Use of methylnaltrexone and related compounds to treat chronic opioid use side effects

Abstract

A method of preventing or treating an opioid-induced side effect in a patient who has been chronically taking opioids, the method comprising administering a quaternary derivative of noroxymorphone in an amount sufficient to prevent or treat the side effect in the patient, but which amount would be insufficient to treat a patient with the same opioid-induced side effect who had not chronically been administered opioids.

1 . A method of preventing or treating an opioid-induced side effect in a patient chronically administered opioids, the method comprising administering a quaternary derivative of noroxymorphone in an amount sufficient to prevent or treat the side effect in the patient, but which would be insufficient to treat a patient with the same opioid-induced side effect who had not chronically been administered opioids.  
     
     
         2 . The method of  claim 1  wherein the quaternary derivative is methylnaltrexone.  
     
     
         3 . The method of  claim 1  wherein the side effect to be prevented or treated is constipation.  
     
     
         4 . The method of  claim 2  wherein the side effect to be prevented or treated is constipation.  
     
     
         5 . The method of  claim 1  wherein the side effect is selected from the group consisting of dysphoria, pruritus, and urinary retention.  
     
     
         6 . The method of  claim 2  wherein the side effect is selected from the group consisting of dysphoria, pruritus, and urinary retention.  
     
     
         7 . The method of  claim 1 , wherein the opioid and the quaternary derivative of noroxymorphone are combined in an oral dose.  
     
     
         8 . The method of  claim 7  wherein the quaternary derivative is enterically coated.  
     
     
         9 . The method of  claim 2  wherein the methylnaltrexone is enterically coated.  
     
     
         10 . The method of  claim 1  wherein the quaternary derivative is administered orally in a form that is not enterically coated.  
     
     
         11 . The method of  claim 2  wherein the methylnaltrexone is administered in a form that is not enterically coated.  
     
     
         12 . The method of  claim 11  wherein the methylnaltrexone is administered orally.  
     
     
         13 . The method of  claim 2  wherein the methylnaltrexone is administered at a dosage of about 0.001 to about 5 mg/kg body weight.  
     
     
         14 . The method of  claim 2  wherein the methylnaltrexone is administered at a dose of less than about 3 mg/kg body weight.  
     
     
         15 . The method of  claim 2  wherein the methylnaltrexone is administered at a dose of less than about 1 mg/kg body weight.  
     
     
         16 . The method of  claim 2  wherein the methylnaltrexone is administered at a dose of less than about 0.1 mg/kg body weight.  
     
     
         17 . The method of  claim 2  wherein the methylnaltrexone is administered in an amount such that peak plasma concentrations do not exceed 100 ng/ml.  
     
     
         18 . The method of  claim 17  wherein the peak plasma concentrations do not exceed 50 ng/ml.  
     
     
         19 . The method of  claim 17  wherein the peak plasma concentrations do not exceed 20 ng/ml.  
     
     
         20 . The method of  claim 17  wherein the peak plasma concentrations do not exceed 10 ng/ml.  
     
     
         21 . A method of preventing or treating opioid-induced constipation, the method comprising: 
 determining how long the patient has been administered opioids;    selecting a dose of a quaternary derivative of noroxymorphone based on the length of time the patient has been administered opioids, wherein the dose selected for a patient chronically administered opioids is at least 10% lower than the dose selected for a patient not chronically administered opioids; and    administering the selected dose of the quaternary derivative of noroxymorphone to the patient.    
     
     
         22 . The method of  claim 21  wherein the dose selected for a patient chronically administered opioids is at least 20% lower than the dose selected for a patient not chronically administered opioids.  
     
     
         23 . The method of  claim 21  wherein the dose selected for a patient chronically administered opioids is at least 30% lower than the dose selected for a patient not chronically administered opioids.  
     
     
         24 . The method of  claim 21  wherein the dose selected for a patient chronically administered opioids is at least 50% lower than the dose selected for a patient not chronically administered opioids.  
     
     
         25 . The method of  claim 21  wherein the dose selected for a patient chronically administered opioids is at least 70% lower than the dose selected for a patient not chronically administered opioids.