IMPORTANT SAFETY INFORMATION AND INDICATIONS
SERIOUS INFECTIONS
Patients treated with infliximab products are at increased
risk for developing serious infections that may lead to
hospitalization or death. Most patients who developed these
infections were taking concomitant immunosuppressants
such as methotrexate or corticosteroids. Discontinue
INFLECTRA® (infliximab-dyyb) if a patient develops a serious
infection or sepsis.
risk for developing serious infections that may lead to
hospitalization or death. Most patients who developed these
infections were taking concomitant immunosuppressants
such as methotrexate or corticosteroids. Discontinue
INFLECTRA® (infliximab-dyyb) if a patient develops a serious
infection or sepsis.
Reported infections include:
-
Active tuberculosis (TB), including reactivation of latent
TB. Patients frequently presented with disseminated or
extrapulmonary disease. Patients should be tested for
latent TB before INFLECTRA® use and during therapy.1,2
Treatment for latent infection should be initiated prior to
INFLECTRA® use. -
Invasive fungal infections including histoplasmosis,
coccidioidomycosis, candidiasis, aspergillosis,
blastomycosis and pneumocystosis. Patients may present
with disseminated, rather than localized, disease. Empiric
anti-fungal therapy should be considered in patients at
risk for invasive fungal infections who develop severe
systemic illness. -
Bacterial, viral, and other infections due to opportunistic
pathogens, including Legionella and Listeria.
The risks and benefits of treatment with INFLECTRA® 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 treatment with INFLECTRA®,
including the possible development of TB in patients who
tested negative for latent TB infection prior to initiating
therapy, who are on treatment for latent TB, or who were
previously treated for TB infection.
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 treatment with INFLECTRA®,
including the possible development of TB in patients who
tested negative for latent TB infection prior to initiating
therapy, who are on treatment for latent TB, or who were
previously treated for TB infection.
Risk of infection may be higher in patients greater than 65
years of age, pediatric patients, patients with co-morbid
conditions and/or patients taking concomitant
immunosuppressant therapy. In clinical trials, other serious
infections observed in patients treated with infliximab products
included pneumonia, cellulitis, abscess, and skin ulceration.
years of age, pediatric patients, patients with co-morbid
conditions and/or patients taking concomitant
immunosuppressant therapy. In clinical trials, other serious
infections observed in patients treated with infliximab products
included pneumonia, cellulitis, abscess, and skin ulceration.
MALIGNANCIES
Lymphoma and other malignancies, some fatal, have been
reported in children and adolescent patients treated with
TNF blockers, including infliximab products. Approximately
half of these cases were lymphomas, including Hodgkin's and
non-Hodgkin's lymphoma. The other cases represented a
variety of malignancies, including rare malignancies that are
usually associated with immunosuppression and malignancies
that are not usually observed in children and adolescents. The
malignancies occurred after a median of 30 months after the
first dose of therapy. Most of the patients were receiving
concomitant immunosuppressants.
reported in children and adolescent patients treated with
TNF blockers, including infliximab products. Approximately
half of these cases were lymphomas, including Hodgkin's and
non-Hodgkin's lymphoma. The other cases represented a
variety of malignancies, including rare malignancies that are
usually associated with immunosuppression and malignancies
that are not usually observed in children and adolescents. The
malignancies occurred after a median of 30 months after the
first dose of therapy. Most of the patients were receiving
concomitant immunosuppressants.
Postmarketing cases of hepatosplenic T-cell lymphoma, a
rare type of T-cell lymphoma, have been reported in patients
treated with TNF blockers, including infliximab products.
These cases have had a very aggressive disease course and
have been fatal. The majority of reported cases have
occurred in patients with Crohn's disease or ulcerative colitis
and most were in adolescent and young adult males. Almost
all patients had received treatment with azathioprine or
6-mercaptopurine concomitantly with a TNF-blocker at or
prior to diagnosis. Carefully assess the risks and benefits of
treatment with INFLECTRA®, especially in these patient
types.
rare type of T-cell lymphoma, have been reported in patients
treated with TNF blockers, including infliximab products.
