2 years
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless the dilution has taken place in controlled and validated aseptic conditions.
Tacrolimus is absorbed by PVC plastics. Tubing, syringes and any other equipment used to prepare and administer Prograf 5 mg/ml concentrate for solution for infusion should not contain PVC.
Tacrolimus is unstable under alkaline conditions. Combination of the reconstituted Prograf 5 mg/ml concentrate for solution for infusion with other pharmaceutical products that produce a marked alkaline solution (e.g. aciclovir and ganciclovir) should be avoided.
Polyoxyethylene hydrogenated castor oil
Dehydrated alcohol
The kidneys and the pancreas were the primary organs affected in toxicity studies performed in rats and baboons. In rats, tacrolimus caused toxic effects to the nervous system and the eyes. Reversible cardiotoxic effects were observed in rabbits following intravenous administration of tacrolimus. When tacrolimus is administered intravenously as rapid infusion/bolus injection at a dose of 0.1 to 1.0 mg/kg, QTc prolongation has been observed in some animal species. Peak blood concentrations achieved with these doses were above 150 ng/mL which is more than 6-fold higher than mean peak concentrations observed with Prograf in clinical transplantation.
Embryofoetal toxicity was observed in rats and rabbits and was limited to doses that caused significant toxicity in maternal animals. In rats, female reproductive function including birth was impaired at toxic dosages and the offspring showed reduced birth weights, viability and growth.
A negative effect of tacrolimus on male fertility in the form of reduced sperm counts and motility was observed in rats.
25 June 2015
Astellas Pharma Ltd.
2000 Hillswood Drive
Chertsey
Surrey
KT16 0RS
United Kingdom
1 ml concentrate for solution for infusion in 2 ml, type I Ph. Eur. clear colourless glass ampoules.
Each carton contains 10 ampoules.
PL 00166/0205
Prograf 5 mg/ml concentrate for solution for infusion must not be injected undiluted.
Prograf 5 mg/ml concentrate for solution for infusion should be diluted in 5 % w/v glucose solution or physiological saline solution in polyethylene, polypropylene or glass bottles, but not in PVC containers. Only transparent and colourless solutions should be used.
The concentration of a solution for infusion should be within the range 0.004 - 0.100 mg/ml. The total volume of infusion during a 24-hour period should be in the range 20 - 500 ml.
The diluted solution should not be given as a bolus.
Any unused concentrate in an opened ampoule or unused reconstituted solution should be disposed of immediately in accordance with local requirements to avoid contamination.
Date of first authorisation: 7 June 1994
Date of last renewal: 27 November 2007
