Approved Drug Label (PDF)
Boxed Warning
Additions
and/or revisions underlined:
WARNING:
SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS,
and THROMBOSIS
SERIOUS INFECTIONS
Patients
treated with XELJANZ (tablets and oral solution) or XELJANZ XR (extended-
release tablets) are at increased risk for developing serious bacterial,
fungal, viral, and opportunistic infections, including tuberculosis
(TB), that may lead to hospitalization or death [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].
Most patients who developed these infections were taking concomitant
immunosuppressants such as methotrexate or corticosteroids. Reported infections
included:
- Active TB, which may present with
pulmonary or extrapulmonary disease. Patients should be tested for latent TB
before XELJANZ/XELJANZ XR use and during therapy. Treatment for latent
infection should be initiated prior to XELJANZ/XELJANZ XR use.
- Invasive fungal infections,
including cryptococcosis and pneumocystosis. Patients with invasive fungal
infections may present with disseminated, rather than localized, disease.
- Bacterial, viral, including herpes
zoster, and other infections due to opportunistic pathogens.
The
risks and benefits of XELJANZ/XELJANZ XR treatment should be carefully
considered prior to initiating therapy in patients with chronic or recurrent
infection.
Patients
should be closely monitored for the development of signs and symptoms of
infection during and after XELJANZ/XELJANZ XR treatment, including the possible
development of TB in patients who tested negative for latent TB infection prior
to initiating therapy. If a serious infection develops, interrupt
XELJANZ/XELJANZ XR until the infection is controlled [see Warnings and Precautions (5.1)].
MORTALITY
In
a large, randomized, postmarketing safety study in rheumatoid arthritis (RA)
patients 50 years of age and older with at least one cardiovascular (CV)
risk factor comparing XELJANZ tablets 5 mg or 10 mg twice a day to tumor
necrosis factor (TNF) blockers, a higher rate of all-cause mortality, including
sudden CV death, was observed with XELJANZ tablets 5 mg or 10 mg twice a
day [see Warnings and Precautions (5.2)].
XELJANZ
10 mg twice daily and XELJANZ XR 22 mg once daily dosages are not
recommended for the treatment of RA, psoriatic arthritis (PsA), ankylosing
spondylitis (AS), or polyarticular course juvenile idiopathic arthritis (pcJIA)
[see Dosage and Administration (2.3,
2.4)].
MALIGNANCIES
Malignancies,
including lymphomas and solid tumors, have occurred in patients treated with XELJANZ
and other Janus kinase inhibitors used to treat inflammatory conditions.
In
RA patients, a higher rate of malignancies (excluding non-melanoma skin
cancer (NMSC)) was observed in patients treated with XELJANZ tablets
5 mg or 10 mg twice a day compared with TNF blockers [see Warnings and Precautions (5.3)].
Lymphomas
and lung cancers were observed at a higher rate in patients treated with
XELJANZ tablets 5 mg or 10 mg twice a day in RA patients compared to
those treated with TNF blockers. Patients who are current or past smokers are
at additional increased risk.
MAJOR ADVERSE CARDIOVASCULAR EVENTS
RA
patients 50 years of age and older with at least one cardiovascular risk
factor, treated with XELJANZ tablets 5 mg or 10 mg twice daily, had a
higher rate of major adverse cardiovascular events (MACE) (defined as
cardiovascular death, myocardial infarction, and stroke), compared to those
treated with TNF blockers. Patients who are current or past smokers are at
additional increased risk. Discontinue XELJANZ/XELJANZ XR in patients that have
experienced a myocardial infarction or stroke [see Warnings and Precautions (5.4)].
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. Many of these events were
serious and some resulted in death. RA patients 50 years of age and older with
at least one cardiovascular risk factor treated with XELJANZ tablets 5
mg or 10 mg twice daily compared to TNF blockers had an observed increase in
incidence of these events. Avoid XELJANZ/XELJANZ XR in patients at risk.
Discontinue XELJANZ/XELJANZ XR and promptly evaluate patients with symptoms of
thrombosis [see Warnings and Precautions
(5.5)].
5
Warnings and Precautions
Extensive
changes; please refer to label for complete information.
6
Adverse Reactions
Extensive
changes; please refer to label for complete information.
7
Drug Interactions
Additions
and/or revisions underlined:
Table
7 includes drugs with clinically significant drug interactions when
concomitantly used with XELJANZ (tablets and oral solution)
and XELJANZ XR (extended-release tablets) and instructions for
preventing or managing them.
Table
7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When
Concomitantly Used with Other Drugs
Extensive
changes to table, please refer to label for complete information.
8
Use in Specific Populations
Extensive
changes; please refer to label for complete information.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION
GUIDE
Additions
and/or revisions underlined:
What
is the most important information I should know about XELJANZ/XELJANZ
XR/XELJANZ oral solution?
XELJANZ/XELJANZ
XR/XELJANZ oral solution may cause serious side effects including:
.
. .
4. Increased risk of
major cardiovascular events such as heart attack, stroke or death in people 50
years of age and older who have at least 1 heart disease (cardiovascular) risk
factor and are taking XELJANZ 5 mg or 10 mg twice daily, especially if you are
a current or past smoker.
Get
emergency help right away if you have any symptoms of a heart attack or stroke
while taking XELJANZ/XELJANZ XR/XELJANZ oral solution, including:
.
. .
What
is XELJANZ/XELJANZ XR/XELJANZ oral solution?
.
. .
- XELJANZ/XELJANZ
XR is used to treat adults and XELJANZ/XELJANZ oral solution is used to
treat children 2 years of age and older with active psoriatic arthritis
when 1 or more TNF blocker medicines have been used, and did not work well or
cannot be tolerated.
.
. .
