Schedule H

Oral

• Upadacitinib 15 mg extended-release tablets

• Upadacitinib 30 mg extended-release tablets

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Rheumatoid Arthritis (Moderate to Severe Active Disease)

Indicated in adults with inadequate response or intolerance to methotrexate or other conventional DMARDs.

Parameter Recommendation

Starting dose 15 mg once daily orally

Titration Not required; fixed dose regimen

Usual maintenance dose 15 mg once daily

Maximum dose 15 mg once daily

Clinical Notes:

• May be used as monotherapy or in combination with methotrexate or other non-biologic DMARDs

• Do not combine with biologic DMARDs or other JAK inhibitors

• Tablets must be swallowed whole; do not split, crush, or chew

• Mandatory pre-treatment screening for latent TB and hepatitis B/C

1. Psoriatic Arthritis (Active Disease)

Indicated in adults with inadequate response or intolerance to one or more DMARDs.

Parameter Recommendation

Starting dose 15 mg once daily orally

Titration Not required

Usual maintenance dose 15 mg once daily

Maximum dose 15 mg once daily

Clinical Notes:

• Can be used as monotherapy or with non-biologic DMARDs

• Evaluate response at 12–16 weeks; discontinue if no clinical benefit observed

1. Ankylosing Spondylitis (Active Axial Spondyloarthritis)

Indicated in adults with inadequate response or intolerance to conventional therapy.

Parameter Recommendation

Starting dose 15 mg once daily orally

Titration Not required

Usual maintenance dose 15 mg once daily

Maximum dose 15 mg once daily

Clinical Notes:

• Assess clinical response at 12–16 weeks

• Continue only if adequate improvement in disease activity indices

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

Atopic Dermatitis (Moderate to Severe) — OFF-LABEL

Parameter Details

Dose 15 mg once daily; may increase to 30 mg once daily in refractory cases

Duration Long-term; assess response at 8–12 weeks

Specialist only Yes — dermatologist supervision mandatory

Evidence basis Phase III trials (Measure Up, AD Up); used in Indian dermatology specialist practice

Note 30 mg dose carries higher adverse event risk

Ulcerative Colitis (Moderate to Severe) — OFF-LABEL

Parameter Details

Induction dose 45 mg once daily for 8 weeks

Maintenance dose 15 mg or 30 mg once daily based on response and severity

Duration Long-term; evaluate response at 8 weeks before maintenance

Specialist only Yes — gastroenterologist supervision mandatory

Evidence basis Phase III trials (U-ACHIEVE, U-ACCOMPLISH); off-label in India

Note 45 mg strength not currently available in India; use multiple tablets or await availability

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India):

Not approved for use in children below 18 years in India.

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

Juvenile Idiopathic Arthritis / Atopic Dermatitis in Adolescents — OFF-LABEL

Parameter Details

Minimum age 12 years (international data only)

Weight requirement ≥40 kg

Dose 15 mg once daily

Duration Long-term; individualized

Specialist only Yes — paediatric rheumatologist or dermatologist supervision mandatory

Evidence basis International investigational trials; no Indian paediatric data available

Monitoring CBC, LFTs, lipid profile, infection surveillance at baseline and regularly

Statement: Use in patients below 18 years is NOT RECOMMENDED except under specialist supervision in exceptional circumstances. No approved Indian paediatric indication exists.

• Known hypersensitivity to upadacitinib or any excipient

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

• Severe hepatic impairment (Child-Pugh C)

• Pregnancy (confirmed or planned)

• Concurrent use with biologic DMARDs (anti-TNF agents, IL-6 inhibitors, abatacept, rituximab)

• Concurrent use with other JAK inhibitors

• Concurrent use with potent immunosuppressants (azathioprine, cyclosporine, tacrolimus in immunosuppressive doses)

• Latent tuberculosis infection — screen and complete anti-TB therapy before initiation

• History of herpes zoster — consider zoster vaccination before starting therapy

• History of recurrent or chronic infections

• Age ≥65 years — increased risk of serious infections, malignancy, and cardiovascular events

• History of venous thromboembolism (DVT/PE) or thrombotic risk factors

• Cardiovascular disease or multiple cardiovascular risk factors

• Known malignancy or history of malignancy (except treated non-melanoma skin cancer)

• Chronic lung disease

• Diverticular disease or concurrent NSAID use (GI perforation risk)

• Hepatitis B carriers — risk of reactivation; consult hepatologist

• Baseline cytopenias — do not initiate if ANC <1000/mm³, ALC <500/mm³, or Hb <8 g/dL

• Dyslipidaemia — monitor and treat per cardiovascular risk

Parameter Details

Risk assessment Contraindicated; teratogenic potential demonstrated in animal studies

Human data Insufficient; fetal harm likely based on mechanism

Preferred alternatives Hydroxychloroquine, sulfasalazine, low-dose corticosteroids for rheumatic conditions

Pre-conception Discontinue and use effective contraception; advise washout of at least 4 weeks before conception

Specialist input Mandatory — rheumatologist and obstetrician coordination required

Monitoring if exposed Detailed fetal anomaly scan; high-risk obstetric follow-up

Parameter Details

Breastfeeding compatibility Not recommended; avoid breastfeeding during therapy

Drug levels in milk Likely secreted (animal data); human data not available

Preferred alternatives Hydroxychloroquine, sulfasalazine (compatible with breastfeeding)

Monitoring in infant If unavoidable use — monitor for GI disturbances, rash, poor weight gain, infection signs

Parameter Recommendation

Starting dose 15 mg once daily (same as adult dose)

