Schedule H

Subcutaneous Injection

• Prefilled Syringe: 25 mg/0.5 mL, 50 mg/mL

• Prefilled Autoinjector: 50 mg/mL

• Powder for Reconstitution: 25 mg/vial

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Rheumatoid Arthritis — Adults

Parameter Recommendation

Starting dose 50 mg subcutaneously once weekly OR 25 mg subcutaneously twice weekly

Titration Not applicable (fixed dosing)

Usual maintenance dose 50 mg subcutaneously once weekly

Maximum dose 50 mg/week

Clinical Notes:

• Combination with methotrexate is more effective than etanercept monotherapy

• Clinical response typically seen within 2–12 weeks

• If no response after 12 weeks, reassess treatment strategy

• May be used as monotherapy if methotrexate is contraindicated or not tolerated

1. Ankylosing Spondylitis

Parameter Recommendation

Starting dose 50 mg subcutaneously once weekly OR 25 mg subcutaneously twice weekly

Titration Not applicable

Usual maintenance dose 50 mg subcutaneously once weekly

Maximum dose 50 mg/week

Clinical Notes:

• Consider switching to alternative biologic if no response after 12 weeks

• Assess disease activity using validated indices (BASDAI, ASDAS)

1. Psoriatic Arthritis

Parameter Recommendation

Starting dose 50 mg subcutaneously once weekly

Titration Not applicable

Usual maintenance dose 50 mg subcutaneously once weekly

Maximum dose 50 mg/week

Clinical Notes:

• Effective both as monotherapy and in combination with methotrexate

• Benefits both joint disease and skin manifestations

• Assess response at 12 weeks

1. Plaque Psoriasis — Moderate to Severe (Candidates for Systemic Therapy)

Parameter Recommendation

Starting dose 50 mg subcutaneously twice weekly for initial 12 weeks

Titration Reduce to maintenance after 12 weeks

Usual maintenance dose 50 mg subcutaneously once weekly

Maximum dose 100 mg/week during initial phase; 50 mg/week for maintenance

Clinical Notes:

• Reserved for patients who have failed or are intolerant to conventional systemic therapies

• Reassess response at 12 weeks using PASI or other validated measures

• Discontinue if inadequate response after 12 weeks of maintenance therapy

Secondary Indications – Adults (Off-label, if any)

Indication Dose Duration Notes

Hidradenitis Suppurativa 50 mg SC twice weekly initially, then 50 mg weekly Long-term; specialist-driven OFF-LABEL; Specialist only (Dermatology); Evidence: Small RCTs; Indian dermatology practice; Used when other agents fail

Refractory Uveitis 25–50 mg SC once weekly Long-term OFF-LABEL; Specialist only (Ophthalmology/Rheumatology); Evidence: Observational studies; Limited controlled evidence

Adult-Onset Still's Disease 50 mg SC once weekly Long-term OFF-LABEL; Specialist only; Evidence: Case series; Indian rheumatology practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Juvenile Idiopathic Arthritis (Polyarticular Course) — Age ≥2 Years

Weight-Based Dosing:

Body Weight Dose Frequency Maximum Dose

<25 kg 0.8 mg/kg SC Once weekly 50 mg/week

25–62 kg 0.8 mg/kg SC Once weekly 50 mg/week

≥63 kg 50 mg SC Once weekly 50 mg/week

Clinical Notes:

• Minimum age: 2 years

• Must be initiated and monitored by paediatric rheumatologist

• Screen for TB and complete age-appropriate vaccinations before initiation

• Avoid live vaccines during treatment and for 5 months after last dose

• May be used with or without methotrexate

Safety Monitoring:

• CBC with differential every 8–12 weeks

• LFTs every 8–12 weeks

• Growth monitoring at each visit

• Monitor for infections and malignancy

1. Paediatric Plaque Psoriasis — Age ≥6 Years

Parameter Recommendation

Starting dose 0.8 mg/kg subcutaneously once weekly (maximum 50 mg)

Titration Not applicable

Usual maintenance dose 0.8 mg/kg subcutaneously once weekly

Maximum dose 50 mg/week

Clinical Notes:

• Minimum age: 6 years

• For moderate to severe plaque psoriasis inadequately controlled by topical therapies

• Specialist (paediatric dermatology/rheumatology) supervision mandatory

Secondary Indications – Paediatrics (Off-label, if any)

Not applicable.

