Interferon Alfa-2aU.S. Brand Names: Roferon-A�(r)
Synonyms: IFLrA; rIFN-A
Generic Available: No
Canadian Brand Names: Roferon-A�(r)
Use: Patients >18 years of age: Hairy cell leukemia, AIDS-related Kaposi's sarcoma, chronic hepatitis C Children and Adults: Chronic myelogenous leukemia (CML), Philadelphia chromosome positive, within 1 year of diagnosis (limited experience in children)
Use - Unlabeled/Investigational: Adjuvant therapy for malignant melanoma, AIDS-related thrombocytopenia, cutaneous ulcerations of Behçet's disease, brain tumors, metastatic ileal carcinoid tumors, cervical and colorectal cancers, genital warts, idiopathic mixed cryoglobulinemia, hemangioma, hepatitis D, hepatocellular carcinoma, idiopathic hypereosinophilic syndrome, mycosis fungoides, Sezary syndrome, low-grade non-Hodgkin's lymphoma, macular degeneration, multiple myeloma, renal cell carcinoma, basal and squamous cell skin cancer, essential thrombocythemia, cutaneous T-cell lymphoma
Pregnancy Risk Factor: C
Pregnancy Implications: Safety and efficacy for use during pregnancy have not been established. Interferon alpha has been shown to decrease serum estradiol and progesterone levels in humans. Menstrual irregularities and abortion have been reported in animals. Effective contraception is recommended during treatment.
Lactation: Enters breast milk/contraindicated (AAP rates "compatible")
Contraindications: Hypersensitivity to alfa interferon, benzyl alcohol, or any component of the formulation; autoimmune hepatitis; visceral AIDS-related Kaposi's sarcoma associated with rapidly-progressing or life-threatening disease; hepatic decompensation (Child-Pugh Class B or C)
Warnings/Precautions: Use caution in patients with a history of depression. May cause severe psychiatric adverse events (psychosis, mania, depression, suicidal behavior/ideation) in patients with and without previous psychiatric symptoms; careful neuropsychiatric monitoring is required during therapy. Use with caution in patients with seizure disorders, brain metastases, or compromised CNS function. Higher doses in the elderly or in malignancies other than hairy cell leukemia may result in severe obtundation. Use caution in patients with autoimmune diseases; development or exacerbation of autoimmune diseases has been reported. Use caution in patients with pre-existing cardiac disease (ischemic or thromboembolic), arrhythmias, renal impairment (Clcr<50 mL/minute), mild hepatic impairment, or myelosuppression. Also use caution in patients receiving therapeutic immunosuppression. May cause thyroid dysfunction or hyperglycemia, use caution in patients with diabetes or pre-existing thyroid disease. Pulmonary dysfunction may be induced or aggravated by interferon alpha; discontinue if persistent unexplained pulmonary infiltrates are noted. Gastrointestinal ischemia, ulcerative colitis and hemorrhage have been associated rarely with alpha interferons; some cases are severe and life-threatening. Ophthalmologic disorders (including retinal hemorrhages, cotton wool spots, and retinal artery or vein obstruction) have occurred in patients receiving alpha interferons; close monitoring is warranted. Treatment should be discontinued in patients with worsening or persistently severe signs/symptoms of autoimmune, infectious, ischemic, or neuropsychiatric disorders (including depression and/or suicidal thoughts/behavior). Discontinue treatment if neutrophils <0.5 x 109/L or platelets <25 x 109/L. Due to differences in dosage, patients should not change brands of interferons. Injection solution contains benzyl alcohol; do not use in neonates or infants. Safety and efficacy in children <18 years of age have not been established.
