belimumab

General

Pronunciation:
be-li-moo-mab


Trade Name(s)

  • Benlysta

Ther. Class.
immunosuppressants

Pharm. Class.
monoclonal antibodies

Indications

  • Active autoantibody-positive systemic lupus erythematosus (SLE) in patients currently receiving standard therapy.
  • Active lupus nephritis in patients currently receiving standard therapy.

Action

A monoclonal antibody produced by recombinant DNA technique that specifically binds to B-lymphocyte stimulator protein (BLyS), thereby inactivating it.

Therapeutic Effect(s):

  • ↓ survival of B cells, including autoreactive ones and ↓ differentiation into immunoglobulin-producing plasma cells. Result is ↓ disease activity with lessened damage/improvement in mucocutaneous, musculoskeletal, and immunologic manifestations of SLE.
  • Improvement in or stabilization of renal function in lupus nephritis.

Pharmacokinetics

Absorption: 74% absorbed after subcut administration; IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 19.4 days.

TIME/ACTION PROFILE (reduction in activated B cells)

ROUTEONSETPEAKDURATION
IV or subcut8 wkunknown52 wk†
†With continuous treatment.

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity;
  • Concurrent use of other biologicals or cyclophosphamide;
  • Concurrent use of live vaccines;
  • Receiving therapy for chronic infection.

Use Cautiously in:

  • Infections (consider temporary withdrawal for acute infections, treat aggressively);
  • Previous history of depression or suicidal ideation (may worsen);
  • OB:   Use during pregnancy only if potential maternal benefit justifies potential fetal risk
  • Lactation: Safety not established in breastfeeding
  • Rep:  Women of reproductive potential;
  • Pedi:   Children <5 yr (safety and effectiveness not established);
  • Geri:  Older adults may be more sensitive to drug effects, consider age-related changes in renal, hepatic and cardiac function, concurrent drug therapy, and chronic disease states.

Adverse Reactions/Side Effects

Derm: rash

GI: nausea, diarrhea

GU: cystitis

Hemat: leukopenia

MS: extremity pain, myalgia

Neuro: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML), SUICIDAL IDEATION/BEHAVIOR, depression, insomnia, migraine, anxiety, fatigue

Misc: ANAPHYLAXIS, INFECTION, infusion reactions, fever, facial edema

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

↑ risk of adverse reactions and ↓ immune response to  live vaccines ; should not be given concurrently.

Route/Dosage

Systemic Lupus Erythematosus

IV (Adults and Children ≥5 yr): 10 mg/kg every 2 wk for 3 doses, then 10 mg/kg every 4 wk.

SC (Adults): 200 mg once weekly; if transitioning from IV therapy, give first subcut dose 1–4 wk after last IV dose.

Lupus Nephritis

IV (Adults and Children ≥5 yr): 10 mg/kg every 2 wk for 3 doses, then 10 mg/kg every 4 wk.

SC (Adults): 400 mg (given as two, 200–mg injections) once weekly for 4 wk, then 200 mg once weekly. May transition from IV therapy after completing first two IV doses, give first subcut dose 1–2 wk after last IV dose.

Availability

Lyophilized powder for injection: 120 mg/vial, 400 mg/vial

Solution for injection (prefilled syringes and autoinjectors): 200 mg/mL

Assessment

  • Monitor patient for signs of anaphylaxis (hypotension, angioedema, urticaria, rash, pruritus, wheezing, dyspnea, facial edema) during and following injection. Medications (antihistamines, corticosteroids, epinephrine) and equipment should be readily available in the event of a severe reaction. Discontinue belimumab immediately if anaphylaxis or other severe allergic reaction occurs.
  • Monitor for infusion reactions (headache, nausea, skin reactions, bradycardia, myalgia, headache, rash, urticaria, hypotension). There is insufficient evidence to determine whether premedication diminishes frequency or severity. Infusion rate may be slowed or interrupted if an infusion reaction occurs.
  • Assess for signs of infection (fever, dyspnea, flu-like symptoms, frequent or painful urination, redness or swelling at the site of a wound), including tuberculosis, prior to injection. Belimumab is contraindicated in patients with active infection. New infections should be monitored closely; most common are upper respiratory tract infections, bronchitis, and urinary tract infections. Signs and symptoms of inflammation may be lessened due to suppression from belimumab. Infections may be fatal, especially in patients taking immunosuppressive therapy. If patient develops a serious infection, consider discontinuing belimumab until infection is controlled.
  • Assess mental status and mood changes. Inform health care professional if patient demonstrates significant ↑ in depressed mood, anxiety, nervousness, or insomnia.
  • Assess for signs of progressive multifocal leukoencephalopathy (hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia) periodically during therapy.

