Titration of Tapentadol

Abstract

The use of tapentadol for the manufacture of a medicament comprising at least one administration unit A containing dose a of tapentadol and at least one administration unit B containing dose b of tapentadol, where dose a<dose b, for the treatment of pain.

What is claimed is: 
     
         1 . Use of tapentadol for the manufacture of a medicament comprising
 at least one administration unit A containing dose a of tapentadol and   at least one administration unit B containing dose b of tapentadol,   where dose a<dose b,   
       for the treatment of pain. 
     
     
         2 . The use according to  claim 1 , where dose a is within the range of from 10 to 90 wt.-% of dose b. 
     
     
         3 . The use according to  claim 1 , where the medicament further comprises at least one administration unit C containing dose c of tapentadol, where dose b<dose c. 
     
     
         4 . The use according to  claim 3 , where dose a is within the range of from 10 to 65 wt.-% of dose c and where dose b is within the range of from 35 to 90 wt.-% of dose c. 
     
     
         5 . The use according to  claim 1 , where the medicament further comprises at least one administration unit D containing dose d of tapentadol, where dose c<dose d. 
     
     
         6 . The use according to  claim 5 , where dose a is within the range of from 10 to 55 wt.-% of dose d, where dose b is within the range of from 35 to 75 wt.-% of dose d, and where dose c is within the range of from 60 to 95 wt.-% of dose d. 
     
     
         7 . The use according to  claim 5 , where the medicament further comprises at least one administration unit E containing dose e of tapentadol, where dose d<dose e. 
     
     
         8 . The use according to  claim 7 , where dose a is within the range of from 10 to 30 wt.-% of dose e, where dose b is within the range of from 30 to 50 wt.-% of dose e, where dose c is within the range of from 50 to 70 wt.-% of dose e, and where dose d is within the range of from 70 to 90 wt.-% of dose e. 
     
     
         9 . The use according to  claim 1 , where dose a, dose b, optional dose c, optional dose d and optional dose e are each independently within the range of from 10 to 275 mg. 
     
     
         10 . The use according to  claim 1 , where the medicament is in the form of a packaging containing one or more administration units A, one or more administration units B, optionally one or more administration units C, optionally one or more administration units D and optionally one or more administration units E. 
     
     
         11 . The use according to  claim 1 , where administration unit A comprises n A  dosage forms, administration unit B comprises n B  dosage forms, optional administration unit C comprises n C  dosage forms, optional administration unit D comprises n D  dosage forms and optional administration unit E comprises n E  dosage forms, where n A =n B  or n A <n B  or n A >n B . 
     
     
         12 . The use according to  claim 11 , wherein n A ≦n B ≦optional n C ≦optional n D ≦optional n E . 
     
     
         13 . The use according to  claim 11 , wherein all dosage forms are identical and n A <n B <optional n C <optional n D <optional n E . 
     
     
         14 . The use according to  claim 11 , wherein n A , n B , optional n C , optional n D  and optional n E  are independently of one another 1, 2, 3, 4 or 5. 
     
     
         15 . The use according to  claim 1 , wherein administration unit A, administration unit B, optional administration unit C, optional administration unit D and optional administration unit E are adapted to be administered sequentially. 
     
     
         16 . The use according to  claim 15 , where administration unit A, administration unit B, optional administration unit C, optional administration unit D and optional administration unit E are adapted to be administered in alphabetical order. 
     
     
         17 . The use according to  claim 1 , wherein administration unit A, administration unit B, optional administration unit C, optional administration unit D and optional administration unit E are each adapted to be administered once daily (sid), twice daily (bid) or thrice daily (tid). 
     
     
         18 . The use according to  claim 1 , wherein dose a is below the pharmaceutically effective pain treating dose of tapentadol. 
     
     
         19 . The use according to  claim 1 , wherein administration unit A, administration unit B, optional administration unit C, optional administration unit D and optional administration unit E each are solid. 
     
