Approved Drug Label (PDF)
5
Warnings and Precautions
5.5 Amyloidosis
Newly added subsection:
Post-marketing cases of
injection site amyloid deposits [see Postmarketing Experience (6.4)] have
been reported in NOMID patients after receiving high doses of Kineret injected
subcutaneously into the same area of skin over long periods of time. Systemic
AIL1RAP (IL-1 receptor antagonist protein) amyloidosis occurred in some of
these patients with injection site amyloid deposits; these patients presented
with proteinuria. Recommend patients to rotate their injection sites. In
patients with confirmed injection site amyloid deposits, monitor proteinuria
for systemic amyloidosis.
6
Adverse Reactions
6.4 Postmarketing Experience
Addition of the
following to the bulleted line listing:
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
…
Injection-site
reactions: Physicians
should explain to patients that almost a quarter of patients in the clinical
trial experienced a reaction at the injection site. Injection-site reactions
may include pain, erythema, swelling, prurities, bruising, mass, inflammation,
dermatitis, edema, urticaria, vesicles, warmth, and hemorrhage. Inform patients
or their caregivers that the prefilled syringe should be removed from
refrigeration and left at room temperature for 30 minutes before injecting.
Patients should be advised to rotate the injection site and to avoid
injecting into an area that is already swollen or red. Any persistent reaction
should be brought to the attention of the prescribing physician.
…
MEDICATION GUIDE
Additions
and/or revisions underlined:
…
What are the
possible side effects of KINERET?
KINERET may cause
serious side effects, including:
…
decreased ability
of your body to fight infections (immunosuppression). It is not known if
treatment with medicines that cause immunosuppression, like KINERET, affect
your risk of getting cancer.
amyloidosis. Change (rotate)
injection sites within the area you chose with each dose to reduce your risk of
getting
injection site amyloid deposits (a hard lump under the skin). If you develop
amyloid deposits, your healthcare provider should monitor for symptoms and
signs of systemic amyloidosis such as protein in urine.
Do not use the exact same
spot for each injection.
Do not inject into
abnormal skin (e.g., skin that is bruised, red, scaly, pitted, scarred, hard,
thickened, lumpy, damaged, tender or a stretch mark).
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.3 Hypersensitivity Reactions
Newly added
information:
Serious cutaneous reactions, including Drug Reaction with Eosinophilia and Systemic
Symptoms (DRESS), have been
reported in patients with autoinflammatory conditions treated with KINERET. If a severe hypersensitivity reaction occurs,
immediately discontinue KINERET; treat promptly and monitor until signs and
symptoms resolve.
6
Adverse Reactions
6.4 Postmarketing Experience
Additions and revisions
underlined:
The following adverse reactions have been identified during postapproval use of KINERET. 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.
Hepato-biliary disorders:
elevations of transaminases,
non-infectious hepatitis Hematologic events:
thrombocytopenia, including severe thrombocytopenia (i.e platelet counts
<10x109/L) Skin
and subcutaneous tissue disorders:
Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS) [see Warnings &
Precautions (5.3)]
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and revisions
underlined:
. . .
Hypersensitivity reactions: Inform patients that serious allergic
and skin reactions
have been reported with KINERET.
Advise patients to stop
taking KINERET and seek immediate medical attention
if they experience any symptoms suggesting allergic reactions (including
rash, hives, and swelling of the face, lips, tongue, and throat
that may cause difficulty in breathing or swallowing).
. . .
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Serious Infections
(Additions and/or
revisions underlined)
KINERET
has been associated with an increased incidence of serious infections (2%) vs.
Placebo (< 1%) in clinical trials in RA. Administration of KINERET in RA should be
discontinued if a patient develops a serious infection. In KINERET treated NOMID and DIRA patients
the risk of a disease flare when discontinuing KINERET treatment should be
weighed against the potential risk of continued treatment. Treatment with KINERET
should not be initiated in patients with active infections. The safety and efficacy
of KINERET in immunosuppressed patients or in patients with chronic infections have
not been evaluated.
Drugs
that affect the immune system by blocking tumor necrosis factor (TNF) have been
associated with an increased risk of reactivation of latent tuberculosis (TB). It
is possible that taking drugs such as KINERET that blocks IL-1 increases the
risk of TB or other atypical or opportunistic infections. Health care providers
should follow current CDC guidelines both to evaluate for and to treat possible
latent tuberculosis infections before initiating therapy with KINERET.
5.3 Hypersensitivity Reactions
(Additions and/or
revisions underlined)
Hypersensitivity
reactions, including anaphylactic reactions and angioedema, have been reported with
KINERET. If a severe hypersensitivity reaction
occurs, administration of KINERET should be discontinued and appropriate therapy
initiated.
KINERET
is the recombinant form of IL-1Ra that DIRA patients are lacking. Patients with
DIRA may have an increased risk of allergic reactions, particularly in the
first several weeks after starting KINERET treatment. Patients should be
closely monitored during this time period. If a severe allergic reaction occurs,
appropriate treatment should be initiated and discontinuation of KINERET should
be considered.