- XELJANZ/XELJANZ
oral solution is used to treat children 2 years of age and older with
active polyarticular course juvenile arthritis when 1 or more TNF blocker
medicines have been used, and did not work well or cannot be tolerated.
It
is not known if XELJANZ/XELJANZ XR/XELJANZ oral solution is safe and
effective in people with Hepatitis B or C.
XELJANZ/XELJANZ
XR/XELJANZ oral solution is not recommended for people with severe liver
problems.
It
is not known if XELJANZ/XELJANZ oral solution is safe and effective in children
for treatment other than active polyarticular course juvenile arthritis and
psoriatic arthritis.
.
. .
How should I take
XELJANZ/XELJANZ XR/XELJANZ oral solution?
.
. .
- For
the treatment of psoriatic arthritis, take XELJANZ/XELJANZ XR/XELJANZ oral
solution in combination with methotrexate, sulfasalazine or leflunomide as
instructed by your healthcare provider.
.
. .
Common
side effects of XELJANZ/XELJANZ XR/XELJANZ oral solution in people with
rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis include:
- upper
respiratory tract infections (common cold, sinus infections)
- headache
- diarrhea
- nasal
congestion, sore throat, and runny nose (nasopharyngitis)
- high
blood pressure (hypertension)
- acne
.
. .
Common
side effects of XELJANZ/XELJANZ oral solution in children with
polyarticular course juvenile arthritis and psoriatic arthritis include:
- upper
respiratory tract infections (common cold, sinus infections)
- nasal
congestion, sore throat, and runny nose (nasopharyngitis)
- headache
- fever
- nausea
- vomiting
- acne
. . .
PATIENT
COUNSELING INFORMATION
Additions
and/or revisions underlined:
.
. .
Serious
Infections
Inform
patients that XELJANZ (tablets and oral solution) and XELJANZ XR
(extended-release tablets) 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
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/XELJANZ XR [see Warnings and Precautions (5.1)].
.
. .
Pregnancy
Advise
pregnant females and females of reproductive potential of the potential
risk to a fetus. Advise females to inform their prescriber of a known or
suspected pregnancy [see Use in Specific
Populations (8.1)].
.
. .
Approved Drug Label (PDF)
Boxed Warning
Box
Warning has been revised; see full information below:
WARNING:
SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS
(MACE), AND THROMBOSIS
See
full prescribing information for complete boxed warning.
•
Increased risk of serious bacterial, fungal, viral, and opportunistic
infections leading to hospitalization or death, including tuberculosis (TB).
Interrupt treatment with XELJANZ/XELJANZ XR/XELJANZ Oral Solution if serious
infection occurs until the infection is controlled. Test for latent TB before
and during therapy; treat latent TB prior to use. Monitor all patients for
active TB during treatment, even patients with initial negative latent TB test.
(5.1)
•
Higher rate of all-cause mortality, including sudden cardiovascular death with
XELJANZ vs. TNF blockers in rheumatoid arthritis (RA) patients. (5.2)
•
Malignancies have occurred in patients treated with XELJANZ. Higher rate of
lymphomas and lung cancers with XELJANZ vs. TNF blockers in RA patients. (5.3)
•
Higher rate of MACE (defined as cardiovascular death, myocardial infarction, and
stroke) with XELJANZ vs. TNF blockers in RA patients. (5.4)
•
Thrombosis has occurred in patients treated with XELJANZ. Increased incidence
of pulmonary embolism, venous and arterial thrombosis with XELJANZ vs. TNF
blockers in RA patients. (5.5)
5
Warnings and Precautions
5.2 Mortality
Additions and/or
revisions underlined:
Rheumatoid arthritis patients 50 years of age and
older with at least one cardiovascular risk factor treated with XELJANZ 5 mg
twice a day or XELJANZ 10 mg twice a day had a higher observed rate
of all-cause mortality, including sudden cardiovascular death, compared
to those treated with TNF blockers in a large, randomized, postmarketing
safety study (RA Safety Study 1). The incidence rate of all-cause
mortality per 100 patient-years was 0.88 for XELJANZ 5 mg twice a day,
1.23 for XELJANZ 10 mg twice a day, and 0.69 for TNF blockers [see Clinical Studies (14.5)]. Consider
the benefits and risks for the individual patient prior to initiating or
continuing therapy with XELJANZ/XELJANZ XR/XELJANZ Oral Solution.
A XELJANZ/XELJANZ Oral Solution 10 mg twice daily (or
a XELJANZ XR 22 mg once daily) dosage is not recommended for the
treatment of RA or PsA [see Dosage and
Administration (2.2)].
For the treatment of UC, use XELJANZ/XELJANZ XR
at the lowest effective dose and for the shortest duration needed to
achieve/maintain therapeutic response [see
Dosage and Administration (2.3)].
5.3 Malignancy and Lymphoproliferative Disorders
Additions and/or
revisions underlined:
Malignancies,
including lymphomas and solid cancers, were observed in clinical studies of
XELJANZ [see Adverse Reactions (6.1)].
In RA Safety Study
1, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC))
was observed in patients treated with XELJANZ 5 mg twice a day or XELJANZ 10 mg
twice a day as compared with TNF blockers. The incidence rate of malignancies
(excluding NMSC) per 100 patient-years was 1.13 for XELJANZ 5 mg twice a day,
1.13 for XELJANZ 10 mg twice a day, and 0.77 for TNF blockers. Patients who are
current or past smokers are at additional increased risk [see Clinical Studies (14.5)].
Lymphomas and lung
cancers, which are a subset of all malignancies in RA Safety Study 1, were
observed at a higher rate in patients treated with XELJANZ 5 mg twice a day and
XELJANZ
10
mg twice a day compared to those treated with TNF blockers. The incidence rate
of lymphomas per 100 patient-years was 0.07 for XELJANZ 5 mg twice a day, 0.11
for XELJANZ 10 mg twice a day, and 0.02 for TNF blockers. The incidence rate of
lung cancers per
100
patient-years among current and past smokers was 0.48 for XELJANZ 5 mg twice a
day,
0.59
for XELJANZ 10 mg twice a day, and 0.27 for TNF blockers [see Clinical Studies (14.5)].
