Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Serious Infections
(Section
title updated)
(Additions and/or revisions underlined)
Interleukin-1 (IL-1) blockade may interfere
with the immune response to infections. Treatment with
another medication that works through inhibition of IL-1
has been associated with an
increased risk of
serious infections, and
serious infections have been reported in patients taking
ARCALYST [see Clinical Studies
(14)]. There was a greater incidence of infections in CAPS and RP patients on ARCALYST compared with placebo.
In the controlled portion
of the CAPS study [see Clinical Studies (14.1)], severe infection (bronchitis) was reported in one patient receiving ARCALYST. In an open-label extension
study in CAPS, one patient
developed bacterial meningitis
and died [see Adverse Reactions (6.1)].
In clinical studies, ARCALYST
has not been administered concomitantly with tumor necrosis factor
(TNF) inhibitors. An increased
incidence of serious infections has been associated
with administration of an IL-1
blocker in combination with TNF
inhibitors. ARCALYST is not recommended for use with TNF inhibitors
because this may increase the risk
of serious infections.
Drugs that affect the immune system by blocking TNF have
been associated with an
increased risk of reactivation
of latent tuberculosis (TB). It is possible
that taking drugs such as ARCALYST that block IL-1 increases
the risk of TB or other atypical
or opportunistic infections.
Refer to current practice guidelines
for evaluation and treatment
of possible latent
tuberculosis infections before initiating
therapy with ARCALYST.
Treatment with ARCALYST should
not be initiated in patients with
an active or chronic infection.
Discontinue ARCALYST if a patient develops a
serious infection.
5.2 Risk of Malignancy
(Newly
added section)
The impact of treatment with ARCALYST
on the development of malignancies is not known. Treatment with immunosuppressants, including
ARCALYST, may result in an increase
in the risk of malignancies.
5.3 Hypersensitivity Reactions
(Newly added section)
(Newly
added information)
Hypersensitivity reactions associated with
ARCALYST occurred in clinical trials.
If a hypersensitivity reaction
occurs, discontinue ARCALYST and initiate appropriate
therapy.
5.4 Lipid Profile Changes
(Additions
and/or revisions underlined)
Cholesterol and lipid levels may be reduced in patients with chronic inflammation. Increases in non-fasting lipid
profile parameters occurred in patients
treated with ARCALYST in clinical
trials. Monitor patients’
lipid profiles and consider lipid lowering
therapies if needed, based on cardiovascular
risk factors and current guidelines [see Adverse Reactions (6.1)].
5.5 Immunizations
(Additions and/or revisions underlined)
Since no data
are available on the risks of
secondary transmission of infection by live vaccines in patients receiving
ARCALYST, avoid administration of live
vaccines during treatment with ARCALYST.
No data are available on the effectiveness of vaccines in patients
receiving ARCALYST. Since ARCALYST
may interfere with normal immune
response to new antigens, vaccines may not be effective in patients
receiving ARCALYST.
Because IL-1
blockade may interfere with immune response to infections, it is recommended that prior to initiation of therapy with ARCALYST adult and pediatric patients receive all recommended
vaccinations, as per current immunization guidelines, including pneumococcal vaccine and inactivated
influenza vaccine.
6
Adverse Reactions
(Additions and/or revisions underlined)
The following clinically significant adverse
reactions are described
elsewhere in the labeling.
Serious Infections [see Warnings
and Precautions (5.1)]
Risk of Malignancy[see Warnings and Precautions (5.2)]
Hypersensitivity Reactions [see
Warnings and Precautions (5.3)]
Lipid Profile Changes [see Warnings and Precautions
(5.4)]
6.1 Clinical Trial Experience
(Additions and/or revisions underlined)
Clinical trials
are conducted under widely varying conditions
and, as such, adverse
reaction rates observed cannot be directly compared to rates in the clinical
trials of another drug and may not
reflect the rates observed in clinical
practice.
The data described
herein reflect exposure to ARCALYST
in over 2,000 patients who received
at least one dose, including approximately
1700 exposed to 160 mg
or more,
of whom 151 patients were
exposed for at least 6
months and 111 patients for at least one year. These included patients
with CAPS and RP,
patients with other diseases,
and healthy volunteers.
CAPS
Approximately 60 patients with CAPS were treated weekly with
160 mg of ARCALYST. The pivotal trial
population included 47 patients
with CAPS. These patients were
between the ages of 22 and 78 years (average 51 years). Thirty-one
patients were female and 16 were
male. All of the patients
were White/Caucasian. Six pediatric
patients (12 to17 years) were enrolled
directly into the open-label extension phase of the
trial.
