Low Dose Topiramate / Phentermine Composition and Methods of Use Thereof

Abstract

A method for effecting weight loss by administering a combination of topiramate and phentermine is provided. The phentermine is generally administered in immediate release form, in a daily dose in the range of 2 mg to 8 mg, in combination with a daily dose of topiramate selected to prevent the loss of effectiveness of phentermine alone. Methods for treating obesity, conditions associated with obesity, and other indications are also provided, as are compositions and dosage forms containing low doses of phentermine and topiramate, e.g., 3.75 mg phentermine and 23 mg topiramate.

1 . A method for effecting weight loss in a subject, comprising administering to the subject continually over a significant period of time a daily dose of phentermine in the range of 2 mg to 8 mg and in combination therewith a daily dose of topiramate selected to prevent the loss of effectiveness of phentermine alone. 
     
     
         2 . The method of  claim 1 , wherein the daily dose of phentermine is in the range of 2 mg to 5 mg. 
     
     
         3 . The method of  claim 1  or  claim 2 , wherein the dose of topiramate is in the range of 15 mg to 50 mg. 
     
     
         4 . The method of  claim 3 , wherein the dose of topiramate is in the range of 15 mg to 25 mg. 
     
     
         5 . The method of  claim 4 , wherein the dose of topiramate is in the range of 17 mg to 23 mg. 
     
     
         6 . A method for effecting weight loss in a subject, comprising administering to the subject, on a daily basis, 3.75 mg phentermine and 23 mg topiramate. 
     
     
         7 . A method for effecting weight loss in a subject, comprising administering to the subject, on a daily basis, 7.5 mg phentermine and 46 mg topiramate. 
     
     
         8 . The method of any one of  claims 1 ,  6 , and  7 , wherein the phentermine and the topiramate are administered orally. 
     
     
         9 . The method of  claim 8 , wherein the phentermine and the topiramate are administered at different times of day. 
     
     
         10 . The method of  claim 9 , wherein the phentermine is administered in the morning and the topiramate is administered in the afternoon or evening. 
     
     
         11 . The method of any one of  claims 1 ,  6 , and  7 , wherein the phentermine and the topiramate are administered simultaneously. 
     
     
         12 . The method of  claim 11 , wherein the phentermine and topiramate are administered in a single dosage form. 
     
     
         13 . The method of  claim 12 , wherein the dosage form provides for immediate release of the phentermine and controlled release of the topiramate. 
     
     
         14 . The method of  claim 13 , wherein the dosage form provides for delayed release of topiramate. 
     
     
         15 . The method of  claim 13 , wherein the dosage form further provides for sustained release of topiramate. 
     
     
         16 . The method of  claim 15 , wherein the dosage form provides for a substantially constant blood level of topiramate over a time period in the range of about 4 to about 12 hours. 
     
     
         17 . The method of  claim 16 , wherein the time period is in the range of about 6 to about 10 hours. 
     
     
         18 . The method of  claim 13 , wherein the dosage form provides for a maximum plasma concentration (T max ) of topiramate in the range of about 6 to about 10 hours. 
     
     
         19 . The method of  claim 13 , wherein the topiramate is contained within a controlled release polymeric core, and the phentermine is provided as an immediate release coating on the core. 
     
     
         20 . The method of  claim 13 , wherein the dosage form comprises a plurality of coated cores in a capsule. 
     
     
         21 . The method of  claim 13 , wherein the dosage form comprises a tablet. 
     
     
         22 . The method of  claim 13 , wherein the tablet comprises at least two discrete segments, at least one of which contains phentermine in immediate release form, and at least another of which contains topiramate in controlled release form. 
     
     
         23 . The method of  claim 1 , wherein the subject is human. 
     
     
         24 . The method of  claim 1 , wherein the subject is overweight. 
     
     
         25 . The method of  claim 24 , wherein the subject is obese. 
     
     
         26 . The method of  claim 25 , wherein the method further comprises simultaneously treating a condition associated with excess weight or obesity. 
     
     
         27 . The method of  claim 26 , wherein the condition is Syndrome X. 
     
     
         28 . The method of  claim 26 , wherein the condition is hypertension. 
     
     
         29 . The method of  claim 26 , wherein the condition is diabetes. 
     
     
         30 . The method of  claim 26 , wherein the condition is a respiratory disorder. 
     
     
         31 . The method of  claim 30 , wherein the respiratory disorder is asthma. 
     
     
         32 . The method or  claim 30 , wherein the respiratory disorder is pulmonary hypertension. 
     
     
         33 . The method of  claim 26 , wherein the condition is migraine headache. 
     
     
         34 . The method of  claim 26 , wherein the condition is sleep apnea. 
     
     
         35 . The method of  claim 26 , wherein the condition is dyslipidemia.