Consider
the benefits and risks for the individual patient prior to initiating or
continuing therapy with XELJANZ/XELJANZ XR/XELJANZ Oral Solution,
particularly in patients with a known malignancy (other than a successfully
treated NMSC), patients who develop a malignancy while on treatment, and
patients who are current or past smokers. A XELJANZ/XELJANZ Oral Solution 10
mg twice daily (or a XELJANZ XR 22 mg once daily) dosage is not recommended for
the treatment of RA or PsA [see
Dosage and Administration (2.2)].
In Phase 2B, controlled
dose-ranging trials in de-novo renal
transplant patients, all of whom received induction therapy with basiliximab,
high-dose corticosteroids, and mycophenolic acid products, Epstein Barr
Virus-associated post-transplant lymphoproliferative disorder was observed in 5
out of 218 patients treated with XELJANZ (2.3%) compared to 0 out of
111
patients treated with cyclosporine.
Other
malignancies were observed in clinical studies and the postmarketing setting,
including, but not limited to, lung cancer, breast cancer, melanoma, prostate
cancer, and pancreatic cancer.
Non-Melanoma Skin
Cancer
Non-melanoma skin
cancers (NMSCs) have been reported in patients treated with XELJANZ. Periodic
skin examination is recommended for patients who are at increased risk for skin
cancer. In the UC population, treatment with XELJANZ 10 mg twice daily was
associated with greater risk of NMSC.
5.4 Major Adverse Cardiovascular Events
Newly
added subsection:
In
RA Safety Study 1, RA patients who were 50 years of age and older with at least
one cardiovascular risk factor treated with XELJANZ 5 mg twice daily or XELJANZ
10 mg twice daily had a higher rate of major adverse cardiovascular events
(MACE) defined as cardiovascular death, non-fatal myocardial infarction (MI),
and non-fatal stroke, compared to those treated with TNF blockers. The
incidence rate of MACE per 100 patient-years was 0.91 for XELJANZ 5 mg twice a
day, 1.11 for XELJANZ 10 mg twice a day, and 0.79 for TNF blockers. The
incidence rate of fatal or non-fatal myocardial infarction per 100
patient-years was 0.36 for XELJANZ 5 mg twice a day, 0.39 for XELJANZ 10 mg
twice a day, and 0.20 for TNF blockers [see
Clinical Studies (14.5)]. Patients who are current or past smokers are at
additional increased risk.
Consider
the benefits and risks for the individual patient prior to initiating or
continuing therapy with XELJANZ/XELJANZ XR/XELJANZ Oral Solution, particularly
in patients who are current or past smokers and patients with other
cardiovascular risk factors. Patients should be informed about the symptoms of
serious cardiovascular events and the steps to take if they occur. Discontinue
XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients that have experienced a
myocardial infarction or stroke. A XELJANZ/XELJANZ Oral Solution 10 mg twice
daily (or a XELJANZ XR 22 mg once daily) dosage is not recommended for the
treatment of RA or PsA [see Dosage and
Administration (2.2)].
5.5 Thrombosis
Additions and/or
revisions underlined:
Thrombosis,
including pulmonary embolism (PE), deep venous thrombosis (DVT),
and arterial thrombosis, have occurred in patients treated with XELJANZ and
other Janus kinase (JAK) inhibitors
used to treat inflammatory conditions. Many of these events were serious and
some resulted in death [see Warnings and
Precautions (5.2)].
Patients with
rheumatoid arthritis 50 years of age and older with at least one cardiovascular
risk factor treated with XELJANZ at both 5 mg or 10 mg twice daily compared to
TNF blockers in RA Safety Study 1 had an observed increase in incidence of
these events. The incidence rate of DVT per 100 patient-years was 0.22 for
XELJANZ 5 mg twice a day, 0.28 for XELJANZ 10 mg twice a day, and 0.16 for TNF
blockers. The incidence rate of PE per 100 patient-years was 0.18 for XELJANZ 5
mg twice a day, 0.49 for XELJANZ 10 mg twice a day, and 0.05 for TNF blockers [see Clinical Studies (14.5)].
A XELJANZ/XELJANZ
Oral Solution 10 mg twice daily (or a XELJANZ XR 22 mg once daily)
dosage is not recommended for the treatment of RA or PsA [see Dosage and Administration (2.2)].
In a long-term
extension study in patients with UC, five cases of pulmonary embolism
were reported in patients taking XELJANZ 10 mg twice daily, including one death
in a patient with advanced cancer.
Promptly evaluate
patients with symptoms of thrombosis and discontinue XELJANZ/XELJANZ XR/XELJANZ
Oral Solution in patients with symptoms of thrombosis.
Avoid
XELJANZ/XELJANZ XR/XELJANZ Oral Solution in patients that may be at increased
risk of thrombosis. For the treatment of UC, use XELJANZ/XELJANZ XR at
the lowest effective dose and for the shortest duration needed to
achieve/maintain therapeutic response [see
Dosage and Administration (2.3)].
6
Adverse Reactions
Addition of the
following to the bulleted line listing:
6.1 Clinical Trials Experience
Additions and/or
revisions underlined:
Because clinical studies are conducted under widely
varying conditions, adverse reaction rates observed in the clinical studies of
a drug cannot be directly compared to rates in the clinical studies of another
drug and may not predict the rates observed in a broader patient population in
clinical practice.
