Dosing Regimens Associated With Extended Release Paliperidone Injectable Formulations

Abstract

The present invention provides a method of treating patients with long acting injectable paliperidone palmitate formulations.

What is claimed is: 
     
         1 . A method for administering paliperidone palmitate to a patient in need thereof who has been administered a first dose of a first paliperidone palmitate extended-release injectable suspension (first suspension), comprising:
 administering in a deltoid muscle of the patient a re-initiation loading dose of a second paliperidone palmitate extended-release injectable suspension (second suspension) at a time that is more than six months and three weeks after administration of said first dose of the first suspension but less than eight months after administration of said first dose of the first suspension; and   administering in the deltoid or gluteal muscle of the patient a maintenance dose of the first suspension at a time that is about one month (±7 days) after administering the re-initiation loading dose of the second suspension.   
     
     
         2 . The method of  claim 1 , wherein the first dose of the first suspension comprises about 1092 mg of paliperidone palmitate; the re-initiation loading dose of the second suspension comprises about 156 mg of paliperidone palmitate; and the maintenance dose of the first suspension comprises about 1092 mg of paliperidone palmitate. 
     
     
         3 . The method of  claim 1 , wherein the first dose of the first suspension comprises about 1560 mg of paliperidone palmitate; the re-initiation loading dose of the second suspension comprises about 234 mg of paliperidone palmitate; and the maintenance dose of the first suspension comprises about 1560 mg of paliperidone palmitate. 
     
     
         4 . A method for administering paliperidone palmitate to a patient in need thereof who has been administered a first dose of a first paliperidone palmitate extended-release injectable suspension (first suspension), comprising:
 administering to the deltoid muscle of the patient a first re-initiation loading dose of about 156 mg paliperidone palmitate of a second paliperidone palmitate extended-release injectable suspension (second suspension) at a time that is from 8 months up to and including 11 months after administration of the first dose of the first suspension;   administering in the deltoid muscle of the patient a second re-initiation loading dose of about 156 mg paliperidone palmitate of the second suspension on about day 8 (±4 days) after administering the first re-initiation loading dose of the second suspension; and   administering in the deltoid or gluteal muscle of the patient from about 1092 mg to about 1560 mg paliperidone palmitate of a maintenance dose of the first suspension about 1 month (±7 days) after administering the second re-initiation loading dose of the second suspension.   
     
     
         5 . The method of  claim 4 , wherein the first dose of the first suspension comprises about 1092 mg paliperidone palmitate and the maintenance dose of the first suspension comprises about 1092 mg paliperidone palmitate. 
     
     
         6 . The method of  claim 4 , wherein the first dose of the first suspension comprises about 1560 mg paliperidone palmitate and the maintenance dose of the first suspension comprises about 1560 mg paliperidone palmitate. 
     
     
         7 . A method for administering paliperidone palmitate to a patient in need thereof who has been administered a first dose of a first paliperidone palmitate extended-release injectable suspension (first suspension), comprising:
 (1) administering in the deltoid muscle of the patient a first re-initiation loading dose of about 234 mg paliperidone palmitate of a second paliperidone palmitate extended-release injectable suspension (second suspension) at a time that is more than 11 months after administration of the first dose of the first suspension;   (2) administering in the deltoid muscle of the patient a second re-initiation loading dose of about 156 mg paliperidone palmitate of the second suspension on about day 8 (±4 days) after administering the first re-initiation loading dose of the second suspension;   (3) administering in the deltoid or gluteal muscle of the patient a first re-initiation maintenance dose of about 39 mg to about 234 mg paliperidone palmitate of the second suspension about 1 month (±7 days) after administering the second re-initiation loading dose of the second suspension;   (4) administering in the deltoid or gluteal muscle of the patient a second re-initiation maintenance dose of from about 39 mg to about 234 mg paliperidone palmitate of the second suspension about 1 month (±7 days) after administering the first re-initiation maintenance dose of the second suspension;   (5) administering in the deltoid or gluteal muscle of the patient a third re-initiation maintenance dose of from about 39 mg to about 234 mg paliperidone palmitate of the second suspension about 1 month (±7 days) after administering the second re-initiation maintenance dose of the second suspension; and   (6) administering in the deltoid or gluteal muscle of the patient from about 1092 mg to about 1560 mg paliperidone palmitate of a maintenance dose of the first suspension about 1 month (±7 days) after administering the third re-initiation maintenance dose of the second suspension.   
     
     
         8 . The method of  claim 7 , wherein the first dose of the first suspension comprises about 1092 mg paliperidone palmitate and the maintenance dose of the first suspension comprises about 1092 mg paliperidone palmitate. 
     
     
         9 . The method of  claim 7 , wherein the first dose of the first suspension comprises about 1560 mg paliperidone palmitate and the maintenance dose of the first suspension comprises about 1560 mg paliperidone palmitate. 
     