These cases have had a very aggressive disease course and
have been fatal. The majority of reported cases have
occurred in patients with Crohn's disease or ulcerative colitis
and most were in adolescent and young adult males. Almost
all patients had received treatment with azathioprine or
6-mercaptopurine concomitantly with a TNF-blocker at or
prior to diagnosis. Carefully assess the risks and benefits of
treatment with INFLECTRA®, especially in these patient
types.
In clinical trials of all TNF inhibitors, more cases of lymphoma
were observed compared with controls and the expected rate in
the general population. However, patients with Crohn’s disease,
rheumatoid arthritis, or plaque psoriasis may be at higher risk
for developing lymphoma. In clinical trials of some TNF
inhibitors, including infliximab products, more cases of other
malignancies were observed compared with controls. The rate
of these malignancies among patients treated with infliximab
products was similar to that expected in the general population,
whereas the rate in control patients was lower than expected.
Cases of acute and chronic leukemia have been reported with
postmarketing TNF-blocker use. As the potential role of TNF
inhibitors in the development of malignancies is not known,
caution should be exercised when considering treatment of
patients with a current or a past history of malignancy or other
risk factors such as chronic obstructive pulmonary disease
(COPD).
were observed compared with controls and the expected rate in
the general population. However, patients with Crohn’s disease,
rheumatoid arthritis, or plaque psoriasis may be at higher risk
for developing lymphoma. In clinical trials of some TNF
inhibitors, including infliximab products, more cases of other
malignancies were observed compared with controls. The rate
of these malignancies among patients treated with infliximab
products was similar to that expected in the general population,
whereas the rate in control patients was lower than expected.
Cases of acute and chronic leukemia have been reported with
postmarketing TNF-blocker use. As the potential role of TNF
inhibitors in the development of malignancies is not known,
caution should be exercised when considering treatment of
patients with a current or a past history of malignancy or other
risk factors such as chronic obstructive pulmonary disease
(COPD).
Melanoma and Merkel cell carcinoma have been reported in
patients treated with TNF-blocker therapy, including infliximab
products. Periodic skin examination is recommended for all
patients, particularly those with risk factors for skin cancer.
patients treated with TNF-blocker therapy, including infliximab
products. Periodic skin examination is recommended for all
patients, particularly those with risk factors for skin cancer.
CONTRAINDICATIONS
INFLECTRA® is contraindicated in patients with moderate to
severe (NYHA Class III/IV) congestive heart failure (CHF) at
doses greater than 5 mg/kg. Higher mortality rates at the 10
mg/kg dose and higher rates of cardiovascular events at the 5
mg/kg dose have been observed in these patients. INFLECTRA®
should be used with caution and only after consideration of
other treatment options. Patients should be monitored closely.
Discontinue INFLECTRA® if new or worsening CHF symptoms
appear. INFLECTRA® should not be (re)administered to patients
who have experienced a severe hypersensitivity reaction or to
patients with hypersensitivity to murine proteins or other
components of the product.
severe (NYHA Class III/IV) congestive heart failure (CHF) at
doses greater than 5 mg/kg. Higher mortality rates at the 10
mg/kg dose and higher rates of cardiovascular events at the 5
mg/kg dose have been observed in these patients. INFLECTRA®
should be used with caution and only after consideration of
other treatment options. Patients should be monitored closely.
Discontinue INFLECTRA® if new or worsening CHF symptoms
appear. INFLECTRA® should not be (re)administered to patients
who have experienced a severe hypersensitivity reaction or to
patients with hypersensitivity to murine proteins or other
components of the product.
HEPATITIS B REACTIVATION
TNF inhibitors, including infliximab products, have been
associated with reactivation of hepatitis B virus (HBV) in
patients who are chronic carriers. Some cases were fatal.
Patients should be tested for HBV infection before initiating
INFLECTRA®. For patients who test positive, consult a physician
with expertise in the treatment of hepatitis B. Exercise caution
when prescribing INFLECTRA® for patients identified as carriers
of HBV and monitor closely for active HBV infection during and
following termination of therapy with INFLECTRA®. Discontinue
INFLECTRA® in patients who develop HBV reactivation and
initiate antiviral therapy with appropriate supportive treatment.
Exercise caution when considering resumption of INFLECTRA®
and monitor patients closely.
associated with reactivation of hepatitis B virus (HBV) in
patients who are chronic carriers. Some cases were fatal.
