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. |
| Molecular Weight | 312.24 |
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. |
| Geriatric use |
| 1st trimester | Avoid due to potential teratogenicity. Animal studies show fetal harm. |
| 2nd trimester | Avoid due to risks of immunosuppression and unknown fetal effects. |
| 3rd trimester | Avoid due to risks of immunosuppression in neonate and maternal complications. |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause serious infections and increased risk of malignancy.
| Placental transfer | Crosses placenta in animal studies; human data limited but expected due to molecular size. |
| Breastfeeding | Present in human milk; avoid breastfeeding due to potential serious adverse reactions in the infant. |
| Lactation Rating |
■ 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 |
Severe active infection (e.g., tuberculosis, sepsis, opportunistic infections)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) |
Loading safety data…
| 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. |
| Avoid |
| 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 | 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. |
| Food/Dietary |
| Avoid grapefruit and grapefruit juice as they can increase tofacitinib levels. No significant food restrictions beyond that. |
| Clinical Pearls | Monitor for serious infections including tuberculosis (TB) and herpes zoster before and during therapy. Assess baseline and periodic liver function tests, lipid profile, and complete blood count. Avoid live vaccines during treatment. Do not use with potent CYP3A4 inhibitors (e.g., ketoconazole) unless dose reduced. Consider dose adjustment in renal impairment (CrCl <60 mL/min). Tofacitinib increases risk of thrombosis, especially in patients with cardiovascular risk factors. |
| Patient Advice | Do not take tofacitinib if you have an active infection, including TB. · Report any signs of infection (fever, cough, painful urination) or shingles (painful rash). · Tell your doctor if you have had blood clots, heart attack, stroke, or cancer. · Avoid live vaccines (e.g., MMR, nasal flu vaccine) while on this medication. · Do not take tofacitinib with alcohol or grapefruit juice without discussing with your doctor. · Take exactly as prescribed; do not change dose without consulting your healthcare provider. |