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. |
| Molecular Weight | 312.37 |
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 | Avoid due to possible teratogenicity. Adequate human data are lacking; animal studies have shown adverse effects. |
| 2nd trimester | Avoid unless no alternative. Human data limited; potential risk of fetal harm. |
| 3rd trimester | Avoid; risk of neonatal immunosuppression and infection. |
Clinical note
Comprehensive clinical and safety monograph for XELJANZ (XELJANZ).
| Placental transfer | Maternal-fetal transfer is expected; molecular weight <500 Da suggests likely placental passage. |
| Breastfeeding | Excreted in human milk in low amounts; potential for serious adverse reactions in nursing infants. Decision to discontinue drug or nursing should consider importance of drug to mother. |
| Lactation Rating |
■ 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 |
Severe hepatic impairmentActive serious infectionsHistory of recurrent infectionsHypersensitivity to tofacitinib or any excipient
| 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. |
| Food/Dietary | XELJANZ may be taken with or without food. No specific food restrictions are required. Grapefruit and grapefruit juice have no known interaction. Avoid alcohol if liver function is impaired. |
Loading safety data…
| L4 |
| 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. |
| 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. |
| Clinical Pearls | XELJANZ (tofacitinib) is a JAK inhibitor used in rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and polyarticular JIA. Monitor for serious infections, including TB, herpes zoster, and opportunistic infections. Perform baseline and periodic lipid monitoring due to dose-dependent increases in LDL and HDL. Avoid use in patients with severe hepatic impairment. Do not use with other JAK inhibitors or potent immunosuppressants. Screen for thrombosis risk; use with caution in patients with risk factors for pulmonary embolism or DVT. Monitor absolute lymphocyte count, neutrophils, and hemoglobin regularly. |
| Patient Advice | Take XELJANZ exactly as prescribed; do not change dose or stop without consulting your doctor. · Report any signs of infection (fever, chills, cough, painful urination) immediately, as XELJANZ can lower your ability to fight infections. · Tell your doctor if you have had TB, shingles, hepatitis B or C, or any recent vaccination. · Avoid live vaccines while taking XELJANZ; get recommended vaccines (e.g., annual flu shot) before starting if possible. · Report any unusual bruising, bleeding, or signs of blood clots (sudden chest pain, shortness of breath, leg swelling). · Do not take XELJANZ if you are pregnant or breastfeeding without discussing risks with your doctor. · Kidney function and blood counts will need regular monitoring; keep all appointments for lab work. · Take missed dose as soon as remembered unless it is almost time for next dose; do not double dose. · Store at room temperature, away from moisture and heat. · Discuss any other medications, including OTC products and supplements, as interactions may occur. |