Schedule H

Oral

• Tofacitinib 5 mg tablet (immediate-release)

• Tofacitinib 10 mg tablet (immediate-release)

• Tofacitinib 11 mg tablet (modified-release/extended-release)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Rheumatoid Arthritis (Moderate to Severe, Active)

In patients with inadequate response or intolerance to methotrexate or other DMARDs

Parameter Recommendation

Starting dose 5 mg twice daily (immediate-release) OR 11 mg once daily (modified-release)

Titration Not routinely required

Usual maintenance dose 5 mg twice daily OR 11 mg once daily

Maximum dose 10 mg/day (5 mg BD or 11 mg OD)

Duration Long-term; reassess response at 12 weeks

Clinical notes Preferably use with methotrexate; monotherapy if MTX-intolerant; screen for latent TB before initiation

1. Psoriatic Arthritis (Active)

In patients with inadequate response or intolerance to DMARDs

Parameter Recommendation

Starting dose 5 mg twice daily

Titration Not required

Usual maintenance dose 5 mg twice daily

Maximum dose 10 mg/day

Duration Long-term; assess response at 12–16 weeks

Clinical notes May be used as monotherapy or with non-biologic DMARDs; avoid combination with biologic DMARDs

1. Ulcerative Colitis (Moderate to Severe, Active)

In patients with inadequate response, loss of response, or intolerance to TNF blockers or conventional therapy

Phase Dose Duration

Induction 10 mg twice daily 8 weeks (may extend to 16 weeks if partial response)

Maintenance 5 mg twice daily Long-term

Parameter Recommendation

Starting dose 10 mg twice daily (induction phase)

Titration Step down to 5 mg twice daily after induction

Usual maintenance dose 5 mg twice daily

Maximum dose 10 mg twice daily (induction only); 5 mg twice daily for maintenance

Clinical notes If inadequate response during maintenance, may increase to 10 mg BD for limited duration; use lowest effective dose due to VTE risk

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

Indication Alopecia Areata

Status OFF-LABEL

Starting dose 5 mg twice daily

Titration Not applicable

Usual maintenance dose 5 mg twice daily

Maximum dose 10 mg/day

Duration 3–6 months trial; reassess response

Specialist only Yes — Dermatologist supervision required

Evidence basis Small RCTs and case series; not CDSCO-approved for this indication

Indication Refractory Dermatomyositis

Status OFF-LABEL

Starting dose 5 mg twice daily

Titration Not applicable

Usual maintenance dose 5 mg twice daily

Maximum dose 10 mg/day

Duration Long-term; based on clinical response

Specialist only Yes — Rheumatology supervision mandatory

Evidence basis Case series from Indian tertiary centres; international case reports

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India):

• NOT APPROVED for paediatric use in India (as of 2024)

Secondary Indications – Paediatric Doses (Off-label, if any):

Indication Polyarticular Juvenile Idiopathic Arthritis (pJIA)

Status OFF-LABEL in India (US FDA approved)

Age group ≥2 years

Dose Weight-based (per international data):

10–<20 kg: 3.2 mg (oral solution) twice daily

20–<40 kg: 4 mg twice daily

≥40 kg: 5 mg twice daily

Duration Long-term; specialist decision

Specialist only Yes — Paediatric Rheumatologist only

Evidence basis US FDA approval; no CDSCO approval; use only in clinical trial or institutional protocol setting in India

Safety monitoring: CBC, LFTs, lipid profile, TB screening before initiation; regular monitoring as per adult protocol

⚠️ Not recommended below 2 years of age.

⚠️ Not recommended below 18 years in India outside specialist paediatric rheumatology care.