Adverse Reactions: Note: A flu-like syndrome (fever, chills, tachycardia, malaise, myalgia, arthralgia, headache) occurs within 1-2 hours of administration; may last up to 24 hours and may be dose-limiting (symptoms in up to 92% of patients). For the listing below, the percentage of incidence noted generally corresponds to highest reported ranges. Incidence depends upon dosage and indication. >10%: Cardiovascular: Chest pain (4% to 11%), edema (11%), hypertension (11%) Central nervous system: Psychiatric disturbances (including depression and suicidal behavior/ideation; reported incidence highly variable, generally >15%), fatigue (90%), headache (52%), dizziness (21%), irritability (15%), insomnia (14%), somnolence, lethargy, confusion, mental impairment, and motor weakness (most frequently seen at high doses [>100 million units], usually reverses within a few days); vertigo (19%); mental status changes (12%) Dermatologic: Rash (usually maculopapular) on the trunk and extremities (7% to 18%), alopecia (19% to 22%), pruritus (13%), dry skin Endocrine & metabolic: Hypocalcemia (10% to 51%), hyperglycemia (33% to 39%), transaminases increased (25% to 30%), alkaline phosphatase increased (48%) Gastrointestinal: Loss of taste, anorexia (30% to 70%), nausea (28% to 53%), vomiting (10% to 30%, usually mild), diarrhea (22% to 34%, may be severe), taste change (13%), dry throat, xerostomia, abdominal cramps, abdominal pain Hematologic (often due to underlying disease): Myelosuppression; neutropenia (32% to 70%); thrombocytopenia (22% to 70%); anemia (24% to 65%, may be dose-limiting, usually seen only during the first 6 months of therapy) Onset: 7-10 days Nadir: 14 days, may be delayed 20-40 days in hairy cell leukemia Recovery: 21 days Hepatic: Elevation of AST (SGOT) (77% to 80%), LDH (47%), bilirubin (31%) Local: Injection site reaction (29%) Neuromuscular & skeletal: Weakness (may be severe at doses >20,000,000 units/day); arthralgia and myalgia (5% to 73%, usually during the first 72 hours of treatment); rigors Renal: Proteinuria (15% to 25%) Respiratory: Cough (27%), irritation of oropharynx (14%) Miscellaneous: Flu-like syndrome (up to 92% of patients), diaphoresis (15%) 1% to 10%: Cardiovascular: Hypotension (6%), supraventricular tachyarrhythmia, palpitation (<3%), acute MI (<1% to 1%) Central nervous system: Confusion (10%), delirium Dermatologic: Erythema (diffuse), urticaria Endocrine & metabolic: Hyperphosphatemia (2%) Gastrointestinal: Stomatitis, pancreatitis (<5%), flatulence, liver pain Genitourinary: Impotence (6%), menstrual irregularities Neuromuscular & skeletal: Leg cramps; peripheral neuropathy, paresthesia (7%), and numbness (4%) are more common in patients previously treated with vinca alkaloids or receiving concurrent vinblastine Ocular: Conjunctivitis (4%) Respiratory: Dyspnea (7.5%), epistaxis (4%), rhinitis (3%) Miscellaneous: Antibody production to interferon (10%) <1%: Abdominal fullness, angioedema, aplastic anemia, arthritis, ascites, autoimmune reaction with worsening of liver disease, bronchospasm, bronchiolitis obliterans, BUN/creatinine increased, cardiomyopathy, coagulopathy, coma, CHF, cutaneous eruptions, distal cyanosis, diffuse encephalopathy, dysphasia, eczema, EEG abnormalities, hallucinations, hemolytic anemia, hyper-/hypothyroidism, hypermotility, hypertriglyceridemia, hyponatremia (SIADH), mania, gait disturbance, gastrointestinal hemorrhage, hepatic failure, idiopathic thrombocytopenia purpura, interstitial nephritis, interstitial pneumonitis, ischemic colitis, leukopenia, libido decreased, lupus erythematosus syndrome, myositis, nasal congestion, nephrotic syndrome, optic neuritis, pneumonia, pneumonitis, presenile dementia, proteinuria, psoriasis, psychotic episodes, Raynaud's phenomenon, renal failure (acute), rhabdomyolysis, sarcoidosis, seborrhea, seizure, stroke, syncope, tachypnea, ulcerative colitis, urticaria, vasculitis, visual acuity decreased
Overdosage/Toxicology: Symptoms of overdose include CNS depression, obtundation, flu-like symptoms, and myelosuppression. Treatment is supportive.
