Transdermal Method and Patch for Nausea

Abstract

Provided, among other things, is a method of treating acute, delayed or anticipatory emesis for a sustained period in an individual, which involves applying to a portion of intact skin on the individual a composition of i. an antiemetically effective amount of a 5-HT 3 receptor antagonist; ii. a permeation enhancing amount of permeation enhancer comprising 0.5% to 15% by weight of the skin-contacting layer; and iii. an adhesive, wherein a plasma concentration of the 5-HT 3 receptor antagonist in a therapeutically effective range is provided for period of time from an onset time to 12 hours or more after the composition is removed.

1 . A method of treating acute, delayed or anticipatory emesis for a sustained period in an individual, the method comprising: 
 applying to a portion of intact skin or mucosa on the individual for 24 hours or more a composition comprising: 
 i. an antiemetically effective amount of a 5-HT 3  receptor antagonist;  
 ii. a permeation enhancing amount of permeation enhancer comprising 0.5% to 15% by weight of the skin-contacting layer; and  
 iii. an adhesive,  
   wherein a plasma concentration of the 5-HT 3  receptor antagonist in a therapeutically effective range is provided for period of time from an onset time to 12 hours or more after the composition is removed.    
     
     
         2 . The method of  claim 1 , wherein, 12 or more hours after removing the composition, applying to a portion of intact skin or mucosa on the individual a second said composition, wherein a plasma concentration of the 5-HT 3  receptor antagonist in a therapeutically effective range is provided for period of time from an onset time to 12 hours or more after the second said composition is removed.  
     
     
         3 . The method of  claim 1 , further comprising administering an antiemetically effective amount of a corticosteroid.  
     
     
         4 . The method of  claim 3 , wherein the corticosteroid is administered transdermally.  
     
     
         5 . The method of  claim 3 , wherein the corticosteroid is administered orally or by injection.  
     
     
         6 . The method of  claim 1 , further comprising administering an antiemetically effective amount of an antiemetic agent in a second dosage form.  
     
     
         7 . The method of  claim 1 , wherein the serotonin 5-HT 3  receptor antagonist is selected from the group consisting of ondansetron, granisetron, tropisetron, dolasetron, hydrodolasetron, azasetron, ramosetron, lerisetron, indisetron, itasetron, palonosetron, lamosetron, allosetron, and mixtures thereof.  
     
     
         8 . The method of  claim 1 , wherein the 5-HT 3  receptor antagonist is granisetron.  
     
     
         9 . The method of  claim 8 , further comprising administering an antiemetically effective amount of a corticosteroid.  
     
     
         10 . The method of  claim 1 , wherein the permeation enhancer consists essentially of 15% or less by weight of the skin-contacting layer of a fatty acid ester of fatty acyl chain length C 12 -C 18 , or mixtures thereof.  
     
     
         11 . The method of  claim 1 , wherein the permeation enhancer consists essentially of 15% or less by weight of the skin-contacting layer of isopropyl myristate.  
     
     
         12 . The method of  claim 1 , further comprising the step of, in coordination with said applying, administering to the individual a pharmaceutical or procedure that creates a risk of emesis.  
     
     
         13 . The method of  claim 12 , wherein said applying occurs prior to said enesis risk-creating administration.  
     
     
         14 . A composition for transdermal administration of an antiemetic comprising: 
 a skin-contacting composition comprising: 
 i. an antiemetically effective amount of a 5-HT 3  receptor antagonist;  
 ii. a permeation enhancing amount of permeation enhancer comprising 0.5% to 15% by weight of the skin-contacting layer; and  
 iii. an adhesive,  
   wherein, when applied to a portion of intact skin on an individual for 24 hours and then removed, the composition provides the individual with a plasma concentration of the 5-HT 3  receptor antagonist in a therapeutically effective range for period of time from an onset time to 12 hours or more after the composition is removed.    
     
     
         15 . A device for transdermal prevention, amelioration or treatment of nausea and vomiting in an individual which comprises a patch comprising: 
 a. a support layer; and    b. a skin-contacting layer comprising: 
 i. an antiemetically effective amount of a 5-HT 3  receptor antagonist;  
 ii. a permeation enhancing amount of permeation enhancer comprising 0.5% to 15% by weight of the skin-contacting layer; and  
 iii. an adhesive,  
   wherein, when applied to a portion of intact skin on an individual for 24 hours and then removed, the device provides the individual with a plasma concentration of the 5-HT 3  receptor antagonist in a therapeutically effective range for period of time from an onset time to 12 hours or more after the device is removed.    
     
