Pegylated interferon alfa-2a warnings and precautions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Warnings And Precautions
WARNINGS
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.
Neuropsychiatric Disorders
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.
Cardiovascular Disorders
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.
Cerebrovascular Disorders
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.
Hypersensitivity
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.
Hepatic Disorders
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.
Gastrointestinal Disorders
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.
Infections
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.
Bone Marrow Toxicity
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
Endocrine Disorders
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.
Pulmonary Disorders
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.
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 (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
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.
PRECAUTIONS
General
In all instances where the use of Roferon-A is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risk of adverse reactions. Most adverse reactions are reversible if detected early. If severe reactions occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgment of the physician. Reinstitution of Roferon-A therapy should be carried out with caution and with adequate consideration of the further need for the drug and, alertness to possible recurrence of toxicity. The minimum effective doses of Roferon-A for treatment of hairy cell leukemia and chronic myelogenous leukemia have not been established.
Variations in dosage and adverse reactions exist among different brands of Interferon. Therefore, do not use different brands of Interferon in a single treatment regimen.
The safety and efficacy of Roferon-A have not been established in organ transplant recipients.
Renal Impairment
Dose-limiting renal toxicities were unusual. Infrequently, severe renal toxicities, sometimes requiring renal dialysis, have been reported with alpha-interferon therapy alone or in combination with IL-2. In patients with impaired renal function, signs and symptomsof interferon toxicity should be closely monitored. Roferon-A should be used with caution in patients with creatinine clearance <50 mL/min.
Autoimmune Disease
Development or exacerbation of autoimmune diseases including idiopathic thrombocytopenic purpura, vasculitis, Raynaud's phenomenon, rheumatoid arthritis, psoriasis, interstitial nephritis, thyroiditis, lupus erythematosus, hepatitis, myositis and rhabdomyolysis have been observed in patients treated with alpha-interferons. Any patient developing an autoimmune disorder during treatment should be closely monitored and, if appropriate, treatment should be discontinued.
Information for Patients
Patients should be cautioned not to change brands of Interferon without medical consultation, as a change in dosage may result. Patients should be informed regarding the potential benefits and risks attendant to the use of Roferon-A. If home use is determined to be desirable by the physician, instructions on appropriate use should be given, including review of the contents of the enclosed Medication Guide. Patients should be well hydrated, especially during the initial stages of treatment.
Patients should be thoroughly instructed in the importance of proper disposal procedures and cautioned against reusing syringes and needles. If home use is prescribed, a puncture-resistant container for the disposal of used syringes and needles should be supplied to the patient. The full container should be disposed of according to directions provided by the physician (see Medication Guide).
Patients should be advised that laboratory evaluations are required before starting therapy and periodically thereafter (see Laboratory Tests).
Patients receiving high-dose alpha-interferon should be cautioned against performing tasks that require complete mental alertness such as operating machinery or driving a motor vehicle. 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.
Laboratory Tests
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.
Complete blood counts with differential platelet counts and clinical chemistry tests should be performed before initiation of Roferon-A therapy and at appropriate periods during therapy. Patients with neutrophil count<1500/mm3, platelet count <75,000/mm3, hemoglobin <10 g/dL and creatinine >1.5 mg/dL were excluded from several major chronic hepatitis C studies; patients with these laboratory abnormalities should be carefully monitored if treated with Roferon-A. Since responses of hairy cell leukemia, chronic hepatitis C and chronic myelogenous leukemia are not generally observed for 1 to 3 months after initiation of treatment, very careful monitoring for severe depression of blood cell counts is warranted during the initial phase of treatment.
Those patients who have preexisting cardiac abnormalities and/or are in advanced stages of cancer should have electrocardiograms taken before and during the course of treatment.
Liver Function
For patients being treated for chronic hepatitis C, serum ALT should be evaluated before therapy to establish baselines and repeated at week 2 and monthly thereafter following initiation of therapy for monitoring clinical response. Patients developing liver function abnormalities during Roferon-A treatment should be closely monitored and if necessary treatment should be discontinued. Use of alpha-interferons has been rarely associated with severe hepatic dysfunction and liver failure.
Thyroid Function
Patients with preexisting thyroid abnormalities may be treated if normal thyroid stimulating hormone (TSH) levels can be maintained by medication. Testing of TSH levels in these patients is recommended at baseline and every 3 months following initiation of therapy.
Triglycerides
Elevated triglyceride levels have been observed in patients treated with interferons including Roferon-A therapy. Triglyceride levels should be monitored periodically during treatment and elevated levels should be managed as clinically appropriate. Hypertriglyceridemia may result in pancreatitis. Discontinuation of Roferon-A therapy should be considered for patients with persistently elevated triglycerides (e.g., triglycerides >1000 mg/dL) associated with symptoms of potential pancreatitis, such as abdominal pain, nausea, or vomiting.[1]
References
- ↑ "http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103964s5204lbl.pdf" (PDF). External link in
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Adapted from the FDA Package Insert.