Benralizumab- Anti-asthmatic- Fasenra -@- (Nov 2017)
Drug Name:Benralizumab- Anti-asthmatic- Fasenra -@- (Nov 2017)
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS-
No formal drug interaction studies have been conducted
Indication:
U.S. FDA APPROVED DRUGS DURING 2017
Sr.No- 38
Name of the Drug- Fasenra
Active Ingredient- Benralizumab
Pharmacological Classification-
For add-on maintenance treatment of patients with severe
asthma aged 12 years and older, and with an eosinophilic
phenotype
Date of Approval- 11-14-2017
(Ref- FDA approved List 2017)
HIGHLIGHTS OF PRESCRIBING INFORMATION-
WARNINGS AND PRECAUTIONS
These highlights do not include all the information needed to use FASENRA™ safely and effectively.
See full prescribing information for FASENRA. FASENRA (benralizumab) injection, for subcutaneous use
Initial U.S. Approval: XXXX
INDICATIONS AND USAGE
FASENRA is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.
Limitations of Use: 1.Not for treatment of other eosinophilic conditions.
2.Not for relief of acute bronchospasm or status asthmaticus.
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (incidence greater than or equal to 5%) include headache and pharyngitis.
Contra-Indications:
CONTRAINDICATIONS-
Known hypersensitivity to benralizumab or excipients.
WARNINGS AND PRECAUTIONS-
Hypersensitivity reactions: hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA.
Discontinue in the event of a hypersensitivity reaction.
Reduction in Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Decrease corticosteroids gradually, if appropriate.
Parasitic (Helminth) Infection: Treat patients with pre-existing helminth infections before therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until the parasitic infection resolves.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
FASENRA is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.
Limitations of Use: 1.Not for treatment of other eosinophilic conditions.
2.Not for relief of acute bronchospasm or status asthmaticus.
DOSAGE AND ADMINISTRATION
Administer by subcutaneous injection. Recommended dose is 30 mg every 4 weeks for the first 3 doses, followed by once every 8 weeks thereafter.
DOSAGE FORMS AND STRENGTHS-
Injection: 30 mg/mL solution in a single-dose prefilled syringe.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity Reactions-
Inform patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA.
These reactions generally occurred within hours of FASENRA administration, but in some instances had a delayed onset (i.e., days).
Instruct patients to contact their healthcare professional if they experience symptoms of an allergic reaction
Not for Acute Symptoms or Deteriorating Disease-
Inform patients that FASENRA does not treat acute asthma symptoms or acute exacerbations.
Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with FASENRA
Reduction of Corticosteroid Dosage-
Inform patients to not discontinue systemic or inhaled corticosteroids except under the direct supervision of a physician.
Inform patients that reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy
Manufactured by AstraZeneca AB Södertälje, Sweden SE-15185 US License No. 2059
Distributed by AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850
FASENRA is a trademark of the AstraZeneca group of companies. ©AstraZeneca XXXX
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY-
1. Mechanism of Action
Benralizumab is a humanized afucosylated, monoclonal antibody (IgG1, kappa) that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Ra) with a dissociation constant of 11 pM.
Pharmacokinetics-
The pharmacokinetics of benralizumab was approximately dose-proportional in patients with asthma following subcutaneous administration over a dose range of 20 to 200 mg.
Absorption:
Following subcutaneous administration to patients with asthma, the absorption half-life was approximately 3.6 days.
Based on population pharmacokinetic analysis, the estimated absolute bioavailability was approximately 58% and there was no clinically relevant difference in relative bioavailability in the administration to the abdomen, thigh, or arm.
Distribution:
Based on population pharmacokinetic analysis, central and peripheral volume of distribution of benralizumab was 3.2 L and 2.5 L, respectively, for a 70kg individual.
Metabolism:
Benralizumab is a humanized IgG1 monoclonal antibody that is degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue.
Elimination:
From population pharmacokinetic analysis, benralizumab exhibited linear pharmacokinetics and no evidence of target receptor-mediated clearance pathway.
The estimated typical systemic clearance (CL) for benralizumab was 0.29 L/d for a subject weighing 70kg. Following subcutaneous administration, the elimination half-life was approximately 15 days.
Specific populations:
Age: Based on population pharmacokinetic analysis, age did not affect benralizumab clearance.
Gender, Race: A population pharmacokinetics analysis indicated that there was no significant effect of gender and race on benralizumab clearance.
Renal impairment:
No formal clinical studies have been conducted to investigate the effect of renal impairment on benralizumab.
Based on population pharmacokinetic analysis, benralizumab clearance was comparable in subjects with creatinine clearance values between 30 and 80 mL/min and patients with normal renal function.
Hepatic impairment:
No formal clinical studies have been conducted to investigate the effect of hepatic impairment on benralizumab. IgG monoclonal antibodies are not primarily cleared via hepatic pathway; change in hepatic function is not expected to influence benralizumab clearance.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy Risk Summary
The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk.
Monoclonal antibodies such as benralizumab 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 the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
2.Lactation-
Risk Summary
There is no information regarding the presence of benralizumab in human or animal milk, and the effects of benralizumab on the breast fed infant and on milk production are not known.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for benralizumab and any potential adverse effects on the breast-fed child from benralizumab or from the underlying maternal condition.
3. Pediatric Use-
The pharmacokinetics of benralizumab in adolescents 12 to 17 years of age were consistent with adults based on population pharmacokinetic analysis and the reduction in blood eosinophil counts was similar to that observed in adults following the same FASENRA treatment.
The safety and efficacy in patients younger than 12 years of age has not been established.
4.Geriatric Use
Of the total number of patients in clinical trials of benralizumab, 13% (n= 320) were 65 and over, while 0.4% (n=9) were 75 and over.
No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
OVERDOSAGE
Doses up to 200 mg were administered subcutaneously in clinical trials to patients with eosinophilic disease without evidence of dose-related toxicities. There is no specific treatment for an overdose with benralizumab. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.
