Schedule H

Subcutaneous

• Dupilumab 300 mg/2 mL solution for injection in prefilled syringe

• Dupilumab 300 mg/2 mL solution for injection in prefilled pen (autoinjector)

Note: Paediatric formulations (200 mg/1.14 mL and 100 mg/0.67 mL) may have limited availability in India — verify before prescribing for children <60 kg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Atopic Dermatitis (Moderate to Severe)

Indicated in adults and adolescents ≥12 years with moderate to severe atopic dermatitis inadequately controlled with topical therapies or when topical therapies are not advisable.

Parameter Recommendation

Starting dose 600 mg SC (two 300 mg injections at different sites on Day 1)

Titration Not required

Usual maintenance dose 300 mg SC every 2 weeks

Maximum dose 300 mg every 2 weeks

Clinical Notes:

• May be used with or without topical corticosteroids

• Assess clinical response at 16 weeks; consider discontinuation if inadequate improvement

• Can be self-administered by patient or caregiver after proper training

• Administer in thigh, abdomen (except 5 cm around navel), or upper arm (if administered by caregiver)

1. Asthma with Type 2 Inflammation (Moderate to Severe)

Indicated as add-on maintenance therapy in patients ≥12 years with moderate to severe asthma characterised by eosinophilic phenotype or oral corticosteroid-dependent asthma.

Dosing Options (select based on clinical profile):

Clinical Profile Starting Dose Maintenance Dose

Standard dosing 400 mg SC (two 200 mg injections) on Day 1 200 mg SC every 2 weeks

OCS-dependent or high eosinophil burden (≥1500 cells/µL) 600 mg SC (two 300 mg injections) on Day 1 300 mg SC every 2 weeks

Parameter Recommendation

Starting dose 400 mg or 600 mg SC on Day 1 (based on profile above)

Titration Not applicable

Usual maintenance dose 200 mg or 300 mg SC every 2 weeks

Maximum dose 300 mg every 2 weeks

Clinical Notes:

• Continue background inhaled corticosteroids (ICS) ± long-acting beta-agonists (LABA)

• Do not use for acute bronchospasm or status asthmaticus

• Evaluate response at 4–6 months

• Systemic corticosteroids should be tapered gradually under supervision once disease control achieved

• NOT indicated for non-eosinophilic (neutrophilic) asthma phenotype

Note: 200 mg prefilled syringe may have limited availability in India — use two 300 mg injections if 200 mg formulation unavailable

1. Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP)

Indicated as add-on therapy in adults with inadequately controlled CRSwNP despite intranasal corticosteroids.

Parameter Recommendation

Starting dose 300 mg SC

Titration Not required

Usual maintenance dose 300 mg SC every 2 weeks

Maximum dose 300 mg every 2 weeks

Clinical Notes:

• Continue intranasal corticosteroids during therapy

• Evaluate clinical benefit at 24 weeks

• May reduce need for systemic corticosteroids and nasal surgery in responders

• Long-term continuation in responders is appropriate

Secondary Indications — Adults (Off-label, if any):

Prurigo Nodularis — OFF-LABEL

Parameter Details

Starting dose 600 mg SC (two 300 mg injections) on Day 1

Maintenance dose 300 mg SC every 2 weeks

Duration Minimum 12–16 weeks to assess response

Specialist only Yes — dermatologist supervision mandatory

Evidence basis Phase III trials (PRIME/PRIME2); not CDSCO-approved for this indication

Eosinophilic Oesophagitis — OFF-LABEL

Parameter Details

Dose 300 mg SC weekly

Duration 12–24 weeks initial assessment; long-term in responders

Specialist only Yes — gastroenterologist supervision mandatory

Evidence basis International RCTs (J Allergy Clin Immunol 2022); not CDSCO-approved

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India):

1. Atopic Dermatitis (Moderate to Severe)

Age ≥12 years: Use adult dosing

Age 6 to <12 years (weight-based dosing):

Body Weight Starting Dose Maintenance Dose

15 kg to <30 kg 600 mg SC (two 300 mg injections) on Day 1 300 mg SC every 4 weeks

30 kg to <60 kg 400 mg SC (two 200 mg injections) on Day 1 200 mg SC every 2 weeks

≥60 kg 600 mg SC (two 300 mg injections) on Day 1 300 mg SC every 2 weeks

Clinical Notes:

• Minimum age: 6 years

• 200 mg prefilled syringe may have limited availability in India — confirm availability before prescribing for 30–60 kg weight category

