Xeljanz

Name: Xeljanz

How should this medicine be used?

Tofacitinib comes as a tablet and as an extended-release (long-acting) tablet to take by mouth. The tablet is usually taken with or without food twice a day. The extended-release tablet is usually taken with or without food once daily. Take tofacitinib at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take tofacitinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the extended-release tablets whole; do not split, chew, or crush them.

Your symptoms may improve as soon as 2 weeks after you begin taking tofacitinib, but it may take 3to 6 months for you to feel the full benefit of the medication. Talk to your doctor about how tofacitinib works for you.

Tofacitinib may help control your condition but will not cure it. Continue to take tofacitinib even if you feel well. Do not stop taking tofacitinib without talking to your doctor.

Descriptions

Tofacitinib is used alone or together with other medicines to treat rheumatoid arthritis. This medicine is used in patients who have taken other medicines (eg, methotrexate) that did not work well. Tofacitinib is a Janus kinase (JAK) inhibitor that works on the immune system.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

  • Tablet
  • Tablet, Extended Release

Xeljanz Dosage

Xeljanz may be used alone or in combination with other medications. The recommended dose of Xeljanz is 5 mg twice daily. Your healthcare provider may reduce your dose or interrupt therapy if you have kidney or liver disease and certain other conditions or if you are experiencing serious side effects.

How should I take tofacitinib?

Before you start treatment with tofacitinib, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take tofacitinib with or without food.

Do not crush, chew, or break an extended-release tablet. Swallow it whole.

Tofacitinib can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Further doses may be delayed based on the results of these tests. Your doctor may also want to check your skin for signs of cancer.

If you have hepatitis B or C you may develop liver symptoms while taking this medicine. Your doctor may want to check your liver function before and during your treatment with tofacitinib.

Store in the original container at room temperature away from moisture and heat.

What other drugs will affect tofacitinib?

Many drugs can interact with tofacitinib. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with tofacitinib, especially:

  • aprepitant, bosentan, haloperidol, imatinib, St. John's wort, ticlopidine;

  • an antibiotic--ciprofloxacin, doxycycline, erythromycin, metronidazole, norfloxacin, tetracycline;

  • an antidepressant--desipramine, fluoxetine, sertraline;

  • antifungal medicine--clotrimazole, fluconazole, voriconazole;

  • heart or blood pressure medicine--amiodarone, diltiazem, dronedarone, lidocaine, verapamil;

  • HIV/AIDS medication--atazanavir, efavirenz, darunavir when given with ritonavir, fosamprenavir, nevirapine, saquinavir;

  • medicines to prevent organ transplant rejection--azathioprine, cyclosporine, tacrolimus;

  • other arthritis medicines--abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab;

  • seizure medicine--carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone;

  • a stomach acid-reducer--cimetidine, esomeprazole, omeprazole; or

  • tuberculosis medicine--rifabutin, rifampin, rifapentine.

This list is not complete and many other drugs can interact with tofacitinib. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

Introduction

Immunomodulating agent and disease-modifying antirheumatic drug (DMARD); Janus kinase (JAK) inhibitor.1 3 4 5 6 7 11

Cautions for Xeljanz

Contraindications

  • No known contraindications.1

Warnings/Precautions

Warnings

Infectious Complications

Serious, sometimes fatal infections (including cryptococcosis, pneumocystosis, tuberculosis and other mycobacterial infections, esophageal candidiasis, multidermatomal herpes zoster, cytomegalovirus infection, BK virus infection) reported, particularly in patients receiving concomitant therapy with immunosuppressive agents.1 3 4 5 Infections may be disseminated.1

Do not initiate tofacitinib in patients with active infections, including localized infections.1 Consider potential risks and benefits of the drug prior to initiating therapy in patients with a history of chronic, recurring, serious, or opportunistic infections; patients with underlying conditions that may predispose them to infections; and patients who have been exposed to tuberculosis or who have resided or traveled in regions where tuberculosis or mycoses are endemic.1

Closely monitor patients during and after treatment with tofacitinib for the development of signs or symptoms of infection.1 If new infection occurs during therapy, perform thorough diagnostic evaluation (appropriate for immunocompromised patient), initiate appropriate anti-infective therapy, and closely monitor patient.1 If serious infection, opportunistic infection, or sepsis develops, discontinue tofacitinib until the infection is controlled.1

Evaluate all patients for active or latent tuberculosis and for risk factors for tuberculosis prior to and periodically during therapy.1 When indicated, initiate appropriate antimycobacterial regimen for treatment of latent tuberculosis infection prior to tofacitinib therapy.1 Consider initiation of antimycobacterial therapy prior to initiation of tofacitinib in individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed and in individuals with a negative test for latent tuberculosis who have risk factors for tuberculosis.1 Consultation with a tuberculosis specialist is recommended when deciding whether to initiate antimycobacterial therapy.1