Moderate impairment (eGFR 30–59) Reduce to 5 mg once daily (for RA/PsA); for UC, reduce induction dose to 5 mg BD and maintenance to 5 mg OD

Severe impairment (eGFR <30) Avoid use; if essential, use 5 mg once daily under specialist supervision only

Haemodialysis Not recommended — insufficient data; drug not significantly dialyzable

Peritoneal dialysis Not recommended — no data available

• Known hypersensitivity to tofacitinib or any excipients

• Active serious infections including tuberculosis, sepsis, opportunistic infections

• Severe hepatic impairment (Child-Pugh C)

• Pregnancy (teratogenic in animal studies)

• Concurrent use with biologic DMARDs (e.g., adalimumab, infliximab, etanercept, tocilizumab)

• Concurrent use with potent immunosuppressants (azathioprine, cyclosporine, tacrolimus) — except methotrexate

• Absolute lymphocyte count <500 cells/mm³

• Absolute neutrophil count <1000 cells/mm³

• Haemoglobin <9 g/dL

• Patients at increased risk of serious infections (history of recurrent infections, diabetes, chronic lung disease)

• Latent tuberculosis — must be screened and treated before initiating therapy

• Risk of herpes zoster reactivation — consider vaccination before starting

• Elderly patients >65 years — higher risk of infections, malignancy, cardiovascular events, and mortality

• History of or current venous thromboembolism (DVT/PE) — use with caution, especially at higher doses

• History of malignancy — increased risk of lymphoma and other malignancies with long-term use

• Cardiovascular risk factors (smoking, hypertension, diabetes, hyperlipidemia) — increased MACE risk in elderly

• History of diverticulitis — risk of GI perforation

• Lipid elevations — monitor and treat as needed

• Concurrent use with moderate CYP3A4 inhibitors — may require dose adjustment

Parameter Details

Risk category Contraindicated — animal studies demonstrate teratogenicity

Human data Limited; insufficient safety data in human pregnancy

Use recommendation Avoid throughout pregnancy; discontinue at least 4 weeks before planned conception

Preferred alternatives in India Certolizumab pegol (anti-TNF with minimal placental transfer); sulfasalazine for mild disease

Contraception Women of childbearing potential must use effective contraception during treatment and for at least 4 weeks after stopping

Monitoring If inadvertent exposure occurs, monitor fetal development with specialist obstetric care

Parameter Details

Compatibility Not recommended — potential immunosuppressive effects on nursing infant

Human data Present in breast milk in animal studies; human data lacking

Expected milk levels Unknown; theoretical concern due to mechanism

Preferred alternatives Certolizumab pegol, sulfasalazine (for compatible indications)

Recommendation Avoid breastfeeding during treatment; if used, withhold breastfeeding for at least 18 hours after dose

Infant monitoring If exposed, monitor for infections, feeding difficulties, and growth pattern

Parameter Recommendation

Starting dose 5 mg once daily or 5 mg twice daily (use lower end of dose range)

Titration Slower titration; reassess frequently

Special risks Significantly increased risk of serious infections, malignancy (especially lymphoma), major adverse cardiovascular events (MACE), venous thromboembolism, and all-cause mortality compared to TNF inhibitors

Age consideration In patients >65 years, use only when no suitable alternatives exist; prefer TNF inhibitors as first-line if eligible

Monitoring More frequent CBC, infection surveillance, cardiovascular assessment

Interacting Drug/Class Mechanism Clinical Recommendation

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) Increased tofacitinib plasma levels Reduce dose to 5 mg once daily when co-administered

Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, phenobarbital) Decreased tofacitinib efficacy Avoid combination — may render tofacitinib ineffective

Biologic DMARDs (adalimumab, infliximab, etanercept, tocilizumab, rituximab) Additive immunosuppression Contraindicated — significantly increased infection and malignancy risk

Potent immunosuppressants (azathioprine, cyclosporine, tacrolimus) Additive immunosuppression Avoid combination

Live vaccines Risk of disseminated infection Contraindicated during treatment and for 2 weeks after stopping

Interacting Drug/Class Effect Clinical Recommendation

Moderate CYP3A4 inhibitors (fluconazole, erythromycin, diltiazem, verapamil) May increase tofacitinib levels Monitor for adverse effects; consider dose reduction if toxicity occurs

Moderate CYP3A4 inducers + CYP2C19 inhibitors (fluconazole) Net effect on levels uncertain Monitor efficacy and toxicity

Methotrexate Additive immunosuppression (but commonly used together) Acceptable combination; monitor CBC and LFTs more frequently

Corticosteroids Additive immunosuppression Use lowest effective steroid dose; taper when possible