     
         16 . The device of  claim 15 , wherein, when applied to a portion of intact skin on an individual for 48 hours and then removed, the device provides the individual with a plasma concentration of the 5-HT 3  receptor antagonist in a therapeutically effective range for period of time from an onset time to 12 hours or more after the device is removed.  
     
     
         17 . The device of  claim 15 , wherein, when applied to a portion of intact skin on an individual for 72 hours and then removed, the device provides the individual with a plasma concentration of the 5-HT 3  receptor antagonist in a therapeutically effective range for period of time from an onset time to 12 hours or more after the device is removed.  
     
     
         18 . The device of  claim 15 , wherein, when applied to a portion of intact skin on an individual for 96 hours and then removed, the device provides the individual with a plasma concentration of the 5-HT 3  receptor antagonist in a therapeutically effective range for period of time from an onset time to 12 hours or more after the device is removed.  
     
     
         19 . The device of  claim 15 , wherein the 5-HT 3  receptor antagonist is in free base form.  
     
     
         20 . A kit comprising the device of  claim 15 , and a dosage form comprising an antiemetically effective amount of a corticosteroid.  
     
     
         21 . The kit of  claim 20 , wherein the dosage form is for oral administration or injection of the corticosteroid.  
     
     
         22 . The kit of  claim 20 , wherein the dosage form is for transdermal administration of the corticosteroid.  
     
     
         23 . A kit comprising the device of  claim 15 , and a dosage form comprising antiemetic agent(s) in forms adapted for oral administration or injection.  
     
     
         24 . The kit of  claim 23 , wherein the agent of the dosage form is a 5-HT 3  receptor antagonist, cannabinoid, NK1 receptor antagonist, dopamine antagonist, corticosteroid, or mixture thereof.  
     
     
         25 . The device of  claim 15 , wherein the 5-HT 3  receptor antagonist is selected from the group consisting of ondansetron, granisetron, tropisetron, dolasetron, hydrodolasetron, azasetron, ramosetron, lerisetron, indisetron, itasetron, palonosetron, lamosetron, allosetron, and mixtures thereof.  
     
     
         26 . The device of  claim 15 , wherein the 5-HT 3  receptor antagonist is granisetron.  
     
     
         27 . The device of  claim 26 , wherein the antiemetically effective amount of granisetron comprises between 0.1% and 15% by weight of the skin-contacting layer.  
     
     
         28 . The device of  claim 15 , wherein the permeation enhancer consists essentially of 15% or less by weight of the skin-contacting layer of a fatty acid ester of fatty acyl chain length C 12 -C 18 , or mixtures thereof.  
     
     
         29 . The device of  claim 15 , wherein the permeation enhancer consists essentially of 15% or less by weight of the skin-contacting layer of isopropyl myristate.  
     
     
         30 . The device of  claim 15 , further comprising packaging presenting labeling describing applying the device to an individual in conjunction with one or both of (a) administration to the individual of a pharmaceutical that creates a risk of emesis or (b) implementing on the individual an operative or other medical procedure that creates a risk of emesis.  
     
     
         31 . The device of  claim 30 , wherein the labeling describes applying the device 30 minutes or more prior to the administration or implementing.  
     
     
         32 . The device of  claim 15 , wherein the device, when applied to a portion of human cadaver skin for 168 hours or more, provides a flux rate of between 1 and 25 μg/cm 2 /hr, the flux rate remaining between 1 and 25 μg/cm 2 /hr for 168 hours or more.  
     
     
         33 . The device of  claim 15 , wherein the device, when applied to a portion of intact skin on an individual for 168 hours, delivers between 10 and 10,000 μg/day of the 5-HT3 receptor antagonist to the individual for each day after an onset period.  
     
     
         34 . The device of  claim 15 , wherein the device, when applied to a portion of intact skin on an individual for a period from 24 hours to 144 hours and then removed, delivers between 10 and 10,000 μg/day of the 5-HT3 receptor antagonist to the individual for each day after an onset period through 12 hours after removal.