Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2012 Publisher: Glaxo Group Limited Glaxo Wellcome House Berkeley Avenue Greenford Middlesex UB6 0NN United Kingdom
Benlysta is indicated as add-on therapy in adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity (e.g positive anti-dsDNA and low complement) despite standard therapy (see section 5.1).
Benlysta treatment should be initiated and supervised by a qualified physician experienced in the diagnosis and treatment of SLE. Benlysta infusions should be administered by a qualified healthcare professional trained to give infusion therapy. Administration of Benlysta may result in severe or life-threatening hypersensitivity reactions and infusion reactions. Patients have been reported to develop symptoms of acute hypersensitivity several hours after the infusion has been administered. Recurrence of clinically significant reactions after initial appropriate treatment of symptoms has also been observed (see section 4.4 and 4.8). Therefore, Benlysta should be administered in an environment where resources for managing such reactions are immediately available. Patients should remain under clinical supervision for a prolonged period of time (for several hours), following at least the first 2 infusions, taking into account the possibility of a late onset reaction.
Patients treated with Benlysta should be made aware of the potential risk of severe or life-threatening hypersensitivity and the potential for delayed onset or recurrence of symptoms. The package leaflet should be provided to the patient each time Benlysta is administered (see section 4.4).
There are no or insufficient data available on the effects of Benlysta in patients with severe active lupus nephritis or severe active central nervous system lupus. Therefore, Benlysta cannot be recommended to treat these conditions (see section 4.4).
Premedication including an antihistamine, with or without an antipyretic, may be administered before the infusion of Benlysta (see section 4.4)..
The recommended dose regimen is 10 mg/kg Benlysta on Days 0, 14 and 28, and at 4-week intervals thereafter. The patient’s condition should be evaluated continuously. Discontinuation of treatment with Benlysta should be considered if there is no improvement in disease control after 6 months of treatment.
Elderly (>65 years): The efficacy and safety of Benlysta in the elderly has not been established. Data on patients >65 years are limited to <1.6% of the studied population. Therefore, the use of Benlysta in elderly patients is not recommended unless the benefits are expected to outweigh the risks. In case administration of Benlysta to elderly patients is deemed necessary, dose adjustment is not required (see section 5.2).
Renal impairment: Belimumab has been studied in a limited number of SLE patients with renal impairment.
On the basis of the available information, dose adjustment is not required in patients with mild, moderate or severe renal impairment. Caution is however recommended in patients with severe renal impairment due to the lack of data (see section 5.2).
Hepatic impairment: No specific studies with Benlysta have been conducted in patients with hepatic impairment. Patients with hepatic impairment are unlikely to require dose adjustment (see section 5.2).
The safety and efficacy of Benlysta in children (less than 18 years of age) has not been established. No data are available.
Benlysta is administered intravenously by infusion, and must be reconstituted and diluted before administration. For instructions on reconstitution, dilution, and storage of the medicinal product before administration, see section 6.6.
Benlysta should be infused over a 1-hour period.
Benlysta must not be administered as an intravenous bolus.
The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. The infusion must be discontinued immediately if the patient experiences a potentially life-threatening adverse reaction (see sections 4.4 and 4.8).
There is no clinical experience with overdose of Benlysta.
Two doses up to 20 mg/kg administered 21 days apart by intravenous infusion have been given to humans with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg.
In the case of inadvertent overdose, patients should be carefully observed and supportive care administered, as appropriate.
Unopened vials: 4 years.
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 – 8°C.
Solution of Benlysta diluted in sodium chloride 9 mg/ml (0.9%) solution for injection may be stored at 2°C-8°C or room temperature (15°C – 25°C).
The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours.
Unopened vials: Store in a refrigerator (2°C – 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.
120 mg vial: Type 1 glass vials (5 ml), sealed with a latex-free, siliconised chlorobutyl rubber stopper and a flip-off aluminum seal.
400 mg vial: Type 1 glass vials (20 ml), sealed with a latex-free, siliconised chlorobutyl rubber stopper and a flip-off aluminum seal.
Pack size: 1 vial.
Reconstitution and dilution must be carried out under aseptic conditions.
Allow 10-15 minutes for the vial to warm to room temperature (15°C – 25°C).
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 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 – 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 colorless 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.
After reconstitution, a volume of 5 ml (corresponding to 400 mg belimumab) can be withdrawn from each vial.
The reconstituted medicinal product is diluted to 250 ml with sodium chloride 9 mg/ml (0.9%) 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%) 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.
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.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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