Fasenra

Drug overview for FASENRA (benralizumab):

Generic name: BENRALIZUMAB (BEN-ra-LIZ-ue-mab)
Drug class: Monoclonal Antibody, Human Interleukin 5 Antagonist
Therapeutic class: Respiratory Therapy Agents

Benralizumab, a recombinant DNA-derived afucosylated humanized monoclonal antibody specific for the alpha chain of the interleukin-5 (IL-5) receptor (IL-5Ralpha), is an antiinflammatory agent. The drug is an IgG1 kappa immunoglobulin.

No enhanced Uses information available for this drug.

DRUG IMAGES

FASENRA 30 MG/ML SYRINGE
FASENRA 10 MG/0.5 ML SYRINGE

The following indications for FASENRA (benralizumab) have been approved by the FDA:

Indications:
Eosinophilic asthma
Eosinophilic granulomatosis with polyangiitis

Professional Synonyms:
Allergic granulomatosis angiitis
Asthma with eosinophilic phenotype
Asthmatic pulmonary eosinophilia
Churg Strauss syndrome

The following dosing information is available for FASENRA (benralizumab):

Dosing
Administration
FASENRA
Generic

Systemic or inhaled corticosteroid therapy should not be discontinued abruptly upon initiation of benralizumab therapy. If appropriate, reduction in corticosteroid dosage should be performed gradually and directly supervised by a clinician. Reduction in corticosteroid dosage may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by corticosteroid therapy.

Benralizumab is administered by subcutaneous injection. Prior to use, benralizumab injection should be stored at 2-8degreesC in the original carton, protected from light, and should not be frozen or shaken. Do not expose to heat.

Prior to administration, benralizumab prefilled syringes and autoinjectors should be allowed to warm at room temperature for about 30 minutes. If not used within 14 days when stored at room temperature, the prefilled syringe or autoinjector should be discarded. Benralizumab injection is commercially available in prefilled syringes and as a single-dose autoinjector.

Benralizumab injection is a clear to opalescent, colorless to slightly yellow solution that may contain a few translucent or white to off-white particles. Prior to administration, benralizumab solution should be inspected visually for particulate matter or discoloration and should not be used if the solution is cloudy, discolored, or if large particles or foreign particulate matter are present. Benralizumab prefilled syringes and autoinjectors are intended for single use only; the drug contains no preservatives.

The entire amount of solution (1 mL) contained within the prefilled syringe or autoinjector, providing 30 mg of benralizumab, should be injected. Benralizumab prefilled syringe should be administered by a clinician. The autoinjector pen may be administered by the patient or caregiver after proper training is provided and the healthcare provider determines it is appropriate.

However, in pediatric patients 6-11 years of age weighing >=35 kg, the autoinjector pen should only be administered by a caregiver or healthcare provider. Subcutaneous injections should be made into the thigh or abdomen. A healthcare provider or caregiver may also administer benralizumab into the upper arm.

Dosing information for FASENRA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FASENRA 30 MG/ML SYRINGE	Maintenance	Adults inject 1 milliliter (30 mg) by subcutaneous route every 8 weeks in the abdomen, thigh, or upper arm

No generic dosing information available.

The following drug interaction information is available for FASENRA (benralizumab):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 2 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)	VYVGART, VYVGART HYTRULO
IgG Antibodies and Derivatives/Nipocalimab-aahu SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)	IMAAVY

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Efgartigimod-alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

VYVGART, VYVGART HYTRULO

IgG Antibodies and Derivatives/Nipocalimab-aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

IMAAVY

There are 1 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)	RYSTIGGO

Drug Interaction

Drug Names

IgG Antibodies and Derivatives/Rozanolixizumab-noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

RYSTIGGO

Severe List
Parasitic infection

The following adverse reaction information is available for FASENRA (benralizumab):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse effects reported in >=5% of patients receiving benralizumab include headache and pharyngitis.

There are 13 severe adverse reactions.

More Frequent	Less Frequent
None.	Hypersensitivity drug reaction

Rare/Very Rare
Adrenocortical insufficiency Anaphylaxis Angioedema Appendicitis Atrial fibrillation Cholecystitis Endometrial polyps Exostosis Leukopenia Lymphadenopathy Ocular hemorrhage Ovarian cyst

There are 27 less severe adverse reactions.

More Frequent	Less Frequent
Headache disorder Pharyngitis	Fever Injection site sequelae Skin rash Urticaria

Rare/Very Rare
Abdominal distension Allergic dermatitis Arthralgia Arthritis Chest pain Chills Conjunctival hemorrhage Cough Dysmenorrhea Gingivitis Hematuria Myalgia Nasal turbinate hypertrophy Nervousness Neuralgia Panic disorder Pelvic pain Respiratory tract congestion Sensation of cold Sinusitis Sleep disorder

The following precautions are available for FASENRA (benralizumab):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of benralizumab in pediatric patients younger than 6 years of age for add-on maintenance treatment of severe asthma with an eosinophilic phenotype have not been established. Phase 3 clinical studies included 108 adolescent patients 12-17 years of age (mean age: 14 years) with severe asthma and an eosinophilic phenotype who received benralizumab. The adverse effect profile in adolescents generally was similar to that seen in the overall population.

Based on a population pharmacokinetic analysis, pharmacokinetics of benralizumab in adolescents were similar to those in adults; reduction in blood eosinophil concentrations also was similar. Data supporting the use of benralizumab in pediatric patients 6-11 years of age with severe asthma and an eosinophilic phenotype include evidence from adequate and well-controlled trials in adults and adolescents with additional pharmacokinetic, pharmacodynamic, and safety data from the open-label, 48-week, TATE trial. In TATE, benralizumab demonstrated a pharmacokinetic and pharmacodynamic profile in pediatric patients 6-11 years of age that was consistent with that seen in prior clinical trials.

In addition, the safety and tolerability of benralizumab was consistent with the known profile of the drug, with no new safety signals observed. Safety and efficacy of benralizumab in pediatric patients younger than 18 years of age with EGPA have not been established.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Data on pregnancy exposure to benralizumab during clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as benralizumab, are transported across the placenta during the third trimester, and potential effects on the fetus are more likely to occur during this time. However, there was no evidence of fetal harm in monkeys following IV administration of benralizumab on gestation day 20 or 22, gestation day 35, and every 14 days thereafter during gestation and for up to 1 month postpartum at dosages producing exposures up to approximately 310 times the exposure at the maximum recommended human dosage.

It is not known whether benralizumab is distributed into human milk. The effects of benralizumab on nursing infants or on milk production also are unknown. Since IgG is distributed into milk in humans, it is expected that benralizumab will be present in human milk. The benefits of breast-feeding and the woman's clinical need for benralizumab should be considered along with any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.

In clinical trials of benralizumab in patients with asthma, 13% of patients were 65 years of age or older and 0.4% were 75 years of age or older. Although no overall differences in safety or efficacy have been observed between geriatric patients and younger adults in controlled studies or in other clinical experience, the possibility of increased sensitivity to benralizumab in some geriatric patients cannot be ruled out.

In clinical trials of benralizumab in patients with EGPA, 19% of patients were 65 years of age and older. Clinical studies did not include a sufficient number of patients >=65 years of age to determine whether response to therapy is different from younger patients.

Eosinophilic asthma
J82.83	Eosinophilic asthma
Eosinophilic granulomatosis with polyangiitis
M30.1	Polyarteritis with lung involvement [churg-strauss]