CLASSES
Immunotherapies for Reactive and Obstructive Airway Diseases
Interleukin-5 (IL-5) Inhibitors
DESCRIPTION
Subcutaneous humanized monoclonal antibody directed against interleukin (IL)-5
Used for add-on maintenance treatment of adult and pediatric patients 12 years and older who have severe asthma with an eosinophilic phenotype
Reduces severe exacerbations of asthma, and with maintenance treatment, may allow for oral corticosteroid dose reduction
COMMON BRAND NAMES
Fasenra
HOW SUPPLIED
Benralizumab/Fasenra Subcutaneous Inj Sol: 1mL, 30mg
DOSAGE & INDICATIONS
For asthma maintenance add-on therapy in severe asthma (eosinophilic phenotype).
Subcutaneous dosage
Adults
30 mg subcutaneously once every 4 weeks for the first 3 doses, followed by 30 mg subcutaneously once every 8 weeks thereafter.
Children and Adolescents 12 to 17 years
30 mg subcutaneously once every 4 weeks for the first 3 doses, followed by 30 mg subcutaneously once every 8 weeks thereafter.
MAXIMUM DOSAGE
Adults
30 mg/dose subcutaneously.
Geriatric
30 mg/dose subcutaneously.
Adolescents
30 mg/dose subcutaneously.
Children
12 years: 30 mg/dose subcutaneously.
1 to 11 years: Safety and efficacy have not been established.
Infants
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
No dosage adjustments are needed.
Renal Impairment
No dosage adjustments are needed. While there are limited data in patient with CrCl less than 30 mL/minute, the drug is not cleared renally.
ADMINISTRATION
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Benralizumab is clear to opalescent, colorless to slightly yellow, and may contain a few translucent or white to off-white particles. Do not use if the liquid is cloudy, discolored, or if it contains large particles or foreign particulate matter. The liquid may contain a small air bubble; this is normal. Do not expel the air bubble(s) prior to administration.
Benralizumab is intended for use under the guidance of a healthcare provider. In line with clinical practice, monitoring of patients after the administration of biologic agents is recommended.
The prefilled syringe should be administered by a healthcare professional.
The autoinjector (pen) can be administered by patients/caregivers after proper training and after the healthcare provider determines it is appropriate.
Subcutaneous Administration
Prefilled Syringe (Fasenra)
For administration by a healthcare provider only.
Preparation of prefilled syringe
Prior to administration, warm the prefilled syringe by leaving carton at room temperature for about 30 minutes.
Do not touch the needle guard activation clips to prevent premature activation of the needle safety guard. Grasp the syringe body, not the plunger, to remove prefilled syringe from the tray.
Do not remove the needle cover until ready to inject. Hold the syringe body and remove the needle cover by pulling straight off. Be careful not hold the plunger or plunger head while removing the needle cover or the plunger may move. If the prefilled syringe is damaged or contaminated (for example, dropped without needle cover in place), discard and use a new prefilled syringe.
Subcutaneous Administration using prefilled syringe
Gently pinch the skin and insert the needle at the recommended injection site (i.e., upper arm, thigh, or abdomen).
Inject all of the medication by pushing in the plunger all the way until the plunger head is completely between the needle guard activation clips. This is necessary to activate the needle guard.
After injection, maintain pressure on the plunger head and remove the needle from the skin. Release pressure on the plunger head to allow the needle guard to cover the needle. Do not re-cap the prefilled syringe.
The prefilled syringe is for single-use only.
Autoinjector (Fasenra Pen)
The autoinjector is appropriate for patient/caregiver use. Patients/caregivers may inject after proper training in subcutaneous injection technique, and after the healthcare provider determines it is appropriate.
Provide proper training in subcutaneous injection technique and on the preparation and administration of benralizumab injection prior to use according to the "Instructions for Use".
Subcutaneous Administration using autoinjector pen:
Choose the injection site. For patient-administered injection, administer into the thigh or abdomen, avoiding the 5 cm (2 inches) around the navel. The upper arm can also be used if a caregiver administers the injection. Never give injections into areas where the skin is tender, bruised, red, or hard.
