Pharmaceutical particulars : מידע רוקחי

6.    PHARMACEUTICAL PARTICULARS
6.1   List of excipients

Sucrose
Sodium citrate dihydrate
Polysorbate
Citric acid monohydrate

6.2   Incompatibilities

Benlysta is not compatible with 5 % glucose.

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

6.3   Shelf life

Unopened vials
The expiry date of the product is indicated on the label and packaging.
Reconstituted solution
After reconstitution with water for injections, the reconstituted solution, if not used immediately, should be protected from direct sunlight, and stored refrigerated at 2°C to 8 °C.

Reconstituted and diluted solution for infusion
Solution of Benlysta diluted in sodium chloride 9 mg/mL (0.9 %), sodium chloride 4.5 mg/mL (0.45 %), or Lactated Ringer’s solution for injection may be stored at 2 °C to 8 °C or room temperature (15 °C to 25 °C).

The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours.

6.4   Special precautions for storage
Store in a refrigerator (2 °C to 8 °C).
Do not freeze.
Store in the original carton in order to protect from light.

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

6.5   Nature and contents of container

Benlysta I.V. 120 mg:
Type 1 glass vials (5 mL), sealed with a siliconised chlorobutyl rubber stopper and a flip-off aluminium seal containing 120 mg of powder.

Pack size: 1 vial

Benlysta I.V. 400 mg:
Type 1 glass vials (20 mL), sealed with a siliconised chlorobutyl rubber stopper and a flip-off aluminium seal containing 400 mg of powder.

Pack size: 1 vial

6.6   Special precautions for disposal and other handling

Preparation of 120 mg solution for infusion

Reconstitution
Reconstitution and dilution must be carried out under aseptic conditions.

Allow 10 to 15 minutes for the vial to warm to room temperature (15°C to 25°C).

It is recommended that a 21-25 gauge needle be used when piercing the vial stopper for reconstitution and dilution.

The 120 mg single-use vial of belimumab is reconstituted with 1.5 mL of water for injections to yield a final concentration of 80 mg/mL belimumab.

The stream of water for injections should be directed toward the side of the vial to minimize foaming. Gently swirl the vial for 60 seconds. Allow the vial to sit at room temperature (15°C to 25°C) during reconstitution, gently swirling the vial for 60 seconds every 5 minutes until the powder is dissolved. Do not shake.
Reconstitution is typically complete within 10 to 15 minutes after the water has been added, but it may take up to 30 minutes.

Protect the reconstituted solution from sunlight.

If a mechanical reconstitution device is used to reconstitute Benlysta it should not exceed 500 rpm and the vial should be swirled for no longer than 30 minutes.

Once reconstitution is complete, the solution should be opalescent and colourless to pale yellow and without particles. Small air bubbles, however, are expected and acceptable.

After reconstitution a volume of 1.5 mL (corresponding to 120 mg belimumab) can be withdrawn from each vial.


Dilution
The reconstituted medicinal product is diluted to 250 mL with sodium chloride 9 mg/mL (0.9 %), sodium chloride 4.5 mg/mL (0.45 %), or Lactated Ringer’s solution for injection. For patients whose body weight is less than or equal to 40 kg, infusion bags with 100 mL of these diluents may be considered providing that the resulting belimumab concentration in the infusion bag does not exceed 4 mg/mL.

5 % glucose intravenous solutions are incompatible with Benlysta and must not be used.
From a 250 mL (or 100 mL) infusion bag or bottle of sodium chloride 9 mg/mL (0.9 %) , sodium chloride 4.5 mg/mL (0.45 %), or Lactated Ringer’s solution for injection, withdraw and discard a volume equal to the volume of the reconstituted Benlysta solution required for the patient’s dose. Then add the required volume of the reconstituted Benlysta solution into the infusion bag or bottle. Gently invert the bag or bottle to mix the solution. Any unused solution in the vials must be discarded.

Inspect the Benlysta solution visually for particulate matter and discoloration prior to administration. Discard the solution if any particulate matter or discoloration is observed.

The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours.

Preparation of 400 mg solution for infusion
Reconstitution
Reconstitution and dilution must be carried out under aseptic conditions.

Allow 10 to 15 minutes for the vial to warm to room temperature (15 °C to 25 °C).

It is recommended that a 21-25 gauge needle be used when piercing the vial stopper for reconstitution and dilution.

The 400 mg single-use vial of belimumab is reconstituted with 4.8 mL of water for injections to yield a final concentration of 80 mg/mL belimumab.

The stream of water for injections should be directed toward the side of the vial to minimize foaming. Gently swirl the vial for 60 seconds. Allow the vial to sit at room temperature (15 °C to 25 °C) during reconstitution, gently swirling the vial for 60 seconds every 5 minutes until the powder is dissolved. Do not shake.
Reconstitution is typically complete within 10 to 15 minutes after the water has been added, but it may take up to 30 minutes.

Protect the reconstituted solution from sunlight.

If a mechanical reconstitution device is used to reconstitute Benlysta it should not exceed 500 rpm and the vial should be swirled for no longer than 30 minutes.

Once reconstitution is complete, the solution should be opalescent and colourless to pale yellow and without particles. Small air bubbles, however, are expected and acceptable.

After reconstitution, a volume of 5 mL (corresponding to 400 mg belimumab) can be withdrawn from each vial.

Dilution
The reconstituted medicinal product is diluted to 250 mL with sodium chloride 9 mg/mL (0.9%), sodium chloride 4.5 mg/mL (0.45%), or Lactated Ringer’s solution for injection.

5% glucose intravenous solutions are incompatible with Benlysta and must not be used.

From a 250 mL infusion bag or bottle of sodium chloride 9 mg/mL (0.9%), sodium chloride 4.5 mg/mL (0.45%), or Lactated Ringer’s solution for injection, withdraw and discard a volume equal to the volume of the reconstituted Benlysta solution required for the patient’s dose. Then add the required volume of the reconstituted Benlysta solution into the infusion bag or bottle. Gently invert the bag or bottle to mix the solution. Any unused solution in the vials must be discarded.

Inspect the Benlysta solution visually for particulate matter and discoloration prior to administration. Discard the solution if any particulate matter or discoloration is observed.


The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours.
Method of administration

Benlysta is infused over a 1 hour period.

Benlysta should not be infused concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the co-administration of Benlysta with other agents.

No incompatibilities between Benlysta and polyvinylchloride or polyolefin bags have been observed.

Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.