Rheumatoid Arthritis
The clinical studies described in the following sections
were conducted using XELJANZ. Although other doses of XELJANZ have been
studied, the recommended dose of XELJANZ is 5 mg twice daily. The recommended
dose for XELJANZ XR is 11 mg once daily. A dosage of XELJANZ 10 mg twice daily
or XELJANZ XR 22 mg once daily is not a recommended regimen for the treatment
of rheumatoid arthritis [see Dosage and
Administration (2.2)]. In RA Safety Study 1, 1455 patients were treated
with XELJANZ 5 mg twice daily, 1456 patients were treated with 10 mg twice
daily, and 1451 patients were treated with a TNF blocker for a median of
4.0 years [see
Clinical Studies (14.5)].
…
During the 2 PsA controlled clinical trials, there
were 3 malignancies (excluding NMSC) in 474 patients receiving XELJANZ plus
non-biologic DMARD (6 to 12 months exposure) compared with 0 malignancies in
236 patients in the placebo plus non-biologic DMARD group (3 months exposure)
and 0 malignancies in 106 patients in the adalimumab plus non-biologic DMARD
group (12 months exposure). No lymphomas were reported.
Malignancies have also been observed in the long-term extension study in
psoriatic arthritis patients treated with XELJANZ.
…
In the long-term extension study, malignancies
(including solid cancers, lymphomas and NMSC) were observed in patients treated
with XELJANZ 5 mg and 10 mg twice daily [see
Warnings and Precautions (5.3)]. Five cases of pulmonary embolism were
reported in patients taking XELJANZ 10 mg twice daily, including one fatality
in a patient with advanced cancer [see
Warnings and Precautions (5.5)].
…
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Extensive changes; please refer
to label
PATIENT COUNSELING INFORMATION
Additions and/or
revisions underlined:
Advise
the patient to read the FDA-approved patient labeling (Medication Guide and
Instructions for Use).
Serious Infections
Inform
patients that XELJANZ/XELJANZ XR/XELJANZ Oral Solution may lower the ability of
their immune system to fight infections. Advise patients not to start taking
XELJANZ/XELJANZ XR/XELJANZ Oral Solution 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/XELJANZ XR [see Warnings and Precautions (5.1)].
Malignancies and
Lymphoproliferative Disorders
Inform
patients that XELJANZ/XELJANZ XR/XELJANZ Oral Solution 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 (5.3)].
Major
Adverse Cardiovascular Events
Inform
patients that XELJANZ/XELJANZ XR/XELJANZ Oral Solution may increase their risk
of major adverse cardiovascular events (MACE) defined as myocardial infarction,
stroke, and cardiovascular death. Instruct all patients, especially current or
past smokers or patients with other cardiovascular risk factors, to be alert
for the development of signs and symptoms of cardiovascular events [see Warnings and Precautions (5.4)].
Thrombosis
Advise
patients to stop taking XELJANZ/XELJANZ XR/XELJANZ Oral Solution and to call
their healthcare provider right away if they experience any symptoms of
thrombosis (sudden shortness of breath, chest pain worsened with breathing,
swelling of leg or arm, leg pain or tenderness, red or discolored skin in the
affected leg or arm) [see Warnings and Precautions
(5.5)].
Hypersensitivity
Advise
patients to stop taking XELJANZ/XELJANZ XR/XELJANZ Oral Solution and to call
their healthcare provider right away if they experience any symptoms of
allergic reactions while taking XELJANZ/XELJANZ XR/XELJANZ Oral Solution [see Warnings and Precautions (5.7)].
Important
Information on Laboratory Abnormalities
Inform
patients that XELJANZ/XELJANZ XR/XELJANZ Oral Solution may affect certain lab
test results, and that blood tests are required before and during
XELJANZ/XELJANZ
XR/XELJANZ Oral Solution treatment [see
Warnings and Precautions (5.8)].
Pregnancy
Advise
pregnant women and females of reproductive potential of the potential risk to a
fetus. Advise females to inform their prescriber of a known or suspected
pregnancy. Inform patients that Pfizer has a registry for pregnant women who
have taken
XELJANZ/XELJANZ
XR/XELJANZ Oral Solution during pregnancy. Advise patients to contact the
registry at 1-877-311-8972 to enroll [see
Use in Specific Populations (8.1)].
Lactation
Advise
women not to breastfeed during treatment with XELJANZ/XELJANZ XR/XELJANZ Oral
Solution and for at least 18 hours after the last dose of XELJANZ/XELJANZ Oral
Solution or 36 hours after the last dose of XELJANZ XR [see Use in Specific Populations (8.2)].
Infertility
Advise
females of reproductive potential that XELJANZ/XELJANZ XR/XELJANZ Oral Solution
may impair fertility [see Use in Specific
Populations (8.3), Nonclinical Toxicology (13.1)]. It is not known if this
effect is reversible.
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.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Mortality
(Additions
underlined)
…
![]()
A dosage of
XELJANZ/XELJANZ Oral Solution 10 mg twice daily or weight-based equivalent twice
daily, or XELJANZ XR 22 mg once daily, is not recommended for the treatment
of RA, PsA, or pcJIA [see Dosage and
Administration (2.2)].
…
5.4 Thrombosis
(Additions
underlined)
…
A dosage of
XELJANZ/XELJANZ Oral Solution 10 mg twice daily or weight-based equivalent twice
daily, or XELJANZ XR 22 mg once daily is not recommended for the treatment
of RA, PsA, or pcJIA [see Dosage and
Administration (2.2)].
…
6
Adverse Reactions
6.1 Clinical Trials Experience
(Additions
underlined)
…
Polyarticular
Course Juvenile Idiopathic Arthritis
XELJANZ/XELJANZ
Oral Solution 5 mg twice daily or weight-based equivalent twice daily was studied
in 225 patients from 2 years to 17 years of age in Study pcJIA-I [see Clinical Studies (14.4)] and one open-label
extension study. The total patient exposure (defined as patients who received
at least one dose of XELJANZ/XELJANZ Oral Solution) was
351
patient-years.
