XELJANZ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XELJANZ (XELJANZ).
Janus kinase (JAK) inhibitor. Selectively inhibits JAK1 and JAK3, mediating signaling of cytokines/growth factors involved in immune response and hematopoiesis.
| Metabolism | Primarily metabolized by CYP3A4 with minor contribution from CYP2C19. |
| Excretion | Approximately 70% of the dose is excreted in urine (30% as unchanged drug, 40% as metabolites) and 20% in feces (10% as unchanged drug). |
| Half-life | Terminal half-life is approximately 3.3 hours. Twice-daily dosing maintains therapeutic concentrations. |
| Protein binding | Approximately 40-50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 1.1 L/kg, indicating extravascular distribution. |
| Bioavailability | Oral bioavailability is 74% (range 59-92%). |
| Onset of Action | Oral: Clinical effect (reduction in rheumatoid arthritis symptoms) observed within 2 weeks; maximal effect by 3-6 months. |
| Duration of Action | Duration corresponds to dosing interval (12 hours); continuous administration required for sustained effect. |
5 mg orally twice daily; for rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. For ulcerative colitis induction, 10 mg orally twice daily for 8 weeks; maintenance at 5 mg orally twice daily.
| Dosage form | SOLUTION |
| Renal impairment | For creatinine clearance 30-59 mL/min: 5 mg orally once daily. For creatinine clearance 15-29 mL/min: 5 mg orally once daily (not recommended for use in induction therapy of ulcerative colitis). For creatinine clearance <15 mL/min or on dialysis: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: 5 mg orally once daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment based on age alone; monitor for infections and malignancies due to higher incidence in elderly. Renal function should guide dosing per renal adjustment guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XELJANZ (XELJANZ).
| Breastfeeding | It is not known whether tofacitinib is excreted in human milk. In lactating rats, tofacitinib was excreted in milk at concentrations 1.5- to 2-fold those in maternal plasma. No M/P ratio is available for humans. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | XELJANZ (tofacitinib) is an immunomodulator. In animal studies, tofacitinib was teratogenic and fetotoxic at doses ≥ 10 mg/kg/day (≈ 7-13 times the human exposure at 10 mg BID). There are no adequate and well-controlled studies in pregnant women. Based on animal data, tofacitinib may cause fetal harm. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester: No human data; animal teratogenicity observed. Second and third trimesters: No human data; animal fetotoxicity observed. |
■ FDA Black Box Warning
Serious infections leading to hospitalization or death; increased risk of lymphoma and other malignancies; thrombosis including pulmonary embolism, deep vein thrombosis, and arterial thrombosis; increased mortality in patients >50 years with at least one cardiovascular risk factor; increased rate of major adverse cardiovascular events; increased rate of thrombosis in patients with inflammatory conditions.
| Serious Effects |
None listed in label; avoid use during active serious infections; not recommended in patients with lymphocyte count <500 cells/mm³, neutrophil count <1000 cells/mm³, or hemoglobin <9 g/dL; caution with severe hepatic impairment.
| Precautions | Serious infections (including opportunistic infections); tuberculosis screening/risk; viral reactivation (herpes zoster); malignancy risk; thrombosis; gastrointestinal perforation; laboratory monitoring (lymphocytes, neutrophils, hemoglobin, liver enzymes, lipids); vaccination; pregnancy; lactation. |
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| Fetal Monitoring | Monitor complete blood count (CBC) with differential, liver function tests (LFTs), and serum creatinine prior to and periodically during therapy. Screen for tuberculosis (TB) and other infections before initiation. Monitor for signs and symptoms of thrombosis, including pulmonary embolism and deep vein thrombosis. In pregnancy, monitor fetal growth and well-being by ultrasound if clinically indicated. |
| Fertility Effects | Based on animal studies, tofacitinib may impair fertility in females and males. In female rats, tofacitinib increased estrous cycle irregularities and reduced fertility indices at exposures ≈ 2 times human exposure. In male rats, tofacitinib reduced sperm count and motility at exposures similar to human exposure. No human data on fertility effects are available. |