Clean the injection site.
Remove the cap to expose the green needle guard.
Place the needle guard flat against the skin at a 90-degree angle to ensure that the viewing window is still visible.
To inject, gently pinch the skin at the recommended injection site or give the injection without pinching the skin. A "click" will be heard when the injection has started, and the green plunger will move down in the viewing window during the injection. A second "click" will be audible to indicate that the injection has finished, and the green plunger will fill the viewing window. If the green plunger does not fill the viewing window, the patient may not have received the full dose; contact the healthcare provider.
Lift the pen straight up and the needle guard will slide down and lock into place over the needle.
Check the injection site to see if there is bleeding, gently hold pressure over the skin with a cotton ball or gauze until the bleeding stops; do not rub injection site. A bandage may be used if needed.
The autoinjector contains only 1 dose. Do not use the pen more than 1 time.
Storage and disposal of prefilled syringes and injectors after removal from the refrigerator:
If needed, an unopened carton that has been brought to room temperature can be stored outside the refrigerator at up to 25 degrees C (77 degrees F) for up to 14 days. Keep in the original carton to protect from light. Do not expose to heat. Dispose of the injection properly if it is left out of the refrigerator in the unopened carton for more than 14 days.
Discard an expired or used syringe or pen autoinjector into a proper sharps disposal container.
STORAGE
Fasenra:
- Avoid exposure to heat
- Discard product if it contains particulate matter, is cloudy, or discolored
- Do not freeze
- Product must be used within 14 days after removal from refrigeration to room temperature (77 degrees F)
- Protect from light
- Refrigerate (between 36 and 46 degrees F)
- Store in original container
CONTRAINDICATIONS / PRECAUTIONS
Hamster protein hypersensitivity
Benralizumab is contraindicated in patients with a history of hypersensitivity to benralizumab or excipients in the formulation. Use with caution in patients with hamster protein hypersensitivity, as the drug is produced in Chinese hamster ovary cells. Hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension, urticaria, rash) have occurred after benralizumab administration. Such reactions generally occur within hours of administration, but may have a delayed onset (i.e., days). If a hypersensitivity reaction occurs, discontinue the drug and institute appropriate treatment.
Acute bronchospasm, status asthmaticus
Benralizumab should not be used to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after benralizumab initiation. Short-acting beta-agonists, such as albuterol, should be available for rescue therapy.
Corticosteroid withdrawal
Do not discontinue systemic or inhaled corticosteroid therapy abruptly upon benralizumab initiation. Corticosteroid withdrawal and dosage reduction, if appropriate, should be done gradually under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Helminth infection
Treat patients with a pre-existing helminth infection prior to initiating therapy with benralizumab. If a patient becomes infected while receiving benralizumab therapy and does not respond to anti-helminth treatment, discontinue benralizumab therapy until the infection resolves. Benralizumab reduces the production and survival of eosinophils, which may be involved in the immunological response to some helminth infections. Although it is not known whether if benralizumab will influence the body's response against parasitic infections, caution is warranted. Patients with known parasitic infections were excluded from clinical trials.
Pregnancy
Pregnancy exposure data for benralizumab is insufficient to inform on drug-associated risk. Monoclonal antibodies, such as benralizumab, are transported across the placenta as pregnancy progresses; therefore, potential fetal effects are likely to be greater during the third trimester. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to benralizumab during pregnancy. In a prenatal and postnatal development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with intravenous benralizumab administration throughout pregnancy at drug exposures approximately 310 times the exposure at the maximum recommended human dose (MRHD, 30 mg subcutaneously). Uncontrolled asthma also presents risks during pregnancy. In women with poorly or moderately controlled asthma, there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Asthma control should be closely monitored during pregnancy and treatment adjusted to maintain optimal control. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to benralizumab; information about the registry can be obtained at mothertobaby.org/ongoing-study/fasenra or by calling 1-877-311-8972.