In
general, the types of adverse drug reactions in patients with pcJIA were consistent
with those seen in adult RA patients [see
Adverse Reactions (6.1)].
8
Use in Specific Populations
8.4 Pediatric Use
(Subsection revised, additions underlined)
The safety and effectiveness of XELJANZ/XELJANZ Oral
Solution for the treatment of active pcJIA have been established in patients 2
years to 17 years of age. Use of XELJANZ/XELJANZ Oral Solution for the
treatment of pediatric patients with active pcJIA in this age group is supported
by evidence from adequate and well-controlled studies of XELJANZ in adult RA patients
with additional data from a clinical trial of XELJANZ/XELJANZ Oral Solution in pediatric
patients (2 years to 17 years of age) with active pcJIA consisting of an 18-week,
open label, run-in period followed by a 26-week placebo-controlled, randomized withdrawal
period [see Clinical Studies (14.4)].
The safety and effectiveness of XELJANZ/XELJANZ Oral Solution have not been established
in pcJIA patients less than 2 years of age.
Adverse reactions observed in pediatric patients
receiving XELJANZ/XELJANZ Oral Solution were consistent with those reported in RA
patients [see Adverse Reactions (6.1)].
Safety and efficacy of XELJANZ/XELJANZ Oral Solution
in pediatric patients for indications other than pcJIA have not been
established.
The safety and effectiveness of XELJANZ XR in pediatric patients have not been established.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(Additions
underlined)
…
What is XELJANZ/XELJANZ
XR/XELJANZ Oral Solution?
…
…
Tell your healthcare
provider about all the medicines you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements. XELJANZ/XELJANZ XR/XELJANZ Oral Solution
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, psoriatic arthritis, ulcerative
colitis or polyarticular juvenile arthritis.
…
How should I take XELJANZ/XELJANZ
XR/XELJANZ Oral Solution? Take XELJANZ/XELJANZ XR/XELJANZ Oral Solution exactly as
your healthcare provider tells you to take it.
…
…
Common
side effects of XELJANZ/XELJANZ XR in rheumatoid arthritis patients and psoriatic
arthritis patients include:
…
Common
side effects of XELJANZ/XELJANZ Oral Solution in polyarticular juvenile arthritis
patients include:
upper respiratory tract infections (common cold, sinus
infections)
nasal congestion, sore throat, and runny nose (nasopharyngitis)
headache
fever
nausea
vomiting
…
How should I store
XELJANZ/XELJANZ XR/XELJANZ Oral Solution?
Store
XELJANZ/XELJANZ XR at room temperature between 68°F to 77°F (20°C to 25°C).
Store XELJANZ Oral Solution at room temperature between
68°F to 77°F (20°C to 25°C) in the original bottle and carton to protect from light.
Safely throw away XELJANZ Oral Solution that is out of
date or no longer needed. Use XELJANZ Oral Solution within 60 days of opening the
bottle. Throw away (discard) remaining oral solution after 60 days.
…
What
are the ingredients in XELJANZ Oral Solution?
Active
ingredient: tofacitinib
citrate
Inactive
ingredients: grape
flavor (natural), hydrochloric acid, lactic acid, purified water, sodium benzoate,
sucralose, and xylitol.
Approved Drug Label (PDF)
Boxed Warning
Box warning title
revised; revisions underlined:
WARNING: SERIOUS
INFECTIONS, MORTALITY, MALIGNANCY AND THROMBOSIS
Newly added (prior
to Malignancies)
MORTALITY
Rheumatoid
arthritis 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.
Newly added
(following Malignancies)
THROMBOSIS
Thrombosis,
including pulmonary embolism, deep venous thrombosis, and arterial thrombosis,
has been observed at an increased incidence in rheumatoid arthritis 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. Many of these events
were serious and some resulted in death. Avoid XELJANZ/XELJANZ XR in patients
at risk. Discontinue XELJANZ/XELJANZ XR and promptly evaluate patients with
symptoms of thrombosis.
For patients with
ulcerative colitis, use XELJANZ at the lowest effective dose and for the
shortest duration needed to achieve/maintain therapeutic response.
5
Warnings and Precautions
Newly
added subsections:
5.2
Mortality
Rheumatoid
arthritis 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.
A dosage of
XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily is not recommended for
the treatment of RA or PsA.
For the treatment
of UC, use XELJANZ at the lowest effective dose and for the shortest duration
needed to achieve/maintain therapeutic response.
5.4
Thrombosis
Thrombosis,
including pulmonary embolism, deep venous thrombosis, and arterial thrombosis,
was observed at an increased incidence in patients with rheumatoid arthritis 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 study. Many of these events were serious and some
resulted in death.
A dosage of
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 patients with 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.
Promptly evaluate
patients with symptoms of thrombosis and discontinue XELJANZ/XELJANZ XR in
patients with symptoms of thrombosis.
Avoid
XELJANZ/XELJANZ XR in patients that may be at increased risk of thrombosis. For
the treatment of UC, use XELJANZ at the lowest effective dose and for the
shortest duration needed to achieve/maintain therapeutic response.
6
Adverse Reactions
Addition
of ‘Mortality’ and ‘Thrombosis’ and ‘Hypersensitivity’ to bulleted line
listing.
6.1
Clinical Trials Experience
Rheumatoid
Arthritis
Newly
added information:
The recommended
dose for XELJANZ XR is 11 mg once daily. A dosage of XELJANZ 10 mg twice daily
or XELJANZ XR 22 mg once daily is not a recommended regimen for the treatment
of rheumatoid arthritis.
