The following adverse reactions are described below and
elsewhere in the warnings and precautions section of the labeling:
- Cardiovascular Disorders [see
WARNINGS AND PRECAUTIONS]
- Neurologic Disorders [see WARNINGS
- Bone Marrow Toxicity [see WARNINGS
- Hepatic Toxicity [see WARNINGS
- Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
- Renal Toxicity [see WARNINGS
Clinical Trials Experience
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in practice.
The following data on adverse reactions are based on the
subcutaneous administration of ACTIMMUNE at a dose of 50 mcg/m²,
three times weekly, in patients with CGD during a clinical trial in the United
States and Europe.
The most common adverse reactions observed in patients
with CGD are shown in the following table:
Table 2: Adverse Reactions Occurring in 2 % or Greater
of CGD Patients Receiving ACTIMMUNE in Clinical Trials
||Percent of Patients
|Injection site erythema or tenderness
Similar safety data were
observed in 34 patients with SMO.
The clinical and laboratory
toxicity associated with multiple dose studies of ACTIMMUNE is dose, route and
The most common adverse
reactions include constitutional symptoms such as fever, headache, chills,
myalgia or fatigue which may decrease in severity as treatment continues.
Less Common Adverse Reactions
The following adverse reactions
are assessed as potentially related to ACTIMMUNE (interferon gamma-1b) therapy:
Blood and Lymphatic System—neutropenia (reversible), febrile neutropenia, leukopenia,
Cardiovascular— angina pectoris, arrhythmia, atrial fibrillation,
atrioventricular block, cardiac failure (including congestive cardiac failure),
tachyarrhythmia, heart block, (acute) myocardial infarction, myocardial
ischemia, syncope, and tachycardia.
Gastrointestinal—abdominal pain, dyspepsia, gastrointestinal bleeding,
granulomatous colitis, hepatic insufficiency, and pancreatitis, including
pancreatitis with fatal outcome.
General Disorders and
Administration Site Conditions—asthenia,
chest pain/discomfort, influenza-like illness/flu-like symptoms, injection site
hemorrhage, injection site pain, malaise, rigors, and weakness.
Hepatobiliary Disorders—hepatic insufficiency and hepatomegaly.
Immunological—hypersensitivity, increased autoantibodies, lupus-like
syndrome (including systemic lupus erythematosus-flares and drug-induced lupus
erythematosus), and Stevens-Johnson syndrome.
Infections and Infestations—upper respiratory tract infection.
Investigations—blood alkaline phosphatase increased, liver function tests
abnormal/ elevation of hepatic enzymes, increased triglycerides, and weight
Metabolic—hyponatremia, hypokalemia, hyperglycemia, and
Musculoskeletal—back pain, clubbing, and muscle spasms.
Nervous System—dizziness (excluding vertigo), gait disturbance, headache,
Parkinsonian symptoms, convulsion/seizure (including grand mal convulsions),
and transient ischemic attacks.
Psychiatric—confusion, depression, disorientation, hallucinations,
mental status changes, and mental status decreased.
Pulmonary—tachypnea, bronchospasm, pulmonary edema, and interstitial
Renal—acute renal failure (which may be reversible) and,
Skin and Subcutaneous Tissue
Disorders—atopic dermatitis, (exacerbation
of) dermatomyositis, transient cutaneous rash, and urticaria.
Vascular Disorder—deep venous thrombosis, hypotension, pulmonary embolism.
Abnormal Laboratory Test
Values: Elevations of ALT and AST have been observed [see WARNINGS AND
The following adverse reactions
have been identified during post approval use of ACTIMMUNE. 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.
Children With CGD Less Than 3 Years Of Age
Data on the safety and activity
of ACTIMMUNE in 37 patients under the age of 3 years was pooled from four
uncontrolled postmarketing studies. The rate of serious infections per
patient-year in this uncontrolled group was similar to the rate observed in the
ACTIMMUNE treatment groups in controlled trials. Developmental parameters
(height, weight and endocrine maturation) for this uncontrolled group conformed
to national normative scales before and during ACTIMMUNE therapy.
In 6 of the 10 patients
receiving ACTIMMUNE therapy before age one year 2-fold to 25-fold elevations
from baseline of AST and/or ALT were observed. These elevations occurred as
early as 7 days after starting treatment. Treatment with ACTIMMUNE was
interrupted in all 6 of these patients and was restarted at a reduced dosage in
4. Liver transaminase values returned to baseline in all patients and
transaminase elevation recurred in one patient upon ACTIMMUNE rechallenge. An
11-fold alkaline phosphatase elevation and hypokalemia in one patient and
neutropenia (ANC = 525 cells/mm³) in another patient resolved with
interruption of ACTIMMUNE treatment and did not recur with rechallenge.
In the postmarketing safety
database clinically significant adverse reactions observed during ACTIMMUNE
therapy in children under the age of three years (n=14) included: two cases of
hepatomegaly, and one case each of Stevens-Johnson syndrome, granulomatous
colitis, urticaria, and atopic dermatitis.
As with all therapeutic
proteins, there is a potential for immunogenicity. In clinical trials, 8 out of
33 ACTIMMUNE-treated patients developed non-neutralizing antibodies to
interferon gamma-1b. No neutralizing antibodies to ACTIMMUNE have been detected
in patients. In a Phase 1 study, none of the 38 ACTIMMUNE-treated healthy
volunteers developed non-neutralizing antibodies to interferon gamma-1b.
The detection of antibody
formation, including neutralizing antibody, in an assay may be influenced by
several factors including assay methodology, sample handling, timing of sample
collection, concomitant medications, and underlying disease. For these reasons,
comparison of the incidence of antibodies to ACTIMMUNE with the incidence of
antibodies to other products may be misleading.