• Off-label paediatric use not routinely recommended outside licensed indications

• Any use beyond approved indications requires paediatric rheumatologist/specialist supervision in tertiary centres

Not recommended below 2 years of age under any circumstances.

• Etanercept is a large protein molecule; not renally eliminated

• Safe in patients on haemodialysis and peritoneal dialysis

• No significant accumulation with renal impairment

• Active serious infections (sepsis, tuberculosis, opportunistic infections)

• Known hypersensitivity to etanercept or any formulation component (including latex in certain prefilled syringes)

• Moderate to severe heart failure (NYHA Class III or IV)

• Active or latent tuberculosis (unless adequately treated)

• Demyelinating diseases (multiple sclerosis, optic neuritis, transverse myelitis)

• Concurrent use with anakinra or abatacept

• History of latent tuberculosis — must screen and treat before initiation

• Hepatitis B carriers — risk of reactivation; specialist hepatology input recommended

• Hepatitis C — monitor closely; limited safety data

• History of recurrent infections or predisposing conditions for infection

• Malignancy history — increased risk of lymphomas and skin cancers; regular surveillance required

• Mild heart failure (NYHA Class I/II) — monitor for worsening

• Elderly patients — increased infection and malignancy risk

• Live vaccines — contraindicated during treatment and for at least 5 months after discontinuation

• Concurrent immunosuppressive biologics — avoid combination

• Neurological symptoms — discontinue if demyelinating disease suspected

• Autoimmune conditions — may develop autoantibodies; lupus-like syndrome possible

Parameter Details

Risk Category Limited human data; animal studies show no teratogenicity

Recommendation Generally avoided in first trimester; may be considered in 2nd and 3rd trimesters for severe, uncontrolled disease

Preferred Alternatives Certolizumab pegol (minimal placental transfer) preferred if biologic needed during pregnancy

When May Be Used Severe, refractory rheumatic disease where benefits clearly outweigh risks; joint rheumatology-obstetric decision

Timing Discontinue by 30–32 weeks gestation if possible to reduce neonatal immunosuppression

Monitoring Maternal infection surveillance; neonatal monitoring for infections; avoid live vaccines in infant for first 5–6 months of life

Parameter Details

Compatibility Compatible with breastfeeding; minimal drug transfer to milk

Drug Levels in Milk Very low; large molecular size limits excretion; not orally bioavailable

Preferred Alternatives Certolizumab pegol if alternative needed; etanercept is acceptable

Infant Monitoring Monitor for infections and normal growth and development

Vaccination Avoid live vaccines in infant for 5–6 months if mother received etanercept in late pregnancy

Parameter Recommendation

Starting dose Same as adult dosing (50 mg SC once weekly)

Titration Not applicable

Special Risks Increased susceptibility to serious infections; higher malignancy risk; potential for CHF exacerbation; falls risk due to fatigue

Monitoring More frequent monitoring of CBC, LFTs, renal function; vigilant infection surveillance; regular skin examination for malignancy

Interacting Drug Mechanism / Effect Recommendation

Live Vaccines (BCG, MMR, varicella, yellow fever, oral polio, oral typhoid, rotavirus) Risk of disseminated vaccine-induced infection due to immunosuppression Contraindicated during treatment and for at least 5 months after last dose

Anakinra (IL-1 receptor antagonist) Additive immunosuppression; significantly increased serious infection risk with no additional efficacy Contraindicated — do not combine

Abatacept Additive immunosuppression; increased infection risk Contraindicated — do not combine

Cyclophosphamide Increased malignancy risk Avoid combination

Other Biologic DMARDs (rituximab, tocilizumab, infliximab) Additive immunosuppression Avoid concurrent use; allow adequate washout when switching

Interacting Drug Mechanism / Effect Recommendation

Methotrexate Commonly co-prescribed; enhances efficacy in RA and PsA; no significant pharmacokinetic interaction Permissible and recommended combination in RA/PsA; standard monitoring

Corticosteroids Additive immunosuppression Monitor for infections; use lowest effective corticosteroid dose

Anti-TB Drugs (isoniazid, rifampicin) Required for latent TB treatment before/during etanercept Complete at least 1 month of anti-TB therapy before initiating etanercept if latent TB; may continue concurrent treatment