Psoriatic
Arthritis
Newly
added information:
Although other
doses of XELJANZ have been studied, the recommended dose of XELJANZ is 5 mg
twice daily. The recommended dose for XELJANZ XR is 11 mg once daily. A dosage
of XELJANZ 10 mg twice daily or XELJANZ XR 22 mg once daily is not recommended
for the treatment of PsA
6.2
Postmarketing Experience
Newly
added information:
The following
adverse reactions have been identified during post-approval use of
XELJANZ/XELJANZ XR. Because these reactions are reported voluntarily from a
population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
What
is the most important information I should know about XELJANZ/XELJANZ XR?
XELJANZ/XELJANZ XR may cause serious side effects including:
Newly
added information:
Blood clots in the
lungs, veins of the legs or arms, and arteries. Blood clots in
the lungs (pulmonary embolism, PE), veins of the legs (deep vein thrombosis,
DVT) and arteries (arterial thrombosis) have happened more often in patients
with rheumatoid arthritis who are 50 years of age and older and with at least 1
heart disease (cardiovascular) risk factor taking a higher than recommended dose
of XELJANZ/XELJANZ XR. The recommended dose in patients with rheumatoid
arthritis and psoriatic arthritis is XELJANZ 5 mg twice daily or XELJANZ XR 11
mg one time each day. Blood clots in the lungs have also happened in patients
with ulcerative colitis. Some people have died from these blood clots.
Stop
taking XELJANZ/XELJANZ XR and tell your healthcare provider right away if you
develop signs and symptoms of a blood clot, such as sudden shortness of breath
or difficulty breathing, chest pain, swelling of the leg or arm, leg pain or
tenderness, or redness or discoloration in the leg or arm.
PATIENT COUNSELING INFORMATION
Newly
added information:
Thrombosis
Advise patients to
stop taking XELJANZ/XELJANZ XR and to call their healthcare provider right away
if they experience any symptoms of thrombosis (sudden shortness of breath,
chest pain worsened with breathing, swelling of leg or arm, leg pain or
tenderness, red or discolored skin in the affected leg or arm).
Approved Drug Label (PDF)
5
Warnings and Precautions
Additions and/or
revisions underlined:
5.1 Serious
Infections
… were often taking concomitant immunomodulating
agents such as methotrexate or corticosteroids.
In the UC population, XELJANZ treatment with 10 mg
twice daily was associated with greater risk of serious infections compared to
5 mg twice daily. Additionally, opportunistic herpes zoster infections
(including meningoencephalitis, ophthalmologic, and disseminated cutaneous)
were seen in patients who were treated with XELJANZ 10 mg twice daily.
Other serious infections that were not reported …
… Discontinuation and monitoring criteria for
lymphopenia are recommended …
5.2 Malignancy and
Lymphoproliferative Disorders
… Lymphomas and solid cancers have also been observed
in the long-term extension studies in rheumatoid arthritis patients treated
with XELJANZ …
During the 2 PsA controlled clinical studies
there were 3 malignancies (excluding NMSC) in 474 patients receiving XELJANZ … in
psoriatic arthritis patients treated with XELJANZ.
During the UC controlled clinical studies
(8-week induction and 52-week
maintenance studies),
which included 1220 patients, 0 cases of solid cancer
or lymphoma were observed
in XELJANZ-treated patients.
In the long-term extension
study, malignancies (including solid cancers and lymphomas) were observed
more often in patients treated with XELJANZ 10 mg twice
daily.
In Phase 2B, controlled dose-ranging trials
…
Non-Melanoma Skin Cancer
… Periodic skin examination is recommended for
patients who are at increased risk for skin cancer. In the UC population, treatment
with XELJANZ 10 mg twice daily was associated with greater risk of NMSC.
5.3
Gastrointestinal Perforations
Events of gastrointestinal perforation have been
reported in clinical studies with XELJANZ, although the role of JAK inhibition
in these events 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/XELJANZ XR 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).
5.4 Laboratory
Abnormalities
Lipid Elevations
Treatment with XELJANZ was associated with dose-dependent
increases in lipid parameters …
Maximum effects were generally observed within 6
weeks. There were no clinically relevant changes in LDL/HDL cholesterol
ratios. The effect of these lipid …
5.6 Risk of
Gastrointestinal Obstruction with a Non-Deformable Extended-Release Formulation
such as XELJANZ XR
As with any other non-deformable material …
6
Adverse Reactions
Addition of the
following:
The following clinically significant adverse reactions
are described elsewhere in the labeling:
- Serious Infections
- Malignancy and Lymphoproliferative Disorders
- Gastrointestinal Perforations
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Table
3: Common Adverse Reactions* in Clinical Trials of XELJANZ
for the Treatment of Rheumatoid Arthritis With or Without Concomitant
DMARDs (0-3 Months)
N
reflects randomized and treated patients from the seven clinical trials.
*reported in greater
than or equal to 2% of patients treated with either dose of XELJANZ and greater
than or equal to 1% greater than that reported for placebo.
**
the recommended dose of XELJANZ for the treatment of rheumatoid arthritis
is 5 mg twice daily.
Other
adverse reactions occurring in controlled and open-label extension studies
included:
... Respiratory, thoracic and mediastinal disorders: Dyspnea, cough, sinus congestion, interstitial lung disease
(cases were limited to patients with rheumatoid arthritis and some were fatal)
Clinical Experience in Methotrexate-Naïve
Patients
Study
RA-VI was an active-controlled clinical trial … was consistent with
Studies RA-I through V.
Psoriatic
Arthritis
Any instance of TNF-inhibitor (TNFi) has
been replaced with TNF blocker.
Addition of the following:
Ulcerative
Colitis
XELJANZ
has been studied in patients with moderately to severely active UC in 4
randomized, double-blind, placebo-controlled trials (UC-I, UC-II, UC-III, and
dose-ranging UC-V) and an open-label long-term extension study (UC-IV).
