rease in ALT ≥2 times baseline value (flare) can occur during INTRON A therapy for chronic hepatitis B. In clinical trials in adults and pediatrics, this flare generally occurred 8 to 12 weeks after initiation of therapy and was more frequent in responders (adults 63%, 24/38; pediatrics 59%, 10/17) than in nonresponders (adults 27%, 13/48; pediatrics 35%, 19/55). However, in adults and pediatrics, elevations in bilirubin ≥3 mg/dL (≥2 times ULN) occurred infrequently (adults 2%, 2/86; pediatrics 3%, 2/72) during therapy. When ALT flare occurs, in general, INTRON A therapy should be continued unless signs and symptoms of liver failure are observed. During ALT flare, clinical symptomatology and liver function tests including ALT, prothrombin time, alkaline phosphatase, albumin, and bilirubin, should be monitored at approximately 2-week intervals (see WARNINGS).
CONTRAINDICATIONS
INTRON® A is contraindicated in patients with:
Hypersensitivity to interferon alpha or any component of the product.
Autoimmune hepatitis
Decompensated liver disease
INTRON A and REBETOL® combination therapy is additionally contraindicated in:
Patients with hypersensitivity to ribavirin or any other component of the product
Women who are pregnant
Men whose female partners are pregnant
Patients with hemoglobinopathies (e.g. thalassemia major, sickle cell anemia)
Patients with creatinine clearance < 50 mL/min
See REBETOL package insert for additional information.
WARNINGS
General
Moderate to severe adverse experiences may require modification of the patient's dosage regimen, or in some cases termination of INTRON® A therapy. Because of the fever and other "flu-like" symptoms associated with INTRON A administration, it should be used cautiously in patients with debilitating medical conditions, such as those with a history of pulmonary disease (e.g., chronic obstructive pulmonary disease) or diabetes mellitus prone to ketoacidosis. Caution should also be observed in patients with coagulation disorders (eg, thrombophlebitis, pulmonary embolism) or severe myelosuppression.
Cardiovascular Disorders
INTRON A therapy should be used cautiously in patients with a history of cardiovascular disease. Those patients with a history of myocardial infarction and/or previous or current arrhythmic disorder who require INTRON A therapy should be closely monitored (see PRECAUTIONS, Laboratory Tests section). Cardiovascular adverse experiences, which include hypotension, arrhythmia, or tachycardia of 150 beats per minute or greater, and rarely, cardiomyopathy and myocardial infarction have been observed in some INTRON A-treated patients. Some patients with these adverse events had no history of cardiovascular disease. Transient cardiomyopathy was reported in approximately 2% of the AIDS-Related Kaposi's Sarcoma patients treated with INTRON A. Hypotension may occur during INTRON A administration, or up to 2 days posttherapy, and may require supportive therapy including fluid replacement to maintain intravascular volume.
Supraventricular arrhythmias occurred rarely and appeared to be correlated with preexisting conditions and prior therapy with cardiotoxic agents. These adverse experiences were controlled by modifying the dose or discontinuing treatment, but may require specific additional therapy.
Cerebrovascular Disorders
