Belimumab

Renal Impairment The safety and efficacy of BENLYSTA were evaluated in studies that included subjects with SLE who had mild (creatinine clearance [CrCl] ≥60 and <90 mL/min), moderate (CrCl ≥30 and <60 mL/min), or severe (CrCl ≥15 and <30 mL/min) renal impairment. No dosage adjustment is recommended in patients with renal impairment.

Hepatic Impairment No formal trials were conducted to examine the effects of hepatic impairment on the pharmacokinetics of belimumab. No dosage adjustment is recommended in patients with hepatic impairment.

Important Administration Instructions BENLYSTA may be administered intravenously or subcutaneously [see Dosage and Administration ( 2.2 , 2.3 )]. 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).

Precautions Prior to Intravenous Use BENLYSTA should be administered by healthcare providers prepared to manage anaphylaxis [see Warnings and Precautions]. Prior to intravenous dosing with BENLYSTA, consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions [see Warnings and Precautions, Adverse Reactions] .

Recommended Intravenous Dosage, and Preparation and Administration Instructions BENLYSTA for intravenous use must be reconstituted and diluted prior to administration. Do not administer as an intravenous push or bolus. Recommended Dosage and Administration The recommended intravenous BENLYSTA dosage in patients 5 years of age and older with active SLE or lupus nephritis 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. Do not concomitantly infuse BENLYSTA 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. 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, Warnings and Precautions] . Preparation of the Intravenous Solution 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: 1. Remove the vial of BENLYSTA from the refrigerator and allow to stand for 10 to 15 minutes for the vial to reach room temperature. 2. 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. 3. Direct the stream of sterile water towards 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. 4. If a mechanical reconstitution device (swirler) is used to reconstitute BENLYSTA, do not exceed 500 rpm or swirl the vial for more than 30 minutes. 5.

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: 1. 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. 2. Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit.

Discard the solution if any particulate matter or discoloration is observed. 3. If the reconstituted solution of BENLYSTA is not used immediately, store, protect from direct sunlight and refrigerate at 36°F to 46°F (2°C to 8°C). Store solutions of BENLYSTA diluted in normal saline, half‑normal saline, or Lactated Ringer’s Injection 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. 4. No incompatibilities between BENLYSTA and polyvinylchloride or polyolefin bags have been observed.

Recommended Subcutaneous Dosage, and Preparation and Administration Instructions The recommended subcutaneous BENLYSTA dosage in patients 5 years of age and older with active SLE or lupus nephritis is provided in Table 1 . Administer BENLYSTA subcutaneously in the abdomen or thigh. For patients less than 10 years of age, BENLYSTA must be administered by a healthcare professional or trained caregiver. [See table below.] Administration Instructions for Subcutaneous Injection 1.

Administer the first subcutaneous injection of BENLYSTA under the supervision of a healthcare provider. Provide patients or caregivers with proper training on subcutaneous administration and education about signs and symptoms of hypersensitivity reactions [see Warnings and Precautions] . For adults and pediatric patients 10 years of age and older, subsequent subcutaneous BENLYSTA administrations may be performed by the patient or trained caregiver, if determined to be appropriate.

For pediatric patients less than 10 years of age, subsequent subcutaneous BENLYSTA administrations must be performed by a healthcare provider or trained caregiver. 2. Instruct the patient or caregiver to follow the directions for administration provided in the Instructions for Use. 3. Instruct the patient or caregiver 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. 4. Prior to administration, instruct the patient or 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 or caregiver not to use the BENLYSTA autoinjector or prefilled syringe if dropped on a hard surface. 5. When injecting in the same body region, advise the patient or caregiver to use a different injection site for each injection; never give injections into areas where the skin is tender, bruised, red, or hard.

When administering a 400‑mg dose, inject each 200‑mg injection at least 5 cm (approximately 2 inches) apart. 6. Instruct the patient or caregiver to administer BENLYSTA, preferably on the same day each week or the same day of alternate weeks, as appropriate. 7. If a dose is missed, instruct the patient or caregiver 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 schedule from the day that the missed dose was administered.