• May be used with or without topical corticosteroids

• Specialist paediatric dermatologist/allergist supervision mandatory

Safety Monitoring in Paediatrics:

• Monitor for conjunctivitis (common)

• Watch for herpes simplex virus infections (eczema herpeticum)

• Monitor eosinophil count

• Ensure age-appropriate vaccinations completed before initiation

1. Asthma with Type 2 Inflammation

Age ≥12 years: Use adult dosing

Age 6 to <12 years (weight-based dosing):

Body Weight Starting Dose Maintenance Dose

15 kg to <30 kg 300 mg SC on Day 1 300 mg SC every 4 weeks

≥30 kg 200 mg SC on Day 1 200 mg SC every 2 weeks

Clinical Notes:

• Paediatric formulations (100 mg, 200 mg) may have limited availability in India — verify before prescribing

• Pulmonologist/allergist supervision mandatory

• Continue background ICS/LABA therapy

Secondary Indications — Paediatrics (Off-label, if any):

Not applicable.

Off-label use in eosinophilic oesophagitis or chronic rhinosinusitis with nasal polyposis in paediatric population is not recommended outside clinical trial settings.

Statement: Use in children below 6 years is NOT RECOMMENDED except under specialist supervision in exceptional circumstances. No approved indication exists for children <6 years in India.

No dose adjustment required.

Dupilumab is a monoclonal antibody and is not eliminated through renal pathways. Formal pharmacokinetic studies in end-stage renal disease or dialysis patients have not been conducted, but dose modification is not expected to be necessary based on mechanism of elimination.

• Known hypersensitivity to dupilumab or any excipient (including histidine, arginine, polysorbate 80)

• Active severe systemic infections (sepsis, severe bacterial infections) — postpone initiation until infection is controlled

• Active helminthic (parasitic) infections — treat and resolve before initiating dupilumab; monitor if infection occurs during therapy

• History of conjunctivitis, keratitis, or other ocular surface diseases — increased risk of ocular adverse events

• Pre-existing eosinophilia or history of eosinophilic granulomatosis with polyangiitis (EGPA) — monitor for eosinophilic exacerbations or vasculitis symptoms

• Herpes virus infections (history of eczema herpeticum, recurrent herpes simplex) — monitor closely; may require antiviral prophylaxis

• Asthmatic patients on systemic corticosteroids — do not abruptly discontinue; taper gradually

• Concurrent live vaccines — avoid administration during treatment (see Drug Interactions)

• Patients with limited dexterity or visual impairment may require assistance for self-injection

Parameter Details

Risk assessment Limited human data; animal studies show no teratogenicity or fetal harm

Overall recommendation Use only if potential benefit justifies potential risk to fetus

Preferred alternatives Topical corticosteroids, topical calcineurin inhibitors for mild-moderate atopic dermatitis; for asthma: ICS/LABA, omalizumab (if indicated)

When it may be used Severe refractory disease unresponsive to safer alternatives; under specialist supervision

Monitoring Fetal growth monitoring; maternal disease control assessment

Specialist input Mandatory — dermatologist/pulmonologist and obstetrician coordination

Parameter Details

Breastfeeding compatibility Likely compatible; IgG monoclonal antibodies are minimally excreted in breast milk and poorly absorbed orally by infant

Drug levels in milk Expected to be low; no significant systemic absorption in infant anticipated

Preferred alternatives Topical therapies for mild-moderate disease if breastfeeding preferred

Monitoring in infant Monitor for adequate feeding, weight gain, signs of infection

Special considerations Use with caution in preterm infants or immunocompromised neonates

Parameter Recommendation

Starting dose Same as adult dosing

Titration Not required

Specific considerations No pharmacokinetic differences observed in elderly patients

Additional risks Increased baseline risk of infections; monitor for conjunctivitis; assess ability for self-injection (manual dexterity, visual acuity)

Monitoring Standard monitoring; ensure caregiver assistance if self-administration is difficult

Interacting Drug/Class Effect & Management

Live vaccines Avoid administration during dupilumab therapy; complete all live vaccine updates at least 4 weeks before initiation; killed/inactivated vaccines may be given during treatment

Other biologic immunosuppressants (cyclosporine, azathioprine, mycophenolate, tacrolimus) Avoid concurrent use; increased risk of serious infections; dupilumab should not be combined with other systemic immunosuppressants except topical corticosteroids

