TOFACITINIB
Clinical safety rating: avoid
Contraindicated (not allowed)
Janus kinase (JAK) inhibitor, primarily inhibiting JAK1 and JAK3, thereby modulating the JAK-STAT signaling pathway to reduce cytokine production and immune cell activation.
| Metabolism | Primarily metabolized by CYP3A4, with minor contribution from CYP2C19. |
| Excretion | Primarily renal (70%) with 30% excreted unchanged in urine. Fecal elimination accounts for 20% (<1% unchanged). Minor biliary excretion. |
| Half-life | Terminal half-life approximately 3.3 hours in healthy volunteers. In patients with rheumatoid arthritis, effective half-life ~3-6 hours due to reversible binding to JAK enzymes. No significant accumulation at steady state. |
| Protein binding | Approximately 40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Apparent Vd ~87 L (or 1.25 L/kg for a 70 kg individual). Indicates extensive extravascular distribution. |
| Bioavailability | Oral immediate-release: 74% (range 62–89%). Extended-release: 74% relative to immediate-release. No significant food effect. |
| Onset of Action | Oral: Clinical improvement observed within 2 weeks, with maximal effect by 3-6 months. |
| Duration of Action | Duration of action corresponds to dosing interval (immediate-release: 12 hours; extended-release: 24 hours). Clinical effect persists with continued dosing. |
5 mg orally twice daily; extended-release formulation 11 mg orally once daily. For rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis. For ulcerative colitis, induction: 10 mg orally twice daily for 8 weeks, then maintenance 5 mg twice daily.
| Dosage form | TABLET |
| Renal impairment | For moderate to severe renal impairment (creatinine clearance [CrCl] <60 mL/min or, for extended-release, CrCl 30-59 mL/min): reduce dose to 5 mg once daily (immediate-release) or 11 mg once daily (extended-release) not recommended; use immediate-release 5 mg once daily. For severe renal impairment (CrCl <30 mL/min): not recommended. No adjustment for mild impairment (CrCl ≥60 mL/min). |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose to 5 mg once daily. Child-Pugh Class C: not recommended. |
| Pediatric use | For polyarticular course juvenile idiopathic arthritis (pcJIA) in patients ≥2 years old: weight-based dosing: 10 kg to <20 kg: 3.2 mg (0.4 mL of 5 mg/mL solution) orally twice daily; 20 kg to <40 kg: 4 mg (0.5 mL of 5 mg/mL solution) orally twice daily; ≥40 kg: 5 mg orally twice daily. For ulcerative colitis in patients ≥2 years old: same weight-based dosing as above for induction and maintenance. For other indications, pediatric safety and efficacy not established. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause serious infections and increased risk of malignancy.
| Breastfeeding | Excreted in rat milk; no human data. M/P ratio unknown. Advise against breastfeeding due to potential for serious adverse reactions in nursing infants. |
| Teratogenic Risk | First trimester: Animal studies show teratogenicity at supratherapeutic doses; limited human data preclude definitive risk. Second/third trimester: Potential for fetal harm based on mechanism (JAK inhibition), no adequate human studies. Use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, and THROMBOSIS. Patients treated with tofacitinib are at increased risk for serious infections leading to hospitalization or death, including tuberculosis, invasive fungal infections, and bacterial, viral, and opportunistic infections. Lymphoma and other malignancies have been observed. Thrombosis, including pulmonary embolism, deep vein thrombosis, and arterial thrombosis, has occurred at increased rates in patients with rheumatoid arthritis.
| Common Effects | psoriatic arthritis |
| Serious Effects |
["Hypersensitivity to tofacitinib or any excipients"]
| Precautions | ["Serious infections","Malignancies","Thrombosis","Gastrointestinal perforations","Hepatotoxicity","Hypersensitivity reactions","Laboratory abnormalities (lymphopenia, neutropenia, anemia, elevated liver enzymes, elevated lipids)"] |
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| Geriatric use |
| No specific dose adjustment based solely on age. However, due to higher risk of infections and malignancies in elderly patients, use with caution. Consider lower starting dose (e.g., 5 mg once daily) for patients ≥65 years with rheumatoid arthritis, but standard dosing is often used. Monitor renal function closely as elderly may have reduced CrCl. |
| Monitor complete blood count, liver function tests, and lipids every 4-8 weeks. Assess for signs of infection. Fetal ultrasound if used during pregnancy. |
| Fertility Effects | Animal studies show no impairment of male or female fertility at human-equivalent doses. No human fertility studies; effect on fertility is unknown. |