Pharmaceutical particulars : מידע רוקחי

 6.    PHARMACEUTICAL PARTICULARS

6.1 List of excipients
Sucrose
Sodium citrate (as dihydrate)
Polysorbate 80
Citric acid monohydrate
6.2   Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3   Shelf life

The expiry date of the product is indicated on the packaging materials.
After reconstitution and dilution
The reconstituted solution should be transferred from the vial into the infusion bag immediately.

Chemical and physical in-use stability of the reconstituted and diluted solution has been demonstrated for 24 hours at 2°C - 8°C and protected from light.

From a microbiological point of view, the solution for infusion 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 protected from light. Do not freeze the reconstituted or diluted solution. The solution for infusion may be stored for a maximum of 8 hours of the total 24 hours at 20°C − 25°C and room light. This 8-hour period should be inclusive of the product administration period.

6.4   Special precautions for storage

Store in a refrigerator (2°C - 8°C).
Do not freeze or shake.
Store in the original package in order to protect from light.
For storage conditions after reconstitution or dilution of the medicinal product, see section 6.3.


6.5   Nature and contents of container
20 mL Type I glass vial, closed with a grey butyl stopper and sealed with aluminium crimp seal with a polypropylene flip off button, containing either 300 mg or 400 mg elotuzumab. The flip-off seal button colour is ivory for the 300 mg presentation and blue for the 400 mg presentation.
Pack size of 1 vial.



6.6    Special precautions for disposal and other handling

Calculating the dose
Calculate the dose (mg) and determine the number of vials needed for the dose (10 mg/kg or 20 mg/kg) based on bw. More than one vial of Empliciti may be needed to give the total dose for the patient.

▪      The total elotuzumab dose in mg equals the patient’s bw in kg multiplied by the elotuzumab dose (10 or 20 mg/kg, see section 4.2).

Reconstitution of vials
Aseptically reconstitute each Empliciti vial with a syringe of adequate size and an 18 gauge or smaller needle as shown in Table 12. A slight back pressure may be experienced during administration of the water for injections, which is considered normal.

Table 12: Reconstitution instructions
Strength          Amount of water for               Final volume of                Post-reconstitution injections, required for          reconstituted Empliciti        concentration reconstitution                    in the vial (including volume displaced by the solid cake)
300 mg vial                13.0 mL                       13.6 mL                   25 mg/mL 400 mg vial                17.0 mL                       17.6 mL                   25 mg/mL

Hold the vial upright and swirl the solution by rotating the vial to dissolve the lyophilised cake. Then invert the vial a few times in order to dissolve any powder that may be present on top of the vial or the stopper. Avoid vigorous agitation, DO NOT SHAKE. The lyophilised powder should dissolve in less than 10 minutes.

After the remaining solids are completely dissolved, allow the reconstituted solution to stand for 5 to 10 minutes. The reconstituted solution is colourless to slightly yellow, and clear to very opalescent.
Empliciti should be inspected visually for particulate matter and discolouration prior to administration. Discard the solution if any particulate matter or discolouration is observed.

Preparation of the solution for infusion
The reconstituted solution should be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose injection to obtain a final infusion concentration range between 1 mg/mL and 6 mg/mL. The volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose injection should be adjusted so as to not exceed 5 mL/kg of bw at any given dose of Empliciti.

Calculate the volume (mL) of diluent (either sodium chloride 9 mg/mL (0.9%) solution for injection or 5% glucose injection) needed to make up the solution for infusion for the patient.

Withdraw the necessary volume for the calculated dose from each vial, up to a maximum of 16 mL from 400 mg vial and 12 mL from 300 mg vial. Each vial contains a slight overfill to ensure sufficient extractable volume.



Transfer the withdrawn volumes of all vials needed according to the calculated dose for this patient into one single infusion bag made of polyvinyl chloride or polyolefin containing the calculated volume of diluent. Gently mix the infusion by manual rotation. Do not shake.

Empliciti is for single use only. Discard any unused portion left in the vial.

Administration
The entire Empliciti infusion should be administered with an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (with a pore size of 0.2-1.2 µm) using an automated infusion pump.

Empliciti infusion is compatible with:
▪    PVC and polyolefin containers
▪    PVC infusion sets
▪    polyethersulfone and nylon in-line filters with pore sizes of 0.2 μm to 1.2 μm.

Empliciti should be initiated at an infusion rate of 0.5 mL/min for 10 mg/kg bw dose and 3 mL/min for 20 mg/kg bw dose. If well tolerated, the infusion rate may be increased stepwise as described in Tables 3 and 4 (see section 4.2 Method of administration). The maximum infusion rate should not exceed 5 mL/min.

The Empliciti infusion solution 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 protected from light. Do not freeze the reconstituted or diluted solution.
The solution for infusion may be stored for a maximum of 8 hours of the total 24 hours at 20°C − 25°C and room light. This 8-hour period should be inclusive of the product administration period.

Disposal
Do not store any unused portion of the infusion solution for reuse. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.