Schedule H

Subcutaneous Injection

• Prefilled Syringe: 40 mg/0.8 mL

• Prefilled Pen Injector: 40 mg/0.8 mL

• Lyophilised Powder for Reconstitution: 40 mg/vial (select brands)

• Paediatric Formulation: 20 mg/0.4 mL (limited availability)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Rheumatoid Arthritis — Adults (Moderate to Severe Active Disease)

In combination with methotrexate or as monotherapy if methotrexate is contraindicated/not tolerated.

Parameter Recommendation

Starting dose 40 mg subcutaneously every other week (every 2 weeks)

Titration May increase to 40 mg weekly if inadequate response (specialist discretion)

Usual maintenance dose 40 mg subcutaneously every 2 weeks

Maximum dose 40 mg subcutaneously weekly

Clinical Notes:

• Mandatory TB screening before initiation

• More effective when combined with methotrexate

• Assess response at 12 weeks; consider switching if no benefit

1. Ankylosing Spondylitis — Adults (Active Disease)

Parameter Recommendation

Starting dose 40 mg subcutaneously every 2 weeks

Titration Not applicable

Usual maintenance dose 40 mg subcutaneously every 2 weeks

Maximum dose 40 mg subcutaneously every 2 weeks

Clinical Notes:

• Evaluate response by 12 weeks using validated indices (BASDAI, ASDAS)

• Discontinue if no clinical benefit at 12 weeks

1. Psoriatic Arthritis — Adults

Parameter Recommendation

Starting dose 40 mg subcutaneously every 2 weeks

Titration May increase to weekly if inadequate response

Usual maintenance dose 40 mg subcutaneously every 2 weeks

Maximum dose 40 mg subcutaneously weekly

Clinical Notes:

• May be used alone or in combination with methotrexate

• Benefits both joint and skin manifestations

1. Plaque Psoriasis — Adults (Chronic Moderate to Severe Disease)

Parameter Recommendation

Starting dose 80 mg subcutaneously once (Week 0)

Titration 40 mg subcutaneously at Week 1, then every 2 weeks

Usual maintenance dose 40 mg subcutaneously every 2 weeks

Maximum dose 40 mg subcutaneously every 2 weeks

Clinical Notes:

• For patients who are candidates for systemic therapy

• Assess response at 16 weeks; discontinue if inadequate

1. Crohn's Disease — Adults (Moderate to Severe Active Disease)

Induction Phase:

Week Dose

Week 0 160 mg SC (may be given as 4 injections on Day 1 OR 2 injections on Day 1 and Day 2)

Week 2 80 mg SC

Maintenance Phase (from Week 4):

Parameter Recommendation

Starting dose 40 mg subcutaneously every 2 weeks

Titration May increase to 40 mg weekly if loss of response

Usual maintenance dose 40 mg subcutaneously every 2 weeks

Maximum dose 40 mg subcutaneously weekly

Clinical Notes:

• For patients with inadequate response to conventional therapy

• Assess response by 12 weeks

1. Ulcerative Colitis — Adults (Moderate to Severe Active Disease)

Induction Phase:

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

10 kg to <30 kg 20 mg SC Every 2 weeks

≥30 kg 40 mg SC Every 2 weeks

Clinical Notes:

• Minimum age: 2 years

• May be used with or without methotrexate

• Specialist paediatric rheumatologist supervision mandatory

1. Paediatric Crohn's Disease — Age 6–17 Years (Moderate to Severe Active Disease)

Induction Phase:

Body Weight Week 0 Week 2

15 kg to <40 kg 80 mg SC 40 mg SC

≥40 kg 160 mg SC 80 mg SC

Maintenance Phase (from Week 4):

Body Weight Dose Frequency Maximum

15 kg to <40 kg 20 mg SC Every 2 weeks; may increase to weekly if needed 20 mg weekly