Warfarin Potential for altered INR Monitor INR closely at initiation and dose changes

NSAIDs Increased GI perforation risk Use with caution, especially in patients with diverticular disease

• Upper respiratory tract infections

• Nasopharyngitis

• Headache

• Diarrhoea

• Hypertension

• Elevated LDL and total cholesterol

• Elevated liver transaminases (ALT/AST)

• Nausea

• Rash

• Fatigue

Adverse Effect Clinical Action

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

Herpes zoster reactivation Interrupt therapy; treat with antivirals; may resume after resolution

Venous thromboembolism (DVT, PE) Discontinue immediately; initiate anticoagulation; avoid rechallenge

Major adverse cardiovascular events (MI, stroke) Discontinue; manage as per cardiology protocols

Malignancy (lymphoma, solid tumours, NMSC) Discontinue; oncology referral

Gastrointestinal perforation Discontinue immediately; surgical consultation

Cytopenias (neutropenia, lymphopenia, anaemia) Interrupt if ANC <1000, ALC <500, or Hb <8 g/dL; may resume when counts recover

Hepatotoxicity Discontinue if ALT/AST >5× ULN or if associated with symptoms

Phase Parameters to Monitor

Baseline CBC with differential, LFTs (ALT, AST, bilirubin), lipid profile (LDL, HDL, TG), serum creatinine, TB screening (Mantoux test or IGRA + chest X-ray), viral hepatitis serology (HBsAg, anti-HCV), vaccination status

After initiation (4–8 weeks) CBC with differential, LFTs, lipid profile

Every 3 months (first year) CBC with differential, LFTs

Long-term CBC every 3–6 months; LFTs every 3–6 months; lipid profile annually; periodic screening for infections, malignancy; cardiovascular risk assessment annually

Lipid management: Initiate statin therapy if LDL elevated at 8–12 weeks and sustained.

• Xeljanz® (Pfizer) — originator brand

• Jaknat® (Natco Pharma)

• Tofajak® (Cipla)

• Tofasure® (Sun Pharma)

• Jakura® (Intas Pharmaceuticals)

• Tofashine® (Zydus Cadila)

• Tofakem® (Alkem)

Note: Not listed under NLEM; not under DPCO price control. Higher out-of-pocket costs; generics significantly more affordable than originator brand.

• Mandatory TB screening before initiation — Mantoux test or IGRA plus chest X-ray; treat latent TB before starting tofacitinib.

• Do NOT combine with biologic DMARDs — combining with anti-TNF or other biologics significantly increases serious infection and malignancy risk.

• Step-down dosing in ulcerative colitis — induction at 10 mg BD for 8 weeks, then step down to 5 mg BD for maintenance; avoid prolonged high-dose therapy due to VTE risk.

• Monitor lipids early — LDL and cholesterol often rise within 4–8 weeks; consider statin initiation if sustained elevation.

• Elderly patients (>65 years) at higher risk — ORAL Surveillance trial showed increased mortality, MACE, malignancy, and VTE compared to anti-TNF therapy; prefer biologics in this population when possible.

• Herpes zoster prophylaxis — consider recombinant zoster vaccine (Shingrix) before initiating therapy, especially in patients >50 years or those with prior herpes zoster.

Tofacitinib; JAK inhibitor; rheumatoid arthritis; psoriatic arthritis; ulcerative colitis; immunosuppressant; TB screening; VTE risk; pregnancy-avoid; renal-dose-adjust; Schedule H; India

RxIndia v1.0 — 11 Jun 2025

• CDSCO product insert (Tofacitinib)

• Indian manufacturer prescribing information (Cipla, Sun Pharma, Natco)

• API Textbook of Medicine (11th edition) — Rheumatoid arthritis, IBD chapters

• ICMR Guidelines for Rheumatoid Arthritis Management (2019)

• AIIMS Rheumatology Department protocols

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Harrison's Principles of Internal Medicine (21st edition)

• ORAL Surveillance Trial (NEJM 2022) — safety data in elderly

• Indian consensus review on JAK inhibitors (Indian Journal of Rheumatology, 2021)

• Drug not currently listed in NLEM 2022