Patients should be tested for HBV infection before initiating
INFLECTRA®. For patients who test positive, consult a physician
with expertise in the treatment of hepatitis B. Exercise caution
when prescribing INFLECTRA® for patients identified as carriers
of HBV and monitor closely for active HBV infection during and
following termination of therapy with INFLECTRA®. Discontinue
INFLECTRA® in patients who develop HBV reactivation and
initiate antiviral therapy with appropriate supportive treatment.
Exercise caution when considering resumption of INFLECTRA®
and monitor patients closely.
HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure, jaundice,
hepatitis, and cholestasis have been reported rarely in patients
receiving infliximab products postmarketing. Some cases were
fatal or required liver transplant. Aminotransferase elevations
were not noted prior to discovery of liver injury in many cases.
Patients with symptoms or signs of liver dysfunction should be
evaluated for evidence of liver injury. If jaundice and/or marked
liver enzyme elevations (eg, ≥5 times the upper limit of normal)
develop, INFLECTRA® should be discontinued, and a thorough
investigation of the abnormality should be undertaken.
hepatitis, and cholestasis have been reported rarely in patients
receiving infliximab products postmarketing. Some cases were
fatal or required liver transplant. Aminotransferase elevations
were not noted prior to discovery of liver injury in many cases.
Patients with symptoms or signs of liver dysfunction should be
evaluated for evidence of liver injury. If jaundice and/or marked
liver enzyme elevations (eg, ≥5 times the upper limit of normal)
develop, INFLECTRA® should be discontinued, and a thorough
investigation of the abnormality should be undertaken.
HEMATOLOGIC EVENTS
Cases of leukopenia, neutropenia, thrombocytopenia, and
pancytopenia (some fatal) have been reported in patients
receiving infliximab products. The causal relationship to
infliximab therapy remains unclear. Exercise caution in patients
who have ongoing or a history of significant hematologic
abnormalities. Advise patients to seek immediate medical
attention if they develop signs and symptoms of blood
dyscrasias or infection. Consider discontinuation of
INFLECTRA® in patients who develop significant hematologic
abnormalities.
pancytopenia (some fatal) have been reported in patients
receiving infliximab products. The causal relationship to
infliximab therapy remains unclear. Exercise caution in patients
who have ongoing or a history of significant hematologic
abnormalities. Advise patients to seek immediate medical
attention if they develop signs and symptoms of blood
dyscrasias or infection. Consider discontinuation of
INFLECTRA® in patients who develop significant hematologic
abnormalities.
HYPERSENSITIVITY
Infliximab products have been associated with hypersensitivity
reactions that differ in their time of onset. Acute urticaria,
dyspnea, and hypotension have occurred in association with
infusions of infliximab products. Serious infusion reactions
including anaphylaxis were infrequent. Medications for the
treatment of hypersensitivity reactions should be available.
reactions that differ in their time of onset. Acute urticaria,
dyspnea, and hypotension have occurred in association with
infusions of infliximab products. Serious infusion reactions
including anaphylaxis were infrequent. Medications for the
treatment of hypersensitivity reactions should be available.
NEUROLOGIC EVENTS
TNF inhibitors, including infliximab products, have been
associated in rare cases with CNS manifestation of systemic
vasculitis, seizure, and new onset or exacerbation of CNS
demyelinating disorders, including multiple sclerosis and optic
neuritis, and peripheral demyelinating disorders, including
Guillain-Barré syndrome. Exercise caution when considering
INFLECTRA® in patients with these disorders and consider
discontinuation if these disorders develop.
associated in rare cases with CNS manifestation of systemic
vasculitis, seizure, and new onset or exacerbation of CNS
demyelinating disorders, including multiple sclerosis and optic
neuritis, and peripheral demyelinating disorders, including
Guillain-Barré syndrome. Exercise caution when considering
INFLECTRA® in patients with these disorders and consider
discontinuation if these disorders develop.
AUTOIMMUNITY
Treatment with infliximab products may result in the formation
of autoantibodies and, rarely, in the development of a
lupus-like syndrome. Discontinue treatment with INFLECTRA® if
symptoms of a lupus-like syndrome develop.
of autoantibodies and, rarely, in the development of a
lupus-like syndrome. Discontinue treatment with INFLECTRA® if
symptoms of a lupus-like syndrome develop.
