Peginterferon alfa-2b


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : SC Chronic hepatitis C 1 mcg/kg/week for 24-48 weeks. As combination therapy with ribavirin (bi-therapy), or ribavirin and other direct-acting antivirals (tri-therapy): 1.5 mcg/kg once weekly. Treatment duration: 48 weeks (for patients with genotype 1 or for previously failed therapy regardless of genotype); 24 weeks (for patients with genotype 2 and 3). Melanoma As adjuvant treatment of cases with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy: Initial: 6 mcg/kg/week for 8 doses, followed by 3 mcg/kg/week for up to 5 years. Dose modification or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Dosage Details
Subcutaneous
Chronic hepatitis C
Adult: In patients with compensated liver disease: As monotherapy: 1 mcg/kg once weekly for 24-48 weeks. As combination therapy with ribavirin (bi-therapy), or ribavirin and other direct-acting antivirals (tri-therapy): 1.5 mcg/kg once weekly. Treatment duration: 48 weeks (for patients with genotype 1 or for previously failed therapy regardless of genotype); 24 weeks (for patients with genotype 2 and 3). Dose modification or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Child: 3-18 years As combination therapy with ribavirin: 60 mcg/m2 once weekly. Treatment duration: 48 weeks (for patients with genotype 1 cases); 24 weeks (for patients with genotype 2 and 3 cases). Dose modification or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Elderly: Dosage reduction may be necessary.

Subcutaneous
Melanoma
Adult: As adjuvant treatment of cases with microscopic or gross nodal involvement within 84 days of definitive surgical resection, including complete lymphadenectomy: Initially, 6 mcg/kg once weekly for 8 doses, followed by 3 mcg/kg once weekly for up to 5 years. Dose modification or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Special Patient Group
Pharmacogenomics information:

Clinical Pharmacogenetics Implementation Consortium (CPIC) identified IFNL3, also known as IL28B, as the strongest baseline predictor of response to peginterferon alfa and ribavirin in previously untreated patients with HCV genotype 1 infection. Among the patients treated for chronic HCV infection, IFNL3 genotype is associated with early viral kinetics and improved sustained virologic response (SVR) which may affect treatment outcomes.

IFNL3 variation is the most established pre-treatment predictor of treatment response, with rs12979860 and rs8099917 as the most common single nucleotide polymorphisms. Favourable response IFNL3 genotypes (CC for rs12979860 and TT for rs8099917) are associated with approx 2-fold increased SVR for HCV genotype 1 patients. However, rs12979860 is less reliable for predicting response to peginterferon alfa and ribavirin treatment in Japanese individuals as compared with rs8099917.

The allele frequency of rs12979860 varies among different ethnic background. The rs12979860 favourable C allele is most prevalent in East Asians, followed by Caucasians and Hispanics, and least common among individuals of African origin.

CPIC recommends IFNL3 genotyping and its implications as part of the decision-making process prior to initiating peginterferon alfa and ribavirin treatment for HCV infection.

Recommendations for peginterferon alfa-containing regimens based on IFNL3 genotype:

Favourable response genotype
Patients who are carriers of 2 favourable response alleles (e.g. rs12979860 CC), may have higher SVR rate to peginterferon alfa and ribavirin therapy as compared with patients having unfavourable response genotype. In peginterferon alfa and ribavirin therapy, approx 70% chance for SVR after 48 weeks of treatment. In protease inhibitor combinations with peginterferon alfa and ribavirin therapy, approx 90% chance for SVR after 24-48 weeks of treatment and approx 80-90% of individuals are eligible for shortened therapy (24-28 weeks vs 48 weeks).

Unfavourable response genotype
Patients who are carriers of at least 1 unfavourable response allele (e.g. rs12979860 CT or TT), may have lower SVR rate to peginterferon alfa and ribavirin therapy as compared with patients having favourable response genotype. In peginterferon alfa and ribavirin therapy, approx 30% chance for SVR after 48 weeks of treatment. In protease inhibitor combinations with peginterferon alfa and ribavirin therapy, approx 60% chance for SVR after 24-48 weeks of treatment and approx 50% of individuals are eligible for shortened therapy (24-28 weeks).
Renal Impairment
Chronic hepatitis C
 CrCl (mL/min) Dosage 
 10-29 and patients undergoing haemodialysis Reduce dose by 50%. Discontinue dosing if renal function declines during treatment.
 30-50  Reduce dose by 25%.

As combination therapy with ribavirin:
 CrCl (mL/min) Dosage
 <50  Contraindicated.