Monitor all patients, including those with a negative tuberculin skin test, for active tuberculosis.1

Viral reactivation, including herpes zoster reactivation, reported.1 Effect on risk of reactivation of chronic viral hepatitis not known; patients with serologic evidence of HBV or HCV infection were excluded from clinical trials.1

Malignancies and Lymphoproliferative Disorders

Lymphoma and other malignancies observed.1 4 5

Increased incidence of Epstein Barr virus-associated posttransplant lymphoproliferative disorder observed in renal allograft recipients receiving tofacitinib and immunosuppressive agents concomitantly.1

Consider risks and benefits of tofacitinib prior to initiating therapy in patients with a known malignancy (other than a successfully treated nonmelanoma skin cancer) or when considering whether to continue tofacitinib in patients who develop a malignancy.1

Other Warnings/Precautions

GI Perforation

GI perforation reported;1 4 role of JAK inhibition by tofacitinib not known.1

Caution in patients at increased risk for GI perforation (e.g., patients with history of diverticulitis).1 Promptly evaluate patients with new-onset abdominal symptoms for early identification of GI perforation.1

Hematologic Effects

Possible lymphopenia, neutropenia, and anemia.1 3 5 6 May require interruption or discontinuance of tofacitinib therapy (see Treatment Interruptions for Toxicity under Dosage and Administration).1

Do not initiate tofacitinib therapy in patients with lymphocyte count <500/mm3, ANC <1000/mm3, or hemoglobin concentration <9 g/dL.1

Lymphocyte counts <500/mm3 associated with increased incidence of treated and serious infections.1

Monitor lymphocyte count at baseline and every 3 months during therapy.1 Monitor neutrophil count and hemoglobin concentration at baseline, 4–8 weeks after initiation of therapy, and every 3 months thereafter.1

Hepatic Effects

Elevated hepatic aminotransferases reported, mainly in patients receiving other DMARDs (primarily methotrexate) concomitantly.1 4 5 Reversible upon modification of the treatment regimen (e.g., dosage reduction of concomitant DMARD or tofacitinib or interruption of tofacitinib therapy).1

Routinely monitor hepatic aminotransferase concentrations.1 In case of elevations, promptly evaluate patient for drug-induced hepatotoxicity.1 If drug-induced hepatic injury is suspected, interrupt tofacitinib therapy until such diagnosis excluded.1

Effects on Serum Lipids

Dose-related increases in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglyceride concentrations reported.1 3 4 5 6 Increases observed at 1 month of therapy and remain stable thereafter; maximum increases generally occur within 6 weeks.1 Effect on cardiovascular morbidity and mortality not known.1 3 4 6

Measure lipid concentrations approximately 4–8 weeks after initiation of therapy.1 Manage hyperlipidemia according to current standards of care.1

Immunizations

Avoid live vaccines during therapy with tofacitinib.1 (See Vaccines under Interactions.) Update immunizations according to current administration guidelines prior to initiation of tofacitinib therapy.1

Specific Populations

Pregnancy

Category C.1 Pregnancy registry at 877-311-8972.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

Increased incidence of serious infections in patients ≥65 years of age compared with younger patients.1 Use with caution.1

Hepatic Impairment

Use not recommended in patients with severe hepatic impairment.1 Dosage adjustment for moderate hepatic impairment (see Hepatic Impairment under Dosage and Administration).1

Safety and efficacy not evaluated in patients with serologic evidence of HBV or HCV infection.1

Renal Impairment

Safety and efficacy not evaluated in patients with rheumatoid arthritis with baseline Clcr <40 mL/minute.1 Dosage adjustment for moderate to severe renal impairment (see Renal Impairment under Dosage and Administration).1

Common Adverse Effects

Diarrhea,1 3 4 6 nasopharyngitis,1 3 4 6 upper respiratory tract infection,1 3 4 6 headache,1 3 4 6 hypertension.1 3 4

Commonly used brand name(s)

In the U.S.

  • Xeljanz
  • Xeljanz XR

Available Dosage Forms:

  • Tablet
  • Tablet, Extended Release

Therapeutic Class: Musculoskeletal Agent

Pharmacologic Class: Tyrosine Kinase Inhibitor

Uses For Xeljanz

Tofacitinib is used alone or together with other medicines to treat rheumatoid arthritis. This medicine is used in patients who have taken other medicines (eg, methotrexate) that did not work well. Tofacitinib is a Janus kinase (JAK) inhibitor that works on the immune system.