(Updated title for Table 1)
RP
In the RP phase 3 study, a total of
86 patients received at least one dose of ARCALYST
with a median treatment
duration of 9 months [see Clinical
Studies (14.3)]. Of
the patients, 49 (57%)
were female and 37 (43%) were
male; 93% were White/Caucasians.
The mean age was 44.7 years. Seven patients
(8%) were aged 12-17 years old. No new adverse reactions were identified in
this study.
Adverse Reactions of Special Interest
Injection-Site Reactions
In patients with CAPS or
RP, the most common and
consistently reported adverse event
associated with ARCALYST
was injection-site reaction (ISR).
The ISRs included erythema,
swelling, pruritus, mass, bruising, inflammation, pain, edema, dermatitis, discomfort,
urticaria, vesicles, warmth and hemorrhage. Most injection-site reactions lasted for one to two days.
Infections
During Part
A in the CAPS study, the incidence of patients
reporting infections was greater
with ARCALYST (48%) than with
placebo (17%). In Part B,
randomized withdrawal, the incidence of
infections was similar in the
ARCALYST (18%) and the placebo
patients (22%). . .
Six serious infections were reported by four
patients during the
CAPS clinical program: Mycobacterium intracellulare infection; gastrointestinal bleeding
and colitis; sinusitis and bronchitis; and Streptococcus pneumoniae meningitis
[see
Adverse Reactions (6)].
One patient
receiving ARCALYST for an unapproved indication in another study developed an infection
in his olecranon bursa with Mycobacterium intracellulare. The
patient was on chronic glucocorticoid
treatment. The infection occurred after an intraarticular glucocorticoid injection
into the bursa with
subsequent local exposure to a suspected source of mycobacteria. . .
Changes in Hematologic Parameters Laboratory
Changes
One patient in a study in an unapproved
indication developed transient neutropenia
(ANC <
1 x 109/L) after
receiving a large dose (2000 mg intravenously)
of ARCALYST.
The
patient did not experience
any infection associated with the neutropenia.
Lipid Profile Changes
Patients with
CAPS treated with ARCALYST experienced
increases in their mean total cholesterol, HDL
cholesterol, LDL cholesterol, and
triglycerides. The mean
increases from baseline
for total cholesterol, HDL
cholesterol, LDL cholesterol,
and triglycerides
were 19 mg/dL, 2 mg/dL,
10 mg/dL, and 57 mg/dL
respectively after 6 weeks of
open-label therapy.
Immunogenicity
(Additions and/or revisions underlined)
As with
all therapeutic proteins, there is potential for
immunogenicity. The detection
of antibody formation is highly dependent
on the sensitivity and specificity
of the assay. The data reflect the percentage
of patients whose test results were
positive for antibodies to the rilonacept
receptor domains in specific assays. Additionally, the observed incidence of antibody (including neutralizing antibody)
positivity in an assay is highly dependent
on several factors including
assay sensitivity and specificity, assay methodology, sample handling, timing of
sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence
of antibodies to rilonacept with the incidence of antibodies in other studies or to other products may be misleading.
Antibodies directed against the
receptor domains of rilonacept
were detected by an ELISA assay in patients
with CAPS after treatment with ARCALYST.
Nineteen of 55 patients (35%)
who had received ARCALYST for
at least 6 weeks tested positive for
treatment-emergent binding
antibodies on at least
one occasion. Of the 19, seven tested positive at the last assessment (Week 18 or 24 of the open-label
extension period), and five
patients tested positive for
neutralizing antibodies on at least
one occasion. There was
no correlation of antibody activity
and either clinical
effectiveness or safety.
In the Phase 3 study of patients with RP there
were no patients who tested positive
for antibodies at baseline. At
any point in time, 26 out of 86
(30%) subjects tested positive
at any assessment and of these,
6 tested positive for
neutralizing antibodies (NAb). At the
last assessment, 10 subjects
remained positive for anti-drug antibodies (ADA) and
1 subject remained positive for NAb. There was
no correlation of antibody activity and either clinical
effectiveness or safety.
8
Use in Specific Populations
8.4 Pediatric Use
(Additions and/or revisions underlined)
Cryopyrin-Associated Periodic
Syndromes (CAPS) and Recurrent Pericarditis (RP)
(Section
title updated)
Safety and
effectiveness in pediatric patients with CAPS
and RP below the age of 12 years have not been established.
