BENLYSTA Powder for concentrate for solution for infusion / Solution for injection Ref.[110232] Active ingredients: Belimumab

2.1 Important Administration Information

BENLYSTA may be administered as an intravenous infusion in patients aged 5 years and older or as a subcutaneous injection in patients aged 18 years and older. Vials are intended for intravenous use only (not for subcutaneous use) and autoinjectors and prefilled syringes are intended for subcutaneous use only (not for intravenous use).

2.2 Recommended Intravenous Dosage for Adult and Pediatric Patients with SLE or Lupus Nephritis

Dosage

BENLYSTA for intravenous use must be reconstituted and diluted prior to administration. Do not administer as an intravenous push or bolus.

The recommended intravenous dosage is 10 mg/kg at 2‑week intervals for the first 3 doses and at 4‑week intervals thereafter. Reconstitute, dilute, and administer as an intravenous infusion over a period of 1 hour. 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 serious hypersensitivity reaction [see Contraindications (4), Warnings and Precautions (5.2)].

Precautions Prior to Intravenous Use

BENLYSTA should be administered by healthcare providers prepared to manage anaphylaxis [see Warnings and Precautions (5.2)].

Prior to intravenous dosing with BENLYSTA, consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions [see Warnings and Precautions (5.2), Adverse Reactions (6.1)].

Preparation of Intravenous Solutions

BENLYSTA for intravenous use is provided as a lyophilized powder in a single‑dose vial and should be reconstituted and diluted by a healthcare professional using aseptic technique as follows. Use of a 21- to 25-gauge needle is recommended when piercing the vial stopper for reconstitution and dilution.

Reconstitution Instructions for Intravenous Use:

• Remove the vial of BENLYSTA from the refrigerator and allow to stand for 10 to 15 minutes for the vial to reach room temperature.
• Reconstitute the BENLYSTA powder with Sterile Water for Injection, USP, as follows. The reconstituted solution will contain a concentration of 80 mg/mL belimumab.
  • Reconstitute the 120-mg vial with 1.5 mL Sterile Water for Injection, USP.
  • Reconstitute the 400-mg vial with 4.8 mL Sterile Water for Injection, USP.
• The stream of sterile water 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 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 sterile water has been added, but it may take up to 30 minutes. Protect the reconstituted solution from sunlight.
• If a mechanical reconstitution device (swirler) is used to reconstitute BENLYSTA, it should not exceed 500 rpm and the vial 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.

Dilution Instructions for Intravenous Use:

• Dextrose intravenous solutions are incompatible with BENLYSTA. BENLYSTA should only be diluted in 0.9% Sodium Chloride Injection, USP (normal saline), 0.45% Sodium Chloride Injection, USP (half-normal saline), or Lactated Ringer’s Injection, USP to a volume of 250 mL for intravenous infusion. To prepare the intravenous infusion solution for patients whose body weight is less than or equal to 40 kg, a 100 mL bag or bottle of normal saline, half-normal saline, or Lactated Ringer’s Injection may be used such that the resulting belimumab concentration in the infusion bag does not exceed 4 mg/mL. From a 250‑mL (or 100‑mL) infusion bag or bottle of normal saline, half-normal saline, or Lactated Ringer’s Injection, withdraw and discard a volume equal to the volume of the reconstituted solution of BENLYSTA required for the patient’s dose. Then add the required volume of the reconstituted solution of BENLYSTA into the intravenous infusion solution in the infusion bag or bottle. Gently invert the bag or bottle to mix the intravenous infusion solution. Any unused solution in the vials must be discarded.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the solution if any particulate matter or discoloration is observed.
• The reconstituted solution of BENLYSTA, if not used immediately, should be stored protected from direct sunlight and refrigerated at 36°F to 46°F (2°C to 8°C). Solutions of BENLYSTA diluted in normal saline, half-normal saline, or Lactated Ringer’s Injection may be stored at 36°F to 46°F (2°C to 8°C) or room temperature. The total time from reconstitution of BENLYSTA to completion of infusion should not exceed 8 hours.
• No incompatibilities between BENLYSTA and polyvinylchloride or polyolefin bags have been observed.