≥40 kg 40 mg SC Every 2 weeks; may increase to weekly if needed 40 mg weekly

Clinical Notes:

• Minimum age: 6 years

• For patients with inadequate response to immunomodulators or corticosteroids

• Paediatric gastroenterology supervision mandatory

1. Paediatric Uveitis — Age ≥2 Years (Non-Infectious)

Weight-Based Dosing:

Body Weight Initial Dose Maintenance (from Week 1)

<30 kg 40 mg SC once 20 mg SC every 2 weeks

≥30 kg 80 mg SC once 40 mg SC every 2 weeks

Clinical Notes:

• Minimum age: 2 years

• Paediatric ophthalmology/rheumatology supervision mandatory

Safety Monitoring in Paediatric Use:

• TB screening before initiation

• CBC with differential every 4–8 weeks initially, then every 3 months

• LFTs every 3 months

• Growth and weight monitoring at each visit

• Immunisation history review; complete age-appropriate vaccines before starting

• Avoid live vaccines during treatment and for 3–5 months after discontinuation

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

Indication Age Dose Notes

Paediatric Plaque Psoriasis ≥4 years 0.8 mg/kg SC (maximum 40 mg) every 2 weeks OFF-LABEL in India; Specialist only (Paediatric Dermatology); Evidence: International trials; Very limited Indian experience

Paediatric Hidradenitis Suppurativa ≥12 years Same as adult dosing OFF-LABEL; Specialist only; Very limited evidence

Not recommended below 2 years of age under any circumstances. Use above 2 years only under specialist supervision in tertiary centres.

• Adalimumab is a large protein molecule; not renally eliminated

• Safe in patients on haemodialysis and peritoneal dialysis

• No significant accumulation with renal impairment

• Known hypersensitivity to adalimumab or any excipient (including latex in certain prefilled syringes)

• Active serious infections (sepsis, tuberculosis, opportunistic infections including invasive fungal infections)

• Active or latent tuberculosis (unless adequately treated)

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

• Demyelinating diseases (multiple sclerosis, Guillain-Barré syndrome, optic neuritis)

• Concurrent use with anakinra or abatacept

• History of latent tuberculosis — mandatory screening and treatment before initiation

• Hepatitis B carriers — risk of reactivation; specialist hepatology input; antiviral prophylaxis may be required

• 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

• History of demyelinating symptoms — avoid if possible

• Elderly patients — increased infection risk

• Diabetes mellitus — increased infection susceptibility

• Live vaccines — contraindicated during treatment and for at least 3–5 months after discontinuation

• Concurrent immunosuppressive biologics — avoid combination

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

• Surgery — consider withholding perioperatively; specialist decision

Parameter Details

Risk Category Limited human data; IgG1 antibody actively transported across placenta (especially in 3rd trimester); animal studies show no teratogenicity

Recommendation May be continued during pregnancy if clinically necessary; preferably discontinue by 30–32 weeks if disease controlled

Preferred Alternatives Certolizumab pegol (minimal placental transfer) may be preferred if initiating biologic during pregnancy

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

Monitoring Neonatal monitoring for immunosuppression and infections if exposed in utero (especially late pregnancy); avoid live vaccines in infant for first 5–6 months of life

Parameter Details

Compatibility Likely compatible with breastfeeding

Drug Levels in Milk Low; large molecular size limits excretion; IgG1 antibodies poorly excreted in milk; not orally bioavailable

Preferred Alternatives Certolizumab pegol if alternative needed; adalimumab 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 adalimumab in late pregnancy

Parameter Recommendation

Starting dose Same as adult dosing

Titration Standard titration; slower if concerns about tolerability

Special Risks Increased susceptibility to serious infections (especially respiratory); higher malignancy risk; potential for CHF exacerbation

Monitoring More frequent monitoring of CBC, LFTs; 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 3–5 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

Alkylating Agents (cyclophosphamide) Additive immunosuppression; increased malignancy risk Avoid combination