Drug Interactions: Inhibits CYP1A2 (weak) Note: May exacerbate the toxicity of other agents with respect to CNS, myelotoxicity, or cardiotoxicity. ACE inhibitors: Interferons may increase the adverse/toxic effects of ACE inhibitors, specifically the development of granulocytopenia. Risk: Monitor Clozapine: A case report of agranulocytosis with concurrent use. Erythropoietin: Case reports of decreased hematopoietic effect Melphalan: Interferon alpha may decrease the serum concentrations of melphalan; this may or may not decrease the potential toxicity of melphalan. Risk: Monitor Prednisone: Prednisone may decrease the therapeutic effects of interferon alpha. Risk: Moderate Theophylline: Interferon alpha may decrease the P450 isoenzyme metabolism of theophylline. Risk: Moderate Warfarin: Interferons may increase the anticoagulant effects of warfarin. Risk: Monitor Zidovudine: Interferons may decrease the metabolism of zidovudine. Risk: Monitor
Stability: Refrigerate (2°C to 8°C/36°F to 46°F); do not freeze; do not shake. Reconstitute vial with the diluent provided, or SWFI, NS, or D5W; concentrations  3 x 10 6 units/mL are hypertonic. After reconstitution, the solution is stable for 24 hours at room temperature and for 1 month when refrigerated.
Compatibility: Stable in LR, NS; not stable in D5W
Mechanism of Action: Following activation, multiple effects can be detected including induction of gene transcription. Inhibits cellular growth, alters the state of cellular differentiation, interferes with oncogene expression, alters cell surface antigen expression, increases phagocytic activity of macrophages, and augments cytotoxicity of lymphocytes for target cells
Pharmacodynamics/Kinetics: Absorption: Filtered and absorbed at the renal tubule Distribution: Vd: 0.223-0.748 L/kg Metabolism: Primarily renal; filtered through glomeruli and undergoes rapid proteolytic degradation during tubular reabsorption Bioavailability: I.M.: 83%; SubQ: 90% Half-life elimination: I.V.: 3.7-8.5 hours (mean ~5 hours) Time to peak, serum: I.M., SubQ: ~6-8 hours
Dosage: Refer to individual protocols Children (limited data): Chronic myelogenous leukemia (CML): I.M.: 2.5-5 million units/m2/day; Note: In juveniles, higher dosages (30 million units/m2/day) have been associated with severe adverse events, including death Adults: Hairy cell leukemia: SubQ, I.M.: 3 million units/day for 16-24 weeks, then 3 million units 3 times/week for up to 6-24 months Chronic myelogenous leukemia (CML): SubQ, I.M.: 9 million units/day, continue treatment until disease progression AIDS-related Kaposi's sarcoma: SubQ, I.M.: 36 million units/day for 10-12 weeks, then 36 million units 3 times/week; to minimize adverse reactions, can use escalating dose (3-, 9-, then 18 million units each day for 3 days, then 36 million units daily thereafter). Hepatitis C: SubQ, I.M.: 3 million units 3 times/week for 12 months Dosage adjustment in renal impairment: Not removed by hemodialysis
Administration: SubQ administration is suggested for those who are at risk for bleeding or are thrombocytopenic; rotate SubQ injection site; patient should be well hydrated
Monitoring Parameters: Baseline ophthalmologic exam should be performed in all patients, with periodic reassessment in patients with impairment. Patients with thyroid dysfunction should be monitored by TSH levels at baseline and every 3 months during therapy. Chronic hepatitis C: Monitor ALT (at baseline, after 2 weeks, and monthly thereafter) and HCV-RNA (particularly in first 3 months of therapy) CML/hairy cell leukemia: Hematologic monitoring should be performed monthly
Patient Education: Use as directed; do not change dosage or schedule of administration without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience flu-like syndrome (acetaminophen may help); nausea, vomiting, dry mouth, or metallic taste (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); or drowsiness, dizziness, agitation, abnormal thinking (use caution when driving or engaging in tasks requiring alertness until response to drug is known). Inform prescriber immediately if you feel depressed or have any thoughts of suicide. Report unusual bruising or bleeding; persistent abdominal disturbances; unusual fatigue; muscle pain or tremors; chest pain or palpitation; swelling of extremities or unusual weight gain; respiratory difficulty; pain, swelling, or redness at injection site; or other unusual symptoms. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Nursing Implications: A flu-like syndrome (fever, chills) occurs in the majority of patients 2-6 hours after a dose; pretreatment with NSAID or acetaminophen can decrease fever and its severity and alleviate headache
Anesthesia and Critical Care Concerns/Other Considerations: Indications and dosage regimens are specific for a particular brand of interferon; other brands have different indications and dosage guidelines.
