INDICATIONS including Limitations of Use Rheumatoid Arthritis – XELJANZ/XELJANZ® XR (tofacitinib) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate.
Psoriatic Arthritis: XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with active psoriatic arthritis who have had an inadequate response or intolerance to methotrexate or other disease-modifying antirheumatic drugs (DMARDs).
Ulcerative Colitis: XELJANZ/XELJANZ XR is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC), who have had an inadequate response or who are intolerant to TNF blockers.
Polyarticular Course Juvenile Idiopathic Arthritis: XELJANZ/XELJANZ Oral Solution is indicated for the treatment of active polyarticular course juvenile idiopathic arthritis (pcJIA) in patients 2 years of age and older.
IMPORTANT SAFETY INFORMATIONScroll for more.
SERIOUS INFECTIONS: Patients treated with XELJANZ* are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.
If a serious infection develops, interrupt XELJANZ until the infection is controlled.
Reported infections include:
The most common serious infections reported with XELJANZ included pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis, and appendicitis. Avoid use of XELJANZ in patients with an active, serious infection, including localized infections, or with chronic or recurrent infection.
In the UC population, XELJANZ 10 mg twice daily was associated with greater risk of serious infections compared to 5 mg twice daily. Opportunistic herpes zoster infections (including meningoencephalitis, ophthalmologic, and disseminated cutaneous) were seen in patients who were treated with XELJANZ 10 mg twice daily.
The risks and benefits of treatment with XELJANZ should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection, or those who have lived or traveled in areas of endemic TB or mycoses. Viral reactivation including herpes virus and hepatitis B reactivation have been reported. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy.
Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with XELJANZ, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Caution is also recommended in patients with a history of chronic lung disease, or in those who develop interstitial lung disease, as they may be more prone to infection.
MORTALITY
Rheumatoid arthritis (RA) patients 50 years of age and older with at least one cardiovascular (CV) risk factor treated with XELJANZ 10 mg twice a day had a higher rate of all-cause mortality, including sudden CV death, compared to those treated with XELJANZ 5 mg given twice daily or TNF blockers in a large, ongoing, postmarketing safety study. XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily is not recommended for the treatment of RA or PsA. For UC, use XELJANZ at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response.
MALIGNANCIES
Lymphoma and other malignancies have been observed in patients treated with XELJANZ. Epstein Barr Virus-associated post-transplant lymphoproliferative disorder has been observed at an increased rate in renal transplant patients treated with XELJANZ and concomitant immunosuppressive medications.
Consider the risks and benefits of XELJANZ treatment prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing XELJANZ in patients who develop a malignancy.
Malignancies (including solid cancers and lymphomas) were observed more often in patients treated with XELJANZ 10 mg twice daily dosing in the UC long-term extension study.
Other malignancies were observed in clinical studies and the post-marketing setting including, but not limited to, lung cancer, breast cancer, melanoma, prostate cancer, and pancreatic cancer. NMSCs have been reported in patients treated with XELJANZ. In the UC population, treatment with XELJANZ 10 mg twice daily was associated with greater risk of NMSC. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.
THROMBOSIS
Thrombosis, including pulmonary embolism, deep venous thrombosis, and arterial thrombosis, have occurred in patients treated with XELJANZ and other Janus kinase inhibitors used to treat inflammatory conditions. RA patients who were 50 years of age and older with at least one CV risk factor treated with XELJANZ 10 mg twice daily compared to XELJANZ 5 mg twice daily or TNF blockers in a large, ongoing postmarketing safety study had an observed increase in incidence of these events. Many of these events were serious and some resulted in death. Avoid XELJANZ in patients at risk. Discontinue XELJANZ and promptly evaluate patients with symptoms of thrombosis. For patients with UC, use XELJANZ at the lowest effective dose and for the shortest duration needed to achieve/maintain therapeutic response. XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily is not recommended for the treatment of RA or PsA. In a long-term extension study in UC, four cases of pulmonary embolism were reported in patients taking XELJANZ 10 mg twice daily, including one death in a patient with advanced cancer.