Breast-feeding
There is no information regarding the presence of benralizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Benralizumab is a humanized monoclonal antibody (IgG1 kappa), and immunoglobulin G (IgG) is present in human milk in small amounts. Consider the developmental and health benefits of breast-feeding, the mother's need for benralizumab therapy, and potential adverse effects of the drug or inadequately treated asthma on the breastfed infant.
Children, infants
Benralizumab safety and efficacy have not been established for infants and children less than 12 years of age.
ADVERSE REACTIONS
Severe
angioedema / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
Moderate
antibody formation / Delayed / 13.0-13.0
Mild
headache / Early / 8.0-8.2
pharyngitis / Delayed / 5.0-5.0
fever / Early / 2.7-3.0
injection site reaction / Rapid / 2.2-2.2
rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
DRUG INTERACTIONS
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
PREGNANCY AND LACTATION
Pregnancy
Pregnancy exposure data for benralizumab is insufficient to inform on drug-associated risk. Monoclonal antibodies, such as benralizumab, are transported across the placenta as pregnancy progresses; therefore, potential fetal effects are likely to be greater during the third trimester. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to benralizumab during pregnancy. In a prenatal and postnatal development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with intravenous benralizumab administration throughout pregnancy at drug exposures approximately 310 times the exposure at the maximum recommended human dose (MRHD, 30 mg subcutaneously). Uncontrolled asthma also presents risks during pregnancy. In women with poorly or moderately controlled asthma, there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Asthma control should be closely monitored during pregnancy and treatment adjusted to maintain optimal control. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to benralizumab; information about the registry can be obtained at mothertobaby.org/ongoing-study/fasenra or by calling 1-877-311-8972.
There is no information regarding the presence of benralizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Benralizumab is a humanized monoclonal antibody (IgG1 kappa), and immunoglobulin G (IgG) is present in human milk in small amounts. Consider the developmental and health benefits of breast-feeding, the mother's need for benralizumab therapy, and potential adverse effects of the drug or inadequately treated asthma on the breastfed infant.
MECHANISM OF ACTION
Benralizumab is a fully humanized monoclonal antibody (IgG1 kappa) that targets human interleukin (IL)-5. IL-5 is the major cytokine responsible for eosinophilic airway inflammation in patients with asthma. IL-5 is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils. Benralizumab selectively binds to IL-5, blocking it from binding to the alpha chain of the IL-5 receptor complex located on the eosinophil cell surface. This, in turn, inhibits IL-5 signaling and reduces the production and survival of eosinophils. Other undefined mechanisms of action may also play a role.
PHARMACOKINETICS
Benralizumab is administered by subcutaneous injection. The central and peripheral volume of distribution (Vd) of benralizumab was 3.2 L and 2.5 L, respectively, for a 70-kg individual. Benralizumab is a humanized IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue. Benralizumab exhibited linear pharmacokinetics and no evidence of target receptor-mediated clearance pathway in a population pharmacokinetic analysis. The estimated typical systemic clearance (CL) for benralizumab was 0.29 L/day for a subject weighing 70-kg. Following subcutaneous administration, the elimination half-life was approximately 15.5 days.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
CYP450 enzymes, efflux pumps and protein-binding mechanisms are not involved in the clearance of benralizumab. There is no evidence of IL-5R alpha expression on hepatocytes and eosinophil depletion does not produce chronic systemic alterations of proinflammatory cytokines. An effect of benralizumab on the pharmacokinetics of co-administered medications is not expected. Based on the population analysis, commonly co-administered medications had no effect on benralizumab clearance in patients with asthma.
Subcutaneous Route
Following subcutaneous administration of benralizumab to patients with asthma, the absorption half-life was approximately 3.5 days. In a pharmacokinetic analysis, the estimated absolute bioavailability was approximately 59% and there was no clinically relevant difference in relative bioavailability in the administration to the abdomen, thigh, or arm.