Drug information of Benralizumab

Mechanism of effect

Interleukin-5 (IL-5) induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils and some mast cells. Benralizumab, unlike IL-5 low-affinity binding, binds with high affinity to the domain I of the α-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent cell lines. On the other hand, Benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcγRIIIa on natural killer cells, macrophages and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity

Pharmacodynamic

Eosinophils are the key target of inflammatory respiratory diseases and they undergo apoptosis in absence of IL-5. Therefore, benralizumab action on the IL-5 receptor in basophils and eosinophils produces the apoptosis and its significant reduction in the blood. On the other hand, Benralizumab binding to natural killer cells FcγRIIIα receptor produces a direct antibody-dependent cell-mediated cytotoxicity. All these effects produce a reduction in eosinophil count in airway mucosa, submucosa, sputum, blood and bone marrow

Pharmacokinetics

Absorption

Absorption half-life: ~3.5 days

Absolute bioavailability: ~59% (no difference between injection sites)

Distribution

Vd: 3.2 L (central); 2.5 L (peripheral)

Metabolism

IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue

Elimination

Elimination half-life: 15.5 days

Systemic clearance: 0.29 L/day

Drug indications

bronchial asthma

Dosage

30 mg SC q4weeks for the first 3 doses, THEN q8weeks thereafter

<12 years: Safety and efficacy not established

≥12 years: 30 mg SC q4weeks for the first 3 doses, THEN q8weeks thereafter

Drug contraindications

Hypersensitivity to this drug

Side effects

Headache , Dermatit , Tachycardia , dizziness , allergic reaction , rash , urticaria , Erythema , fever , Arthralgia , dysphagia , itching , tiredness , shortness of breath , swelling of the face , swelling of the tongue

Interactions

Estradiol Valerate , Infliximab , Bevacizumab , Trastuzumab , Ethinyl Estradiol , Adalimumab , Abciximab , Tocilizumab , Siltuximab , sirukumab , secukinumab , mepolizumab , RESLIZUMAB , alirocumab

Alerts

Hypersensitivity reactions (eg, anaphylaxis, angioedema, urticaria, rash) reported; these reactions generally occur within hours of administration, but in some instances have a delayed onset (ie, days); discontinue if hypersensitivity occurs

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiating benralizumab; corticosteroid dose reductions, if appropriate, should be gradual and performed under the direct supervision of a physician; monitor for systemic withdrawal symptoms and/or unmasking of conditions previously suppressed by systemic corticosteroid therapy

Eosinophils may be involved in the immunological response to some helminth infections; unknown if benralizumab influences immunologic response against helminth infections; treat patients with preexisting helminth infections before initiating therapy; if parasitic infection occurs while receiving treatment and does not respond to antihelminth treatment, discontinue benralizumab until infection resolves

Avoid use in acute asthma symptoms or acute exacerbations; do not use to treat acute bronchospasm or status asthmaticus

Points of recommendation

SC Preparation

Instruct patients regarding SC injection technique and proper disposal of syringe and needles

Prior to administration, warm by leaving carton at room temperature for about 30 minutes

Once removed from refrigerator, administer within 24 hr or discard into sharps container

Visually inspect; solution should appear clear to opalescent, colorless to slightly yellow, and may contain a few translucent or white to off-white particles Do not use if solution is cloudy, discolored, or if it contains large particles or foreign particulate matter

SC Administration

For subcutaneous use only

Administer SC in upper arm if given by care giver or clinician, or in thigh or abdomen by self-injection with autoinjector

Discard used syringe into a sharps container

Storage

All formulations

• Refrigerate at 2-8°C (36-46°F)
• Store in the original carton to protect from light
• Do not freeze
• Do not shake

Pregnancy level

HAVE NOT BEEN ESTABLISHED

No data are available regarding use in pregnant women; a pregnancy exposure registry monitors pregnancy outcomes in women exposed to drug during pregnancy; healthcare providers can enroll patients or encourage patients to enroll themselves by calling 1-877-311-8972 or visiting mothertobaby.org/Fasenra

Monoclonal antibodies are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy

In women with poorly or moderately controlled asthma, evidence demonstrates an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate; closely monitor in pregnant women and adjust treatment as necessary

Breast feeding warning

No information is available regarding the presence of benralizumab in human or animal milk, and the effects of benralizumab on the breastfed infant and on milk production are not known

Humanized monoclonal antibodies and immunoglobulin G are present in human milk in small amounts

The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

Related drugs

RESLIZUMAB , mepolizumab , sirukumab , secukinumab

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