This medicine is available only with your doctor's prescription.

Xeljanz Dosage and Administration

Dosage in Rheumatoid Arthritis

  • Xeljanz/Xeljanz XR may be used as monotherapy or in combination with methotrexate or other nonbiologic disease-modifying antirheumatic drugs (DMARDs). The recommended dose of Xeljanz is 5 mg twice daily and the recommended dose of Xeljanz XR is 11 mg once daily.
  • Xeljanz/Xeljanz XR is given orally with or without food.
  • Swallow Xeljanz XR tablets whole and intact. Do not crush, split, or chew.

Switching from Xeljanz Tablets to Xeljanz XR Tablets

Patients treated with Xeljanz 5 mg twice daily may be switched to Xeljanz XR 11 mg once daily the day following the last dose of Xeljanz 5 mg.

Dosage Modifications due to Serious Infections and Cytopenias

(see Tables 1, 2, and 3 below)

  • It is recommended that Xeljanz/Xeljanz XR not be initiated in patients with an absolute lymphocyte count less than 500 cells/mm3, an absolute neutrophil count (ANC) less than 1000 cells/mm3 or who have hemoglobin levels less than 9 g/dL.
  • Dose interruption is recommended for management of lymphopenia, neutropenia and anemia [see Warnings and Precautions (5.4) and Adverse Reactions (6.1)].
  • Avoid use of Xeljanz/Xeljanz XR if a patient develops a serious infection until the infection is controlled.

Dosage Modifications due to Drug Interactions

  • In patients receiving:
    • potent inhibitors of Cytochrome P450 3A4 (CYP3A4) (e.g., ketoconazole), or
    • one or more concomitant medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole),
    the recommended dose is Xeljanz 5 mg once daily.
  • Coadministration of potent inducers of CYP3A4 (e.g., rifampin) with Xeljanz/Xeljanz XR may result in loss of or reduced clinical response to Xeljanz/Xeljanz XR.
  • Coadministration of potent inducers of CYP3A4 with Xeljanz/Xeljanz XR is not recommended.

Dosage Modifications in Patients with Renal or Hepatic Impairment

  • In patients with:
    • moderate or severe renal insufficiency, or
    • moderate hepatic impairment,
    the recommended dose is Xeljanz 5 mg once daily.
  • Use of Xeljanz/Xeljanz XR in patients with severe hepatic impairment is not recommended.
Table 1: Dose Adjustments for Lymphopenia
Low Lymphocyte Count [see Warnings and Precautions (5.4)]
Lab Value
(cells/mm3)
Recommendation
Lymphocyte count greater than or equal to 500 Maintain dose
Lymphocyte count less than 500 Discontinue Xeljanz/Xeljanz XR
(Confirmed by repeat testing)
Table 2: Dose Adjustments for Neutropenia
Low ANC [see Warnings and Precautions (5.4)]
Lab Value
(cells/mm3)
Recommendation
ANC greater than 1000 Maintain dose
ANC 500–1000 For persistent decreases in this range, interrupt dosing until ANC is greater than 1000
When ANC is greater than 1000, resume Xeljanz 5 mg twice daily/Xeljanz XR 11 mg once daily
ANC less than 500 Discontinue Xeljanz/Xeljanz XR
(Confirmed by repeat testing)
Table 3: Dose Adjustments for Anemia
Low Hemoglobin Value [see Warnings and Precautions (5.4)]
Lab Value
(g/dL)
Recommendation
Less than or equal to 2 g/dL decrease and greater than or equal to 9.0 g/dL Maintain dose
Greater than 2 g/dL decrease or less than 8.0 g/dL Interrupt the administration of Xeljanz/Xeljanz XR until hemoglobin values have normalized
(Confirmed by repeat testing)

Contraindications

None

Drug Interactions

All information provided in this section is applicable to Xeljanz and Xeljanz XR as they contain the same active ingredient (tofacitinib).

Potent CYP3A4 Inhibitors

Tofacitinib exposure is increased when Xeljanz is coadministered with potent inhibitors of cytochrome P450 (CYP) 3A4 (e.g., ketoconazole) [see Dosage and Administration (2.3) and Figure 3].

Moderate CYP3A4 and Potent CYP2C19 Inhibitors

Tofacitinib exposure is increased when Xeljanz is coadministered with medications that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g., fluconazole) [see Dosage and Administration (2.3) and Figure 3].

Potent CYP3A4 Inducers

Tofacitinib exposure is decreased when Xeljanz is coadministered with potent CYP3A4 inducers (e.g., rifampin) [see Dosage and Administration (2.3) and Figure 3].