     
         20 . The use according to  claim 1 , wherein the medicament comprises
 (i) a plurality of administration units A containing dose a of tapentadol that are adapted to be administered during a first administration interval of at least 2 days,   (ii) a plurality of administration units B containing dose b of tapentadol that are adapted to be administered during a second administration interval of at least 2 days following the first administration interval,   (iii) optionally, a plurality of administration units C containing dose c of tapentadol that are adapted to be administered during a third administration interval of at least 2 days following the second administration interval,   (iv) optionally, a plurality of administration units D containing dose d of tapentadol that are adapted to be administered during a fourth administration interval of at least 2 days following the third administration interval, and   (v) optionally, a plurality of administration units E containing dose e of tapentadol that are adapted to be administered during a fifth administration interval of at least 2 days following the fourth administration interval.   
     
     
         21 . The use according to  claim 20 , where the medicament comprises
 (i) a plurality of administration units A containing dose a of tapentadol that are adapted to be orally administered twice daily (bid) during a first administration interval of at least α consecutive days,   (ii) a plurality of administration units B containing dose b of tapentadol that are adapted to be orally administered twice daily (bid) during a second administration interval of at least β consecutive days following the first administration interval,   (iii) optionally, a plurality of administration units C containing dose c of tapentadol that are adapted to be orally administered twice daily (bid) during a third administration interval of at least χ consecutive days following the second administration interval,   (iv) optionally, a plurality of administration units D containing dose d of tapentadol that are adapted to be orally administered twice daily (bid) during a fourth administration interval of at least δ consecutive days following the third administration interval, and   (v) optionally, a plurality of administration units E containing dose e of tapentadol that are adapted to be orally administered twice daily (bid) during a fifth administration interval of at least ε consecutive days following the fourth administration interval;   where a, b, c, d, e and α, β, χ, δ, ε satisfy requirement P, Q, R, or S:   
       
         
           
                 
                 
                 
                 
                 
               
                     
                 
                   [mg]/ 
                     
                     
                     
                     
                 
                   [days] 
                   P 
                   Q 
                   R 
                   S 
                 
                     
                 
                   (a/α) 
                    (25 ± 5%/≧2) 
                    (50 ± 5%/≧2) 
                   (100 ± 5%/ 
                   (100 ± 5%/≧2) 
                 
                     
                     
                     
                   ≧2) 
                 
                   (b/β) 
                    (50 ± 5%/≧2) 
                   (100 ± 5%/≧2) 
                   (150 ± 5%/ 
                   (150 ± 5%/≧2) 
                 
                     
                     
                     
                   ≧2) 
                 
                   (c/χ) 
                   (100 ± 5%/≧2) 
                   (150 ± 5%/≧0) 
                   (250 ± 5%/ 
                   (200 ± 5%/≧0) 
                 
                     
                     
                     
                   ≧0) 
                 
                   (d/δ) 
                   (150 ± 5%/≧0) 
                   (200 ± 5%/≧0) 
                     
                   (250 ± 5%/≧0) 
                 
                   (e/ε) 
                   (200 ± 5%/≧0) 
                   (250 ± 5%/≧0) 
                 
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         22 . The use according to  claim 1 , wherein the pain is neuropathic pain, malignant pain or chronic pain. 
     
     
         23 . A kit comprising at least one administration unit A, at least one administration unit B, optionally at least one administration unit C, optionally at least one administration unit D and optionally at least one administration unit E, as defined in  claim 1 . 
     
     
         24 . A pharmaceutical oral dosage form containing tapentadol, which comprises a notch, that divides the dosage form into at least two portions and mechanically weakens the dosage form so that it may be manually broken at the notch along a predetermined site of fracture, which contains 40 to 260 mg of tapentadol so that, after being broken at the notch along the predetermined site of fracture, each portion contains about 20 to about 130 mg of tapentadol. 
     
     
         25 . The dosage form according to  claim 24 , wherein the notch is linear or assumes the shape of a cross. 
     
     
         26 . A method of treating pain in a subject in need thereof, said method comprising administering said subject
 dose a of tapentadol during a first administration interval and   dose b of tapentadol during a second administration interval following the first administration interval,   
       where dose a<dose b. 
     
     
         27 . The method according to  claim 26 , where dose a and dose b of tapentadol are administered orally. 
     
     
         28 . The method according to  claim 26 , wherein dose a and dose b of tapentadol are administered once daily (sid), twice daily (bid) or thrice daily (tid). 
     