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

Interacting Drug Mechanism / Effect Recommendation

Methotrexate Commonly co-prescribed; reduces adalimumab immunogenicity and may slightly reduce clearance; enhances efficacy 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 adalimumab Complete at least 1 month of anti-TB therapy before initiating adalimumab 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

Warfarin Adalimumab may affect warfarin metabolism (through cytokine effects) Monitor INR when starting or adjusting adalimumab

• Injection site reactions (pain, erythema, itching, swelling, bruising) — most common

• Upper respiratory tract infections

• Sinusitis

• Headache

• Rash / Pruritus

• Nausea

• Abdominal pain

• Fatigue

• Elevated liver enzymes

• Musculoskeletal pain

Adverse Effect Clinical Action

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

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

Hepatitis B Reactivation Discontinue; urgent hepatology referral; antiviral therapy

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

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

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

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

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

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

Hepatotoxicity (elevated transaminases, hepatitis) Monitor LFTs; discontinue if significant elevation

4–8 Weeks Post-Initiation CBC with differential, LFTs, clinical assessment for infection

Every 3 Months (First Year) CBC, LFTs, clinical assessment for infection and disease activity

Every 6 Months (Long-term) CBC, LFTs, disease activity assessment

Annually TB re-screening if ongoing risk factors; skin examination for malignancy

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

Paediatric-Specific Growth and weight monitoring; immunisation history review

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 adalimumab; continue anti-TB treatment for full course

Biosimilars (Commonly Used):

• Exemptia (Zydus Cadila)

• Adfrar (Torrent)

• Adalimumab (Intas Biosciences)

• AdaliRel (Reliance Life Sciences)

• Adbio (Biocon)

• Mabura (Hetero)

Originator:

• Humira (AbbVie) — Limited availability; imported

Note: Biosimilars are widely used in India with comparable efficacy and safety to the originator. FDCs not applicable.

• Included in NLEM 2022 under Biologics category

• May be available at subsidised rates or free in select government rheumatology/gastroenterology tertiary centres

• Some patient assistance programmes available through manufacturers

• Significant price advantage of biosimilars over originator

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

• Combination with methotrexate in RA and PsA significantly improves efficacy and reduces adalimumab immunogenicity (development of anti-drug antibodies) — combine unless methotrexate is contraindicated

• Biosimilar adalimumab (e.g., Exemptia, Adfrar) is widely used in India at significantly lower cost with similar efficacy — cost should not be a barrier to appropriate use

• Weekly dosing (instead of every 2 weeks) is an effective rescue strategy for patients losing response — consider before switching to alternative biologic

• Complete all age-appropriate live vaccinations at least 4 weeks before starting adalimumab — no live vaccines during treatment or for 3–5 months after stopping; killed/inactivated vaccines can be given

• Educate patients to report signs of infection immediately (fever, cough, weight loss, night sweats) — early recognition of TB reactivation or serious infection is critical

Adalimumab; TNF inhibitor; biologic DMARD; rheumatoid arthritis; ankylosing spondylitis; psoriatic arthritis; plaque psoriasis; Crohn's disease; ulcerative colitis; uveitis; juvenile idiopathic arthritis; tuberculosis screening; biosimilar; NLEM India; Schedule H

RxIndia v1.0 — 10 Apr 2025

• CDSCO approved product information

• Indian Pharmacopoeia (IP) — Biologics section

• National List of Essential Medicines (NLEM) 2022

• National Formulary of India (NFI)

• API Textbook of Medicine — Rheumatology and Gastroenterology chapters

• AIIMS Rheumatology and Gastroenterology Department Treatment Protocols

• Indian Rheumatology Association Consensus Guidelines

• Indian Academy of Pediatrics (IAP) Guidelines for JIA

• ICMR TB Screening Guidelines

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

• Harrison's Principles of Internal Medicine

• International RCTs (for off-label indications — marked accordingly)