Immunosuppressive Drugs

There is a risk of added immunosuppression when Xeljanz/Xeljanz XR is coadministered with potent immunosuppressive drugs (e.g., azathioprine, tacrolimus, cyclosporine). Combined use of multiple-dose Xeljanz/Xeljanz XR with potent immunosuppressants has not been studied in rheumatoid arthritis. Use of Xeljanz/Xeljanz XR in combination with biologic DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is not recommended.

Use in specific populations

All information provided in this section is applicable to Xeljanz and Xeljanz XR as they contain the same active ingredient (tofacitinib).

Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Xeljanz/Xeljanz XR during pregnancy. Patients should be encouraged to enroll in the Xeljanz/Xeljanz XR pregnancy registry if they become pregnant. To enroll or obtain information from the registry, patients can call the toll free number 1-877-311-8972.

Risk Summary

There are no adequate and well-controlled studies of Xeljanz/Xeljanz XR use in pregnant women.

The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. The background risks in the U.S. general population of major birth defects and miscarriages are 2–4% and 15–20% of clinically recognized pregnancies, respectively.

Based on animal studies, Xeljanz/Xeljanz XR has the potential to affect a developing fetus. Fetocidal and teratogenic effects were noted when pregnant rats and rabbits received tofacitinib during the period of organogenesis at exposures multiples of 146 times and 13 times the human dose of 5 mg twice daily, respectively [see Data]. Further, in a peri and post-natal study in rats, tofacitinib resulted in reductions in live litter size, postnatal survival, and pup body weights at exposure multiples of approximately 73 times the human dose of 5 mg twice daily.

Data

Human Data

In the tofacitinib clinical development program in rheumatoid arthritis, birth defects and miscarriages were reported.

Animal Data

In a rat embryofetal developmental study, in which pregnant rats received tofacitinib during organogenesis, tofacitinib was teratogenic at exposure levels approximately 146 times the human dose of 5 mg twice daily (on an AUC basis at oral doses of 100 mg/kg/day in rats). Teratogenic effects consisted of external and soft tissue malformations of anasarca and membranous ventricular septal defects, respectively; and skeletal malformations or variations (absent cervical arch; bent femur, fibula, humerus, radius, scapula, tibia, and ulna; sternoschisis; absent rib; misshapen femur; branched rib; fused rib; fused sternebra; and hemicentric thoracic centrum). In addition, there was an increase in post-implantation loss, consisting of early and late resorptions, resulting in a reduced number of viable fetuses. Mean fetal body weight was reduced. No developmental toxicity was observed in rats at exposure levels approximately 58 times the human dose of 5 mg twice daily (on an AUC basis at oral doses of 30 mg/kg/day in pregnant rats).

In a rabbit embryofetal developmental study in which pregnant rabbits received tofacitinib during the period of organogenesis, tofacitinib was teratogenic at exposure levels approximately 13 times the MRHD human dose of 5 mg twice daily (on an AUC basis at oral doses of 30 mg/kg/day in rabbits) in the absence of signs of maternal toxicity. Teratogenic effects included thoracogastroschisis, omphalocele, membranous ventricular septal defects, and cranial/skeletal malformations (microstomia, microphthalmia), mid-line and tail defects. In addition, there was an increase in post-implantation loss associated with late resorptions. No developmental toxicity was observed in rabbits at exposure levels approximately 3 times the human dose of 5 mg twice daily (on an AUC basis at oral doses of 10 mg/kg/day in pregnant rabbits).

In a peri- and postnatal development study in pregnant rats that received tofacitinib from gestation day 6 through day 20 of lactation, there were reductions in live litter size, postnatal survival, and pup body weights at exposure levels approximately 73 times the human dose of 5 mg twice daily (on an AUC basis at oral doses of 50 mg/kg/day in rats). There was no effect on behavioral and learning assessments, sexual maturation or the ability of the F1 generation rats to mate and produce viable F2 generation fetuses in rats at exposure levels approximately 17 times the human dose of 5 mg twice daily (on an AUC basis at oral doses of 10 mg/kg/day in rats).

Lactation

Risk Summary

It is not known whether tofacitinib is excreted in human milk. Additionally, there are no data to assess the effects of the drug on the breastfed child. However, tofacitinib is excreted in rat milk at concentrations higher than in maternal serum [see Data]. Women should not breastfeed while treated with Xeljanz/Xeljanz XR. A decision should be made whether to discontinue breastfeeding or to discontinue Xeljanz/Xeljanz XR.

Data

Human Data

There are no adequate and well-controlled studies of Xeljanz/Xeljanz XR use during breastfeeding.

Animal Data

Following administration of tofacitinib to lactating rats, concentrations of tofacitinib in milk over time paralleled those in serum, and were approximately 2 times higher in milk relative to maternal serum at all time points measured.

Females and Males of Reproductive Potential

Contraception

Females

Embryofetal toxicity including malformations occurred in embryofetal development studies in rats and rabbits [see Use in Specific Populations (8.1)].

Females of reproductive potential should be advised to use effective contraception during treatment with Xeljanz/Xeljanz XR and for at least 4 weeks after the last dose. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with Xeljanz/Xeljanz XR.

Infertility

Females

Based on findings in rats, treatment with Xeljanz/Xeljanz XR may result in reduced fertility in females of reproductive potential [see Nonclinical Toxicology (13.1)].

Pediatric Use

The safety and effectiveness of Xeljanz/Xeljanz XR in pediatric patients have not been established.

Geriatric Use

Of the 3315 patients who enrolled in Studies I to V, a total of 505 rheumatoid arthritis patients were 65 years of age and older, including 71 patients 75 years and older. The frequency of serious infection among Xeljanz-treated subjects 65 years of age and older was higher than among those under the age of 65. As there is a higher incidence of infections in the elderly population in general, caution should be used when treating the elderly.

Use in Diabetics

As there is a higher incidence of infection in diabetic population in general, caution should be used when treating patients with diabetes.

Hepatic Impairment

Xeljanz-treated patients with moderate hepatic impairment had greater tofacitinib levels than Xeljanz-treated patients with normal hepatic function [see Clinical Pharmacology (12.3)]. Higher blood levels may increase the risk of some adverse reactions, therefore, the recommended dose is Xeljanz 5 mg once daily in patients with moderate hepatic impairment [see Dosage and Administration (2.4)]. Xeljanz/Xeljanz XR has not been studied in patients with severe hepatic impairment; therefore, use of Xeljanz/Xeljanz XR in patients with severe hepatic impairment is not recommended. No dose adjustment is required in patients with mild hepatic impairment. The safety and efficacy of Xeljanz/Xeljanz XR have not been studied in patients with positive hepatitis B virus or hepatitis C virus serology.

Renal Impairment

Xeljanz-treated patients with moderate and severe renal impairment had greater tofacitinib blood levels than Xeljanz-treated patients with normal renal function; therefore, the recommended dose is Xeljanz 5 mg once daily in patients with moderate and severe renal impairment [see Dosage and Administration (2.4)]. In clinical trials, Xeljanz/Xeljanz XR was not evaluated in rheumatoid arthritis patients with baseline creatinine clearance values (estimated by the Cockroft-Gault equation) less than 40 mL/min. No dose adjustment is required in patients with mild renal impairment.

Xeljanz Description

Xeljanz/Xeljanz XR are formulated with the citrate salt of tofacitinib, a JAK inhibitor.

Tofacitinib citrate is a white to off-white powder with the following chemical name: (3R,4R)-4-methyl-3-(methyl-7H-pyrrolo [2,3-d]pyrimidin-4-ylamino)-ß-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-propanetricarboxylate (1:1) .

The solubility of tofacitinib citrate in water is 2.9 mg/mL.

Tofacitinib citrate has a molecular weight of 504.5 Daltons (or 312.4 Daltons as the tofacitinib free base) and a molecular formula of C16H20N6O∙C6H8O7. The chemical structure of tofacitinib citrate is:

Xeljanz is supplied for oral administration as 5 mg tofacitinib (equivalent to 8 mg tofacitinib citrate) white round, immediate-release film-coated tablet. Each tablet of Xeljanz contains the appropriate amount of tofacitinib as a citrate salt and the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, HPMC 2910/Hypromellose 6cP, titanium dioxide, macrogol/PEG3350, and triacetin.

Xeljanz XR is supplied for oral administration as 11 mg tofacitinib (equivalent to 17.77 mg tofacitinib citrate) pink, oval, extended release film-coated tablet with a drilled hole at one end of the tablet band. Each tablet of Xeljanz XR contains the appropriate amount of tofacitinib as a citrate salt and the following inactive ingredients: sorbitol, hydroxyethyl cellulose, copovidone, magnesium stearate, cellulose acetate, hydroxypropyl cellulose, HPMC 2910/Hypromellose, titanium dioxide, triacetin, and red iron oxide. Printing ink contains shellac glaze, ammonium hydroxide, propylene glycol, and ferrosoferric oxide/black iron oxide.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide).