Leflunomide Additive immunosuppression Monitor for infections and hepatotoxicity

Azathioprine Additive immunosuppression Use with caution; monitor closely

Sulfasalazine May be combined; no significant interaction Standard monitoring

• Injection site reactions (erythema, pain, itching, swelling) — most common; usually mild and transient

• Upper respiratory tract infections

• Headache

• Rhinitis

• Rash / Pruritus

• Nausea

• Diarrhoea

• Abdominal pain

• Fatigue

• Cough

Adverse Effect Clinical Action

Serious Infections (sepsis, pneumonia, cellulitis, tuberculosis reactivation, opportunistic infections) Discontinue immediately; initiate appropriate antimicrobial therapy; do not resume until infection resolved

Tuberculosis Reactivation Discontinue; initiate full anti-TB treatment; specialist input

Demyelinating Disorders (optic neuritis, transverse myelitis, MS exacerbation) Discontinue permanently; neurology referral

Heart Failure Exacerbation Discontinue if new or worsening heart failure; cardiology referral

Malignancies (lymphoma, skin cancers including melanoma) Discontinue; oncology referral; regular dermatological surveillance

Hepatotoxicity Monitor LFTs; discontinue if significant elevation; hepatology input

Lupus-like Syndrome (anti-dsDNA antibodies, rash, serositis) Consider discontinuation; usually resolves after stopping

Pancytopenia / Aplastic Anaemia (rare) Discontinue immediately; haematology referral

Severe Allergic Reactions (anaphylaxis — rare) Discontinue permanently; emergency management

Before Each Dose (Initial Phase) Clinical assessment for infection symptoms

Every 8–12 Weeks CBC with differential, LFTs

Every 6 Months Clinical assessment of disease activity; check for new symptoms suggestive of TB, malignancy, neurological disease

Annually Skin examination for malignancy; reassess TB risk if ongoing exposure

Ongoing Vigilance for signs of infection, TB reactivation, malignancy, demyelinating disease, heart failure

TB Screening Protocol:

• Mantoux test (≥5 mm positive in immunosuppressed) OR IGRA (QuantiFERON/T-SPOT)

• Chest X-ray

• If latent TB detected: complete at least 1 month of anti-TB therapy before starting etanercept; continue anti-TB treatment for full course

• Enbrel (Pfizer) — Originator

• Etacept (Intas)

• Intacept (Intas)

• Etanib (Reliance Life Sciences)

• Avent (Cipla)

Note: FDCs not applicable for etanercept.

• Not included in NLEM; pricing not NPPA-controlled

• Significant price variation between originator and biosimilars

• May be available at subsidised rates through select government rheumatology centres

• Some patient assistance programmes available through manufacturers

• Mandatory TB screening (IGRA or Mantoux + Chest X-ray) before initiation — India has high TB prevalence; treat latent TB for at least 1 month before starting etanercept and continue full course concurrently

• Clinical response typically begins within 2–4 weeks; assess efficacy at 12 weeks — if inadequate response, consider switching to alternative biologic rather than increasing dose

• Combination with methotrexate in RA and PsA is more effective than etanercept monotherapy — combine unless methotrexate is contraindicated

• Injection site reactions are common but usually mild and transient — rotate injection sites; reactions typically decrease with continued use

• Complete all age-appropriate live vaccinations at least 4 weeks before starting etanercept — no live vaccines during treatment or for 5 months after stopping

• Avoid in patients with NYHA Class III/IV heart failure — may worsen cardiac function; use with caution even in Class I/II

Etanercept; TNF inhibitor; biologic DMARD; rheumatoid arthritis; ankylosing spondylitis; psoriatic arthritis; juvenile idiopathic arthritis; plaque psoriasis; tuberculosis screening; immunosuppression; infection risk; specialist-only; Schedule H

RxIndia v1.0 — 06 Apr 2025

• CDSCO approved product information (Enbrel, Etacept)

• Indian Pharmacopoeia (IP)

• National Formulary of India (NFI)

• API Textbook of Medicine — Rheumatology chapter

• AIIMS Rheumatology Department Treatment Protocols

• Indian Rheumatology Association Guidelines

• ICMR TB Screening Guidelines

• Indian Academy of Pediatrics (IAP) Immunisation Guidelines

• Goodman & Gilman's: The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine