Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Mannitol (E421)
Sucrose
L-histidine
Hydrochloric acid (for pH adjustment)
Polysorbate 20

6.2   Incompatibilities
This medicinal product must not be mixed with other medicinal products, except those mentioned in section 6.6.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
After reconstitution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C and for 24 hours at 2°C – 8°C, when protected from light and kept in the original vial.

From a microbiological point of view, the medicinal 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 25°C or 24 hours in a refrigerator (2°C – 8°C), protected from light.

After dilution: Chemical and physical in-use stability has been demonstrated for 4 hours at 25°C when the diluted product was held in a disposable syringe, or 4 hours in a refrigerator
(2°C – 8°C) when the diluted product was held in the original vial.

From a microbiological point of view, the diluted medicinal 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 4 hours at 25°C in disposable syringes, or 4 hours in a refrigerator (2°C – 8°C) in the original vials, protected from light.


6.4   Special precautions for storage
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Store in the original carton in order to protect from light.
May be removed from the refrigerator for a period of 30 days at room temperature (up to 25°C) when stored in the original carton.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5   Nature and contents of container

5 mL single-dose vial (type 1 clear glass) with a stopper (chlorobutyl rubber), seal (aluminum) and a flip-off cap (polypropylene).

Carton containing 1 vial of romiplostim.

6.6   Special precautions for disposal and other handling
Reconstitution

Nplate is a sterile but unpreserved medicinal product and is intended for single-use only.
Nplate should be reconstituted in accordance with good aseptic practice.

Nplate 250 micrograms powder for solution for injection
Nplate 250 micrograms powder for solution for injection should be reconstituted with 0.72 mL sterile water for injections, yielding a deliverable volume of 0.5 mL. An additional overfill is included in each vial to ensure that 250 mcg of romiplostim can be delivered (see vial content table below).

Vial Content:

Nplate           Total vial         Volume of              Deliverable         Final single-use       content of         sterile water          product and         concentration vial             romiplostim        for injections         volume
250 mcg          375 mcg          + 0.72 mL              = 250 mcg in          500 mcg/mL
0.50 mL

Sterile water for injections only should be used when reconstituting the medicinal product.
Sodium chloride solutions or bacteriostatic water should not be used when reconstituting the medicinal product.

Water for injections should be injected into the vial. The vial contents may be swirled gently and inverted during dissolution. The vial should not be shaken or vigorously agitated.
Generally, dissolution of Nplate takes less than 2 minutes. Visually inspect the solution for particulate matter and discoloration before administration. The reconstituted solution should be clear and colorless and should not be administered if particulate matter and/or discoloration are observed.

For the storage condition after reconstitution of the medicinal product, see section 6.3.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Dilution (required when the calculated individual patient dose is less than 23 mcg) 
Initial reconstitution of romiplostim with designated volumes of sterile water for injections results in a concentration of 500 mcg/mL in all vial sizes. If the calculated individual patient dose is less than 23 mcg (see section 4.2), an additional dilution step to 125 mcg/mL with preservative-free, sterile, sodium chloride 9 mg/mL (0.9%) solution for injection is required to ensure accurate volume (see table below).

Dilution Guidelines:

Nplate single-use vial      Add this volume of preservative-free,       Concentration after sterile, sodium chloride 9 mg/mL            dilution
(0.9%) solution for injection to the reconstituted vial
250 mcg                     2.25 mL                                     125 mcg/mL

Preservative-free, sterile, sodium chloride 9 mg/mL (0.9%) solution for injection only must be used for dilution. Dextrose (5%) in water or sterile water for injections should not be used for the dilution.

No other diluents have been tested.

For the storage condition after dilution of the reconstituted medicinal product, see section 6.3.

7.    MARKETING AUTHORIZATION HOLDER

Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands