Belimumab (Benlysta)

BELIMUMAB (Benlysta) is a targeted, human monoclonal antibody that binds to soluble B lymphocyte stimulator (BLyS). Benlysta does not bind to B cells directly. By binding BLyS, Benlysta allows more B cells to undergo the normally occurring process of apoptosis, which inhibits the survival of B cells, including autoreactive B cells and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

Benlysta is a B-lymphocyte stimulator (BLyS)-specific inhibitor indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus who are receiving standard therapy. Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations.

Resources from Manufacturer

Patient Medication Guide
Full Prescribing Information
Contact a Benlysta support specialist: 1-877-4-BENLYSTA (1-877-423-6597)

FDA-Approved Indications and Dosing

Benlysta is indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy.

Benlysta is administered as a 1-hour IV infusion only and given every 4 weeks after the loading phase.

  • 3 infusions at 2-week intervals
  • 1 infusion every 4 weeks thereafter

Contraindications

Benlysta is contraindicated in patients who have had anaphylaxis with belimumab.

Warnings and Precautions

  1. Mortality: There were more deaths reported with Benlysta than with placebo during the controlled period of clinical trials.
  2. Serious Infections: Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including Benlysta. Use with caution in patients with chronic infections. Consider interrupting therapy with Benlysta if patients develop a new infection during treatment with Benlysta.
  3. Progressive Multifocal Leukoencephalopathy (PML): Patients presenting with new-onset or deteriorating neurological signs and symptoms should be evaluated for PML by an appropriate specialist. If PML is confirmed, consider discontinuation of immunosuppressant therapy, including Benlysta.
  4. Hypersensitivity Reactions, Including Anaphylaxis: Serious and fatal reactions have been reported. Benlysta should be administered by healthcare providers prepared to manage anaphylaxis. Monitor patients during and for an appropriate period of time after administration of Benlysta.
  5. Depression: Depression and suicidality have been reported in trials with Benlysta. Patients should be instructed to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts or other mood changes.
  6. Immunization: Live vaccines should not be given concurrently with Benlysta.
  7. Concomitant Use with Other Biologic Therapies or Intravenous Cyclophosphamide: Use of Benlysta is not recommended in combination with biologic therapies or intravenous cyclophosphamide.

Common Adverse Effects after Administration of Benlysta

  • Nausea
  • Diarrhea
  • Pyrexia
  • Nasopharyngitis
  • Bronchitis
  • Insomnia
  • Pain in extremity
  • Depression
  • Migraine
  • Pharyngitis

Rare Adverse Effects after Administration of Benlysta

  • Infection, serious
  • Hypersensitivity Reaction
  • Anaphylaxis
  • Infusion reaction, severe
  • Antibody against Benlysta

Pre-Infusion Checklist

  1. Live vaccines should not be given for 30 days before or concurrently with Benlysta as clinical safety has not been established. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving Benlysta or the effect of Benlysta on new immunizations. Because of its mechanism of action, Benlysta may interfere with the response to immunizations.
  2. Before preparing Benlysta for infusion, ask patient if he/she

(If the answer is yes to any of these questions, review with ordering provider.)

    • Has any current or recent bout of illness or infection?
    • Is taking any antibiotics or other antimicrobial therapy?
    • Has had a recent vaccination?
    • Have any upcoming surgeries?
    • Could be pregnant?

Medication Preparation

Benlysta is provided as a lyophilized powder in a single-use vial for intravenous infusion only and should be reconstituted and diluted by a healthcare professional using aseptic technique as follows:

Reconstitution Instructions

  1. Remove Benlysta from the refrigerator and allow to stand 10 - 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. 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 - 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, it should not exceed 500 rpm and the vial swirled for no longer 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.
  6. Dextrose intravenous solutions are incompatible with Benlysta. Benlysta should only be diluted in 0.9% Sodium Chloride Injection, USP. Dilute the reconstituted product to 250 mL in 0.9% Sodium Chloride Injection, USP (normal saline) for intravenous infusion. From a 250-mL infusion bag or bottle of normal saline, 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 infusion bag or bottle. Gently invert the bag or bottle to mix the solution. Any unused solution in the vials must be discarded.
  7. 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.
  8. The reconstituted solution of Benlysta, if not used immediately, should be stored protected from direct sunlight and refrigerated at 2 - 8 degrees Celsius. (36 - 46 Farenheit). Solutions of Benlysta diluted in normal saline may be stored at at 2 - 8 degrees Celsius. (36 - 46 Farenheit) or room temperature. The total time from reconstitution of Benlysta to completion of infusion should not exceed 8 hours.
  9. No incompatibilities between Benlysta and polyvinylchloride or polyolefin bags have been observed.

Medication Administration and Monitoring

  1. The diluted solution of Benlysta should be administered by intravenous infusion only, over a period of 1 hour.
  2. Benlysta should be administered by healthcare providers prepared to manage anaphylaxis. Benlysta should be administered by healthcare providers prepared to manage infusion reactions. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely.
  3. 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.

Vital Signs Monitoring
There were no specific guidelines in the medication guide from the manufacturer for vital signs monitoring. It is reasonable and prudent however, to obtain vital signs (patient temperature, blood pressure and pulse) upon arrival, after the start of Benlysta, upon discontinuing infusion, and before the patient departs the facility. If the patient has a prior history of an acute infusion reaction, monitor vitals every 10 minutes for 30 minutes and for 30 minutes after infusion.

Review Orders and Obtain IV Access

**Do not reconstitute Benlysta vials until after obtaining intravenous access**

Prior to dosing with Benlysta, the provider should consider administering premedication for prophylaxis against infusion reactions and hypersensitivity reactions. The infusion nurse should check for pre-medication orders.

Managing Infusion Reactions

Acute infusion reaction can occur during the administration of this agent. Patients may also have an infusion reaction the following day after the infusion. Anaphylactoid and anaphylaxis reactions can result. If patient reports mild reactions (such as dizziness, hives, flushing, chills, etc.), slow down the infusion rate and assess patient. For more severe reactions (such as difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, fever, chills or anaphylaxis) or where mild reactions persist, stop the infusion and treat the acute reaction. Notify the supervising provider immediately to coordinate next plan of action. Patients should be informed that infusion reactions can be delayed, and should contact their provider at the first sign of an allergic reaction which may include:

  • Itching
  • swelling of the face, lips, mouth, tongue, or throat
  • trouble breathing
  • anxiousness
  • low blood pressure
  • dizziness or fainting
  • headache
  • nausea
  • skin rash, redness, or swelling

Additional Considerations

Perioperative Management of Medications Used in the Treatment of Rheumatoid Arthritis

Updated January 2017 - ARHP Practice Committee

DISCLAIMER:The information contained in this biologic reference guide is offered solely for purposes of providing health care professionals with a quick and initial reference. Before prescribing or administering any drug contained in this biologic reference guide, health professionals should read the manufacturer's complete prescribing information in order to be informed of the various clinical considerations to be taken into account. The American College of Rheumatology is providing this information as a benefit and service in furtherance of its educational mission. By providing this information, ACR is not endorsing or recommending any of the listed companies or any of their drugs or other products. The information contained in the biologic reference guides reflect the conclusions of the individual companies and not those of the ACR which specifically disclaims any responsibility or liability for the use of such information and/or for the performance of any of the drugs listed in this biologic reference guide.