6
Adverse Reactions
6.3 Clinical Study Experience in DIRA
(Newly added subsection)
The
safety data described in this section reflect exposure to KINERET in 9 patients
with DIRA treated for up to 10 years in a natural history study (study 17-I- 0016).
Most patients received a starting dose of 1 to 2 mg/kg/day and thereafter doses
were individually adjusted to reach a stable efficacious dose. The highest dose
given was 7.5 mg/kg/day. Overall, the safety profile observed in patients with DIRA
treated with KINERET was consistent with the safety profile in NOMID patients.
There
were 16 serious adverse events (SAEs) reported in 4 out of 9 treated patients. The
most common type of SAEs reported (5 events in 2 patients) were infections [see Warnings and Precautions (5.1)].
The
most common adverse events in patients with DIRA were upper respiratory tract
infections, rash, pyrexia, influenza like illness and gastroenteritis. There were
no permanent discontinuations of KINERET treatment due to AEs.
Infections
There
were 16 infections in 5 patients (reporting rate: 0.28 infections / patient year).
The most common infections were upper respiratory tract infections, cellulitis and
gastroenteritis.
Hypersensitivity Reactions
One
patient with DIRA had a serious event of urticaria on day 10 of KINERET treatment
[see Warnings and Precautions (5.3)].
Injection site reactions
There
was one report of injection site pain, which did not cause discontinuation of KINERET
treatment.
8
Use in Specific Populations
8.4 Pediatric Use
(Additions and/or
revisions underlined)
Neonatal-Onset
Multisystem Inflammatory Disease (NOMID)
The
NOMID study included 36 pediatric patients: 13 below 2 years, 18 between 2 and
11 years, and 5 between 12 and 17 years of age. A subcutaneous KINERET starting dose of 1–2
mg/kg/day was administered in all age groups. An average maintenance dose of 3–4
mg/kg/day was adequate to maintain clinical response throughout the study irrespective
of age but a higher dose was, on occasion, required in severely affected
patients. The prefilled syringe does not allow doses lower than 20 mg to be
administered.
Deficiency of Interleukin-1
Receptor Antagonist (DIRA)
The
study in DIRA patients included 9 pediatric patients (ages 1 month to 9 years
at start of KINERET treatment). Most patients received a starting dose of 1 to 2
mg/kg/day. Doses up to 7.5 mg/kg/day were given. The prefilled syringe does not
allow doses lower than 20 mg to be administered.
Juvenile
Rheumatoid Arthritis (JRA)
The
safety and effectiveness of KINERET in the treatment of pediatric patients with
Juvenile Rheumatoid Arthritis (JRA) have not been established. KINERET was studied
in a single randomized, blinded multi-center trial in 86 patients with polyarticular
course JRA; ages 2-17 years receiving a dose of 1 mg/kg subcutaneously daily, up
to a maximum dose of 100 mg. The 50
patients who achieved a clinical response after a 12-week open-label run-in were
randomized to KINERET (25 patients) or placebo (25 patients), administered
daily for an additional 16 weeks. A subset
of these patients continued open-label treatment with KINERET for up to 1 year
in a companion extension study. An adverse
event profile similar to that seen in adult RA patients was observed in these
studies. These study data are insufficient to demonstrate efficacy and, therefore,
KINERET is not recommended for pediatric use in JRA.
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 (Patient Information and Instructions
for Use).
Instruct
patients and their caregivers on the proper dosage and administration of KINERET
and provide all patients with the “Patient information and Instructions for Use”
insert. While this Patient Information and Instructions for Use provides information
about the product and its use, it is not intended to take the place of regular discussions
between the patient and healthcare provider. The ability to inject subcutaneously
should be assessed to ensure proper administration of KINERET. Thoroughly instruct
patients and their caregivers on the importance of proper disposal and caution
against the reuse of needles, syringes, and drug product. A puncture- resistant
container for the disposal of used syringes should be available to the patient.
The full container should be disposed of according to the directions provided by
the healthcare provider.
Infections:
Inform patients that KINERET may lower the ability of their immune system to
fight infections. Advise patients of the importance of contacting their doctor
if they develop any symptoms of infection.
Injection-site
reactions: Physicians should explain to patients that almost a quarter of patients
in the clinical trial experienced a reaction at the injection site.
Injection-site
reactions may include pain, erythema, swelling, prurities, bruising, mass, inflammation,
dermatitis, edema, urticaria, vesicles, warmth, and hemorrhage. Inform patients
or their caregivers that the prefilled syringe should be removed from refrigeration
and left at room temperature for 30 minutes before injecting. Patients should be
cautioned to avoid injecting into an area that is already swollen or red. Any persistent reaction should be brought to the
attention of the prescribing physician.
Allergic
or other drug reactions: Inform patients about the signs and symptoms of allergic
and other adverse drug reactions and the appropriate actions they should take if
they experience any of these signs and symptoms. Inform patients with DIRA and their caregivers,
that DIRA patients may have an increased risk of allergic reactions,
particularly in the first several weeks of treatment and they should be
monitored closely.
PATIENT INFORMATION
(Extensive
changes; please refer to label)
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