Treatment with Infergen should be administered under the guidance of a qualified physician, and may lead to moderate-to-severe adverse experiences requiring dose reduction, temporary dose cessation, or discontinuation of further therapy.

Withdrawal from study for adverse events occurred in 7% of patients initially treated with 9 mcg INFERGEN (including 4% due to psychiatric events). Withdrawal from study due to adverse events occurred in 5% of patients subsequently treated with 15 mcg INFERGEN for 24 weeks and 11% of patients subsequently treated with 15 mcg INFERGEN for 48 weeks.

SEVERE PSYCHIATRIC ADVERSE EVENTS MAY MANIFEST IN PATIENTS RECEIVING THERAPY WITH INTERFERON, INCLUDING INFERGEN. DEPRESSION, SUICIDAL IDEATION, AND SUICIDE ATTEMPT MAY OCCUR. The incidence of psychiatric events of suicidal ideation was small (1%) for patients treated with 9 mcg Infergen compared to the overall incidence (55%) of psychiatric events. Infergen should be used with caution in patients who report a history of depression and physicians should monitor all patients for evidence of depression. Physicians should inform patients of the possible development of depression prior to initiation of Infergen therapy, and patients should report any sign or symptom of depression immediately. Other prominent psychiatric adverse events may also occur, including nervousness, anxiety, emotional lability, abnormal thinking, agitation, or apathy (see PRECAUTIONS).

INFERGEN SHOULD BE ADMINISTERED WITH CAUTION TO PATIENTS WITH PRE-EXISTING CARDIAC DISEASE. Hypertension and supraventricular arrhythmias, chest pain and myocardial infarction have been associated with interferon therapies.⁸

No studies with Infergen have been conducted in patients with decompensated hepatic disease. Patients with decompensated hepatic disease should not be treated with Infergen, and patients who develop symptoms of hepatic decompensation, such as jaundice, ascites, coagulopathy, or decreased serum albumin, should halt further interferon therapy.

Bone Marrow Toxicity: 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 be obtained pretreatment and monitored routinely during therapy. Alpha interferon therapy should be discontinued in patients who develop severe decreases in neutrophil (< 0.5 x 10⁹ /L) or platelet counts (< 50 x 10⁹ /L).

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 lnterferon alfacon-1 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 alfacon-1 therapy should be discontinued in patients who develop new or worsening ophthalmologic disorders.

General

Since the use of type-I interferons has been associated with depression, Infergen therapy should not be used in patients with a history of severe psychiatric disorders and should be discontinued in patients developing severe depression, suicidal ideation, or other severe psychiatric disorders (see WARNINGS).

INFERGEN should be used with caution in patients with a history of cardiac disease. Hypertension (5%), tachycardia (4%), and palpitation (3%) were the most common cardiovascular adverse events reported for 9 mcg INFERGEN therapy, with 1% of patients reporting tachyarrhythmias which were dose-limiting (see WARNINGS).

INFERGEN should be used cautiously in patients with abnormally low peripheral blood cell counts or who are receiving agents that are known to cause myelosuppression. Transplantation patients, or other chronically immunosuppressed patients, should receive alfa interferon therapy with caution.

Serious acute hypersensitivity reactions have been reported in rare instances following treatment with alpha interferons.⁸ If hypersensitivity reactions occur (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis), the drug should be discontinued immediately and appropriate medical treatment instituted.

INFERGEN should be administered with caution to patients with a history of endocrine disorders. Abnormal thyroid stimulating hormone (TSH) and free thyroxine (T ₄) with hypothyroidism occurred in 4% of patients administered 9 mcg INFERGEN, and thyroid supplements were required in approximately two-thirds of those patients.

Exacerbation of autoimmune disease has been reported in patients receiving type-I interferon therapy.⁸ INFERGEN should not be used in patients with autoimmune hepatitis and be used with caution in patients with other autoimmune disorders.

While fever may be related to the flu-like symptoms reported in patients treated with INFERGEN, when fever occurs, other possible causes of persistent fever should be ruled out.

Laboratory Tests

Laboratory tests are recommended for all patients on INFERGEN therapy, prior to beginning treatment (baseline), 2 weeks after initiation of therapy, and periodically thereafter during the 24 or 48 weeks of therapy at the discretion of the physician. Following completion of INFERGEN therapy, any abnormal test values should be monitored periodically. The entrance criteria that were used for the clinical study of INFERGEN may be considered as a guideline to acceptable baseline values for initiation of treatment:

• Platelet count ≥ 75 x 10 9 /L
• Hemoglobin concentration ≥ 100 g/L
• ANC ≥1500 x 10 6 /L
• Serum creatinine concentration < 180 µmol/L (< 2.0 mg/dL) or creatinine clearance > 0.83 mL/second (> 50 mL/minute)
• Serum albumin concentration ≥ 25 g/L
• Bilirubin within normal limits
• TSH and T ₄ within normal limits

Neutropenia, thrombocytopenia, hypertriglyceridemia, and thyroid disorders have been reported with administration of Infergen (see ADVERSE REACTIONS). Therefore, these laboratory parameters should be monitored closely.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: No carcinogenicity data for Infergen are available in animals or humans.

Mutagenesis: Infergen was not mutagenic when tested in several in vitro assays, including the Ames bacterial mutagenicity assay and an in vitro cytogenetic assay in human lymphocytes, either in the presence or absence of metabolic activation.

Impairment of Fertility: Infergen at doses as high as 100 mcg/kg did not selectively affect reproductive performance or the development of the offspring when administered SC to male and female golden Syrian hamsters for 70 and 14 days before mating, respectively, and then through mating and to day 7 of pregnancy.

Pregnancy Category C

Infergen has been shown to have embryolethal or abortifacient effects in golden Syrian hamsters when given at 135 times the human dose and in cynomolgus and rhesus monkeys when given at 9 to 81 times (based on body surface area) the human dose. There are no adequate and well-controlled studies in pregnant women. Infergen should not be used during pregnancy. If a woman becomes pregnant or plans to become pregnant while taking Infergen, she should be informed of the potential hazards to the fetus. Males and females treated with Infergen should be advised to use effective contraception.

Nursing Mothers

It is not known whether Infergen is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if Infergen is administered to a nursing woman. The effect on the nursing neonate of orally ingested Infergen in breast milk has not been evaluated.

Pediatric Use

The safety and effectiveness of Infergen have not been established in patients below the age of 18 years. Infergen therapy is not recommended in pediatric patients.

Geriatric Use

Clinical studies of INFERGEN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently than younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. However, treatment with interferons, including INFERGEN, is associated with psychiatric, cardiac, and systemic (flu-like) adverse effects. Since decreased hepatic, renal or cardiac function, concomitant disease and the use of other drug therapies in elderly patients may produce adverse reactions of greater severity, caution should be exercised in the use of INFERGEN in this population.

Bookmark this page: