Xeljanz

Adults w/ moderate to severe active RA who have had inadequate response or intolerance to MTX; active psoriatic arthritis; active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. Induction & maintenance treatment in adults w/ moderate to severe active ulcerative colitis (UC) w/ inadequate & loss of response or intolerance to corticosteroids, azathioprine, 6-mercaptopurine or tumor necrosis factor (TNF) antagonists. Active polyarticular course juvenile idiopathic arthritis (pcJIA) in patients weighing ≥40 kg.

RA 5 mg bid as monotherapy or in combination w/ MTX or other non-biologic DMARDs. Psoriatic arthritis 5 mg bid in combination w/ conventional synthetic DMARDs. AS 5 mg bid. Moderate to severe active UC Induction: 10 mg bid for at least 8 wk. Maintenance: 5 mg or 10 mg bid depending on therapeutic response. Refractory patients eg, those who failed prior TNF antagonist therapy Continue maintenance dose of 10 mg bid. Patient who fail to maintain therapeutic benefit w/ 5 mg bid May increase dose to 10 mg bid. pcJIA Patient weighing ≥40 kg 5 mg bid as monotherapy or in combination w/ MTX. Moderate or severe renal impairment (including but not limited to those undergoing hemodialysis), moderate hepatic impairment, patient receiving potent CYP3A4 inhibitors (eg, ketoconazole) or ≥1 medication resulting in both moderate CYP3A4 & potent CYP2C19 inhibition (eg, fluconazole) Reduce dose to 5 mg once daily (if dose in normal renal/hepatic function is 5 mg bid) or 5 mg bid (if dose in normal renal/hepatic function is 10 mg bid).

May be taken with or without food.

Hypersensitivity. Serious infection & hepatic disease.

Not to be initiated in patients w/ active infection, including localized infections; low lymphocyte count & who develop confirmed absolute lymphocyte count <500 cells/mm³; low neutrophil count (ie, ANC <1,000 cells/mm³) & who develop confirmed ANC <500 cells/mm³; low Hb values (ie, <9 g/dL). Discontinue treatment while evaluating suspected VTE regardless of dose or indication; if serious hypersensitivity reaction occurs. Reduce dose or interrupt dosing in patients who develop persistent ANC of 500-1,000 cells/mm³, until ANC is >1,000 cells/mm³. Interrupt treatment if serious or opportunistic infection, or sepsis develops; in patients who develop Hb levels <8 g/dL or whose Hb level drops >2 g/dL. Serious & sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens; ILD; VTE; DVT; major adverse CV events including MI; lymphomas; lung, breast, prostate & pancreatic cancer, melanoma; non-melanoma skin cancers (NMSCs); GI perforation; fractures; angioedema & urticaria; EBV-associated post-transplant lymphoproliferative disorder at increased rate in renal transplant patients treated w/ Xeljanz & concomitant immunosuppressive medications; hepatitis B & herpes virus reactivation (eg, herpes zoster). Increased lipid parameters eg, total cholesterol, LDL-C, HDL-C. Hypoglycemia in diabetics. Patients w/ chronic or recurrent infections, those who have been exposed to TB, w/ history of serious or opportunistic infection, have resided or travelled in areas of endemic TB or mycoses, or have underlying conditions that may predispose to infection; history of chronic lung disease, NMSC & multiple allergies; in whom VTE risk factors are identified (eg, history of thrombosis); who are current or past, long-time smokers & w/ other CV risk factors (eg, history of ASCVD); w/ other malignancy risk factors (eg, current or history of malignancy); RA particularly those w/ highly active disease; increased risk for GI perforation (eg, patients w/ history of diverticulitis); known risk factors for fractures eg, females & patients on corticosteroid use; +ve HBV or HCV serology; ≥50 yr w/ at least 1 additional CV risk factor. Higher risk of infection w/ increasing degrees of lymphopenia; herpes zoster in Japanese & Korean patients. Closely monitor patients for development of signs & symptoms of infection during & after treatment; signs & symptoms of TB including patients w/ -ve test for latent TB infection prior to initiating therapy. Evaluate promptly for early identification of GI perforation in patients presenting w/ new onset abdominal symptoms; patients w/ signs & symptoms of VTE. Evaluate & test for latent or active infection prior to & during administration. Assess patients for VTE risk factors before starting & periodically during treatment. Monitor lymphocytes at baseline & every 3 mth thereafter; neutrophils & Hb at baseline & after 4-8 wk & every 3 mth thereafter. Perform screening test for viral hepatitis before starting therapy; periodic skin exam for patients who are at increased risk for skin cancer; assessment of lipid parameters approx 4-8 wk following initiation of therapy. Prompt & appropriate complete diagnostic testing for immunocompromised patients who develop new infection during treatment. Treat patients w/ standard antimycobacterial therapy before administration if w/ latent TB. Consider anti-TB therapy prior to administration in patients w/ history of latent or active TB in whom adequate course of treatment cannot be confirmed, & for patients w/ -ve test for latent TB but have risk factors. Concomitant use w/ phosphodiesterase 4 inhibitors in patients w/ active psoriasis arthritis. Not to be given concurrently w/ live vaccines. Vaccination should occur at least 2 wk but preferably 4 wk before initiating immunomodulatory agents. Avoid use in combination w/ biological DMARDs eg, TNF, IL-1R, IL-6R, IL-17, & IL-12/IL-23 antagonists, anti-CD20 monoclonal Ab, anti-integrins, selective co-stimulation modulators & potent immunosuppressants (eg, azathioprine, cyclosporine & tacrolimus). Not to be used in severe hepatic impairment. Patients w/ baseline CrCl <40 mL/min. Women of reproductive potential should use effective contraception during treatment & for at least 4 wk after last dose. Pregnancy. Not to breastfeed during treatment. Elderly ≥65 yr.

Pneumonia, flu, herpes zoster, UTI, sinusitis, bronchitis, nasopharyngitis, pharyngitis; anaemia; hyperlipidaemia; headache; HTN; cough; abdominal pain, vomiting, diarrhoea, nausea, gastritis, dyspepsia; rash, acne; arthralgia; pyrexia, peripheral oedema, fatigue; increased γ-glutamyltransferase, blood cholesterol & creatine phosphokinase, & wt.

Increased exposure, AUC & C_max w/ potent CYP3A4 inhibitors (eg, ketoconazole) & moderate CYP3A4 & strong CYP2C19 inhibitor (eg, fluconazole). Decreased exposure, AUC & C_max w/ potent CYP inducers (eg, rifampin). Increased AUC & decreased C_max w/ tacrolimus & cyclosporine. Decreased AUC & C_max of MTX.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

L04AF01 - tofacitinib ; Belongs to the class of Janus-associated kinase (JAK) inhibitors. Used as immunosuppressants.

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