Interferon alfa-2a, recombinant

Roferon-A (Interferon alfa-2a, recombinant) is a sterile protein product for use by injection. Roferon-A (interferon alfa-2a, recombinant) is manufactured by recombinant DNA technology that employs a genetically engineered Escherichia coli bacterium containing DNA that codes for the human protein. Interferon alfa-2a, recombinant is a highly purified protein containing 165 amino acids, and it has an approximate molecular weight of 19,000 daltons. Fermentation is carried out in a defined nutrient medium containing the antibiotic tetracycline hydrochloride, 5 mg/L. However, the presence of the antibiotic is not detectable in the final product. Roferon-A (interferon alfa-2a, recombinant) is supplied in prefilled syringes. Each glass syringe barrel contains 0.5 mL of product. In addition, there is a needle, which is ½ inch in length.

Single Use Prefilled Syringes

3 million IU (11.1 mcg/0.5 mL) Roferon-A (interferon alfa-2a, recombinant) 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 (interferon alfa-2a, recombinant) 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 (interferon alfa-2a, recombinant) 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.

Roferon-A should be administered under the guidance of a qualified physician (see DOSAGE AND ADMINISTRATION ). Appropriate management of the therapy and its complications is possible only when adequate facilities are readily available.

DEPRESSION AND SUICIDAL BEHAVIOR INCLUDING SUICIDAL IDEATION, SUICIDAL ATTEMPTS AND SUICIDES HAVE BEEN REPORTED IN ASSOCIATION WITH TREATMENT WITH ALFA INTERFERONS, INCLUDING ROFERON-A. Patients to be treated with Roferon-A 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. 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 severe preexisting cardiac disease, severe renal or hepatic disease, 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 (ie, 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 alfa interferons.

Patients with a history of autoimmune hepatitis or a history of autoimmune disease and patients who are immunosuppressed transplant recipients should not be treated with Roferon-A. Controlled studies of Roferon-A therapy in patients with advanced cirrhosis and/or decompensated liver disease have not been performed. 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.

Leukopenia and elevation of hepatic enzymes occurred frequently but were rarely dose-limiting. Thrombocytopenia occurred less frequently. Proteinuria and increased cells in urinary sediment were also seen infrequently. Dose-limiting hepatic or renal toxicities were unusual. Infrequently, severe renal toxicities, sometimes requiring renal dialysis, have been reported with alfa-interferon therapy alone or in combination with IL-2 (see PRECAUTIONS ).

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

Alpha interferons suppress bone marrow function and may result in severe cytopenias including very rare events of aplastic anemia. 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 × 10 9 /L) or platelet counts (<25 × 10 9 /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

Hyperglycemia has been observed rarely 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.

The injectable solutions contain benzyl alcohol and should not be used by patients with a known allergy to benzyl alcohol. This product is not indicated for use in neonates or infants and should not be used by patients in that age group. There have been rare reports of death in neonates and infants associated with excessive exposure to benzyl alcohol. There have been reports of permanent neuropsychiatric deficits and multiple system organ failure associated with benzyl alcohol in neonates and infants. The amount of benzyl alcohol at which toxicity or adverse effects may occur in neonates or infants is not known (see CONTRAINDICATIONS ).

Ophthalmologic Disorders:   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 (eg, 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.

There are no reports of overdosage, but repeated large doses of interferon can be associated with profound lethargy, fatigue, prostration, and coma. Such patients should be hospitalized for observation and appropriate supportive treatment given.