Pharmaceutical composition containing a compound having a thrombopoietin receptor agonistic activity

Abstract

The present inventor has found out that the following criteria enable to ensure an effect for increasing the platelet count while preventing an excessive increase in the platelet count; “when the platelet count has increased by a certain amount and reached to a sufficient level of the platelet count during administration of a pharmaceutical composition containing a compound having a thrombopoietin receptor agonistic activity, administration of the pharmaceutical composition is discontinued thereafter”.

1 . A pharmaceutical composition for increasing platelets containing a compound having a thrombopoietin receptor agonistic activity, characterized by discontinuing administration of the pharmaceutical composition to a patient at the time point when a platelet count in the patient has increased by 2×10 4 /μL or more from a platelet count before initiation of administration and has reached to 5×10 4 /μL or higher. 
     
     
         2 . The pharmaceutical composition according to  claim 1 , which is administered to a thrombocytopenia patient. 
     
     
         3 . The pharmaceutical composition according to  claim 1 , wherein the platelet count in the patient before initiation of administration of the pharmaceutical composition is less than 5×10 4 /μL. 
     
     
         4 . The pharmaceutical composition according to  claim 2 , wherein the patient is scheduled to undergo invasive procedures. 
     
     
         5 . The pharmaceutical composition according to  claim 4 , wherein the invasive procedures are elective invasive procedures. 
     
     
         6 . The pharmaceutical composition according to  claim 4 , wherein the invasive procedures are radiofrequency ablation. 
     
     
         7 . The pharmaceutical composition according to  claim 6 , wherein the radiofrequency ablation is performed on liver cancer. 
     
     
         8 . The pharmaceutical composition according to  claim 7 , wherein the liver cancer is primary liver cancer. 
     
     
         9 . The pharmaceutical composition according to  claim 1 , wherein the patient has chronic liver disease. 
     
     
         10 . The pharmaceutical composition according to  claim 9 , wherein the chronic liver disease is caused by hepatitis B virus or hepatitis C virus. 
     
     
         11 . The pharmaceutical composition according to  claim 1 , wherein the compound having a thrombopoietin receptor agonistic activity is (E)-3-[2,6-dichloro-4-[4-[3-[(S)-1-hexyloxyethyl]-2-methoxyphenyl]-thiazol-2-ylcarbamoyl]-phenyl]-2-methylacrylic acid or a salt thereof. 
     
     
         12 . The pharmaceutical composition according to  claim 11 , which is orally administered. 
     
     
         13 . The pharmaceutical composition according to  claim 12 , which is administered at 2.0 to 4.0 mg/day as an amount of (E)-3-[2,6-dichloro-4-[4-[3-[(S)-1-hexyloxyethyl]-2-methoxyphenyl]-thiazol-2-ylcarbamoyl]-phenyl]-2-methylacrylic acid or a salt thereof. 
     
     
         14 . The pharmaceutical composition according to  claim 13 , wherein a maximum administration period with once daily administration is 14 days or less. 
     
     
         15 . The pharmaceutical composition according to  claim 1 , for promoting production of platelets before invasive procedures in thrombocytopenic patients with chronic liver disease. 
     
     
         16 . The pharmaceutical composition according to  claim 1 , for promoting production of platelets before elective invasive procedures in thrombocytopenic patients with chronic liver disease. 
     
     
         17 . The pharmaceutical composition according to  claim 1 , for promoting production of platelets before local therapy for primary liver cancer. 
     
     
         18 . The pharmaceutical composition according to  claim 1 , for promoting production of platelets before radiofrequency ablation for primary liver cancer. 
     
     
         19 . The pharmaceutical composition according to  claim 1 , for promoting production of platelets before various minimally invasive procedures in thrombocytopenic patients with chronic liver disease. 
     
     
         20 . A method for increasing platelets comprising the steps of:
 administering a pharmaceutical composition containing a compound having a thrombopoietin receptor agonistic activity to a patient; and   discontinuing administration at the time point when a platelet count in the patient has increased by 2×10 4 /μL or more from a platelet count before initiation of administration and has reached to 5×10 4 /μL or higher.   
     
     
         21 . A compound having a thrombopoietin receptor agonistic activity for use in increasing platelets, characterized by discontinuing administration of the compound to a patient at the time point when a platelet count in the patient has increased by 2×10 4 /μL or more from a platelet count before initiation of administration and has reached to 5×10 4 /μL or higher. 
     
     
         22 . Use of a compound having a thrombopoietin receptor agonistic activity for manufacturing a medicament for increasing platelets, characterized by discontinuing administration of the medicament to a patient at the time point when a platelet count in the patient has increased by 2×10 4 /μL or more from a platelet count before initiation of administration and has reached to 5×10 4 /μL or higher.