blinatumomab: package leaflet

injection that usually contains a total volume of 265 to 275 mL.

to the infusion bag. Gently mix the contents of the bag to avoid foaming. Discard the remaining solution (stabiliser).

into the infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection and the solution (stabiliser). Gently mix the contents of the bag to avoid foaming.
- Refer to table 1 for patients weighing greater than or equal to 45 kg for the specific volume of reconstituted BLINCYTO.
- Refer to table 2 for patients weighing less than 45 kg (dose based on BSA) for the specific volume of reconstituted BLINCYTO.
- Discard the vial containing any unused BLINCYTO reconstituted solution.

infusion pump.

0.2 micron in-line filter. Ensure that the intravenous tubing is compatible with the infusion pump.

prepared BLINCYTO solution for infusion.
7.
Store refrigerated at 2°C - 8°C if not used immediately.

Table 1. For patients weighing greater than or equal to 45 kg: volumes of sodium chloride 9 mg/mL (0.9%) solution for injection, solution (stabiliser), and reconstituted BLINCYTO to add to infusion bag

Sodium chloride 9 mg/mL (0.9%) solution for injection
(starting volume)
250 mL
(usual overfill volume of 265 to 275 mL)
Solution (stabiliser) (fixed volume for 24, 48, 72, and
96-hour infusion durations)
5.5 mL

Infusion duration
Dose
Infusion rate
Reconstituted BLINCYTO
Volume
Vials
24 hours
9 mcg/day
10 mL/hour
0.83 mL
28 mcg/day
10 mL/hour
2.6 mL

48 hours
9 mcg/day
5 mL/hour
1.7 mL
28 mcg/day
5 mL/hour
5.2 mL

72 hours
9 mcg/day
3.3 mL/hour
2.5 mL
28 mcg/day
3.3 mL/hour
8 mL

96 hours
9 mcg/day
2.5 mL/hour
3.3 mL
28 mcg/day
2.5 mL/hour
10.7 mL

Table 2. For patients weighing less than 45 kg: volumes of sodium chloride 9 mg/mL (0.9%) solution for injection, solution (stabiliser), and reconstituted BLINCYTO to add to infusion bag

Sodium chloride 9 mg/mL (0.9%) solution for injection
(starting volume)
250 mL
(usual overfill volume of 265 to
275 mL)
Solution (stabiliser) (fixed volume for 24, 48, 72, and
96-hour infusion durations)
5.5 mL
Infusion duration
Dose
Infusion rate
BSA (m2)*
Reconstituted BLINCYTO
Volume
Vials
24 hours
5 mcg/m2/day
10 mL/hour
1.5 – 1.59
0.7 mL
1.4 – 1.49
0.66 mL
1.3 – 1.39
0.61 mL
1.2 – 1.29
0.56 mL
1.1 – 1.19
0.52 mL
1 – 1.09
0.47 mL
0.9 – 0.99
0.43 mL
0.8 – 0.89
0.38 mL
0.7 – 0.79
0.33 mL
0.6 – 0.69
0.29 mL
0.5 – 0.59
0.24 mL
0.4 – 0.49
0.2 mL

24 hours
15 mcg/m2/day
10 mL/hour
1.5 – 1.59
2.1 mL
1.4 – 1.49
2 mL
1.3 – 1.39
1.8 mL
1.2 – 1.29
1.7 mL
1.1 – 1.19
1.6 mL
1 – 1.09
1.4 mL
0.9 – 0.99
1.3 mL
0.8 – 0.89
1.1 mL
0.7 – 0.79
1 mL
0.6 – 0.69
0.86 mL
0.5 – 0.59
0.72 mL
0.4 – 0.49
0.59 mL

Sodium chloride 9 mg/mL (0.9%) solution for injection
(starting volume)
250 mL
(usual overfill volume of 265 to
275 mL)
Solution (stabiliser) (fixed volume for 24, 48, 72, and
96-hour infusion durations)
5.5 mL
Infusion duration
Dose
Infusion rate
BSA (m2)*
Reconstituted BLINCYTO
Volume
Vials
48 hours
5 mcg/m2/day
5 mL/hour
1.5 – 1.59
1.4 mL
1.4 – 1.49
1.3 mL
1.3 – 1.39
1.2 mL
1.2 – 1.29
1.1 mL
1.1 – 1.19
1 mL
1 – 1.09
0.94 mL
0.9 – 0.99
0.85 mL
0.8 – 0.89
0.76 mL
0.7 – 0.79
0.67 mL
0.6 – 0.69
0.57 mL
0.5 – 0.59
0.48 mL
0.4 – 0.49
0.39 mL

48 hours
15 mcg/m2/day
5 mL/hour
1.5 – 1.59
4.2 mL
1.4 – 1.49
3.9 mL
1.3 – 1.39
3.7 mL
1.2 – 1.29
3.4 mL
1.1 – 1.19
3.1 mL
1 – 1.09
2.8 mL
0.9 – 0.99
2.6 mL
0.8 – 0.89
2.3 mL
0.7 – 0.79
2 mL
0.6 – 0.69
1.7 mL
0.5 – 0.59
1.4 mL
0.4 – 0.49
1.2 mL

