- Xeljanz XR
Treatment of adults with moderately to severely active rheumatoid arthritis who have had an inadequate response/intolerance to methotrexate (can be used as monotherapy or with methotrexate or other nonbiologic disease-modifying antirheumatic drugs [DMARDs]) (not to be used with biologic DMARDs or potent immunosuppressants including azathioprine and cyclosporine).
Acts as a Janus kinase (JAK) inhibitor. Some results of inhibition include decreased hematopoiesis and immune cell function. Decreases circulating killer cells, increases in B cell count and decreases serum C-reactive protein (CRP).
Improvement in clinical and symptomatic parameters of rheumatoid arthritis.
Absorption: Well absorbed following oral administration (74%).
Distribution: Distributes equally between red blood cells and plasma.
Metabolism and Excretion: 70% metabolized by the liver (primarily CYP3A4 with some contribution from CYP2C19). 30% renal excretion of the parent drug.
Half-life: 3 hr.
TIME/ACTION PROFILE (clinical improvement)
|PO||within 2 wk||3 mo||unknown|
- Active infection;
- Administration of live vaccines;
- Severe hepatic impairment;
- Lymphocyte count <500 cells/mm3, absolute neutrophil count (ANC) <1000 cells/mm3, or hemoglobin levels <9 g/dL;
- Lactation: Should not be used in nursing mothers.
Use Cautiously in:
- Patients with risk of gastric perforation;
- Japanese patients (↑ risk of herpes zoster);
- Geri: Infection risk may be ↑
- OB: Use during pregnancy only if potential benefit justifies potential fetal risk;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: fatigue, headache, insomnia
CV: peripheral edema
GI: GASTRIC PERFORATION, abdominal pain, diarrhea, dyspepsia, gastritis, ↑ liver enzymes, vomiting
GU: ↑ serum creatinine
Derm: erythema, pruritus, rash
F and E: dehydration
Hemat: anemia, neutropenia
Metabolic: ↑ lipids
MS: arthralgia, joint swelling, musculoskeletal pain, tendonitis
Misc: MALIGNANCY, serious infections including tuberculosis, invasive fungal infections, bacterial, viral, and other infections due to opportunistic pathogens, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- May ↑ risk of adverse reactions and ↓ antibody response to live vaccines; avoid concurrent use.
- Blood levels and effects may be ↑ by strong CYP3A4 inhibitors including ketoconazole or moderate CYP3A4 inhibitors/strong CYP2C19 inhibitors including fluconazole; dose ↓ recommended.
- Blood levels and effectiveness may be ↓ strong CYP3A4 inducers including rifampin; avoid concurrent use.
- ↑ risk of immunosuppression when used concurrently with other potent immunosuppressants including azathioprine, cyclosporine, tacrolimus, antineoplastics, or radiation therapy.
PO (Adults) Immediate-release–5 mg twice daily; Extended-release–11 mg once daily; Concurrent use of strong CYP3A4 inhibitors or ≥1 medication that results in moderate CYP3A4 inhibition and strong CYP2C19 inhibition–5 mg once daily (immediate-release).
PO (Adults) Moderate to severe renal impairment–5 mg once daily (immediate-release).Hepatic Impairment
PO (Adults) Moderate hepatic impairment–5 mg once daily (immediate-release).
Extended-release tablets: 11 mg
Immediate-release tablets: 5 mg
- Assess pain and range of motion before and periodically during therapy.
- Assess for signs of infection (fever, dyspnea, flu-like symptoms, frequent or painful urination, redness or swelling at the site of a wound), including tuberculosis, prior to and periodically during therapy. Tofacitinib is contraindicated in patients with active infection. New infections should be monitored closely; most common are pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis, and appendicitis. Infections may be fatal, especially in patients taking immunosuppressive therapy.
- Assess for signs and symptoms of systemic fungal infections (fever, malaise, weight loss, sweats, cough, dypsnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock). Ascertain if patient lives in or has traveled to areas of endemic mycoses. Consider empiric antifungal treatment for patients at risk of histoplasmosis and other invasive fungal infections until the pathogens are identified. Consult with an infectious diseases specialist. Consider stopping tofacitinib until the infection has been diagnosed and adequately treated.
Lab Test Considerations:
Monitor CBC prior to and periodically during therapy. Do not initiate tofacitinib in patients with lymphocyte count <500 cells/mm3, an ANC <1000 cells/mm3, or who have hemoglobin level <9 g/dL.
- Monitor lymphocyte count at baseline and every 3 mo thereafter. If lymphocyte count ≥500 cells/mm3 maintain dose. If lymphocyte count <500 cells/mm3 and confirmed by repeat testing, discontinue tofacitinib.
- Monitor neutrophil count at baseline, after 4–8 wk of therapy, and every 3 mo thereafter. If ANC >1000 cells/mm3, maintain dose. If ANC 500–1000 cells/mm3, for persistent decreases in this range, interrupt dosing until ANC is >1000 cells/mm3. If ANC <500 cells/mm3 and confirmed by repeat testing, discontinue tofacitinib.
- Monitor hemoglobin at baseline, after 4–8 wk of therapy, and every 3 mo thereafter. If hemoglobin ≤2 g/dL decrease and ≥9.0 g/dL and confirmed by repeat testing, maintain dose. If hemoglobin >2 dL decrease and <8.0 g/dL, interrupt administration of tofacitinib until hemoglobin values have normalized.
- Monitor liver enzymes prior to and periodically during therapy.
- Monitor total cholesterol, LDL cholesterol, HDL cholesterol 4–8 wk following initiation of therapy.
- Administer a tuberculin skin test prior to administration of tofacitinib. Patients with active latent TB should be treated for TB prior to therapy.
- Immunizations should be current prior to initiating therapy. Patients on tofacitinib should not receive live vaccines.
- Screen patient for viral hepatitis before starting therapy.
- PO Administer twice daily without regard to food. Swallow extended release tablets whole; do not crush. break, or chew.
- Instruct patient to take tofacitinib as directed. Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
- Caution patient to notify health care professional immediately if signs of infection (fever, sweating, chills, muscle aches, cough, shortness of breath, blood in phlegm, weight loss, warm, red, or painful skin or sores, diarrhea or stomach pain, burning on urination or urinating more often than normal, feeling very tired) or stomach or intestinal perforation (fever, stomach-area pain that does not go away, change in bowel habits) occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
- Inform patient of increased risk of lymphoma and other cancers. Advise patient to have periodic skin exams for new lesions of skin cancer.
- Rep: Advise female patients to notify health care professional if pregnancy is planned or suspected and to avoid breast feeding during therapy. Encourage patient to contact the pregnancy registry by calling 1-877-311-8972 if pregnant.
- Emphasize the importance of follow-up lab tests to monitor for adverse reactions.
Decreased pain and swelling with improved physical functioning and decreased rate of joint destruction in patients with rheumatoid arthritis.
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