the subject. 
     
     
         15 . The method of  claim 12 , wherein the dosage form comprises a second dosing unit. 
     
     
         16 . The method of  claim 15 , wherein the second dosing unit contains 100 μl of an application fluid comprising naloxone or a pharmaceutically acceptable salt thereof in a final concentration equivalent to 4 mg naloxone HCl per ml application fluid. 
     
     
         17 . The method of  claim 16 , further comprising consecutively administering the second dosing unit in a second nostril of the subject. 
     
     
         18 . The method of  claim 8 , wherein the dosage form comprises at least two dosing units, at least three dosing units, at least four dosing units, or at least five dosing units and is for multiple uses. 
     
     
         19 . The method of  claim 8 , wherein naloxone is the only pharmaceutically active compound in the dosing unit. 
     
     
         20 . The method of  claim 8 , wherein the symptom is selected from the group consisting of respiratory depression, postoperative opioid respiratory depression, altered level consciousness, miotic pupils, hypoxemia, acute lung injury, and aspiration pneumonia. 
     
     
         21 . The method of  claim 8 , further comprising re-administering the dosage form of  claim 1  during an initial titration period in order to provide an effective amount of naloxone. 
     
     
         22 . The method of  claim 8 , further comprising administering to the subject an intramuscular and/or intravenous dosage form comprising naloxone or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The method of  claim 22 , wherein the amount of intravenous or intramuscular naloxone or pharmaceutically acceptable salt thereof is from about 0.4 mg to about 2 mg naloxone or an equivalent amount of a pharmaceutically acceptable salt thereof.