Administration Instructions for Intravenous Use

• The diluted solution of BENLYSTA should be administered by intravenous infusion over a period of 1 hour.
• 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 coadministration of BENLYSTA with other agents.

2.3 Recommended Subcutaneous Dosage for Adult Patients with SLE or Lupus Nephritis

Subcutaneous dosing of BENLYSTA has not been evaluated and is not approved for patients younger than 18 years of age.

Adult Patients with SLE

The recommended dosage is 200 mg once weekly given as a subcutaneous injection in the abdomen or thigh. Subcutaneous dosing is not based on weight.

If transitioning from intravenous therapy with BENLYSTA to subcutaneous administration, administer the first subcutaneous dose 1 to 4 weeks after the last intravenous dose.

Adult Patients with Lupus Nephritis

In patients initiating therapy with BENLYSTA for active lupus nephritis [see Clinical Studies (14.2)], the recommended dosage is a 400-mg dose (two 200-mg injections) once weekly for 4 doses, then 200 mg once weekly thereafter. The dose is given via subcutaneous injection in the abdomen or thigh. The 400-mg dose for active lupus nephritis requires administration of 2 autoinjectors or 2 prefilled syringes as described below.

A patient with lupus nephritis may transition from intravenous therapy with BENLYSTA to subcutaneous therapy any time after the patient completes the first 2 intravenous doses. If transitioning, administer the first subcutaneous dose of 200 mg 1 to 2 weeks after the last intravenous dose.

Administration Instructions for Subcutaneous Injection

• It is recommended that the first subcutaneous injection of BENLYSTA should be under the supervision of a healthcare professional. The healthcare provider should provide proper training in subcutaneous technique and education about signs and symptoms of hypersensitivity reactions [see Warning and Precautions (5.2)]. A patient may self-inject or the patient caregiver may administer BENLYSTA subcutaneously after the healthcare provider determines it is appropriate.
• Instruct the patient or patient caregiver to follow the directions for administration provided in the Instructions for Use.
• Instruct the patient to remove the autoinjector or prefilled syringe from the refrigerator and allow it to sit at room temperature for 30 minutes prior to the subcutaneous injection. Do not warm BENLYSTA in any other way.
• Prior to administration, instruct the patient or patient caregiver to visually inspect the window of the autoinjector or the prefilled syringe for particulate matter or discoloration. BENLYSTA should be clear to opalescent and colorless to pale yellow. Do not use BENLYSTA if the product exhibits discoloration or particulate matter. Instruct the patient not to use the BENLYSTA autoinjector or prefilled syringe if dropped on a hard surface.
• When injecting in the same body region, advise the patient to use a different injection site for each injection; never give injections into areas where the skin is tender, bruised, red, or hard. When a 400-mg dose is administered at the same site, it is recommended that the 2 individual 200-mg injections be administered at least 5 cm (approximately 2 inches) apart.
• Instruct the patient to administer BENLYSTA 200 mg once a week, preferably on the same day each week.
• If a dose is missed, instruct the patient to administer a dose as soon as the patient remembers. Thereafter, the patient can resume dosing on their usual day of administration or start a new weekly schedule from the day that the missed dose was administered.

There is limited experience with overdosage of belimumab.

Two doses of up to 20 mg/kg have been given intravenously to humans with no increase in incidence or severity of adverse reactions compared with doses of 1, 4, or 10 mg/kg.

Intravenous Infusion

Refrigerate vials at 36°F to 46°F (2°C to 8°C). Store vials in the original carton until use to protect from light. Do not freeze. Avoid exposure to heat.

Subcutaneous Injection

Prior to Dispensing

Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake. Avoid exposure to heat.

Following Dispensing

Refrigerate prefilled autoinjectors and prefilled syringes at 36°F to 46°F (2°C to 8°C). Keep the product in the original carton to protect from light until the time of use. Do not freeze. Do not shake. Avoid exposure to heat.

BENLYSTA may be stored outside of the refrigerator up to 86°F (30°C) for up to 12 hours if protected from sunlight. Do not use and do not place back in refrigerator if left out for more than 12 hours.