Schedule H

Subcutaneous injection

• Prefilled syringe for subcutaneous injection: 30 mg/mL

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

▶ Severe Eosinophilic Asthma (Add-on maintenance therapy)

Eligibility Criteria:

• Age ≥18 years

• Severe asthma inadequately controlled on high-dose ICS + LABA

• Peripheral blood eosinophil count ≥300 cells/μL

• History of frequent exacerbations or oral corticosteroid dependence

Dosing:

Parameter Recommendation

Starting dose 30 mg SC at Week 0

Titration 30 mg SC at Week 4 and Week 8 (induction phase — 3 doses at 4-week intervals for eosinophil depletion)

Usual maintenance dose 30 mg SC every 8 weeks (after induction)

Maximum dose 30 mg per dose (fixed-dose, non-weight-based)

Clinical Notes:

• Initiate under pulmonologist/allergist supervision

• Confirm eosinophilic phenotype before starting

• Not indicated for acute bronchospasm or rescue therapy

• Not for use as monotherapy — continue ICS/LABA

Secondary Indications – Adults (Off-label)

▶ Hypereosinophilic Syndrome (HES) — OFF-LABEL

Parameter Details

Indication Hypereosinophilic syndrome refractory to conventional therapy

Dose 30 mg SC every 4 weeks

Duration Individualized; typically >6 months

Prescriber Specialist only (haematology/immunology)

Evidence Limited data; RCTs supporting anti-IL-5 pathway agents in HES; minimal Indian experience

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

▶ Severe Eosinophilic Asthma (Age ≥12 years)

Note: Approval for adolescents ≥12 years based on international regulatory data; verify current CDSCO status before prescribing.

Dosing:

Parameter Recommendation

Starting dose 30 mg SC at Week 0

Titration 30 mg SC at Week 4 and Week 8

Usual maintenance dose 30 mg SC every 8 weeks

Maximum dose 30 mg per dose (fixed-dose)

Safety Monitoring:

• Growth velocity assessment periodically

• Eosinophil count monitoring

• Infection surveillance

NOT RECOMMENDED below age 12 years in India except under strict specialist supervision.

Secondary Indications – Paediatric Doses (Off-label)

Not established. Any off-label paediatric use requires strict specialist guidance with individualized risk-benefit assessment.

• Known hypersensitivity to benralizumab or any excipient in the formulation

• History of anaphylaxis to monoclonal antibody therapies

• Active helminth (parasitic) infections — treat and resolve before initiating therapy

• Immunocompromised individuals — heightened infection susceptibility

• Prior hypersensitivity reactions to injectable biological agents

• Possible increased risk of herpes zoster reactivation

• Post-injection observation recommended, especially during induction phase

Parameter Details

Risk statement Limited human data; animal studies have not demonstrated teratogenicity or fetal harm

Recommendation Not routinely recommended; use only when potential maternal benefit clearly outweighs fetal risk

Preferred alternatives Optimized ICS/LABA therapy; omalizumab (if anti-IgE therapy appropriate)

Monitoring Maternal asthma control; fetal growth surveillance via ultrasound

Parameter Details

Compatibility Unknown whether excreted in human milk

Expected transfer Likely minimal — large molecular weight (~150 kDa) limits milk transfer

Preferred alternatives Inhaled corticosteroids and LABAs for asthma control during lactation

Infant monitoring Routine monitoring; significant systemic exposure to infant unlikely

Parameter Recommendation

Starting dose 30 mg SC (same as younger adults)

Titration Standard induction regimen

Special considerations Assess for multiple comorbidities; consider heightened infection risk in frail elderly

Monitoring Infection surveillance; overall tolerability assessment

Interacting Agent Mechanism / Risk Recommendation

Live vaccines Immunomodulatory effect may impair vaccine efficacy or increase infection risk Avoid co-administration; complete live vaccinations before initiating therapy

Note: Benralizumab is not metabolized via CYP450 enzymes — negligible pharmacokinetic interaction potential with small-molecule drugs.

Interacting Agent Concern Recommendation

Inactivated vaccines Potentially reduced immunogenicity during biologic therapy Consider optimal timing; monitor vaccine response

Concomitant immunosuppressants Additive infection risk Enhanced infection surveillance required

• Injection site reactions (erythema, pain, swelling)

• Headache

• Pharyngitis

• Pyrexia

• Anti-drug antibody development (generally non-neutralizing)

Adverse Effect Clinical Notes

Anaphylaxis Rare; requires immediate treatment and permanent discontinuation

Severe hypersensitivity reactions May require hospitalization; urticaria, angioedema possible

Serious infections Opportunistic infections rarely reported

Eosinophil rebound Described in HES upon abrupt cessation — specialist monitoring essential

Baseline:

• Asthma control assessment (ACT score, exacerbation history)

• Spirometry (FEV1)

• Peripheral blood eosinophil count

• Screen for and treat active parasitic infections

After initiation:

• Post-injection observation for hypersensitivity (especially first 3 doses)

• Eosinophil count at 1–2 months

Long-term:

• Asthma control parameters (exacerbation frequency, OCS requirement, ACT score)

• Reassess need for continued biologic therapy at 6–12 months

• Periodic infection surveillance

• Fasenra® (AstraZeneca)

Parameter Details

NLEM status Not listed under NLEM

NPPA price control Not applicable

Recommendation Insurance reimbursement or patient assistance programs advised due to high cost

• Benralizumab causes near-complete eosinophil depletion via antibody-dependent cell-mediated cytotoxicity (ADCC), unlike mepolizumab which neutralizes circulating IL-5 only

• Fixed-dose regimen (30 mg) — no weight-based calculations needed, simplifying prescribing

• After 3-dose induction, 8-weekly maintenance reduces clinic visit burden and improves compliance

• Confirm eosinophilic phenotype (blood eosinophils ≥300 cells/μL) before initiation — non-eosinophilic asthma will not respond

• Not effective for acute exacerbations; always continue standard ICS/LABA controller therapy

• Reassess clinical response at 6–12 months; consider discontinuation if inadequate benefit

benralizumab; Fasenra; eosinophilic asthma; severe asthma; biologic therapy; anti-IL-5 receptor; monoclonal antibody; subcutaneous; specialist-only; high-cost therapy

RxIndia v0.2 — 20 Apr 2025

• CDSCO (product approval and labeling information)

• NLEM — not listed

• IP/NFI — not listed

• AIIMS Drug Formulary

• ICMR Guidelines on Bronchial Asthma

• API Textbook of Medicine

• Indian respiratory specialist practice inputs

• CALIMA, SIROCCO, BORA trials (efficacy data for approved indications)

• FDA/EMA product labels (supportive reference for off-label HES use only)