Names and pronunciation
(toe′fa-sye′ti-nib) Xeljanz, Xeljanz XR
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Drug reference
(toe′fa-sye′ti-nib) Xeljanz, Xeljanz XR
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Func. class.: Antirheumatic agent (disease modifying), immunomodula- tor/biologic DMARD
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Chem. class.: Janus kinase inhibitor
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ACTION: Affects the signaling pathway of Janus kinase
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USES: Rheumatoid arthritis (moderately to severely active) in those who have taken methotrexate with inadequate response or intolerance, juvenile arthritis
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CONTRAINDICATIONS: Hyper- sensitivity Precautions: Pregnancy, breastfeeding, neonates, infants, children, geriatric patients, neoplastic disease, ulcerative coli- tis, neutropenia, peptic ulcer disease, active infections, risk of lymphomas/leukemias, TB, posttransplant lymphoproliferative dis- order (PTLD), kidney disease, diabetes mellitus, HIV, hypercholesterolemia, herpes virus infection reactivation, Asian patients
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Black Box Warning: Infection, secondary malignancy Black Box Warning: Do not use with TNF modifiers, vaccines, potent immunosup- pressants, other biologic DMARDS; seri- ous infections may occur Increase: tofacinib effect—CYP3A4 inhib- itors (amprenavir, boceprevir, delavirdine, ketoconazole, indinavir, itraconazole, dal- fopristin/quinupristin, ritonavir, tipranavir, fluconazole, isoniazid, miconazole) Decrease: tofacinib effect—CYP3A4 inducers (rifAMPin, rifapentine, rifabutin, primidone, phenytoin, PHENobarbital, nevirapine, nafcillin, modafinil, griseoful- vin, etravirine, efavirenz, barbiturates, bexarotene, bosentan, carBAMazepine, enzalutamide, dexamethasone) Drug/Lab Test Increase: LFTs, cholesterol Decrease: neutrophils, lymphocytes, Hct, HB Black Box Warning: Active infection, including localized infection: evaluate for latent or active TB before use; treat with antimycobacterials before use; may cause serious fatal infections (pulmonary or extrapulmonary TB; invasive fungal infections; and bacterial, viral, and op- portunistic infections); during and after use, monitor for infection including TB in those who tested negative for latent TB before use; if a serious infection devel- ops, interrupt receipt until the infection is controlled, reactivation of viral infections is higher in Asian patients Black Box Warning: Secondary ma- lignancy: lymphoma and other malig- nancies have been noted with product use • Epstein-Barr virus–associated post- transplant lymphoproliferative disor- der (PTLD): in kidney transplant patients when used with this product and immu nosuppressives • Liver disease: not recommended in severe liver disease, impairment; dose modification is needed with moderate liver impairment, monitor LFTs • GI perforation: assess in those with diverticulitis, peptic ulcer disease, or ul cerative colitis Black Box Warning: Immunosuppres- sion: obtain neutrophil and lymphocyte counts before use; do not start the prod- uct in lymphocyte count <500 cells/mm3 or ANC <1000 cells/mm3; for ANC >1000 cells/mm3, monitor neutrophil counts after 4-8 wk and every 3 mo thereafter; lymphocyte count >500 cells/mm3, mon- itor lymphocyte counts every 3 mo • Anemia: determine HB, do not start in HB <9 g/dL; in HB ≥9 g/dL, monitor HB af ter 4-8 wk and every 3 mo thereafter • Pregnancy/breastfeeding: use dur ing pregnancy only if the potential benefit justifies the potential risk to the fetus; if pregnancy occurs, enrollment in the preg nancy registry is encouraged by calling T 1-877-311-8972; discontinue product or breastfeeding; serious adverse reactions can occur in nursing infants Black Box Warning: Neoplastic disease (lymphomas/leukemias)
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SIDE EFFECTS CNS: Headache, paresthesias, insomnia, fatigue CV: Hypertension, increased PR interval GI: Abdominal pain, nausea, liver dam age, dyspepsia, vomiting, diarrhea, gas- tritis, GI perforation, steatosis HEMA: Anemia, lymphocytosis, lympho- penia, neutropenia INTEG: Rash, pruritus, angioedema MISC: Increased cancer risk, risk of infection (TB, invasive fungal infections, other opportunistic infections), may be fatal, posttransplant lymphoproliferative disorder (PTLD), osteoarthritis
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INTERACTIONS
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DOSAGE AND ROUTES Psoriatic arthritis • Adult: PO 5 mg bid with a DMARD if receiving potent CYP3A4 inhibitor, 5 mg/ day if receiving moderate CYP3A4 inhibi- tor and 2C19 inhibitors; EXT REL 11 mg/day with a DMARD Moderate to severe rheumatoid arthritis • Adult: PO 5 mg bid with or without methotrexate or a DMARD; EXT REL 11 mg/day Juvenile arthritis • Child ≥2 yr and ≥10 kg/adolescents: PO 10-20 kg: PO solution 3.2 mg bid; 20-40 kg: 4 mg bid; ≥40 kg (solution/ tablet) 5 mg bid Ulcerative colitis • Adult: PO 10 mg bid × 8 wk or more, then 5 or 10 mg bid (immediate release)
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Available forms: Tabs 5 mg; ext rel tab 11 mg; oral solution
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Administer: PO route • Without regard to food • Do not chew, crush, split XR tablet, swallow whole • Do not take missed dose, resume nor- mal schedule
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Assess: • Monitor lipid profile, Hct/HB, WBC, LFTs • RA: Pain, stiffness, ROM, swelling of joints before, during treatment
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Evaluate: • Therapeutic response: decreased in- flammation, pain in joints, decreased joint destruction
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • Not to take any live virus vaccines dur- ing treatment; vaccines should be brought up-to-date before starting treatment • To report signs of infection, allergic reaction • Pregnancy: to report if pregnancy is planned or suspected; not to breastfeed
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PHARMACOKINETICS Bioavailability 70%, protein binding 40% (albumin), metabolism mediated by CYP3A4, half-life 3 hr, peak 0.5-1 hr
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• Adult: PO 5 mg bid with a DMARD if receiving potent CYP3A4 inhibitor, 5 mg/ day if receiving moderate CYP3A4 inhibi- tor and 2C19 inhibitors; EXT REL 11 mg/day with a DMARD Moderate to severe rheumatoid arthritis
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• Adult: PO 5 mg bid with or without methotrexate or a DMARD; EXT REL 11 mg/day Juvenile arthritis
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• Adult: PO 10 mg bid × 8 wk or more, then 5 or 10 mg bid (immediate release)
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