Roferon-a

DEPRESSION AND SUICIDAL BEHAVIOR INCLUDING SUICIDAL IDEATION, SUICIDAL ATTEMPTS AND SUICIDES HAVE BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALFA INTERFERONS, INCLUDING ROFERON-A, IN PATIENTS WITH AND WITHOUT PREVIOUS PSYCHIATRIC ILLNESS. Roferon-A should be used with extreme caution in patients who report a history of depression. Patients should be informed that depression and suicidal ideation may be side effects of treatment and should be advised to report these side effects immediately to the prescribing physician. Patients receiving Roferon-A therapy should receive close monitoring for the occurrence of depressive symptomatology. Psychiatric intervention and/or cessation of treatment should be considered for patients experiencing depression. Although dose reduction or treatment cessation may lead to resolution of the depressive symptomatology, depression may persist and suicides have occurred after withdrawing therapy (see PRECAUTIONS and ADVERSE REACTIONS).

Central nervous system adverse reactions have been reported in a number of patients. These reactions included decreased mental status, dizziness, impaired memory, agitation, manic behavior and psychotic reactions. More severe obtundation and coma have been rarely observed. Most of these abnormalities were mild and reversible within a few days to 3 weeks upon dose reduction or discontinuation of Roferon-A therapy. Careful periodic neuropsychiatric monitoring of all patients is recommended. Roferon-A should be used with caution in patients with seizure disorders and/or compromised central nervous system function.

Roferon-A should be administered with caution to patients with cardiac disease or with any history of cardiac illness. Acute, self-limited toxicities (i.e., fever, chills) frequently associated with Roferon-A administration may exacerbate preexisting cardiac conditions. Rarely, myocardial infarction has occurred in patients receiving Roferon-A. Cases of cardiomyopathy have been observed on rare occasions in patients treated with alpha interferons.

Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including Roferon-A. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and a causal relationship between interferon alfa-based therapies and these events is difficult to establish.

Serious, acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction and anaphylaxis), as well as skin rashes have been rarely observed during alpha-interferon therapy, including interferon alfa-2a. If a serious reaction develops during treatment with Roferon-A, discontinue treatment and institute appropriate medical therapy immediately. Transient rashes do not necessitate interruption of treatment.

In chronic hepatitis C, initiation of alfa-interferon therapy, including Roferon-A, has been reported to cause transient liver abnormalities, which in patients with poorly compensated liver disease can result in increased ascites, hepatic failure or death.

Infrequently, severe or fatal gastrointestinal hemorrhage has been reported in association with alpha-interferon therapy.

Ulcerative, and hemorrhagic/ischemic colitis, sometimes fatal, have been observed within 12 weeks of starting alpha interferon treatment. Abdominal pain, bloody diarrhea, and fever are the typical manifestations of colitis. Roferon-A should be discontinued immediately if these symptoms develop. The colitis usually resolves within 1 to 3 weeks of discontinuation of alpha interferon.

While fever may be associated with the flu-like syndrome reported commonly during interferon therapy, other causes of high or persistent fever must be ruled out, particularly in patients with neutropenia. Serious and severe infections (bacterial, viral, fungal), some fatal, have been reported during treatment with alpha interferons including Roferon-A. Appropriate anti-infective therapy should be started immediately and discontinuation of therapy should be considered.

Alpha-interferons suppress bone marrow function and may result in severe cytopenias and anemia including very rare events of aplastic anemia. Cytopenias (e.g., leukopenia, thrombocytopenia) can lead to an increased risk of infections or hemorrhage. It is advised that complete blood counts (CBC) be obtained pretreatment and monitored routinely during therapy. Alpha interferon therapy should be discontinued in patients who develop severe decreases in neutrophil (<0.5 × 109/L) or platelet counts (<25 × 109/L).

Caution should be exercised when administering Roferon-A to patients with myelosuppression or when Roferon-A is used in combination with other agents that are known to cause myelosuppression. Synergistic toxicity has been observed when Roferon-A is administered in combination with zidovudine (AZT).9

Roferon-A causes or aggravates hypothyroidism and hyperthyroidism. Hyperglycemia has been observed in patients treated with Roferon-A. Symptomatic patients should have their blood glucose measured and followed-up accordingly. Patients with diabetes mellitus may require adjustment of their anti-diabetic regimen.

Dyspnea, pulmonary infiltrates, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis, some resulting in respiratory failure and/or patient deaths, may be induced or aggravated by alpha interferon therapy. Patients who develop persistent or unexplained pulmonary infiltrates or pulmonary function impairment should discontinue treatment with Roferon-A.

Decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, and papilledema are induced or aggravated by treatment with Interferon alfa-2a or other alpha interferons. All patients should receive an eye examination at baseline. Patients with preexisting ophthalmologic disorders (e.g., diabetic or hypertensive retinopathy) should receive periodic ophthalmologic exams during interferon alpha treatment. Any patient who develops ocular symptoms should receive a prompt and complete eye examination. Interferon alfa-2a treatment should be discontinued in patients who develop new or worsening ophthalmologic disorders.

Pancreatitis has been observed in patients receiving alpha interferon treatment, including those who developed marked triglyceride elevations. In some cases, fatalities have been observed. Although a causal relationship to Roferon-A has not been established, marked triglyceride elevation is a risk factor for development of pancreatitis. Roferon-A should be suspended if symptoms or signs suggestive of pancreatitis are observed. In patients diagnosed with pancreatitis, discontinuation of therapy with Roferon-A should be considered.

Roferon-A is indicated for use in patients with chronic hepatitis C diagnosed by HCV antibody and/or a history of exposure to hepatitis C who have compensated liver disease and are 18 years of age or older. A liver biopsy and a serum test for the presence of antibody to HCV should be performed to establish the diagnosis of chronic hepatitis C. Other causes of hepatitis, including hepatitis B, should be excluded prior to therapy with Roferon-A.

3 million IU (11.1 mcg/0.5 mL) Roferon-A per syringe — The solution is colorless and each 0.5 mL contains 3 MIU of Interferon alfa-2a, recombinant, 3.605 mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as a preservative and 0.385 mg ammonium acetate.

6 million IU (22.2 mcg/0.5 mL) Roferon-A per syringe — The solution is colorless and each 0.5 mL contains 6 MIU of Interferon alfa-2a, recombinant, 3.605 mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as a preservative and 0.385 mg ammonium acetate.

9 million IU (33.3 mcg/0.5 mL) Roferon-A per syringe — The solution is colorless and each 0.5 mL contains 9 MIU of Interferon alfa-2a, recombinant, 3.605 mg sodium chloride, 0.1 mg polysorbate 80, 5 mg benzyl alcohol as a preservative and 0.385 mg ammonium acetate.

The route of administration is by subcutaneous injection.