     
         10 . The method of  claim 1 , wherein the first dose of the first suspension and the maintenance dose of the first suspension is administered in the gluteal muscle. 
     
     
         11 . The method of  claim 1 , wherein the patient is in need of treatment for psychosis, schizophrenia, schizoaffective disorder, schizophreniform disorder, or bipolar disorder. 
     
     
         12 . The method of  claim 11 , wherein the patient is in need of treatment for schizophrenia. 
     
     
         13 . The method of  claim 1 , wherein the first suspension comprises:
 about 280 mg/mL to about 350 mg/mL of the paliperidone palmitate;   about 8 mg/mL to about 12 mg/mL of a wetting agent;   one or more buffering agents;   about 65 mg/mL to about 85 mg/mL of a suspending agent; and   water q.s. ad 100%.   
     
     
         14 . The method of  claim 13 , wherein the first suspension is from about pH 6.0 to about pH 8.0. 
     
     
         15 . The method of  claim 13 , wherein the one or more buffering agents comprise citric acid monohydrate, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous, or sodium hydroxide. 
     
     
         16 . The method of  claim 13 , wherein the first suspension comprises:
 about 312 mg/mL of paliperidone palmitate;   about 10 mg/mL of polysorbate 20; and   about 75 mg/mL of polyethylene glycol 4000.   
     
     
         17 . The method of  claim 13 , wherein the second suspension comprises:
 about 140 mg/mL to about 180 mg/ml of the paliperidone palmitate;   about 8 mg/mL to about 16 mg/ml of a wetting agent;   one or more buffering agents;   about 20 mg/mL to about 40 mg/ml of a suspending agent; and   water q.s. ad 100%.   
     
     
         18 . The method of  claim 17 , wherein the second suspension is from about pH 6.0 to about pH 8.0. 
     
     
         19 . The method of  claim 17 , wherein the one or more buffering agents comprise citric acid monohydrate, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate anhydrous, or sodium hydroxide. 
     
     
         20 . The method of  claim 17 , wherein the second suspension comprises:
 about 156 mg/mL of paliperidone palmitate;   about 12 mg/mL of polysorbate 20; and   about 30 mg/μL of polyethylene glycol 4000.   
     
     
         21 . The method of  claim 4 , wherein the patient is in need of treatment for psychosis, schizophrenia, schizoaffective disorder, schizophreniform disorder, or bipolar disorder. 
     
     
         22 . The method of  claim 4 , wherein the first suspension comprises:
 about 280 mg/mL to about 350 mg/mL of the paliperidone palmitate;   about 8 mg/mL to about 12 mg/mL of a wetting agent;   one or more buffering agents;   about 65 mg/mL to about 85 mg/mL of a suspending agent; and   water q.s. ad 100%.   
     
     
         23 . The method of  claim 22 , wherein the first suspension comprises:
 about 312 mg/mL of paliperidone palmitate;   about 10 mg/mL of polysorbate 20; and   about 75 mg/mL of polyethylene glycol 4000.   
     
     
         24 . The method of  claim 22 , wherein the second suspension comprises:
 about 140 mg/mL to about 180 mg/ml of the paliperidone palmitate;   about 8 mg/mL to about 16 mg/ml of a wetting agent;   one or more buffering agents;   about 20 mg/mL to about 40 mg/ml of a suspending agent; and   water q.s. ad 100%.   
     
     
         25 . The method of  claim 24 , wherein the second suspension comprises:
 about 156 mg/mL of paliperidone palmitate;   about 12 mg/mL of polysorbate 20; and   about 30 mg/mL of polyethylene glycol 4000.   
     
     
         26 . The method of  claim 7 , wherein the patient is in need of treatment for psychosis, schizophrenia, schizoaffective disorder, schizophreniform disorder, or bipolar disorder. 
     
     
         27 . The method of  claim 7 , wherein the first suspension comprises:
 about 280 mg/mL to about 350 mg/mL of the paliperidone palmitate;   about 8 mg/mL to about 12 mg/mL of a wetting agent;   one or more buffering agents;   about 65 mg/mL to about 85 mg/mL of a suspending agent; and   water q.s. ad 100%.   
     
     
         28 . The method of  claim 27 , wherein the first suspension comprises:
 about 312 mg/mL of paliperidone palmitate;   about 10 mg/mL of polysorbate 20; and   about 75 mg/mL of polyethylene glycol 4000.   
     
     
         29 . The method of  claim 27 , wherein the second suspension comprises:
 about 140 mg/mL to about 180 mg/ml of the paliperidone palmitate;   about 8 mg/mL to about 16 mg/ml of a wetting agent;   one or more buffering agents;   about 20 mg/mL to about 40 mg/ml of a suspending agent; and   water q.s. ad 100%.   
     
     
         30 . The method of  claim 29 , wherein the second suspension comprises:
 about 156 mg/mL of paliperidone palmitate;   about 12 mg/mL of polysorbate 20; and   about 30 mg/mL of polyethylene glycol 4000.