ll 95% confidence intervals for the differences were within ±10 percentage points, indicating in particular non-inferiority of the low to the high radioiodine dose. Analyses of T3 patients and N1 patients showed that these subgroups had equally good ablation success rates as did lower-risk patients. The ESTIMABL study randomised 752 patients with low-risk thyroid cancer (tumour stages pT1 < 1 cm and N1 or Nx, pT1 >1-2 cm and any N stage, or pT2 N0, all patients M0) at 24 centres. Based on 684 eva luable patients, the overall ablation success rate assessed by neck ultrasounds and stimulated Tg levels was 92%, without any statistically significant difference among the four groups. Considering the design of each of these two studies, it should be noted that long term data (beyond approximately 9 months) in relation to use of the lower dose of radioiodine are not yet available. In summary, these studies suggest that low dose radioiodine plus thyrotropin alpha is an effective treatment (with reduced radiation exposure) and Thyrogen was non-inferior to thyroid hormone withdrawal for pre-therapeutic stimulation in combination with radioiodine for post-surgical ablation of thyroid remnant tissue.
5.2 Pharmacokinetic properties
The pharmacokinetics of Thyrogen were studied in patients with well-differentiated thyroid cancer following a single 0.9 mg intramuscular injection. After injection, the mean peak (Cmax) level obtained was 116 ± 38 mU/l and occurred approximately 13 ± 8 hours after administration. The elimination half-life was 22 ± 9 hours. The major elimination route of thyrotropin alfa is believed to be renal and to a lesser extent hepatic.
5.3 Preclinical safety data
Non-clinical data are limited, but reveal no special hazard for humans from use of Thyrogen.
6. Pharmaceutical particulars
6.1 List of excipients
Mannitol
Sodium phosphate monobasic, monohydrate
Sodium phosphate dibasic, heptahydrate
Sodium chloride
6.2 Incompatibilities
In the absence of compatibility studies, Thyrogen should not be administered as a mixture with other medicinal products in the same injection.
6.3 Shelf life
Unopened vials
3 years.
Shelf-life after reconstitution
It is recommended that the Thyrogen solution be injected within three hours.
The reconstituted solution can be stored for up to 24 hours in a refrigerator (2°C - 8°C) under protection from light, while avoiding microbial contamination.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C).
Keep the vial in the outer carton in order to protect from light.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5 Nature and contents of container
Clear Type I glass 5 ml vials. The closure consists of a siliconised butyl stopper with a tamper proof flip-off cap. Each vial contains 1.1 mg thyrotropin alfa. After reconstitution with 1.2 ml water for injection, 1.0 ml of solution (equal to 0.9 mg Thyrogen) is withdrawn and administered to the patient.
To provide sufficient volume to allow accurate dispensing, each vial of Thyrogen is formulated to contain an overfill of 0.2 ml.
Package size: one and two vials of Thyrogen per carton.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
The powder for solution for injection has to be reconstituted with water for injection. Only one vial of Thyrogen is r |