GASTROINTESTINAL PERFORATIONS
Gastrointestinal perforations have been reported in XELJANZ clinical trials, although the role of JAK inhibition is not known. In these studies, many patients with rheumatoid arthritis were receiving background therapy with Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). There was no discernable difference in frequency of gastrointestinal perforation between the placebo and the XELJANZ arms in clinical trials of patients with UC, and many of them were receiving background corticosteroids. XELJANZ should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis or taking NSAIDs).
HYPERSENSITIVITY
Angioedema and urticaria that may reflect drug hypersensitivity have been observed in patients receiving XELJANZ and some events were serious. If a serious hypersensitivity reaction occurs, promptly discontinue tofacitinib while evaluating the potential cause or causes of the reaction.
LABORATORY ABNORMALITIES
Lymphocyte Abnormalities: Treatment with XELJANZ was associated with initial lymphocytosis at one month of exposure followed by a gradual decrease in mean lymphocyte counts. Avoid initiation of XELJANZ treatment in patients with a count less than 500 cells/mm3. In patients who develop a confirmed absolute lymphocyte count less than 500 cells/mm3, treatment with XELJANZ is not recommended. Risk of infection may be higher with increasing degrees of lymphopenia and consideration should be given to lymphocyte counts when assessing individual patient risk of infection. Monitor lymphocyte counts at baseline and every 3 months thereafter.
Neutropenia: Treatment with XELJANZ was associated with an increased incidence of neutropenia (less than 2000 cells/mm3) compared to placebo. Avoid initiation of XELJANZ treatment in patients with an ANC less than 1000 cells/mm3. For patients who develop a persistent ANC of 500-1000 cells/mm3, interrupt XELJANZ dosing until ANC is greater than or equal to 1000 cells/mm3. In patients who develop an ANC less than 500 cells/mm3, treatment with XELJANZ is not recommended. Monitor neutrophil counts at baseline and after 4-8 weeks of treatment and every 3 months thereafter.
Anemia: Avoid initiation of XELJANZ treatment in patients with a hemoglobin level less than 9 g/dL. Treatment with XELJANZ should be interrupted in patients who develop hemoglobin levels less than 8 g/dL or whose hemoglobin level drops greater than 2 g/dL on treatment. Monitor hemoglobin at baseline and after 4-8 weeks of treatment and every 3 months thereafter.
Liver Enzyme Elevations: Treatment with XELJANZ was associated with an increased incidence of liver enzyme elevation compared to placebo. Most of these abnormalities occurred in studies with background DMARD (primarily methotrexate) therapy. If drug-induced liver injury is suspected, the administration of XELJANZ should be interrupted until this diagnosis has been excluded. Routine monitoring of liver tests and prompt investigation of the causes of liver enzyme elevations is recommended to identify potential cases of drug-induced liver injury.
Lipid Elevations: Treatment with XELJANZ was associated with dose-dependent increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Maximum effects were generally observed within 6 weeks. There were no clinically relevant changes in LDL/HDL cholesterol ratios. Manage patients with hyperlipidemia according to clinical guidelines. Assessment of lipid parameters should be performed approximately 4-8 weeks following initiation of XELJANZ therapy.
VACCINATIONS
Avoid use of live vaccines concurrently with XELJANZ. The interval between live vaccinations and initiation of tofacitinib therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents. Update immunizations in agreement with current immunization guidelines prior to initiating XELJANZ therapy.
PATIENTS WITH GASTROINTESTINAL NARROWING
Caution should be used when administering XELJANZ XR to patients with pre-existing severe gastrointestinal narrowing. There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of other drugs utilizing a non-deformable extended release formulation.
HEPATIC and RENAL IMPAIRMENT
Use of XELJANZ in patients with severe hepatic impairment is not recommended.
For patients with moderate hepatic impairment or with moderate or severe renal impairment taking XELJANZ 5 mg twice daily, reduce to XELJANZ 5 mg once daily.
For UC patients with moderate hepatic impairment or with moderate or severe renal impairment taking XELJANZ 10 mg twice daily, reduce to XELJANZ 5 mg twice daily.