ADVERSE REACTIONS
In clinical trials with infliximab products, the most common
adverse reactions occurring in >10% of patients included
infections (eg, upper respiratory, sinusitis, and pharyngitis),
infusion-related reactions, headache, and abdominal pain.
adverse reactions occurring in >10% of patients included
infections (eg, upper respiratory, sinusitis, and pharyngitis),
infusion-related reactions, headache, and abdominal pain.
USE WITH OTHER DRUGS
Concomitant use of INFLECTRA® with anakinra, abatacept,
tocilizumab, or other biologics used to treat the same
conditions as INFLECTRA® is not recommended because of the
possibility of an increased risk of infection. Care should be
taken when switching from one biologic to another, since
overlapping biological activity may further increase the risk of
infection.
tocilizumab, or other biologics used to treat the same
conditions as INFLECTRA® is not recommended because of the
possibility of an increased risk of infection. Care should be
taken when switching from one biologic to another, since
overlapping biological activity may further increase the risk of
infection.
LIVE VACCINES/THERAPEUTIC INFECTIOUS AGENTS
Live vaccines or therapeutic infectious agents should not be
given with INFLECTRA® due to the possibility of clinical
infections, including disseminated infections.
given with INFLECTRA® due to the possibility of clinical
infections, including disseminated infections.
Bring pediatric patients up to date with all vaccinations prior to
initiating INFLECTRA®. At least a 6-month waiting period
following birth is recommended before the administration of
any live vaccine to infants exposed in utero to infliximab
products.
initiating INFLECTRA®. At least a 6-month waiting period
following birth is recommended before the administration of
any live vaccine to infants exposed in utero to infliximab
products.
References:
1. American Thoracic Society, Centers for Disease Control and
Prevention. Targeted tuberculin testing and treatment of
latent tuberculosis infection. Am J Respir Crit Care Med.
2000;161:S221-S247.
Prevention. Targeted tuberculin testing and treatment of
latent tuberculosis infection. Am J Respir Crit Care Med.
2000;161:S221-S247.
2. See latest Centers for Disease Control guidelines and
recommendations for tuberculosis testing in
immunocompromised patients.
recommendations for tuberculosis testing in
immunocompromised patients.
INDICATIONS
Crohn's Disease
-
Reducing signs and symptoms and inducing and maintaining
clinical remission in adult patients with moderately to
severely active Crohn's disease (CD) who have had an
inadequate response to conventional therapy -
Reducing the number of draining enterocutaneous and
rectovaginal fistulas and maintaining fistula closure in adult
patients with fistulizing CD
Pediatric Crohn's Disease
-
Reducing signs and symptoms and inducing and maintaining
clinical remission in pediatric patients 6 years of age and
older with moderately to severely active Crohn’s disease who
have had an inadequate response to conventional therapy
Ulcerative Colitis
-
Reducing signs and symptoms, inducing and maintaining
clinical remission and mucosal healing, and eliminating
corticosteroid use in adult patients with moderately to
severely active ulcerative colitis who have had an inadequate
response to conventional therapy
Rheumatoid Arthritis
-
Reducing signs and symptoms, inhibiting the progression of
structural damage, and improving physical function in
patients with moderately to severely active rheumatoid
arthritis, in combination with methotrexate
Ankylosing Spondylitis
-
Reducing signs and symptoms in patients with active
ankylosing spondylitis
Psoriatic Arthritis
-
Reducing signs and symptoms of active arthritis, inhibiting
the progression of structural damage, and improving physical
function in patients with psoriatic arthritis
Plaque Psoriasis
-
Treatment of adult patients with chronic severe (ie, extensive
and/or disabling) plaque psoriasis who are candidates for
systemic therapy and when other systemic therapies are
medically less appropriate -
INFLECTRA® should only be administered to patients who will
be closely monitored and have regular follow-up visits with a
physician
Please see full Prescribing Information, including BOXED
WARNING and Medication Guide, for INFLECTRA.
WARNING and Medication Guide, for INFLECTRA.
INFLECTRA® is a trademark of Hospira UK, a Pfizer company.
Remicade is a registered trademark of Janssen Biotech Inc.
Remicade is a registered trademark of Janssen Biotech Inc.
PP-IFA-USA-0110-01 © 2017 Pfizer Inc. All rights reserved. 