o 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.
6. Pharmaceutical particulars
6.1 List of excipients
Prograf 0.5 mg hard capsules
Capsule content:
Hypromellose
Croscarmellose sodium
Lactose monohydrate
Magnesium stearate
Capsule shell:
Titanium dioxide (E 171)
Yellow iron oxide (E 172)
Gelatine
Printing ink of capsule shell: Shellac, lecithin (soya), hydroxypropyl cellulose, simeticone, red iron oxide (E 172).
Prograf 1 mg hard capsules
Capsule content:
Hypromellose
Croscarmellose sodium
Lactose monohydrate
Magnesium stearate
Capsule shell:
Titanium dioxide (E 171)
Gelatine
Printing ink of capsule shell: Shellac, lecithin (soya), hydroxypropyl cellulose, simeticone, red iron oxide (E 172).
Prograf 5 mg hard capsules
Capsule content:
Hypromellose
Croscarmellose sodium
Lactose monohydrate
Magnesium stearate
Capsule shell:
Titanium dioxide (E 171)
Red iron oxide (E 172)
Gelatine
Printing ink of capsule shell: Shellac, titanium dioxide (E 171) and propylene glycol.
6.2 Incompatibilities
Tacrolimus is not compatible with PVC. Tubing, syringes and other equipment used to prepare or administer a suspension of Prograf capsule contents should not contain PVC.
6.3 Shelf life
3 years
After opening the aluminium wrapper: 1 year
6.4 Special precautions for storage
This medicinal product does not require any special temperature storage conditions.
Store in the original package in order to protect from moisture.
Hard capsules should be taken immediately following removal from the blister.
6.5 Nature and contents of container
PVC/PVDC/Aluminium blisters or PVC/PVDC/Aluminium perforated unit-dose blisters. Ten capsules per blister. Two, three, five, six, nine or ten blisters with a desiccant in an aluminium wrapper.
Prograf 0.5 mg hard capsules
Packs of 20, 30, 50, 60 and 100 hard capsules in blisters.
Packs of 20x1, 30x1, 50x1, 60x1 and 100x1 hard capsules in perforated unit-dose blisters.
Prograf 1 mg hard capsules
Packs of 20, 30, 50, 60, 90 and 100 hard capsules in blisters.
Packs of 20x1, 30x1, 50x1, 60x1, 90x1 and 100x1 hard capsules in perforated unit-dose blisters.
Prograf 5 mg hard capsules
Packs of 30, 50, 60 and 100 hard capsules in blisters.
Packs of 30x1, 50x1, 60x1 and 100x1 hard capsules in perforated unit-dose blisters.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and o
