Pegylated interferon (peginterferon) alfa-2b

Treatment of chronic hepatitis C (CHC; in combination with ribavirin) , Adjuvant treatment of melanoma (with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including lymphadenectomy).

Hypersensitivity (including urticaria, angioedema, bronchoconstriction, anaphylaxis, Stevens Johnson syndrome and toxic epidermal necrolysis) to peginterferon alfa-2b, interferon alfa-2b, other alfa interferons, or any component of the formulation; autoimmune hepatitis; decompensated liver disease (Child-Pugh score >6, classes B and C)
Combination therapy with peginterferon alfa-2b and ribavirin is also contraindicated in pregnancy, women who may become pregnant, males with pregnant partners; hemoglobinopathies (eg, thalassemia major, sickle-cell anemia); renal dysfunction (Clcr <50 mL/minute)

 Use appropriate precautions for handling and disposal.

Bone marrow suppression, Colitis, Dental/periodontal disorders, Hypersensitivity, Hypertriglyceridemia, Neuropsychiatric disorders, Ophthalmologic disorders (including decreased visual acuity, blindness, macular edema, retinal hemorrhages, optic neuritis, papilledema, cotton wool spots, retinal detachment [serous], and retinal artery or vein thrombosis) , Pancreatitis, Pulmonary effects, Anemia, Autoimmune disease, Cardiovascular disease, Diabetes mellitus, epatic decompensation, Infectious disorders, Ischemic disorders, Renal impairment, may cause or aggravate hyper- or hypothyroidism; Elderly, Pediatrics, pregnancy.
Combination treatment with ribavirin may cause birth defects and/or fetal mortality, hemolytic anemia (which may worsen cardiac disease), genotoxicity, mutagenicity, and may possibly be carcinogenic.

Central nervous system: Fatigue, fever, headache, chills, depression, dizziness, anxiety/emotional liability/irritability, insomnia, olfactory nerve disorder, Concentration impaired, malaise, nervousness, agitation, suicidal behavior
Cardiovascular: Chest pain, flushing
Dermatologic: Rash, alopecia, pruritus, dry skin
Endocrine & metabolic: Hypothyroidism, menstrual disorder, hyperthyroidism
Gastrointestinal: Anorexia, nausea, taste perversion, diarrhea, vomiting, abdominal pain, weight loss, Dyspepsia, xerostomia, constipation
Hematologic: Neutropenia, thrombocytopenia, anemia
Hepatic: Transaminases increased, alkaline phosphatase increased, GGT increased, hepatomegaly
Local: Injection site inflammation/reaction, Injection site pain
Neuromuscular & skeletal: Myalgia, weakness, arthralgia, musculoskeletal pain, rigors, paresthesia
Ocular: Conjunctivitis, blurred vision
Renal: Proteinuria
Respiratory: Pharyngitis, cough, sinusitis, dyspnea, rhinitis
Miscellaneous: Viral infection, Diaphoresis, neutralizing antibodies

Ethanol: Avoid use in patients with hepatitis C virus.

One of the major mechanisms of PEG-interferon alpha-2b utilizes the JAK-STAT signaling pathway. The basic mechanism works such that PEG-interferon alpha-2b will bind to its receptor, interferon-alpha receptor 1 and 2 (IFNAR1/2). Upon ligand binding the Tyk2 protein associated with IFNAR1 is phosphorylated which in turn phosphorylates Jak1 associated with IFNAR2. This kinase continues its signal transduction by phosphorylation of signal transducer and activator of transcription (STAT) 1 and 2 via Jak 1 and Tyk2 respectively. The phosphorylated STATs then dissociate from the receptor heterodimer and form an interferon transcription factor with p48 and IRF9 to form the interferon stimulate transcription factor-3 (ISGF3). This transcription factor then translocates to the nucleus where it will transcribe several genes involved in cell cycle control, cell differentiation, apoptosis, and immune response.
PEG-interferon alpha-2b acts as a multifunctional immunoregulatory cytokine by transcribing several genes, including interleukin 4 (IL4). This cytokine is responsible for inducing T helper cells to become type 2 helper T cells. This ultimately results in the stimulation of B cells to proliferate and increase their antibody production. This ultimately allows for an immune response, as the B cells will help to signal the immune system that a foreign antigen is present.
Another major mechanism of type I interferon alpha (IFNα) is to stimulate apoptosis in malignant cell lines. Previous studies have shown that IFNα can cause cell cycle arrest in U266, Daudi, and Rhek-1 cell lines.

C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

In combination with ribavirin: X

Excretion in breast milk unknown/not recommended