Xeljanz

Tofacitinib

In combination w/ MTX for reducing the signs & symptoms of RA in adults w/ moderately to severely active RA who had inadequate response to MTX; monotherapy in cases of intolerance to MTX. In combination w/ MTX for active psoriatic arthritis (PsA) in adults who had inadequate response or who have been intolerant to a prior DMARD therapy. In adults w/ moderately to severely active ulcerative colitis (UC) who had inadequate, lost response, or intolerant to either conventional therapy or biologic agent.

RA 5 mg bd in combination w/ MTX. Monotherapy may be considered in cases of intolerance to MTX. Moderate or severe renal impairment Reduce to 5 mg once daily. Moderate hepatic impairment Reduce to 5 mg once daily. Patient receiving potent CYP3A4 inhibitors (eg, ketoconazole); or ≥1 medication resulting to both moderate CYP3A4 & potent CYP2C19 inhibition (eg, fluconazole) Reduce to 5 mg once daily. PsA 5 mg bd. Moderate or severe renal impairment Reduce to 5 mg once daily. Moderate hepatic impairment 5 mg once daily. Patient receiving potent CYP3A4 inhibitors (eg, ketoconazole); or ≥1 medication resulting to both moderate CYP3A4 & potent CYP2C19 inhibition (eg, fluconazole) Reduce to 5 mg once daily. UC Induction: 10 mg bd for 8 wk, may be extended for an additional 8 wk, followed by 5 mg bd for maintenance. Maintenance: 5 mg bd. 10 mg bd may be considered in patient w/o increased risk for VTE, if the patient experiences decreased response on 5 mg bd & failed to respond to alternative treatment options for UC (eg, tumor necrosis factor inhibitor treatment); use 10 mg bd for maintenance treatment for the shortest duration possible. Re-treatment: 10 mg bd may be considered. Severe renal impairment 5 mg once daily (if normal renal function dose is 5 mg bd) or 5 mg bd (if normal renal function dose is 10 mg bd). Moderate hepatic impairment 5 mg once daily (if normal hepatic function dose is 5 mg bd) or 5 mg bd (if normal hepatic function dose is 10 mg bd). Patient receiving potent CYP3A4 inhibitors (eg, ketoconazole); or ≥1 medication resulting to both moderate CYP3A4 & potent CYP2C19 inhibition (eg, fluconazole) Reduce to 5 mg once daily (if patient is taking 5 mg bd dose) or 5 mg bd (if patient is taking 10 mg bd dose).

May be taken with or without food.

Promptly discontinue use if serious hypersensitivity reaction occurs. Risk of serious & potentially fatal, or opportunistic infections. Do not initiate in patients w/ an active infection including localized infections. Patients w/ chronic or recurrent infections, or those who have been exposed to TB, history of serious or opportunistic infection, resided or traveled in areas of endemic TB or mycoses; underlying conditions that may predispose to infection. Patients w/ history of chronic lung disease. Possible events of ILD. Closely monitor for development of signs & symptoms of infection during & after treatment; TB including patients who tested -ve for latent TB prior to initiating therapy. Interrupt use if patient develops serious or opportunistic infection, or sepsis. Perform prompt & complete diagnostic testing & initiate appropriate antimicrobial therapy in patient who develops new infection during treatment. Evaluate & test patients for latent or active infection prior to & during administration. Treat patients w/ latent TB w/ standard antimycobacterial therapy before Xeljanz administration. Perform viral hepatitis screening before therapy. Higher risk of herpes zoster in Japanese & Korean patients & those treated w/ 10 mg bd dose. Assess patients for risk factors & urgently evaluate patients w/ signs & symptoms of VTE; discontinue use while evaluating suspected VTE. Possible major adverse CV events including MI. Consider risks & benefits of treatment prior to therapy initiation in patients w/ current or history of malignancy other than successfully treated non-melanoma skin cancer (NMSC) or when considering continuing Xeljanz in patients who develop malignancy. Possible lymphoma; patients w/ highly active RA may be at higher risk. Possible lung cancer. Patients ≥65 yr, who are current or past or long-time smokers & those w/ other CV or malignancy risk factors (eg, history of ASCVD; current or history of malignancy). Higher risk of NMSC in patients treated w/ 10 mg bd dose; perform periodic skin exam in patients at increased risk of skin cancer. Patients who may be at increased risk for GI perforation (eg, history of diverticulitis). Patients w/ known risk factors for fractures (eg, elderly, female & those w/ corticosteroid use). Not recommended to initiate in patients w/ lymphocyte count <500 cells/mm³, or ANC <1,000 cells/mm³, or Hb <9 g/dL. Monitor lymphocyte at baseline & every 3 mth thereafter; neutrophils & Hb at baseline & after 4-8 wk of treatment & every 3 mth thereafter. Routinely monitor liver enzymes. Interrupt administration if drug-induced liver injury is suspected. Assess lipid parameters approx 4-8 wk following therapy initiation. Do not concurrently give w/ live vaccines. Avoid use in combination w/ biological DMARDs (for RA & PsA); w/ biological agents (for UC). Not recommended to co-administer w/ potent CYP3A4 inducers. Patients w/ baseline CrCl <40 mL/min. Not to be used in patients w/ severe hepatic impairment. Advise women of reproductive potential to use effective contraception during treatment & for at least 4 wk after the last dose. Pregnancy. Do not breastfeed during treatment. Childn <18 yr.

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

Increased exposure w/ potent (eg, ketoconazole) & moderate CYP3A4 inhibitors; potent CYP2C19 inhibitors (eg, fluconazole). Decreased exposure 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) / Immunosuppressants

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

POM