Six pediatric
patients with CAPS between the ages of 12 and 16 were
treated with ARCALYST at a weekly, subcutaneous
dose of 2.2 mg/kg (up to a maximum
of 160 mg) for 24-weeks during the open-label extension
phase. These patients showed
improvement from baseline
in their symptom
scores and in objective markers of inflammation
(e.g., Serum Amyloid A and
C-Reactive Protein). The adverse
reactions included injection site reactions and upper respiratory symptoms as were commonly
seen in the adult patients.
The trough drug levels
for four pediatric patients measured
at the end of the weekly dose interval (mean
20 mcg/mL,
range 3.6 to 33 mcg/mL) were similar to those observed
in adult patients with CAPS (mean 24 mcg/mL, range 7 to 56 mcg/mL).
In the Phase 3 study RHAPSODY,
7 patients
aged 12 years to 17 years were treated with ARCALYST
subcutaneously with an initial
loading dose of 4.4 mg/kg
(up to a maximum of 320 mg) followed
by 2.2 mg/kg (up to a maximum
of 160 mg) weekly. These patients were treated for
a median
time of 15 weeks. There
were no apparent differences
in efficacy,
safety or tolerability across age groups.
When administered
to pregnant primates, rilonacept
treatment may have contributed to alterations in bone ossification in the
fetus. It is not known
if ARCALYST will alter bone development in pediatric patients. Pediatric patients treated with ARCALYST
should undergo appropriate monitoring for growth
and development. [see Use
in Specific Populations (8.1)]
Deficiency of Interleukin-1 Receptor Antagonist
(DIRA)
Safety and effectiveness in pediatric
patients with DIRA weighing 10 kg or more have been established [see
Adverse Reactions (6.1) and
Clinical Studies (14.2)].Safety and effectiveness of ARCALYST have not been established in pediatric patients weighing less
than 10 kg for maintenance of remission of DIRA.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(Additions and/or revisions underlined)
Advise the patient to read the FDA-approved
patient labeling labeling (Patient Information and Instructions for Use).
Assessment of Patient’s or
Caregiver’s Administration of Arcalyst: The first
injection of ARCALYST should be performed under the supervision
of a qualified healthcare professional. . .
Instruct patients
or caregivers in proper vial, syringe, and needle disposal, and should be cautioned against reuse
of these items [see Dosage and Administration (2.5)].
Patient Information
(Additions and/or revisions underlined)
ARCALYST is used to treat Recurrent Pericarditis (RP)
and reduce the risk of recurrence in adults
and children 12 years and older.
It is not known if ARCALYST is safe and effective in
children under 12 years of age.
How should I take ARCALYST?
See the Instructions for Use at the end of this Patient
Information leaflet.
• Take or give ARCALYST exactly as prescribed by the
healthcare provider.
• ARCALYST is given by injection under the skin
(subcutaneous injection) 1 time each week.
• ARCALYST should not be given more than 1 time each
week. . .
What are the possible side effects of ARCALYST?
ARCALYST can cause serious side effects, including:
• See “What is the most important information I should know
about ARCALYST?”
• Risk of Cancer. Medicines that affect the immune system
may increase the risk of getting cancer.
• Allergic Reaction. Stop taking or giving ARCALYST and call
the healthcare provider or get
emergency care right away if you or your child get any of
the following symptoms of an allergic
reaction while taking ARCALYST:
o rash
o swollen face
o trouble breathing
• Changes in your blood cholesterol and triglycerides
(lipids). Your or your child’s healthcare
provider will do blood tests to check for these changes.
In people with CAPS and RP, the most common side
effects of ARCALYST include:
• Injection-site reactions including: pain, redness,
swelling, itching, bruising, lumps,
inflammation, skin rash, blisters, warmth, and bleeding at
the injection site.
• Upper respiratory tract infections
• Joint and muscle aches in RP
In people with DIRA, the most common side effects of
ARCALYST include:
• Upper respiratory infection
• Rash
• Ear infection
• Sore throat
• Runny nose
These are not all the possible side effects of ARCALYST.
Tell your or your child’s healthcare provider if
you or your child have any side effect that bothers
you or does not go away. For more information, ask
your or your child’s healthcare provider or pharmacist.
Call your or your child’s healthcare provider for
medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
How should I store ARCALYST?
• Keep ARCALYST in the carton it comes in to protect from
light.
• Store ARCALYST in the refrigerator between 36°F to 46°F
(2°C to 8°C). Call your pharmacy if you
have any questions.
• Refrigerated ARCALYST can be used until the expiration
date printed on the vial and carton.
• ARCALYST may be kept at room temperature after mixing
with Sterile Water for Injection, USP,
and should be used within 3 hours of mixing.
Get Email Alerts |
Guide
