Method of providing pirfenidone therapy to a patient

Abstract

The invention relates to methods for decreasing adverse events associated with pirfenidone (5-methyl-1-phenyl-2-(1H)-pyridone) therapy. The invention discloses an optimized dose escalation scheme that results in the patient having increased tolerance to adverse events associated with the administration of pirfenidone. The invention also discloses a starter pack that may be used in conjunction with the dose escalation scheme.

What is claimed: 
     
         1 . A method of providing pirfenidone therapy to a patient comprising:
 providing a first daily dosage of pirfenidone to the patient in a first amount for the duration of a first period of time;   providing a second daily dosage of pirfenidone to the patient in a second amount for a second period of time; and   providing a third daily dosage of pirfenidone to the patient in a third amount for a third period of time, wherein the first and second periods of time total at least about 7 days.   
     
     
         2 . The method according to  claim 1 , wherein the first amount is in the range of about 400 mg/day to about 1,200 mg/day. 
     
     
         3 . The method according to  claim 2 , wherein the first amount is in the range of about 700 mg/day to about 900 mg/day. 
     
     
         4 . The method according to  claim 3 , wherein the first amount is in the range of about 780 mg/day to about 820 mg/day. 
     
     
         5 . The method according to  claim 4 , wherein the first amount is about 801 mg/day. 
     
     
         6 . The method according to  claim 1 , wherein the second amount is in the range of about 1,200 mg/day to about 2,000 mg/day. 
     
     
         7 . The method according to  claim 6 , wherein the second amount is in the range of about 1,500 mg/day to about 1,700 mg/day. 
     
     
         8 . The method according to  claim 7 , wherein the second amount is in the range of about 1,580 mg/day to about 1,620 mg/day. 
     
     
         9 . The method according to  claim 8 , wherein the second amount is about 1,602 mg/day. 
     
     
         10 . The method according to  claim 1 , wherein the third amount is in the range of about 2,000 mg/day to about 3,000 mg/day. 
     
     
         11 . The method according to  claim 10 , wherein the third amount is in the range of about 2,300 mg/day to about 2,400 mg/day. 
     
     
         12 . The method according to  claim 11 , wherein the third amount is in the range of about 2,380 mg/day to about 2,420 mg/day. 
     
     
         13 . The method according to  claim 12 , wherein the third amount is about 2,403 mg/day. 
     
     
         14 . The method according to  claim 1 , wherein the first period of time is in the range of about 3 days to about 10 days. 
     
     
         15 . The method according to  claim 14 , wherein the first period of time is about 7 days. 
     
     
         16 . The method according to  claim 1 , wherein the second period of time is in the range of about 3 days to about 10 days. 
     
     
         17 . The method according to  claim 16 , wherein the second period of time is about 7 days. 
     
     
         18 . The method according to  claim 1 , wherein the third period of time is at least one day. 
     
     
         19 . The method according to  claim 18 , wherein the third period of time is more than one day. 
     
     
         20 . A method of providing pirfenidone therapy to a patient comprising:
 providing a first daily dosage of pirfenidone to the patient in an amount of 801 mg/day over the course of Day 1 to Day 7;   providing a second daily dosage of pirfenidone to the patient in an amount of 1602 mg/day over the course of Day 8 to Day 14; and   providing a third daily dosage of pirfenidone to the patient in an amount of 2403 mg/day on the beginning of Day 15 and continuing with the 2403 mg/day dosage on each day following Day 15.   
     
     
         21 . The method according to  claim 20 ,
 wherein the patient is administered one capsule comprising 267-mg of pirfenidone three times a day over the course of Day 1 to Day 7;   wherein the patient is administered two capsules comprising 267-mg of pirfenidone three times a day over the course of Day 8 to Day 14; and   wherein the patient is administered three capsules comprising 267-mg of pirfenidone three times a day on Day 15 and each day thereafter where the therapy continues after Day 15.   
     
     
         22 . A starter pack comprising:
 a first set of compartments each having a first dosage amount of pirfenidone according to a first daily or first sub-daily periodic dosage of pirfenidone;and   at least one additional set of compartments each having a dosage amount of pirfenidone that is higher than the first dosage amount of pirfenidone and is according to a higher daily or higher sub-daily periodic dosage of pirfenidone.   
     
     
         23 . The starter pack according to  claim 22 , wherein the starter pack comprises a row for each Day that the first daily periodic dosage is to be taken and for each Day that the higher daily periodic dosage is to be taken and separate columns for each of the first sub-daily periodic dosage to be taken and for each of the higher sub-daily periodic dosage to be taken, and wherein the first out of compartments are arranged within the rows and columns, and wherein the at least one additional set of compartments is arranged within the rows and columns. 
     