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Patient Counseling

Advise patients of the potential benefits and risks of Xeljanz/Xeljanz XR.

Serious Infection

Inform patients that Xeljanz/Xeljanz XR may lower the ability of their immune system to fight infections. Advise patients not to start taking Xeljanz/Xeljanz XR if they have an active infection. Instruct patients to contact their healthcare provider immediately during treatment if symptoms suggesting infection appear in order to ensure rapid evaluation and appropriate treatment [see Warnings and Precautions (5.1)].

Advise patients that the risk of herpes zoster, some cases of which can be serious, is increased in patients treated with Xeljanz [see Warnings and Precautions (5.1)].

Malignancies and Lymphoproliferative Disorders

Inform patients that Xeljanz/Xeljanz XR may increase their risk of certain cancers, and that lymphoma and other cancers have been observed in patients taking Xeljanz. Instruct patients to inform their healthcare provider if they have ever had any type of cancer [see Warnings and Precautions (5.2)].

Important Information on Laboratory Abnormalities

Inform patients that Xeljanz/Xeljanz XR may affect certain lab test results, and that blood tests are required before and during Xeljanz/Xeljanz XR treatment [see Warnings and Precautions (5.4)].

Pregnancy

Inform patients that Xeljanz/Xeljanz XR should not be used during pregnancy unless clearly necessary, and advise patients to inform their doctors right away if they become pregnant while taking Xeljanz/Xeljanz XR. Inform patients that Pfizer has a registry for pregnant women who have taken Xeljanz/Xeljanz XR during pregnancy. Advise patients to contact the registry at 1-877-311-8972 to enroll [see Use in Specific Populations (8.1)]. Women of reproductive potential should be advised to use effective contraception during treatment with Xeljanz/Xeljanz XR and for at least 4 weeks after the last dose [see Use in Specific Populations (8.3)]. Inform patients that they should not breastfeed while taking Xeljanz/Xeljanz XR [see Use in Specific Populations (8.2)].

Residual Tablet Shell

Patients receiving Xeljanz XR may notice an inert tablet shell passing in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the inert tablet shell.

This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com.

LAB-0445-11.0

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: August 2017    
Medication Guide
Xeljanz (ZEL' JANS')
Xeljanz XR (ZEL' JANS' EKS-AHR)
(tofacitinib)

What is the most important information I should know about Xeljanz/Xeljanz XR?

Xeljanz/Xeljanz XR may cause serious side effects including:

1. Serious infections.

Xeljanz/Xeljanz XR is a medicine that affects your immune system. Xeljanz/Xeljanz XR can lower the ability of your immune system to fight infections. Some people can have serious infections while taking Xeljanz/Xeljanz XR, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections.

  • Your healthcare provider should test you for TB before starting Xeljanz/Xeljanz XR and during treatment.
  • Your healthcare provider should monitor you closely for signs and symptoms of TB infection during treatment with Xeljanz/Xeljanz XR.

You should not start taking Xeljanz/Xeljanz XR if you have any kind of infection unless your healthcare provider tells you it is okay. You may be at a higher risk of developing shingles.

Before starting Xeljanz/Xeljanz XR, tell your healthcare provider if you:

  • think you have an infection or have symptoms of an infection such as:
  • fever, sweating, or chills
  • cough
  • blood in phlegm
  • warm, red, or painful skin or sores on your body
  • burning when you urinate or urinating more often than normal
  • muscle aches
  • shortness of breath
  • weight loss
  • diarrhea or stomach pain
  • feeling very tired
  • are being treated for an infection.
  • get a lot of infections or have infections that keep coming back.
  • have diabetes, chronic lung disease, HIV, or a weak immune system. People with these conditions have a higher chance for infections.
  • have TB, or have been in close contact with someone with TB.
  • live or have lived, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may happen or become more severe if you use Xeljanz/Xeljanz XR. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common.
  • have or have had hepatitis B or C.

After starting Xeljanz/Xeljanz XR, call your healthcare provider right away if you have any symptoms of an infection. Xeljanz/Xeljanz XR can make you more likely to get infections or make worse any infection that you have.

