SERIOUS INFECTIONS
Patients treated with REMICADE®
(infliximab) 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 REMICADE® if a patient develops a serious infection or sepsis.
Reported infections include:
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Active tuberculosis (TB), including reactivation of latent
TB. Patients frequently presented with disseminated or extrapulmonary
disease. Patients should be tested for latent TB before and during
treatment with REMICADE®.1,2 Treatment for latent infection should be initiated prior to treatment with REMICADE®.
-
Invasive fungal infections, including histoplasmosis, coccidioidomycosis,
candidiasis, aspergillosis, blastomycosis, pneumocystosis, and cryptococcosis.
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, Listeria, and Salmonella.
The risks and benefits of treatment with REMICADE®
should be carefully considered prior to initiating therapy in patients
with chronic or recurrent infection. Closely monitor patients for the
development of signs and symptoms of infection during and after
treatment with REMICADE®, 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 REMICADE® 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 REMICADE®. 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 REMICADE®. These cases have had a very aggressive disease course and have been fatal. The majority of reported REMICADE®
cases have occurred in patients with Crohn's disease or ulcerative
colitis and most were in adolescent and young adult males. Almost all of
these patients had received treatment with azathioprine or
6-mercaptopurine concomitantly with REMICADE® at or prior to diagnosis. Carefully assess the risks and benefits of treatment with REMICADE®, 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 REMICADE®,
more cases of other malignancies were observed compared with controls.
The rate of these malignancies among patients treated with REMICADE®
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 REMICADE®. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
A population-based retrospective cohort study found a 2- to 3-fold increase in the incidence of
invasive cervical cancer in women with rheumatoid arthritis treated with REMICADE® compared to
biologics-naïve patients or the general population, particularly those over 60 years of age. A
causal relationship between REMICADE® and cervical cancer cannot be excluded. Periodic
screening should continue in women treated with REMICADE®.
CONTRAINDICATIONS
REMICADE® 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. REMICADE®
should be used with caution and only after consideration of other
treatment options. Patients should be monitored closely. Discontinue
REMICADE® if new or worsening CHF symptoms appear. REMICADE®
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 REMICADE®, 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
REMICADE®. For patients who test positive,
consult a physician with expertise in the treatment of hepatitis B.
Exercise caution when prescribing REMICADE®
for patients identified as carriers of HBV and monitor closely for
active HBV infection during and following termination of therapy with
REMICADE®. Discontinue REMICADE®
in patients who develop HBV reactivation and initiate antiviral therapy
with appropriate supportive treatment. Exercise caution when
considering resumption of REMICADE® and monitor patients closely.
HEPATOTOXICITY
Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have
been reported in patients receiving REMICADE® 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, REMICADE® 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. The causal relationship to REMICADE®
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 REMICADE® in patients who develop significant hematologic abnormalities.
HYPERSENSITIVITY
REMICADE® has been associated with hypersensitivity reactions that differ in their time of onset.
Anaphylaxis, acute urticaria, dyspnea, and hypotension have occurred in association with
infusions of REMICADE®. Medications for the treatment of hypersensitivity reactions should be
available.
CARDIOVASCULAR AND CEREBROVASCULAR REACTIONS DURING AND AFTER INFUSION
Serious cerebrovascular accidents, myocardial ischemia/infarction (some fatal), hypotension,
hypertension, and arrhythmias have been reported during and within 24 hours of initiation of
REMICADE® infusion. Cases of transient visual loss have been reported during or within 2 hours
of REMICADE® infusion. Monitor patients during infusion and if a serious reaction occurs,
discontinue infusion. Manage reactions according to signs and symptoms.
NEUROLOGIC EVENTS
TNF inhibitors, including REMICADE®, have been associated 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 REMICADE® in patients with these disorders and consider discontinuation if these disorders develop.
AUTOIMMUNITY
Treatment with REMICADE® may result in the formation of autoantibodies and in the development
of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop
ADVERSE REACTIONS
In clinical trials, the most common REMICADE® 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 REMICADE® with anakinra, abatacept, tocilizumab, or other biologics used to treat the same conditions as REMICADE®
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 REMICADE® due to the possibility of clinical infections, including disseminated infections.
Bring pediatric patients up to date with all vaccinations prior to initiating REMICADE®.
At least a 6-month waiting period following birth is recommended before the administration of any live vaccine
to infants exposed in utero to REMICADE®.
For more information, please see full Prescribing Information and Medication Guide for REMICADE®. Provide the Medication Guide to your patients and encourage discussion. (Requires Adobe® Reader®. Click here to download.)
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.
2. See latest Centers for Disease Control guidelines and recommendations for tuberculosis testing in immunocompromised patients.