     
         24 . The starter pack according to  claim 23 , wherein the first set of compartments and the at least one additional set of compartments each comprise three columns for each Day pirfenidone is to be taken. 
     
     
         25 . The starter pack according to  claim 24 , wherein the starter pack comprises separate rows for Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, and 14. 
     
     
         26 . The starter pack according to  claim 25 , wherein the first set of compartments are for administering the first dosage amount of pirfenidone for Days 1, 2, 3, 4, 5, 6, and 7, and each compartment in the first set of compartments contains one pill of 267-mg pirfenidone. 
     
     
         27 . The starter pack according to  claim 25 , wherein the at least one additional set of compartments comprises a second set of compartments for administering a second dosage amount of pirfenidone higher than the first dosage amount and for Days 8, 9, 10, 11, 12, 13, and 14, and each compartment in the second set of compartments contains two pills of 267-mg pirfenidone. 
     
     
         28 . The starter pack according to  claim 27 , wherein the starter pack comprises separate rows for Days 15, 16, 17, 18, 19, 20, and 21. 
     
     
         29 . The starter pack according to  claim 28 , wherein the at least one additional set of compartments comprises a third set of compartments for administering a third dosage amount of pirfenidone higher than the second dosage amount and for Days 15, 16, 17, 18, 19, 20, and 21, and each compartment in the third set of compartments contains three pills of 267-mg pirfenidone. 
     
     
         30 . The starter pack according to  claim 22 , further comprising a first panel having the first set of compartments and an additional panel for each of the at least one additional set of compartments, each of the first and additional panels containing an equal number of compartments 
     
     
         31 . The starter pack according to  claim 22 , wherein the compartments are blisters. 
     
     
         32 . The starter pack according to  claim 22 , wherein the starter pack comprises at least two panels and at least one fold separating the two panels, and wherein a first panel comprises dosage amount for a first period of time and wherein a second panel comprises dosage amounts for a second period of time. 
     
     
         33 . The starter pack of  claim 22 , further comprising a casing for holding several containers each container comprising a panel bearing one of the first set of compartments or one of the at least one additional set of compartments. 
     
     
         34 . A starter pack comprising:
 an initial dosage amount, a second dosage amount, and a third dosage amount of pirfenidone; and   a plurality of compartments that separate the initial, second, and third dosage amounts according to a daily dosage of pirfenidone,   
       wherein the compartments are formed in columns and in rows; and the compartments are arranged in such a manner that a user of the starter pack is instructed to take the pirfenidone in accordance with the method disclosed by  claim 21 . 
     
     
         35 . A method for administering pirfenidone therapy to a patient, comprising:
 administering a predetermined first daily dosage of pirfenidone to the patient; and   escalating the dosage administered to the patient to a predetermined final daily dosage of pirfenidone, wherein the time of escalation is measured from the initial first dosage and is about 7 to about 20 days.   
     
     
         36 . The method of  claim 35 , wherein the time of escalation is 13 or 14 days. 
     
     
         37 . The method of  claim 36 , wherein the first dosage is about 801 mg/day. 
     
     
         38 . The method of  claim 37 , wherein the final dosage is about 2,403 mg/day. 
     
     
         39 . The method of  claim 38 , wherein each daily dosage is split into three daily oral administrations. 
     
     
         40 . A starter pack comprising:
 a first panel having a plurality of compartments each providing a first daily dosage of pirfenidone for a patient in a first amount for the duration of a first period of time;   a second panel having a plurality of compartments each providing a second daily dosage of pirfenidone for the patient in a second amount for a second period of time; and   a third panel having a plurality of compartments each providing a third daily dosage of pirfenidone for the patient in a third amount for a third period of time, wherein the first and second periods of time each total at least about 7 days.   
     
     
         41 . The starter pack according to  claim 40 , wherein the first daily dosage is in the range of about 700 mg/day to about 900 mg/day. 
     
     
         42 . The starter pack according to  claim 40 , wherein the second daily dosage is in the range of about 1,500 mg/day to about 1,700 mg/day. 
     
     
         43 . The starter pack according to  claim 40 , wherein the third daily dosage is in the range of about 2,300 mg/day to about 2,400 mg/day. 
     
     
         44 . The starter pack according to  claim 40 , wherein the first period of time is in the range of about 3 days to about 10 days. 
     
     
         45 . The starter pack according to  claim 40 , wherein the second period of time is in the range of about 3 days to about 10 days. 
     
     
         46 . The starter pack according to  claim 40 , wherein the third period of time is more than one day.