Interacting Drug/Class Effect & Management

Topical corticosteroids Can be continued concomitantly; taper based on clinical response once disease control achieved

Inhaled corticosteroids (ICS) / LABA Continue during dupilumab therapy for asthma; do not abruptly discontinue

Systemic corticosteroids Taper gradually once dupilumab effect established; abrupt discontinuation may cause disease flare

Antivirals (acyclovir, valacyclovir) May be needed for treatment/prophylaxis of herpes simplex or zoster; no pharmacokinetic interaction

CYP450 substrates Dupilumab does not affect CYP450 enzyme activity; no dose adjustment needed for CYP-metabolised drugs

• Injection site reactions (erythema, oedema, pruritus, pain) — 5–10%

• Conjunctivitis and keratitis — 5–10% (more common in atopic dermatitis patients)

• Blepharitis

• Oral herpes (cold sores)

• Headache

• Nasopharyngitis

• Eosinophilia (transient, usually asymptomatic)

• Arthralgia

• Anaphylaxis and severe hypersensitivity reactions — rare; requires immediate discontinuation, epinephrine, and emergency care

• Eosinophilic conditions (eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis-like presentation) — rare; investigate if respiratory symptoms or systemic eosinophilia develop; may require discontinuation

• Severe conjunctivitis/keratitis — may require ophthalmology referral and treatment interruption in severe cases

• Eczema herpeticum / disseminated herpes infections — requires prompt antiviral therapy and dupilumab interruption

• Serum sickness-like reactions — rare; discontinue and provide supportive care

Phase Parameters

Baseline (before initiation) Complete blood count with eosinophil count; baseline disease severity assessment (SCORAD/EASI for AD, lung function for asthma); eye examination if history of ocular disease; screen for helminthic infections in endemic areas; ensure vaccinations updated

At 4–8 weeks Injection site reactions; conjunctivitis symptoms; clinical response assessment

At 12–16 weeks Therapeutic response evaluation (consider discontinuation if no improvement); eosinophil count if symptomatic

Long-term (every 6–12 months) Clinical disease control; annual eye examination for atopic dermatitis patients; monitor for herpes virus infections; eosinophil count if indicated

Ongoing Symptoms of eosinophilic conditions (dyspnoea, worsening pulmonary symptoms); signs of serious infection

• Dupixent (Sanofi/Regeneron) — originator brand

Note: Currently only the originator brand is available in India. No Indian generic biosimilars available as of this version.

Notes:

• Not included in National List of Essential Medicines (NLEM) 2022

• Not under NPPA price control

• Not routinely available through government supply; primarily private sector procurement

• Monthly maintenance cost: approximately ₹90,000–₹1,10,000 (for every 2-week dosing)

• Patient assistance programmes may be available through manufacturer

• Set realistic expectations: Clinical improvement in atopic dermatitis may take 4–16 weeks; premature discontinuation is common if patients are not counselled appropriately

• Eosinophil count predicts response: Higher baseline eosinophils (especially in asthma) correlate with better therapeutic response; consider checking before initiation

• Managing conjunctivitis: Dupilumab-associated conjunctivitis can often be managed conservatively with preservative-free lubricants or low-potency topical ophthalmic corticosteroids; rarely requires treatment discontinuation

• Do not abruptly stop corticosteroids: In asthma patients on systemic corticosteroids, taper gradually once dupilumab effect is established to avoid adrenal insufficiency and disease flare

• Add-on therapy in asthma: Dupilumab is an add-on to ICS/LABA, not a replacement; continue background controller therapy

• Not for neutrophilic asthma: Dupilumab targets Type 2 (Th2) inflammation; it is ineffective in neutrophilic or non-eosinophilic asthma phenotypes

dupilumab; monoclonal antibody; IL-4 inhibitor; atopic dermatitis; eczema; asthma; eosinophilic asthma; nasal polyposis; biologic therapy; injectable; conjunctivitis-risk; Schedule H

RxIndia v1.0 — 02 Jun 2025

• CDSCO approved prescribing information (Dupixent)

• Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) guidelines for atopic dermatitis management

• Global Initiative for Asthma (GINA) 2023 — India-relevant components

• API Textbook of Medicine (Allergy and Immunology sections)

• National Formulary of India (NFI)

• NLEM 2022 (Dupilumab not listed)

• AIIMS Essential Drug List (Biologics section)

• Sanofi India — Dupixent Prescribing Information

• Phase III trial data for off-label indications (prurigo nodularis, eosinophilic oesophagitis)