Interferon Alfa-2a

Pronunciation: IN-ter-FEER-ahn AL-fuh-2a
Class: Immunomodulator

Trade Names

Roferon-A
- Solution for injection 6 million units/mL, 0.5 mL single-use prefilled syringes (3 million units/syringe)
- Solution for injection 12 million units/mL, 0.5 mL single-use prefilled syringes (6 million units/syringe)
- Solution for injection 18 million units/mL, 0.5 mL single-use prefilled syringes (9 million units/syringe)

Pharmacology

Interferon alfa-2a has antiproliferative and immunomodulatory activities. Its elimination half-life is 3.7 to 8.5 h after IV infusion.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

The mean T max is 3.8 h (IM) and 7.3 h (subcutaneous). The mean C max is 2,020 pg/mL for IM and 1,730 pg/mL for subcutaneous. The apparent bioavailability is more than 80% for IM.

Distribution

The Vd ss is 0.223 to 0.748 L/kg.

Metabolism

Totally filtered through the glomeruli and undergoes rapid proteolytic degradation during tubular reabsorption. The hepatic metabolism has a minor pathway.

Elimination

The t ½ is 3.7 to 8.5 h. The mean Cl is 2.79 mL/min/kg.

Indications and Usage

Adult

Hairy cell leukemia, AIDS-related Kaposi sarcoma, chronic myelogenous leukemia.

Children

Chronic myelogenous leukemia.

Unlabeled Uses

Adults

Bladder tumors, mycosis fungoides, essential thrombocythemia, non-Hodgkin lymphoma, ovarian and cervical cancer, renal cell carcinoma, melanoma.

Children

Hemangiomas of infancy, pulmonary hemangiomatosis.

Contraindications

Standard considerations.

Dosage and Administration

Hairy Cell Leukemia
Adults

IM or Subcutaneous Induction : 3 million units/day, for 16 to 24 wk; Maintenance : 3 million units IM or Subcutaneous 3 times/wk. Treat patients for about 6 mo before determining whether to continue therapy.

AIDS-Related Kaposi Sarcoma
Adults

IM or Subcutaneous Induction : 36 million units/day, for 10 to 12 wk. Alternative induction : 3 million units for 3 days, then 9 million units for 3 days, then 18 million units for 3 days, then 36 million units daily for a total of 10 to 12 wk. Maintenance : 36 million units IM or Subcutaneous 3 times/wk. Continue therapy until no evidence of tumor exists or rapid disease progression, severe opportunistic infection, or adverse reactions require discontinuation.

Chronic Myelogenous Leukemia
Adults

IM or Subcutaneous 9 million units/day. Alternative regimen : 3 million units/day for 3 days, then 6 million units/day for 3 days, then 9 million units/day for the duration of therapy. Treat patients for several months before determining whether to continue therapy.

Children

IM 2.5 to 5 million units/m 2 /day. Treat patients for several months before determining whether to continue therapy; some patients may require therapy for up to 18 mo.

Hemangiomas of Infancy, Pulmonary Hemangiomatosis
Children

Subcutaneous 1 to 3 million units/m 2 /day once daily.

Drug Interactions

Aldesleukin

There is an increased risk of renal failure when using aldesleukin with interferon alfa-2a.

Melphalan

Coadministration of melphalan and interferon alfa-2a may decrease serum levels of melphalan.

Theophylline and possibly barbiturates

Alfa-interferon may inhibit hepatic metabolism of theophylline and possibly barbiturates, leading to increased serum concentrations of theophylline or barbiturates.

Vidarabine

Alfa-interferon may potentiate neurotoxicity when administered with vidarabine.

Zidovudine, acyclovir

There are synergestic antiviral effects with alfa-interferon and zidovudine and acyclovir.

Laboratory Test Interactions

Leukopenia, neutropenia, thrombocytopenia, decreased hemoglobulin, severe anemia, severe cytopenias, AST, alkaline phosphatase, LDH, proteinuria, uric acid.

Adverse Reactions

Cardiovascular

Edema; hypotension.

CNS

Perioral tingling; dizziness; depression and suicidal ideation; paresthesia; sleep disturbances; confusion; hallucination; seizures; encephalopathy; gait disturbance; ataxia; tremor.

Dermatologic

Rash; transient alopecia or thinning of the hair; excessive sweating or night sweats.

Endocrine

Hypothyroidism; hyperthyroidism.

GI

Moderate potential for nausea and vomiting; dysgeusia; diarrhea; dry mouth; gingivitis; anorexia; weight loss; elevated LFTs.

Hematologic

Neutropenia; thrombocytopenia.

Hypersensitivity

Antinuclear antibodies; anaphylaxis; neutralizing antibody formation.

Musculoskeletal

Severe lower extremities myalgias in chronic myelogenous leukemia patients.

Renal

Proteinuria; acute renal failure; nephrotic syndrome.

Respiratory

Dyspnea; cough; pharyngitis; sinusitis; drying of the oropharynx.

Special Senses

Visual disturbance; ocular pain.

Miscellaneous

Flu-like syndrome.

Precautions

Warnings

Neuropsychiatric, autoimmune, ischemic, and infectious disorders

Interferons may cause or aggravate fatal or life-threatening disorders of this nature. Persistent severe or worsening signs or symptoms may necessitate discontinuation of therapy. Closely monitor patients with periodic clinical and laboratory evaluations.


Pregnancy

Category C .

Lactation

Discontinue breast-feeding or discontinue the drug.

Hypersensitivity

Avoid use in patients with hypersensitivity to mouse immunoglobulin.

Special Risk Patients

Administer with caution in patients with severe renal or hepatic disease, cardiac disease, seizure disorders, or compromised CNS function.

Anemia

Leukopenia and thrombocytopenia may occur.

Depression and suicidal behavior

Depression and suicidal behavior including suicidal ideation, suicidal attempts, and suicides reported in association with alfa-interferon treatment.

Dosage reduction

Dosage reduction by 50% or withholding therapy may be needed when severe adverse reactions occur.

Leukopenia and elevation of hepatic enzymes

Leukopenia and elevation of hepatic enzymes occurred frequently.

Neutralizing antibodies

Neutralizing antibodies can develop during alfa-interferon therapy and may contribute to therapeutic failure in some patients. In some studies, development of neutralizing antibodies was more common with interferon alfa-2a than with interferon alfa-2b.

Patient Information

  • Warn patients not to change brands of interferon; changes in dosage may be necessary.
  • Well hydrate patients, especially during initial treatment.

Copyright © 2009 Wolters Kluwer Health.

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