ADVERSE REACTIONS
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 Chronic Granulomatous Disease (CGD) during an investigational trial in the United States and Europe.
The most common adverse events observed in patients with CGD are shown in the following table:
|
Percent of Patients |
| Clinical Toxicity |
ACTIMMUNE
|
Placebo |
|
CGD (n=63) |
CGD (n=65) |
| Fever |
52 |
28 |
| Headache |
33 |
9 |
| Rash |
17 |
6 |
| Chills |
14 |
0 |
| Injection site erythema or tenderness |
14 |
2 |
| Fatigue |
14 |
11 |
| Diarrhea |
14 |
12 |
| Vomiting |
13 |
5 |
| Nausea |
10 |
2 |
| Myalgia |
6 |
0 |
| Arthralgia |
2 |
0 |
| Injection site pain |
0 |
2 |
Miscellaneous adverse events which occurred infrequently in patients with CGD and may have been related to underlying disease included back pain (2 percent versus 0 percent), abdominal pain (8 percent versus 3 percent) and depression (3 percent versus 0 percent) for ACTIMMUNE and placebo treated patients, respectively.
Similar safety data were observed in 34 patients with severe malignant osteopetrosis.
ACTIMMUNE has also been evaluated in additional disease states in studies in which patients have generally received higher doses (>100 mcg/m2/three times weekly) administered by intramuscular or subcutaneous injection, or intravenous infusion. All of the previously described adverse reactions which occurred in patients with Chronic Granulomatous Disease have also been observed in patients receiving higher doses. Adverse reactions not observed in patients with Chronic Granulomatous Disease but reported in patients receiving ACTIMMUNE (Interferon gamma-1b) in other studies include: Cardiovascular—hypotension, syncope, tachyarrhythmia, heart block, heart failure, and myocardial infarction. Central Nervous System—confusion, disorientation, gait disturbance, Parkinsonian symptoms, seizure, hallucinations, and transient ischemic attacks. Gastrointestinal—dyspepsia, hepatic insufficiency, gastrointestinal bleeding, and pancreatitis, including pancreatitis with fatal outcome. General Disorders and Administration Site Conditions—malaise, injection site hemorrhage. Hematologic—deep venous thrombosis and pulmonary embolism. Immunological— increased autoantibodies, lupus-like syndrome. Metabolic— hyponatremia, hyperglycemia, and hypertriglyceridemia. Musculoskeletal—clubbing, muscle spasms. Pulmonary—tachypnea, bronchospasm, and interstitial pneumonitis. Renal—reversible renal insufficiency. Other— chest discomfort, exacerbation of dermatomyositis.
Abnormal Laboratory Test Values
Elevations of ALT and AST, neutropenia, thrombocytopenia, and proteinuria have been observed (see
WARNINGS
and
PRECAUTIONS: Laboratory Tests).
No neutralizing antibodies to ACTIMMUNE have been detected in any Chronic Granulomatous Disease patients receiving ACTIMMUNE.
Post-Marketing Experience
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 post-marketing 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 post-marketing safety database clinically significant adverse events 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.
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