Adverse
reactions reported in greater than or equal to 5% of patients treated with
either 5 mg or 10 mg twice daily of XELJANZ and greater than or equal to 1%
greater than reported in patients receiving placebo in either the induction or
maintenance clinical trials were: nasopharyngitis, elevated cholesterol levels,
headache, upper respiratory tract infection, increased blood creatine
phosphokinase, rash, diarrhea, and herpes zoster.
Induction Trials (Study UC-I, UC-II, and
UC-V):
Common
adverse reactions reported in greater than or equal to 2% of patients treated
with XELJANZ 10 mg twice daily and greater than or equal to 1% greater than
that reported in patients receiving placebo in the 3 induction trials were:
headache, nasopharyngitis, elevated cholesterol levels, acne, increased blood
creatine phosphokinase, and pyrexia.
Maintenance Trial (Study UC-III)
Common
adverse reactions reported in greater than or equal to 4% of patients treated
with either dose of XELJANZ and greater than or equal to 1% greater than
reported in patients receiving placebo are shown in Table 4.
Table
4: Common Adverse Reactions* in -UC Patients during the Maintenance Trial
(Study UC-III) Newly added table; please refer to label for complete information.
*reported
in greater than or equal to 4% of patients treated with either dose of XELJANZ
and greater than or equal to 1% greater than reported for placebo.
**
includes hypercholesterolemia, hyperlipidemia, blood cholesterol increased,
dyslipidemia, blood triglycerides increased, low density lipoprotein increased,
low density lipoprotein abnormal, or lipids increased.
In
the long-term extension study, malignancies (including solid cancers, lymphomas
and NMSC) were observed more often in patients treated with XELJANZ 10 mg twice
daily. Four cases of pulmonary embolism
were reported in patients taking XELJANZ 10 mg twice daily, including one
fatality in a patient with advanced cancer.
Dose-dependent
adverse reactions seen in patients treated with XELJANZ 10 mg twice daily, in
comparison to 5 mg twice daily, include the following: herpes zoster
infections, serious infections, and NMSC.
7
Drug Interactions
Newly added information:
Table
5 includes drugs with clinically important drug interactions when administered
concomitantly with XELJANZ/XELJANZ XR and instructions for preventing or
managing them.
Table
5: Clinical Relevant Interactions Affecting XELJANZ and XELJANZ XR When
Coadministered with Other Drugs Newly added table; please refer to label for complete information.
8
Use in Specific Populations
The following three subsections have substantive
changes; please refer to label for complete information:
8.1 Pregnancy
8.2 Lactation
8.3 Females and Males of Reproductive
Potential
8.5 Geriatric Use
Addition of the following:
Of
the 1156 XELJANZ-treated patients in the UC program, a total of 77 patients
(7%) were 65 years of age or older. The number of patients aged 65 years and
older was not sufficient to determine whether they responded differently from
younger patients.
Newly added subsection:
8.7 Renal Impairment
Moderate
and Severe Impairment
XELJANZ-treated
patients with moderate or severe renal impairment had greater tofacitinib blood
concentrations than XELJANZ-treated patients with normal renal function.
Therefore, dosage adjustment of XELJANZ is recommended in patients with
moderate or severe renal impairment.
Mild
impairment
No
dosage adjustment is required in patients with mild renal impairment.
8.8 Hepatic Impairment
Additions and/or revisions underlined:
Severe
Impairment
XELJANZ/XELJANZ
XR has not been studied in patients with severe hepatic impairment …
Moderate
Impairment
XELJANZ-treated
patients with moderate hepatic impairment had greater tofacitinib blood
concentration than XELJANZ-treated patients with normal hepatic function. Higher blood concentrations may increase
the risk of some adverse reactions. Therefore, dosage adjustment of
XELJANZ is recommended in patients with moderate hepatic impairment.
Mild
Impairment
No
dosage adjustment of XELJANZ/XELJANZ XR is required in patients with mild hepatic
impairment.
Hepatitis
B or C Serology
The
safety and efficacy of XELJANZ/XELJANZ XR have not been studied …
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
Additions and/or revisions underlined:
Serious infections … You may be at a
higher risk of developing shingles (herpes zoster).
People
taking the higher dose (10 mg twice daily) of XELJANZ have a higher risk of
serious infections and shingles.
Cancer and immune
system problems. …
PATIENT COUNSELING INFORMATION
Additions and/or revisions underlined:
Pregnancy
Advise
pregnant women and females of reproductive potential of the potential risk to a
fetus. Advise females to inform their prescriber of a known or suspected pregnancy. Inform patients
that Pfizer has a registry … at 1-877-311-8972 to enroll.
Lactation
Advise
women not to breastfeed during treatment with XELJANZ/XELJANZ XR and for at
least 18 hours after the last dose of XELJANZ or 36 hours after the last dose of
XELJANZ XR.
Infertility
Advise
females of reproductive potential that XELJANZ/XELJANZ XR may impair fertility.
It is not known if this effect is
reversible.
Approved Drug Label (PDF)
Boxed Warning
(addition underlined)
…
Reported
infections include:
Active
tuberculosis, which may present with pulmonary or extrapulmonary disease.
Patients should be tested for latent tuberculosis before XELJANZ/XELJANZ XR use
and during therapy. Treatment for latent
infection should be initiated prior to XELJANZ/XELJANZ XR use.
Invasive
fungal infections, including cryptococcosis and pneumocystosis. Patients with
invasive fungal infections may present with disseminated, rather than
localized, disease.
Bacterial,
viral, including herpes zoster, and other infections due to
opportunistic pathogens.