2. Cancer and immune system problems. Xeljanz/Xeljanz XR may increase your risk of certain cancers by changing the way your immune system works.
  • Lymphoma and other cancers including skin cancers can happen in patients taking Xeljanz/Xeljanz XR. Tell your healthcare provider if you have ever had any type of cancer.
  • Some people who have taken Xeljanz with certain other medicines to prevent kidney transplant rejection have had a problem with certain white blood cells growing out of control (Epstein Barr Virus-associated post-transplant lymphoproliferative disorder).
3. Tears (perforation) in the stomach or intestines.
  • Tell your healthcare provider if you have had diverticulitis (inflammation in parts of the large intestine) or ulcers in your stomach or intestines. Some people taking Xeljanz/Xeljanz XR can get tears in their stomach or intestines. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.
    Tell your healthcare provider right away if you have fever and stomach-area pain that does not go away, and a change in your bowel habits.
4. Changes in certain laboratory test results. Your healthcare provider should do blood tests before you start receiving Xeljanz/Xeljanz XR and while you take Xeljanz/Xeljanz XR to check for the following side effects:
  • changes in lymphocyte counts. Lymphocytes are white blood cells that help the body fight off infections.
  • low neutrophil counts. Neutrophils are white blood cells that help the body fight off infections.
  • low red blood cell count. This may mean that you have anemia, which may make you feel weak and tired.

Your healthcare provider should routinely check certain liver tests.

You should not receive Xeljanz/Xeljanz XR if your lymphocyte count, neutrophil count, or red blood cell count is too low or your liver tests are too high.

Your healthcare provider may stop your Xeljanz/Xeljanz XR treatment for a period of time if needed because of changes in these blood test results.

You may also have changes in other laboratory tests, such as your blood cholesterol levels. Your healthcare provider should do blood tests to check your cholesterol levels 4 to 8 weeks after you start receiving Xeljanz/Xeljanz XR, and as needed after that. Normal cholesterol levels are important to good heart health.

See "What are the possible side effects of Xeljanz/Xeljanz XR?" for more information about side effects.

What is Xeljanz/Xeljanz XR?

Xeljanz/Xeljanz XR is a prescription medicine called a Janus kinase (JAK) inhibitor.

Xeljanz/Xeljanz XR is used to treat adults with moderately to severely active rheumatoid arthritis in which methotrexate did not work well.

It is not known if Xeljanz/Xeljanz XR is safe and effective in people with Hepatitis B or C.

Xeljanz/Xeljanz XR is not for people with severe liver problems.

It is not known if Xeljanz/Xeljanz XR is safe and effective in children.

What should I tell my healthcare provider before taking Xeljanz/Xeljanz XR?

Xeljanz/Xeljanz XR may not be right for you. Before taking Xeljanz/Xeljanz XR, tell your healthcare provider if you:

  • have an infection. See "What is the most important information I should know about Xeljanz/Xeljanz XR?"
  • have liver problems
  • have kidney problems
  • have any stomach area (abdominal) pain or been diagnosed with diverticulitis or ulcers in your stomach or intestines
  • have had a reaction to tofacitinib or any of the ingredients in Xeljanz/Xeljanz XR
  • have recently received or are scheduled to receive a vaccine. People who take Xeljanz/Xeljanz XR should not receive live vaccines. People taking Xeljanz/Xeljanz XR can receive non-live vaccines.
  • have any other medical conditions.
  • plan to become pregnant or are pregnant. It is not known if Xeljanz/Xeljanz XR will harm an unborn baby. You should use effective birth control while you are taking Xeljanz/Xeljanz XR and for at least 4 weeks after you take your last dose.
    • Pregnancy Registry: Pfizer has a registry for pregnant women who take Xeljanz/Xeljanz XR. The purpose of this registry is to check the health of the pregnant mother and her baby. If you are pregnant or become pregnant while taking Xeljanz/Xeljanz XR, talk to your healthcare provider about how you can join this pregnancy registry or you may contact the registry at 1-877-311-8972 to enroll.
  • plan to breastfeed or are breastfeeding. You and your healthcare provider should decide if you will take Xeljanz/Xeljanz XR or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Xeljanz/Xeljanz XR and other medicines may affect each other causing side effects.

Especially tell your healthcare provider if you take:

  • any other medicines to treat your rheumatoid arthritis. You should not take tocilizumab (Actemra®), etanercept (Enbrel®), adalimumab (Humira®), infliximab (Remicade®), rituximab (Rituxan®), abatacept (Orencia®), anakinra (Kineret®), certolizumab (Cimzia®), golimumab (Simponi®), azathioprine, cyclosporine, or other immunosuppressive drugs while you are taking Xeljanz or Xeljanz XR. Taking Xeljanz or Xeljanz XR with these medicines may increase your risk of infection.
  • medicines that affect the way certain liver enzymes work. Ask your healthcare provider if you are not sure if your medicine is one of these.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Xeljanz/Xeljanz XR?