Titration Not applicable; fixed dose

Specific risks Increased risk of serious infections, herpes zoster, malignancy (especially lymphoma, NMSC), cardiovascular events, and thromboembolic events

Renal consideration Assess renal function; more frequent monitoring in those with declining eGFR

Clinical note Risk-benefit assessment essential; consider patient's cardiovascular risk profile, infection history, and malignancy risk before initiating

Interacting Drug/Class Effect & Management

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) Increases upadacitinib exposure (~75% increase with ketoconazole); use 15 mg dose only; avoid 30 mg or 45 mg doses with strong inhibitors

Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital) Significantly decreases upadacitinib levels (~60% reduction with rifampicin); avoid combination due to loss of efficacy

Other JAK inhibitors Contraindicated — additive immunosuppression risk

Biologic DMARDs (adalimumab, etanercept, tocilizumab, infliximab, abatacept) Contraindicated — increased serious infection and immunosuppression risk

Potent immunosuppressants (cyclosporine, tacrolimus, azathioprine) Avoid combination — additive immunosuppression

Live vaccines Contraindicated during therapy; administer at least 2–4 weeks before initiation

Interacting Drug/Class Effect & Management

Methotrexate Can be used concomitantly; monitor for additive hepatotoxicity with regular LFTs

Moderate CYP3A4 inhibitors (fluconazole, erythromycin, diltiazem, verapamil) Mild increase in upadacitinib levels; usually safe but monitor for adverse effects

Isoniazid, ethambutol, pyrazinamide Safer anti-TB options compared to rifampicin; monitor LFTs as both may cause hepatotoxicity

Statins Monitor lipid profile; upadacitinib itself elevates LDL; adjust statin therapy as needed

NSAIDs Additive GI perforation risk, especially in patients with diverticular disease; use with caution

Corticosteroids Can be used concomitantly; taper corticosteroids once disease control achieved

• Upper respiratory tract infections

• Nasopharyngitis

• Nausea

• Headache

• Acne

• Elevated LDL and HDL cholesterol

• Elevated creatine phosphokinase (CPK)

• Cough

• Abdominal pain

• Pyrexia

• Fatigue

• Serious infections (tuberculosis, pneumonia, bacterial sepsis, opportunistic infections) — may require immediate discontinuation

• Herpes zoster reactivation (including disseminated)

• Venous thromboembolism (deep vein thrombosis, pulmonary embolism)

• Arterial thrombotic events (myocardial infarction, stroke)

• Malignancy (lymphoma, non-melanoma skin cancer, solid tumours)

• Gastrointestinal perforation (rare; particularly with NSAID use or diverticular disease)

• Hepatotoxicity (significant transaminase elevation)

• Severe cytopenias (neutropenia, lymphopenia, anaemia)

• Hypersensitivity reactions

Phase Parameters

Baseline (before initiation) TB screening (Mantoux/IGRA + chest X-ray), Hepatitis B surface antigen, anti-HCV antibody, CBC with differential, LFTs (ALT, AST, bilirubin), fasting lipid profile, serum creatinine/eGFR, pregnancy test in women of childbearing potential

At 4 weeks CBC, LFTs

At 12 weeks CBC, LFTs, fasting lipid profile

Every 3–6 months (long-term) CBC with differential, LFTs, renal function

Annually Lipid profile, clinical assessment for malignancy (skin examination, lymph node assessment), cardiovascular risk evaluation

Ongoing Monitor for signs/symptoms of infection, herpes zoster, thromboembolic events

• Rinvoq 15 mg (AbbVie)

• Rinvoq 30 mg (AbbVie)

Note: Currently only originator brand (Rinvoq) available in India

Notes:

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

• Not under NPPA price control

• High-cost specialty medication; typically dispensed through specialty pharmacy channels or hospital pharmacies

• Patient assistance programmes may be available through manufacturer

• JAK1 selectivity: Upadacitinib has greater selectivity for JAK1 compared to older pan-JAK inhibitors (tofacitinib), potentially offering improved safety profile regarding haematological effects

• Mandatory TB screening: Screen all patients for latent TB before initiation; high TB burden in India makes this essential

• Lipid management: Expect LDL elevation in most patients; initiate or optimise statin therapy based on cardiovascular risk assessment

• Extended-release formulation: Tablets must be swallowed whole; do not crush or split — this affects drug release and efficacy

• Vaccination strategy: Complete all recommended vaccinations including herpes zoster vaccine (non-live recombinant preferred) before starting therapy; avoid live vaccines during treatment

• No combination with biologics: Never combine with biologic DMARDs or other JAK inhibitors — serious infection risk without added efficacy

upadacitinib; JAK inhibitor; JAK1 selective; rheumatoid arthritis; psoriatic arthritis; ankylosing spondylitis; immunosuppressant; DMARD; TB-screening-required; hepatitis-B-screening; thrombosis-risk; pregnancy-contraindicated; Schedule H

RxIndia v1.0 — 02 Jun 2025

• CDSCO approved prescribing information

• Indian Rheumatology Association (IRA) guidelines for rheumatoid arthritis management

• API Textbook of Medicine (Rheumatology section)

• AIIMS Drug Formulary

• National Formulary of India (NFI)

• NLEM 2022 (Upadacitinib not listed)

• AbbVie India — Rinvoq Prescribing Information

• SELECT trial programme data (for RA/PsA/AS dosing reference)

• Measure Up, AD Up trials (off-label atopic dermatitis reference)

• U-ACHIEVE, U-ACCOMPLISH trials (off-label ulcerative colitis reference)