     
         29 . The method according to  claim 26 , wherein dose a is within the range of from 10 to 90 wt.-% of dose b. 
     
     
         30 . The method according to  claim 26 , further comprising orally administering dose c of tapentadol once daily (sid), twice daily (bid) or thrice daily (tid) during a third administration interval following the second administration interval, where dose b<dose c. 
     
     
         31 . The method according to  claim 30 , where dose a is within the range of from 10 to 65 wt.-% of dose c and where dose b is within the range of from 35 to 90 wt.-% of dose c. 
     
     
         32 . The method according to  claim 30 , further comprising orally administering dose d of tapentadol once daily (sid), twice daily (bid) or thrice daily (tid) during a fourth administration interval following the third administration interval, where dose c<dose d. 
     
     
         33 . The method according to  claim 32 , where dose a is within the range of from 10 to 55 wt.-% of dose d, where dose b is within the range of from 35 to 75 wt.-% of dose d, and where dose c is within the range of from 60 to 95 wt.-% of dose d. 
     
     
         34 . The method according to  claim 32 , further comprising orally administering dose e of tapentadol once daily (sid), twice daily (bid) or thrice daily (tid) during a fifth administration interval following the fourth administration interval, where dose d<dose e. 
     
     
         35 . The method according to  claim 34 , where dose a is within the range of from 10 to 30 wt.-% of dose e, where dose b is within the range of from 30 to 50 wt.-% of dose e, where dose c is within the range of from 50 to 70 wt.-% of dose e, and where dose d is within the range of from 70 to 90 wt.-% of dose e. 
     
     
         36 . The method according to  claim 26 , wherein dose a, dose b, optional dose c, optional dose d and optional dose e are independently selected so that the daily dose of tapentadol is always within the range of from 20 to 550 mg. 
     
     
         37 . The method according to  claim 26 , comprising orally administering
 (i) dose a of tapentadol twice daily (bid) during a first administration interval of at least α consecutive days,   (ii) dose b of tapentadol twice daily (bid) during a second administration interval of at least β consecutive days following the first administration interval,   (iii) optionally, dose c of tapentadol twice daily (bid) during a third administration interval of at least χ consecutive days following the second administration interval,   (iv) optionally, dose d of tapentadol twice daily (bid) during a fourth administration interval of at least δ consecutive days following the third administration interval, and   (v) optionally, dose e of tapentadol twice daily (bid) during a fifth administration interval of at least ε consecutive days following the fourth administration interval;   where a, b, c, d, e and α, β, χ, δ, ε satisfy requirement P, Q, R, or S:   
       
         
           
                 
                 
                 
                 
                 
               
                     
                 
                   [mg]/ 
                     
                     
                     
                     
                 
                   [days] 
                   P 
                   Q 
                   R 
                   S 
                 
                     
                 
                   (a/α) 
                    (25 ± 5%/≧2) 
                    (50 ± 5%/≧2) 
                   (100 ± 5%/ 
                   (100 ± 5%/≧2) 
                 
                     
                     
                     
                   ≧2) 
                 
                   (b/β) 
                    (50 ± 5%/≧2) 
                   (100 ± 5%/≧2) 
                   (150 ± 5%/ 
                   (150 ± 5%/≧2) 
                 
                     
                     
                     
                   ≧2) 
                 
                   (c/χ) 
                   (100 ± 5%/≧2) 
                   (150 ± 5%/≧0) 
                   (250 ± 5%/ 
                   (200 ± 5%/≧0) 
                 
                     
                     
                     
                   ≧0) 
                 
                   (d/δ) 
                   (150 ± 5%/≧0) 
                   (200 ± 5%/≧0) 
                     
                   (250 ± 5%/≧0) 
                 
                   (e/ε) 
                   (200 ± 5%/≧0) 
                   (250 ± 5%/≧0) 
                 
                     
                 
             
                
                
                
                
               
               
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         38 . The method according to  claim 26 , wherein tapentadol is administered in a regimen including at least 30 consecutive days. 
     
     
         39 . The method according to  claim 38 , wherein at the end of the regimen the administration of tapentadol is terminated without drug tapering.