ADVERSE REACTIONS
The most common serious adverse reactions were serious infections. The most commonly reported adverse reactions during the first 3 months in controlled clinical trials in patients with RA with XELJANZ 5 mg twice daily and placebo, respectively, (occurring in greater than or equal to 2% of patients treated with XELJANZ with or without DMARDs) were upper respiratory tract infection, nasopharyngitis, diarrhea, headache, and hypertension. The safety profile observed in patients with active PsA treated with XELJANZ was consistent with the safety profile observed in RA patients.
Adverse reactions reported in ≥5% of patients treated with either 5 mg or 10 mg twice daily of XELJANZ and ≥1% greater than reported in patients receiving placebo in either the induction or maintenance clinical trials for UC were: nasopharyngitis, elevated cholesterol levels, headache, upper respiratory tract infection, increased blood creatine phosphokinase, rash, diarrhea, and herpes zoster.
USE IN PREGNANCY
Available data with XELJANZ use in pregnant women are insufficient to establish a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with rheumatoid arthritis and UC in pregnancy. In animal studies, tofacitinib at 6.3 times the maximum recommended dose of 10 mg twice daily demonstrated adverse embryo-fetal findings. The relevance of these findings to women of childbearing potential is uncertain. Consider pregnancy planning and prevention for females of reproductive potential.
*Unless otherwise stated, "XELJANZ" in the Important Safety Information refers to XELJANZ, XELJANZ XR, and XELJANZ Oral Solution.
Dx=diagnosis; FDA=Food and Drug Administration; JAK=Janus kinase; Rx=prescription.
CO-PAY CARD TERMS AND CONDITIONS
By using the XELJANZ Co-pay Savings Card (the “Card”), you acknowledge that you currently meet the eligibility criteria and will comply with the terms and conditions described below:
Patients are not eligible to use the Card if they are enrolled in a state- or federally funded insurance program, including but not limited to Medicare, Medicaid, TRICARE, Veterans Affairs health care, a state prescription drug assistance program, or the Government Health Insurance Plan available in Puerto Rico (formerly known as “La Reforma de Salud”). Patient must have private insurance. Offer is not valid for cash-paying patients. You will receive a maximum benefit of $15,000 per calendar year, which is defined by the date of enrollment through December 31st of the enrollment year, and may pay as little as $0 per month co-pay. After a maximum of $15,000, you will be responsible for paying the remaining monthly out-of-pocket costs. This Card is not valid when the entire cost of your prescription drug is eligible to be reimbursed by your private insurance plan or other private health or pharmacy benefit programs. You must deduct the value of this Card from any reimbursement request submitted to your private insurance plan, either directly by you or on your behalf. You are responsible for reporting use of the Card to any private insurer, health plan, or other third party who pays for or reimburses any part of the prescription filled using the Card, as may be required. You should not use the Card if your insurer or health plan prohibits use of manufacturer Cards. The Card is not valid where prohibited by law. The Card cannot be combined with any other savings, free trial, or similar offer for the specified prescription. The Card will be accepted only at participating pharmacies. If your pharmacy does not participate, you may be able to submit a request for a rebate in connection with this offer. The Card is not health insurance. Offer good only in the U.S. and Puerto Rico. The Card is limited to 1 per person during this offering period and is not transferable. The Card may not be redeemed more than once per 30 days per patient. No other purchase is necessary. Data related to your redemption of the Card may be collected, analyzed, and shared with Pfizer, for market research and other purposes related to assessing Pfizer’s programs. Data shared with Pfizer will be aggregated and de-identified; it will be combined with data related to other Card redemptions and will not identify you. Pfizer reserves the right to rescind, revoke, or amend the program without notice. The Card is applicable to all XELJANZ formulations. Card and Program expires 12/31/2022.
If you have questions or are in need of additional support, call 1-844-935-5269 or visit www.XELJANZ.com.
INTERIM CARE Rx PROGRAM TERMS & CONDITIONS
Reference: 1. XELJANZ [prescribing information]. New York, NY: Pfizer Inc.; October 2020. 2. Cohen MD, Keystone EC. JAK inhibitors for rheumatoid arthritis. Curr Treatm Opt Rheumatol. 2015;1:305-319. 3. Data on file. Pfizer Inc., New York, NY.
PP-XEL-USA-6339-02
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January 2021
Full Prescribing Information, including BOXED WARNING.