Perfusion dosage form

Abstract

The present invention relates to a method for enabling hospitals or clinics to administer a dose of a drug to patients in need thereof while avoiding steps of manipulation, dilution, reconstitution, dispensing, sterilization, transfer, handling or compounding before intravenous administration. The present invention further relates to a perfusion system comprising different sets of perfusion containers, each container comprising a ready-to-infuse, stable, sterile, aqueous perfusion solution of a drug, wherein the set of perfusion containers alone or in combination provides for direct intravenous administration of a desired dose of the drug to a patient in need thereof, such that the delivered dose is equal to or within ±5% of the calculated dose.

1 . A method for enabling hospitals or clinics to administer a dose of a drug to patients in need thereof while avoiding steps of manipulation, dilution, reconstitution, dispensing, sterilization, transfer, handling or compounding before intravenous administration, the method comprising:
 (a) manufacturing a first set of perfusion containers containing a ready-to-infuse, stable, sterile, aqueous perfusion solution of the drug at a first higher concentration, and a second set of top-up perfusion containers containing a ready-to-infuse, stable, sterile, aqueous perfusion solution of the drug at a second concentration and optionally a third set of top-up perfusion containers having a ready-to-infuse, stable, sterile, aqueous perfusion solution of the drug at a third concentration, the first concentration of drug being higher than the second and third concentrations, the containers within each set of perfusion containers ranging in volume from a lower to a higher volume,   (b) calculating the dose to be administered to patients according to at least one patient parameter and providing instructions for selecting one or more perfusion container(s) from the first set and if required one or more top-up perfusion container(s) from the second or third set and for directly administering the drug from the selected perfusion containers such that the delivered dose is equal to or within ±5% of the calculated dose,   (c) supplying to the distributors or hospitals or clinics, the first set of perfusion containers and second or third set of top-up containers along with the instructions.   
     
     
         2 . The method as claimed in  claim 1 , wherein the drug is selected from irinotecan, topotecan, pemetrexed, docetaxel, paclitaxel, gemcitabine, cisplatin, oxaliplatin, carboplatin, leukovorin, etoposide, doxorubicin, daunonibicin, epirubicin, idarubicin, vincristine, vinblastine, vinorelbine, 5-fluorouracil, ifosfamide, cyclophosphamide, mechlorethamine, carmustine, dacarbazine, cladribine, fulvestrant, pegfilgrastim, pamidronate, mitoxantrone, streptozocin, mitomycin, gentamicin, teniposide, vancomycin, methicillin, daptomycin, tobramycin, amikacin, midazolam, propofol, fentanyl, remifentanil, rocuronium, vecuronium, atracurium, voriconazole or acyclovir. 
     
     
         3 . The method as claimed in  claim 1 , wherein drug is irinotecan or its pharmaceutically acceptable salt. 
     
     
         4 . The method as claimed in  claim 3 , wherein irinotecan or its pharmaceutically acceptable salt is irinotecan hydrochloride and wherein the ready-to-infuse, stable, sterile, aqueous perfusion solution of irinotecan hydrochloride has a pH ranging from about 3.0 to 4.5, and wherein irinotecan hydrochloride is present in the first set of infusion containers at concentration ranging from about 1.0 mg/ml to 3.0 mg/ml and in the second or third set of infusion containers at a concentration ranging from about 0.1 mg/ml to 0.6 mg/ml. 
     
     
         5 . The method as claimed in  claim 4 , wherein irinotecan hydrochloride is present in the first set of infusion containers at a concentration of 1.5 mg/ml and at a volume ranging from about 50 ml to about 300 ml, in the second set of infusion containers at a concentration of 0.4 mg/ml and at a volume ranging from about 10 ml to about 100 ml and in the third set of infusion containers at a concentration of 0.2 mg/ml and at a volume ranging from about 10 ml to about 100 ml. 
     
     
         6 . The method as claimed in  claim 1 , wherein the perfusion containers filled with the aqueous solution of drug are terminally sterilized. 
     
     
         7 . The method as claimed in  claim 1 , wherein the perfusion containers are packaged in a secondary packaging, comprising an overwrap pouch and an oxygen scavenger in between the perfusion container and the pouch. 
     
     
         8 . The method as claimed in  claim 7 , wherein at least one of perfusion container or the secondary packaging is designed to protect the solution of drug from light. 
     
     
         9 . The method as claimed in  claim 4 , wherein the ready-to-infuse, stable, sterile, aqueous perfusion solution of irinotecan hydrochloride comprises an osmotic agent in an amount sufficient to make the solution isoosmolar and a pH adjusting agent or a buffer to adjust and maintain the pH in the range of 3.0 to 4.5. 
     
     
         10 . A perfusion system comprising:
 a first set of perfusion containers comprising a ready-to-infuse, stable, sterile, aqueous perfusion solution of a drug at a first higher concentration, and a second set of top-up perfusion containers comprising a ready-to-infuse, stable, sterile, aqueous perfusion solution of the drug at a second concentration and optionally a third set of top-up perfusion containers comprising a ready-to-infuse, stable, sterile, aqueous perfusion solution of the drug at a third concentration, the first concentration of drug being higher than the second and third concentrations, the first to the third sets of perfusion containers ranging in volume from a higher volume to a lower volume,   instructions for selecting one or more perfusion container(s) from the first set and if required one or more top-up perfusion container(s) from the second or third set and for directly administering the drug from the selected perfusion containers such that the delivered dose is equal to or within ±5% of a dose calculated according to at least one patient parameter,   wherein the set of perfusion containers alone or in combination provides for direct intravenous administration of a desired dose of the drug to a patient in need thereof, such that the delivered dose is equal to or within ±5% of the calculated dose.