…
5
Warnings and Precautions
5.2 Malignancy and Lymphoproliferative Disorders
(additions underlined)
…
In the 2 controlled Phase 3 clinical trials in
patients with active psoriatic arthritis, there were 3 malignancies (excluding
NMSC) in 474 patients receiving XELJANZ plus non-biologic
DMARD (6 to 12 months exposure) compared with 0
malignancies in 236 patients in the placebo plus non-biologic DMARD group (3 months
exposure) and 0 malignancies in 106 patients in the adalimumab plus
non-biologic DMARD group (12 months exposure). No lymphomas were reported.
Malignancies have also been observed in the long-term extension study in
psoriatic arthritis patients treated with XELJANZ.
…
6
Adverse Reactions
6.1 Clinical Trial Experience
(additions underlined)
…
Rheumatoid Arthritis
The clinical studies described in the following
sections were conducted using XELJANZ. Although other doses of XELJANZ have
been studied, the recommended dose of XELJANZ is 5 mg twice daily.
The recommended dose for XELJANZ XR is 11 mg once
daily.
…
Psoriatic Arthritis
XELJANZ 5 mg twice daily and 10 mg twice daily were
studied in 2 double-blind Phase 3 clinical trials in patients with active psoriatic
arthritis (PsA).
Study PsA-I (NCT01877668) had a duration of 12
months and enrolled patients who had an inadequate response to a nonbiologic
DMARD and who were naïve to treatment with a TNF-inhibitor (TNFi). Study PsA-I
included a 3-month placebo-controlled period and also included adalimumab 40 mg
subcutaneously once every 2 weeks for 12 months.
Study PsA-II (NCT01882439) had a duration of 6
months and enrolled patients who had an inadequate response to at least one
approved TNFi. This clinical trial included a 3-month placebo controlled
period.
In these combined Phase 3 clinical trials, 238
patients were randomized and treated with XELJANZ 5 mg twice daily and 236
patients were randomized and treated with XELJANZ 10 mg twice daily. All
patients in the clinical trials were required to receive treatment with a
stable dose of a nonbiologic DMARD [the majority (79%) received methotrexate].
The study population randomized and treated with XELJANZ (474 patients)
included 45 (9.5%) patients aged 65 years or older and 66 (13.9%) patients with
diabetes at baseline.
The safety profile observed in patients with active
psoriatic arthritis treated with XELJANZ was consistent with the safety profile
observed in rheumatoid arthritis patients.
7
Drug Interactions
7.4 Immunosuppressive Drugs
(additions underlined)
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 and
psoriatic arthritis. Use of XELJANZ/XELJANZ XR in combination with biologic
DMARDs or potent immunosuppressants such as azathioprine and cyclosporine is
not recommended.
8
Use in Specific Populations
8.5 Geriatric Use
(additions underlined)
Of the 3315 patients who enrolled in rheumatoid
arthritis 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.
8.8 Renal Impairment
(additions underlined)
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 (2.5)].
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 (or in patients with active
psoriatic arthritis with creatinine clearance values less than 50 mL/min).
No dose adjustment is required in patients with mild renal impairment.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(additions underlined)
…
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 (herpes zoster).
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Serious Infections
(additions
underlined)
Serious
and sometimes fatal infections due to bacterial, mycobacterial, invasive
fungal, viral, or other opportunistic pathogens have been reported in
rheumatoid arthritis patients receiving XELJANZ. The most common serious
infections reported with XELJANZ included pneumonia, cellulitis, herpes zoster,
urinary tract infection, diverticulitis, and appendicitis. Among
opportunistic infections, tuberculosis and other mycobacterial infections,
cryptococcosis, esophageal candidiasis, pneumocystosis, multidermatomal herpes
zoster, cytomegalovirus infections, BK virus infection, and
listeriosis were reported with XELJANZ. Some patients have presented with
disseminated rather than localized disease, and were often taking concomitant
immunomodulating agents such as methotrexate or corticosteroids.
Other
serious infections that were not reported in clinical studies may also occur
(e.g., histoplasmosis and coccidioidomycosis).
![]()
…
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
infections.
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. Discontinuation and monitoring criteria for
lymphopenia are discussed in Dosage Modifications due to Serious Infections and
Cytopenias.
![]()
Tuberculosis
Patients
should be evaluated and tested for latent or active infection prior to and
per applicable guidelines during administration of XELJANZ /XELJANZ XR.
…
5.2 Malignancy and Lymphoproliferative Disorders
![]()
…
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.
5.5 Vaccinations
(additions
underlined)
![]()
Avoid use of live vaccines concurrently with XELJANZ/XELJANZ XR. The
interval between live vaccinations and initiation of tofacitinib therapy should
be in accordance with current vaccination guidelines regarding
immunosuppressive agents.
A
patient experienced dissemination of the vaccine strain of varicella zoster
virus, 16 days after vaccination with live attenuated (Zostavax) virus vaccine
and 2 days after treatment start with tofacitinib 5 mg twice daily. The patient
was varicella virus naïve, as evidenced by no previous history of varicella infection
and no anti-varicella antibodies at baseline. Tofacitinib was discontinued and
the patient recovered after treatment with standard doses of antiviral
medication.
Update
immunizations in agreement with current immunization guidelines prior to initiating
XELJANZ/XELJANZ XR therapy.
8
Use in Specific Populations
8.1 Pregnancy
(PLLR
conversion; please refer to label)
8.2 Lactation Risk
(PLLR
conversion)
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.
8.3 Females and Males of Reproductive Potential
(PLLR
conversion)
Contraception
Females
Embryofetal
toxicity including malformations occurred in embryofetal development studies in
rats and rabbits.
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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Medication Guide
(additions
underlined)
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.
…
Before starting
XELJANZ/XELJANZ XR, tell your healthcare provider if you:
…
have diabetes, chronic
lung disease, HIV, or a weak immune system. People with these conditions
have a higher chance for infections.
PATIENT COUNSELING INFORMATION
(additions
underlined)
…
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. 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. Inform patients
that they should not breastfeed while taking XELJANZ/XELJANZ XR.
…
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