Dental Health: Effects on Dental Treatment: Key adverse event(s) related to dental treatment: Significant xerostomia (normal salivary flow resumes upon discontinuation), metallic taste, taste change, loss of taste, cough, irritation of oropharynx.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions: No information available to require special precautions
Mental Health: Effects on Mental Status: Severe psychiatric disorders including depression, suicidal behavior, ideation, attempts, and suicides have been reported with alfa interferons in patients with and without a previous psychiatric history. Extreme caution should be used in individuals who report a history of depression and patients should be informed of these potential side effects and how to respond if they occur. Careful neuropsychiatric monitoring for depressive symptoms is recommended. Dizziness and drowsiness are common. May cause memory impairment, agitation, manic behavior, and psychotic reactions; may rarely cause delirium.
Mental Health: Effects on Psychiatric Treatment: May cause leukopenia; use caution with clozapine and carbamazepine; concurrent use with psychotropics may produce additive sedation and dry mouth
Oncology: Emetic Potential: Moderate (30% to 60%); usually mild to moderate, aggressive therapy with serotonin antagonists is usually not necessary
Oncology: Vesicant: No
Dosage Forms: Injection, solution, [single-dose prefilled syringe; SubQ use only]: 3 million units/0.5 mL (0.5 mL); 6 million units/0.5 mL (0.5 mL); 9 million units/0.5 mL (0.5 mL) [contains benzyl alcohol]
References: "American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,"Pediatrics, 2001, 108(3):776-89. Gresser I, "Biologic Effects of Interferons,"J Invest Dermatol, 1990, 95(6 Suppl):66-71. Haria M and Benfield P, "Interferon-Alpha-2a. A Review of Its Pharmacological Properties and Therapeutic Use in the Management of Viral Hepatitis,"Drugs, 1995, 50(5):873-96. Hirsch MS, Tolkoff-Rubin NE, Kelly AP, et al, "Pharmacokinetics of Human and Recombinant Leukocyte Interferon in Patients With Chronic Renal Failure Who Are Undergoing Hemodialysis,"J Infect Dis, 1983, 148(2):335. Legha SS, "The Role of Interferon Alfa in the Treatment of Metastatic Melanoma,"Semin Oncol, 1997, 24(1 Suppl 4):24-31. Morris DJ, "Adverse Effects and Drug Interactions of Clinical Importance With Antiviral Drugs,"Drug Saf, 1994, 10(4):281-91. Read SJ, Crawford DH, and Pender MP, "Trigeminal Sensory Neuropathy Induced by Interferon-Alpha Therapy,"Aust N Z J Med, 1995, 25(1):54. Soto Alvarez J, Sacristan JA, and Alsar MJ, "Interferon Alpha-2a-Induced Impotence,"DICP, 1991, 25(12):1397. Tilg H, "New Insights Into the Mechanisms of Interferon Alfa: An Immunoregulatory and Anti-Inflammatory Cytokine,"Gastroenterology, 1997, 112(3):1017-21. Vial T and Descotes J, "Clinical Toxicity of the Interferons,"Drug Saf, 1994, 10(2):115-50. White CW, Sondheimer HM, Crouch EC, et al, "Treatment of Pulmonary Hemangiomatosis With Recombinant Interferon Alfa-2a,"N Engl J Med, 1989, 320(18):1197-200. Williams CD and Linch DC, "Interferon Alfa-2a,"Br J Hosp Med, 1997, 57(9):436-9. Wills RJ, "Clinical Pharmacokinetics of Interferons,"Clin Pharmacokinet, 1990, 19(5):390-9.
International Brand Names: Roferon-A�(r) (CA)
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