Potential Diagnoses

Implementation

  • Consider premedication for prophylaxis against infusion reactions and hypersensitivity reactions.
  • SC Allow autoinjector or prefilled syringe to sit at room temperature for 30 min prior to injection; do not use other methods of warming. Solution is clear to opalescent and colorless to pale yellow. Do not inject solutions that are discolored or contain particulate matter. Administer first injection under supervision of health care professional into abdomen or thigh. Rotate injection sites each wk. Avoid areas of tenderness, bruising, redness, or hardness. Refrigerate autoinjectors and prefilled syringes prior to use; do not freeze or shake. Avoid exposure to heat. May be stored at room temperature if protected from sunlight for up to 12 hrs.

IV Administration

  • Intermittent Infusion:  Remove belimumab from refrigerator and allow to stand 10–15 min to reach room temperature.  Reconstitution: Using a 21–25 gauge needle, reconstitute 120 mg vial with 1.5 mL and 400 mg vial with 4.8 mL of sterile water for injection by directing stream toward side of vial to minimize foaming. Swirl gently for 60 sec. Allow vial to sit at room temperature during reconstitution, swirling gently for 60 sec every 5 min until powder is dissolved. Do not shake. Reconstitution usually takes 10–15 min, but may take up to 30 min. Protect from sunlight. Solution is opalescent and colorless to pale yellow and without particles. Small bubbles are expected and acceptable. Concentration: 80 mg/mL. Diluent:   0.9% NaCl, 0.45% NaCl or LR. Remove volume of patient's dose from a 250 mL infusion bag and discard. Replace with required amount of reconstituted solution. Gently invert bag to mix. Do not administer solutions that are discolored or contain particulate matter. Discard unused solution in vial. If not used immediately, refrigerate and protect from light. Solution is stable for 8 hrs.
  • Rate: Infuse over 1 hr; may slow or interrupt rate if patient develops an infusion reaction.
  • Y-Site Incompatibility: Do not administer with dextrose solutions or other solutions or medications.

Patient/Family Teaching

  • Instruct patient in correct technique for subcut injection, care, and disposal of equipment. Inject on the same day each wk. Inject missed doses as soon as remembered, then resume on usual day or start a new weekly schedule from the day missed dose was administered. Do not inject 2 doses on same day. Advise patient to read  Medication Guide  prior to each treatment session in case of changes.
  • Caution patient to notify health care professional immediately if signs of infection (fever, sweating, chills, muscle aches, cough, shortness of breath, blood in phlegm, weight loss, warm, red or painful skin or sores, diarrhea or stomach pain, burning on urination, urinary frequency, feeling tired), progressive multifocal leukoencephalopathy, severe rash, swollen face, or difficulty breathing occurs while taking.
  • Advise patient, family, and caregivers to look for depression and suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide; new or worse depression or anxiety; agitation or restlessness; panic attacks; insomnia; new or worse irritability; aggressiveness; acting on dangerous impulses, mania, or other changes in mood or behavior, or if symptoms of serotonin syndrome occur.
  • Caution patient to avoid receiving live vaccines for 30 days before and during belimumab therapy.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Rep:  Advise females of reproductive potential to use effective contraception during and for at least 4 mo after final treatment and to notify health care professional if breast feeding. Encourage pregnant patients to enroll in pregnancy registry by calling 1-877-681-6296.

Evaluation/Desired Outcomes

  • Improvement in mucocutaneous, musculoskeletal, and immunologic disease activity in patients with SLE.
  • Improvement in or stabilization of renal function in lupus nephritis.

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