BLACK BOX WARNING
- serious infections; malignancy; thrombosis (DVT, PE, arterial thrombosis); cardiovascular events — increased risk vs TNF inhibitors in patients ≥50 years with CV risk factors or smoking history; use only if no suitable alternative
tofacitinib (GI indication)
Brand: Xeljanz
⚠ BBW Prototype: tofacitinib
Drug Class: Janus kinase (JAK) inhibitor
Drug Family: targeted synthetic DMARD
Subclass: pan-JAK inhibitor (JAK1/JAK3-preferring)
Organ Systems: gastrointestinalimmunology
Mechanism of Action
Small molecule inhibitor of JAK1 and JAK3 that blocks signal transduction downstream of multiple cytokine receptors (IL-2, IL-4, IL-6, IL-7, IL-15, IL-21, IFN-gamma). This reduces inflammatory cytokine signaling in the intestinal mucosa, suppressing the inflammatory cascade in ulcerative colitis.
JAK1 and JAK3 (preferential)JAK2 (less potent)
Indications
- moderately to severely active ulcerative colitis (adults)
Contraindications
- active serious infection
- severe hepatic impairment
- Hepatitis B or C without treatment
Adverse Effects
Common
- upper respiratory infections
- nasopharyngitis
- headache
- diarrhea
- nausea
Serious
- serious bacterial, viral, fungal, opportunistic infections
- malignancy (lymphoma, lung cancer)
- major adverse cardiovascular events (MACE)
- deep vein thrombosis and pulmonary embolism
- herpes zoster reactivation
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~74%; not affected by food |
| Distribution | Vd ~87 L; moderately distributed |
| Metabolism | hepatic via CYP3A4 (major) and CYP2C19 (minor) |
| Excretion | renal (30%) and fecal (70%) |
| Half-life | ~3 hours |
| Onset | weeks (clinical response) |
| Peak | 0.5–1 hour |
| Duration | continuous dosing |
| Protein Binding | 40% |
| Vd | 87 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inhibitors (ketoconazole) | increased tofacitinib exposure; reduce dose | major |
| strong CYP3A4 inducers (rifampin) | decreased tofacitinib levels; reduced efficacy | major |
| immunosuppressants | additive immunosuppression and infection risk | major |
Nursing Considerations
- Screen for TB (latent and active), hepatitis B and C, and varicella before initiating; live vaccines are contraindicated.
- Monitor CBC, lipids, and LFTs at baseline and periodically; lymphopenia and hyperlipidemia are common.
- Counsel patients ≥50 years with cardiovascular risk factors or current/past smoking about the increased MACE and thrombosis risk per the 2021 FDA safety update.
- Shingles (herpes zoster) vaccination is recommended prior to initiation if not previously vaccinated; tofacitinib significantly increases herpes zoster risk.
Clinical Pearls
- For UC, induction dosing is 10 mg twice daily for ≥8 weeks, then reduce to 5 mg twice daily maintenance — this higher induction dose contributes to the increased risk profile.
- Tofacitinib's oral administration and rapid onset (~2 weeks) are advantages over biologics in certain clinical scenarios, despite the more extensive black box warnings.
Safety Profile
Pregnancy avoid
Lactation contraindicated
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.