Sodium chloride 9 mg/mL (0.9%) solution for injection
(starting volume)
250 mL
(usual overfill volume of 265 to
275 mL)
Solution (stabiliser) (fixed volume for 24, 48, 72, and
96-hour infusion durations)
5.5 mL
Infusion duration
Dose
Infusion rate
BSA (m2)*
Reconstituted BLINCYTO
Volume
Vials
72 hours
5 mcg/m2/day
3.3 mL/hour
1.5 – 1.59
2.1 mL
1.4 – 1.49
2 mL
1.3 – 1.39
1.8 mL
1.2 – 1.29
1.7 mL
1.1 – 1.19
1.6 mL
1 – 1.09
1.4 mL
0.9 – 0.99
1.3 mL
0.8 – 0.89
1.1 mL
0.7 – 0.79
1 mL
0.6 – 0.69
0.86 mL
0.5 – 0.59
0.72 mL
0.4 – 0.49
0.59 mL

72 hours
15 mcg/m2/day
3.3 mL/hour
1.5 – 1.59
6.3 mL
1.4 – 1.49
5.9 mL
1.3 – 1.39
5.5 mL
1.2 – 1.29
5.1 mL
1.1 – 1.19
4.7 mL
1 – 1.09
4.2 mL
0.9 – 0.99
3.8 mL
0.8 – 0.89
3.4 mL
0.7 – 0.79
3 mL
0.6 – 0.69
2.6 mL
0.5 – 0.59
2.2 mL
0.4 – 0.49
1.8 mL

Sodium chloride 9 mg/mL (0.9%) solution for injection
(starting volume)
250 mL
(usual overfill volume of 265 to
275 mL)
Solution (stabiliser) (fixed volume for 24, 48, 72, and
96-hour infusion durations)
5.5 mL
Infusion duration
Dose
Infusion rate
BSA (m2)*
Reconstituted BLINCYTO
Volume
Vials
96 hours
5 mcg/m2/day
2.5 mL/hour
1.5 – 1.59
2.8 mL
1.4 – 1.49
2.6 mL
1.3 – 1.39
2.4 mL
1.2 – 1.29
2.3 mL
1.1 – 1.19
2.1 mL
1 – 1.09
1.9 mL
0.9 – 0.99
1.7 mL
0.8 – 0.89
1.5 mL
0.7 – 0.79
1.3 mL
0.6 – 0.69
1.2 mL
0.5 – 0.59
0.97 mL
0.4 – 0.49
0.78 mL

96 hours
15 mcg/m2/day
2.5 mL/hour
1.5 – 1.59
8.4 mL
1.4 – 1.49
7.9 mL
1.3 – 1.39
7.3 mL
1.2 – 1.29
6.8 mL
1.1 – 1.19
6.2 mL
1 – 1.09
5.7 mL
0.9 – 0.99
5.1 mL
0.8 – 0.89
4.6 mL
0.7 – 0.79
4 mL
0.6 – 0.69
3.4 mL
0.5 – 0.59
2.9 mL
0.4 – 0.49
2.3 mL
BSA = body surface area
*The safety of the administration of BLINCYTO for BSA of less than 0.4 m2 has not been established.

For instructions on administration, see Summary of Product Characteristics, section 4.2.

Method of administration

Important note: Do not flush the BLINCYTO infusion line, especially when changing infusion bags. Flushing when changing bags or at completion of infusion can result in excess dosage and complications thereof. When administering via a multi-lumen venous catheter, BLINCYTO should be infused through a dedicated lumen.

BLINCYTO solution for infusion is administered as a continuous intravenous infusion delivered at a constant flow rate using an infusion pump over a period of up to 96 hours.

The BLINCYTO solution for infusion must be administered using intravenous tubing that contains a sterile, non-pyrogenic, low protein-binding 0.2 micrometre in-line filter.

The infusion bag must be changed at least every 96 hours by a healthcare professional for sterility reasons.

Storage conditions and shelf life

Unopened vials:

5 years (2°C - 8°C)

Reconstituted solution:

Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C - 8°C or 4 hours at or below 27°C.

From a microbiological point of view, unless the method of reconstituting precludes the risks of microbial contamination, the reconstituted solution should be diluted immediately. If not diluted immediately, in-use storage times and conditions are the responsibility of the user.

Diluted solution (prepared infusion bag)

Chemical and physical in-use stability has been demonstrated for 10 days at 2°C - 8°C or 96 hours at or below 27°C.

From a microbiological point of view, the prepared infusion bags 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°C - 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

ANNEX IV

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS
OF THE MARKETING AUTHORISATION(S)

Scientific conclusions

Taking into account the PRAC Assessment Report for the non-interventional imposed PASS final study report for the medicinal product(s) mentioned above, the scientific conclusions of CHMP are as follows:

The MAH has fulfilled the commitment in annex II to present the final results of a non-interventional post-authorisation safety study:

Study number 20150136: An Observational Study of Blinatumomab Safety and Effectiveness, Utilisation, and Treatment Practices.

The study results are in line with the results observed in registrational and other clinical trials. The study also brings data on patients with R/R ALL PH- experiencing late first relapse and upon the assessment of the results, the positive benefit risk ratio in this study population can be confirmed.

Therefore, in view of available data regarding the PASS final study report, the PRAC considered that changes to the product information and the conditions of the marketing authorisation were warranted.

The CHMP agrees with the scientific conclusions made by the PRAC.

Grounds for the variation to the terms of the marketing authorisation(s)

On the basis of the scientific conclusions for the results of the study for the medicinal product(s) mentioned above, the CHMP is of the opinion that the benefit-risk balance of these medicinal product(s) is unchanged, subject to the proposed changes to the product information.

The CHMP is of the opinion that the terms of the marketing authorisation(s) of the medicinal product(s) mentioned above should be varied.