XELJANZ XR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XELJANZ XR (XELJANZ XR).
Janus kinase (JAK) inhibitor; inhibits JAK1, JAK2, JAK3, and TYK2, modulating cytokine signaling pathways involved in immune responses.
| Metabolism | Primarily metabolized by CYP3A4; minor contribution from CYP2C19. |
| Excretion | Renal excretion accounts for approximately 70% of total clearance (30% unchanged drug, 40% as metabolites); biliary/fecal excretion accounts for approximately 30% of total clearance (metabolites). |
| Half-life | Terminal elimination half-life is approximately 3.3 hours for the immediate-release formulation; for XELJANZ XR (extended-release), effective half-life is prolonged due to extended absorption, but terminal half-life remains ~3.3 hours. Clinical context: Twice-daily dosing for IR, once-daily for XR. |
| Protein binding | Approximately 40% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.6 L/kg (based on population pharmacokinetics), indicating distribution into total body water and some tissue binding. |
| Bioavailability | Absolute oral bioavailability of tofacitinib is approximately 74%. For XELJANZ XR, relative bioavailability compared to immediate-release is 100% (dose-adjusted), with no food effect. |
| Onset of Action | Oral (extended-release): Clinical effects (e.g., reduction in rheumatoid arthritis symptoms) observed within 2–4 weeks of starting therapy; maximum effect may take up to 3–6 months. |
| Duration of Action | Duration of action is approximately 12 hours after a single XR dose; however, steady-state is achieved within 2–3 days. Continuous therapy required for sustained effect; discontinuation leads to gradual return of disease symptoms over weeks. |
| Action Class | Janus kinase inhibitors |
| Brand Substitutes | Rocenib 5mg Tablet, Tofaxen 5mg Tablet, Tofakin 5mg Tablet, Jaknat Tablet, Evertop 5mg Tablet |
11 mg orally once daily, with or without food, for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis; for ulcerative colitis, use 5 mg twice daily if switching from immediate-release tofacitinib 5 mg twice daily.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | For severe renal impairment (CrCl <30 mL/min) or ESRD on hemodialysis: 5 mg once daily. For moderate impairment (CrCl 30-49 mL/min): 5 mg twice daily. Not recommended with severe hepatic impairment. |
| Liver impairment | Mild (Child-Pugh A): no adjustment. Moderate (Child-Pugh B): 5 mg once daily. Severe (Child-Pugh C): not recommended. |
| Pediatric use | Not approved for pediatric use. Safety and efficacy not established. Limited data in juvenile idiopathic arthritis (JIA) from studies; dosing not established. |
| Geriatric use | No specific dose adjustment. Use with caution due to increased infection risk and higher rate of adverse events. Monitor renal function and consider lower starting dose if CrCl <50 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XELJANZ XR (XELJANZ XR).
| Breastfeeding | Excreted in animal milk. Human M/P ratio not determined. Due to potential serious adverse reactions in nursing infants (immunosuppression, growth retardation), breastfeeding is contraindicated during therapy and for at least 18 hours after the last dose of XELJANZ XR. |
| Teratogenic Risk | Pregnancy Category X. Tofacitinib is contraindicated in pregnancy. Animal studies show teratogenicity (skeletal and visceral malformations) at exposures similar to human therapeutic doses. First trimester: high risk of major congenital malformations. Second and third trimesters: risk of fetal growth restriction and developmental toxicity. No adequate human studies. |
■ FDA Black Box Warning
Serious infections leading to hospitalization or death, including tuberculosis, invasive fungal infections, and bacterial/viral/opportunistic infections; malignancy including lymphoma; thrombosis (PE, DVT, arterial thrombosis); increased all-cause mortality in patients ≥50 years with at least one CV risk factor; major adverse cardiovascular events; and serious hypersensitivity reactions.
| Serious Effects |
["Hypersensitivity to tofacitinib or excipients","Severe hepatic impairment","Active serious infections (including TB)","Pregnancy (not recommended)","Breastfeeding (not recommended)"]
| Precautions | ["Serious infections: screen for TB; avoid use during active infection","Malignancy risk: monitor for skin cancers","Thrombosis: avoid in patients at high risk","Gastrointestinal perforations: monitor for new-onset abdominal pain","Vaccinations: avoid live vaccines during treatment","Hepatotoxicity: monitor LFTs"] |
Loading safety data…
| Fetal Monitoring | If inadvertent exposure during pregnancy occurs, monitor fetus via ultrasound for structural anomalies and growth parameters. Assess maternal renal and hepatic function monthly. Monitor for infections, cytopenias (CBC with differential), and lipid profile every 4-8 weeks. |
| Fertility Effects | In animal studies, tofacitinib at high doses impaired female fertility (decreased implantation, increased postimplantation loss) and caused reduced sperm count and motility in males. Human data are lacking; however, reversible impairment of fertility may occur. Consider fertility preservation counseling in patients of childbearing potential. |