Method for treating a patient at risk for developing an nsaid-associated ulcer

Abstract

The present disclosure is directed to a method for treating a disease or disorder in a patient at risk of developing an NSAID-associated ulcer by administering to said patient in need thereof a pharmaceutical composition in unit dose form comprising naproxen, or pharmaceutically acceptable salt thereof, and esomeprazole, or pharmaceutically acceptable salt thereof to said at risk patient and thereby decreasing the patient's risk of developing an ulcer.

1 - 61 . (canceled) 
     
     
         62 . A method of treating a disease or disorder in a patient in need thereof comprising administering to the patient an NSAID and a proton pump inhibitor concomitant with administration of low dose aspirin,
 wherein the NSAID and proton pump inhibitor comprise a unit dosage form that provides:
 a) 20 mg of esomeprazole, or pharmaceutically acceptable salt thereof, in a form and route sufficient to raise the gastric pH of the patient to at least 3.5 upon administration of one or more of the dosage forms, 
 b) 500 mg of naproxen, or pharmaceutically acceptable salt thereof; 
 c) a coordinated release of the esomeprazole and the naproxen, and 
 d) release of at least a portion of the esomeprazole, or pharmaceutically acceptable salt thereof, independent of the pH of the surrounding medium; 
   wherein concomitant administration of the dosage form and low dose aspirin reduces the incidence of NSAID-associated gastric ulcers in the patient relative to administration of the dosage form without concomitant administration of low dose aspirin.   
     
     
         63 . The method of  claim 62 , wherein the dosage form releases less than 10% of the naproxen or a pharmaceutically acceptable salt thereof after 2 hours when tested using the USP Paddle Method in 1000 ml of 0.1N HCl at 75 rpm at 37° C. and ±0.5° C. 
     
     
         64 . The method of  claim 62 , wherein the disease or disorder is selected from inflammation and pain. 
     
     
         65 . The method of  claim 62 , wherein the disease or disorder is selected from osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and a combination thereof. 
     
     
         66 . The method of  claim 62 , wherein the low dose aspirin comprises no more than 325 mg aspirin. 
     
     
         67 . The method of  claim 62 , wherein the dosage form is administered once a day. 
     
     
         68 . The method of  claim 62 , wherein the dosage form is administered twice a day. 
     
     
         69 . The method of  claim 62 , wherein the dosage form is at least about 95% free of sodium bicarbonate. 
     
     
         70 . The method of  claim 62 , wherein the dosage form begins to release the naproxen, or a pharmaceutically acceptable salt thereof, when the pH of the surrounding medium is at about 4.5 or greater. 
     
     
         71 . The method of  claim 62 , wherein the dosage form begins to release the naproxen, or a pharmaceutically acceptable salt thereof, when the pH of the surrounding medium is at about 4.0 or greater. 
     
     
         72 . The method of  claim 62 , wherein administration of the dosage form is more effective at reducing the incidence of NSAID-associated gastric ulcer than treatment with enteric coated naproxen or a pharmaceutically acceptable salt thereof. 
     
     
         73 . The method of  claim 62 , wherein the dosage form is administered to the patient daily for at least about a month. 
     
     
         74 . The method of  claim 62 , wherein the dosage form is administered to the patient daily for at least about three months. 
     
     
         75 . The method according to  claim 62 , wherein the pharmaceutical composition in dosage form is administered to the patient daily for at least about 6 months. 
     
     
         76 . A method of treating a disease or disorder in a patient in need thereof comprising administering to the patient an NSAID and a proton pump inhibitor concomitant with administration of low dose aspirin.
 wherein the NSAID and proton pump inhibitor comprise a unit dosage form in the form of a tablet that provides:
 a) 20 mg of esomeprazole, or pharmaceutically acceptable salt thereof, in a form and route sufficient to raise the gastric pH of the patient to at least 3.5 upon administration of one or more of the dosage forms, 
 b) 500 mg of naproxen, or pharmaceutically acceptable salt thereof; 
 c) release of at least a portion of the esomeprazole, or pharmaceutically acceptable salt thereof, independent of the pH of the surrounding medium; and 
 d) release of at least a portion of the naproxen, or pharmaceutically acceptable salt thereof, when the pH of the surrounding medium is at about 3.5 or greater; 
   wherein concomitant administration of the dosage form and low dose aspirin reduces the incidence of NSAID-associated gastric ulcers in the patient relative to administration of the dosage form without concomitant administration of low dose aspirin.   
     
     
         77 . The method of  claim 76 , wherein the dosage form releases less than 10% of the naproxen or a pharmaceutically acceptable salt thereof after 2 hours when tested using the USP Paddle Method in 1000 ml of 0.1N HCl at 75 rpm at 37° C. and ±0.5° C. 
     
     
         78 . The method of  claim 76 , wherein the disease or disorder is selected from inflammation and pain. 
     
     
         79 . The method of  claim 76 , wherein the disease or disorder is selected from osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and a combination thereof. 
     
     
         80 . The method of  claim 76 , wherein the low dose aspirin comprises no more than 325 mg aspirin. 
     
     
         81 . The method of  claim 76 , wherein the dosage form is administered once a day. 
     
     
         82 . The method of  claim 76 , wherein the dosage form is administered twice a day. 
     
     
         83 . The method of  claim 76 , wherein the dosage form is at least about 95% free of sodium bicarbonate. 
     
     
         84 . The method of  claim 76 , wherein the dosage form begins to release the naproxen, or a pharmaceutically acceptable salt thereof, when the pH of the surrounding medium is at about 4.5 or greater. 
     
     
         85 . The method of  claim 76 , wherein the dosage form begins to release the naproxen, or a pharmaceutically acceptable salt thereof, when the pH of the surrounding medium is at about 4.0 or greater. 
     
     
         86 . The method of  claim 76 , wherein administration of the dosage form is more effective at reducing the incidence of NSAID-associated gastric ulcer than treatment with enteric coated naproxen or a pharmaceutically acceptable salt thereof. 
     
     
         87 . The method of  claim 76 , wherein the dosage form is administered to the patient daily for at least about a month. 
     
     
         88 . The method of  claim 76 , wherein the dosage form is administered to the patient daily for at least about three months. 
     
     
         89 . The method according to  claim 76 , wherein the pharmaceutical composition in dosage form is administered to the patient daily for at least about 6 months.