  • Take Xeljanz/Xeljanz XR exactly as your healthcare provider tells you to take it.
  • Take Xeljanz 2 times a day with or without food.
  • Take Xeljanz XR 1 time a day with or without food.
  • Swallow Xeljanz XR tablets whole and intact. Do not crush, split, or chew.
  • When you take Xeljanz XR, you may see something in your stool that looks like a tablet. This is the empty shell from the tablet after the medicine has been absorbed by your body.
  • If you take too much Xeljanz/Xeljanz XR, call your healthcare provider or go to the nearest hospital emergency room right away.

What are possible side effects of Xeljanz/Xeljanz XR?

Xeljanz/Xeljanz XR may cause serious side effects, including:

  • See "What is the most important information I should know about Xeljanz/Xeljanz XR?"
  • Hepatitis B or C activation infection in people who carry the virus in their blood. If you are a carrier of the hepatitis B or C virus (viruses that affect the liver), the virus may become active while you use Xeljanz/Xeljanz XR. Your healthcare provider may do blood tests before you start treatment with Xeljanz and while you are using Xeljanz/Xeljanz XR. Tell your healthcare provider if you have any of the following symptoms of a possible hepatitis B or C infection:
  • feel very tired
  • little or no appetite
  • clay-colored bowel movements
  • chills
  • muscle aches
  • skin rash
  • skin or eyes look yellow
  • vomiting
  • fevers
  • stomach discomfort
  • dark urine

Common side effects of Xeljanz/Xeljanz XR include:

  • upper respiratory tract infections (common cold, sinus infections)
  • headache
  • diarrhea
  • nasal congestion, sore throat, and runny nose (nasopharyngitis)

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Xeljanz/Xeljanz XR. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

You may also report side effects to Pfizer at 1-800-438-1985.

How should I store Xeljanz/Xeljanz XR?

  • Store Xeljanz/Xeljanz XR at room temperature between 68°F to 77°F (20°C to 25°C).
  • Safely throw away medicine that is out of date or no longer needed.

Keep Xeljanz/Xeljanz XR and all medicines out of the reach of children.

General information about the safe and effective use of Xeljanz/Xeljanz XR.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Xeljanz/Xeljanz XR for a condition for which it was not prescribed. Do not give Xeljanz/Xeljanz XR to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Xeljanz/Xeljanz XR. If you would like more information, talk to your healthcare provider. You can ask your pharmacist or healthcare provider for information about Xeljanz/Xeljanz XR that is written for health professionals.

What are the ingredients in Xeljanz?

Active ingredient: tofacitinib citrate

Inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, HPMC 2910/Hypromellose 6cP, titanium dioxide, macrogol/PEG3350, and triacetin.

What are the ingredients in Xeljanz XR?

Active ingredient: tofacitinib citrate

Inactive ingredients: sorbitol, hydroxyethyl cellulose, copovidone, magnesium stearate, cellulose acetate, hydroxypropyl cellulose, HPMC 2910/Hypromellose, titanium dioxide, triacetin, and red iron oxide. Printing ink contains shellac glaze, ammonium hydroxide, propylene glycol, and ferrosoferric oxide/black iron.

LAB-0535-5.0

Important information

You should not use Xeljanz if you have severe liver disease.

You should not use Xeljanz if you have a serious infection. Before you start treatment, your doctor may perform tests to make sure you do not have an infection.

Serious and sometimes fatal infections may occur during treatment with Xeljanz. Stop using this medicine and call your doctor right away if you have signs of infection such as: fever, chills, sore throat, flu symptoms, sores or white patches in your mouth or throat, night sweats, stomach pain, diarrhea, weight loss, skin redness and swelling, or cough and chest pain.

Do not receive a "live" vaccine while using Xeljanz, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you.

Before taking this medicine

You should not use Xeljanz if you are allergic to tofacitinib, or if you have a serious infection.

Tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where tuberculosis is common.

To make sure Xeljanz is safe for you, tell your doctor if you have:

  • an active or chronic infection;

  • any type of infection caused by bacteria, fungus, or virus;

  • a history of shingles (herpes zoster);

  • an infected skin wound;

  • diabetes;

  • liver disease (especially hepatitis B or C);

  • kidney disease;

  • HIV or AIDS;

  • a history of skin cancer or melanoma;

  • a history of diverticulitis, stomach ulcer, or perforation (a hole or tear) in your esophagus, stomach, or intestines; or

  • a weak immune system caused by disease or by using certain medicines (especially methotrexate or steroid medicine such as dexamethasone).

Xeljanz may increase your risk of certain cancers by changing the way your immune system works. If you have had a kidney transplant, Xeljanz may cause your body to produce too much of a certain type of white blood cell.

It is not known whether Xeljanz will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of Xeljanz on the baby.

It is not known whether tofacitinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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