Melanoma
 CrCl (mL/min)  Dosage
 <30 and ESRD (on haemodialysis)  Initially, 3 mcg/kg once weekly for 8 weeks, followed by 1.5 mcg/kg once weekly for 5 years.
 30-50  Initially, 4.5 mcg/kg once weekly for 8 weeks, followed by 2.25 mcg/kg once weekly for 5 years.
Reconstitution
Vial: Add 0.7 mL of sterile water for inj (supplied diluent), then swirl gently to dissolve the powder. Do not shake. For the treatment of melanoma, do not withdraw >0.5 mL of the reconstituted solution from each vial. Discard any unused portion.
Contraindications
Hypersensitivity to peginterferon alfa-2b, interferon alfa-2b or other alfa interferons. Autoimmune hepatitis, decompensated liver disease (Child-Pugh score >6; classes B and C). In combination with ribavirin: Haemoglobinopathies (e.g. thalassaemia major, sickle-cell anaemia); Renal impairment (CrCl <50 mL/min); Pregnancy. Contraindications of concurrently used agents (e.g. ribavirin) are applicable (refer to respective detailed product guideline).
Special Precautions
Patients with history of psychiatric disorders, including depression or substance abuse; chronic immunosuppression, debilitating conditions, CV disease, pulmonary disease, diabetes mellitus or if prone to diabetic ketoacidosis; autoimmune disorders, thyroid disorders, HIV or hepatitis B co-infection. Organ transplant recipients. Patients with IFNL3 favourable or unfavourable response genotypes. Hepatic and moderate to severe renal impairment. Children and elderly. Lactation.
Adverse Reactions
Significant: Cardiovascular events (e.g. hypotension, supraventricular arrhythmia, bundle-branch block, ventricular tachycardia, cardiomyopathy, angina pectoris, MI), endocrine disorders (e.g. hyperglycaemia, hypo- or hyperthyroidism), ophthalmologic disorders (e.g. decreased visual acuity, blindness, macular oedema, retinal haemorrhage, serous retinal detachment, optic neuritis, papilledema, cotton wool spots, retinal artery or vein thrombosis), bone marrow suppression, flu-like symptoms, hypertriglyceridaemia, increased serum creatinine levels, dental or periodontal disorders, inhibited growth velocity (in children). Rarely, acute hypersensitivity reactions (e.g. urticaria, angioedema, bronchoconstriction, anaphylaxis), and cutaneous reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis).
Blood and lymphatic system disorders: Neutropenia, anaemia, leucopenia.
Gastrointestinal disorders: Nausea, diarrhoea, vomiting, dysgeusia, abdominal pain, dry mouth, dyspepsia.
General disorders and admin site conditions: Fatigue, asthenia, pyrexia, chills, inj site reactions (e.g. inflammation).
Hepatobiliary disorders: Hepatomegaly.
Investigations: Increased ALT/AST and blood alkaline phosphatase, weight decreased.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Myalgia, arthralgia.
Nervous system disorders: Headache, dizziness, paraesthesia.
Psychiatric disorders: Insomnia, anxiety, irritability, emotional lability.
Reproductive system and breast disorders: Menstrual disorder.
Respiratory, thoracic and mediastinal disorders: Cough, pharyngitis, rhinitis.
Skin and subcutaneous tissue disorders: Rash, alopecia, pruritus, dry skin.
Potentially Fatal: Aggravation of neuropsychiatric, autoimmune ischaemic, infectious, and pulmonary disorders; ulcerative or haemorrhagic/ischaemic colitis, pancreatitis, hepatic decompensation.
Parenteral: X (when used in combination with ribavirin.); SC: X (when used in combination with ribavirin.)
Patient Counseling Information
Do not switch between brands unless instructed by your doctor (product variability)
MonitoringParameters
Perform pregnancy test prior to treatment initiation. Obtain serum HCV RNA levels at baseline, 12 weeks, and 24 weeks after initiation and treatment completion. Monitor TSH at baseline within 4 weeks prior to initiation, then periodically thereafter (for patients with melanoma); CBC with differential and platelets, serum chemistries, LFT, renal function tests, serum triglycerides, serum glucose or HbA1c in diabetic patients; baseline and periodic dental and exams; baseline ECG in patients with cardiac disease; growth velocity and weight in children. Monitor for depression and other psychiatric symptoms before and after treatment initiation; decreased pulmonary function or ophthalmic changes.
Overdosage
Symptoms: Severe fatigue, headache, myalgia, neutropenia, and thrombocytopenia. Management: Symptomatic and supportive treatment.
Drug Interactions
Enhanced adverse effects of telbivudine, zidovudine. May increase the risk of toxicities of narrow therapeutic CYP1A2 substrates (e.g. caffeine) or CYP2D6 substrates (e.g. desipramine, thioridazine). May increase serum concentrations of theophylline and methadone.
Potentially Fatal: Increased risk of hepatic decompensation and haemolytic anaemia with ribavirin.
Action
Description: Peginterferon alfa-2b, an interferon protein that has antiviral, antiproliferative and immune-regulating activity. It induces the innate anti-hepatitis C virus (HCV) immune response by binding to the human type 1 interferon receptor, thereby activating multiple intracellular signal transduction pathways. Its exact mechanism in melanoma is unknown; however, the effects in the body includes induction of gene transcription, inhibition of cellular growth, oncogene expression interference, alteration of cell surface antigen expression, increased phagocytic macrophage activity, and augmentation of cytotoxicity of lymphocytes for target cells.
Pharmacokinetics:
Absorption: Bioavailability: Increases with long-term dosing. Time to peak plasma concentration: 15-44 hours.
Excretion: Via urine (approx 30%). Elimination half-life: Approx 40 hours (in chronic hepatitis C); approx 43-51 hours (in melanoma).
Chemical Structure

Chemical Structure Image
Peginterferon alfa-2B

Source: National Center for Biotechnology Information. PubChem Database. Interferon alfa-2B, CID=71306834, https://pubchem.ncbi.nlm.nih.gov/compound/Interferon-alfa-2B (accessed on Apr. 28, 2020)

Storage
Pre-filled pen: Store between 2-8°C. Vial: Store at 25°C. Do not freeze. Protect from heat. After reconstitution, use immediately or may be stored for ≤24 hours between 2-8°C.
MIMS Class
ATC Classification
L03AB10 - peginterferon alfa-2b ; Belongs to the class of interferons. Used as immunostimulants.
References
Muir AJ, Gong L, Johnson SG, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for IFNL3 (IL28B) Genotype and PEG Interferon-α-Based Regimens. CPIC Guidelines. 2014 Feb;95(2):141-146. doi: 10.1038/clpt.2013.203. Accessed 28/11/2019

Annotation of CPIC Guideline for Peginterferon alfa-2a, Peginterferon alfa-2b, Ribavirin and IFNL3. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 28/11/2019.

Anon. Peginterferon Alfa (Antineoplastic Agents). AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 28/11/2019.

Anon. Peginterferon Alfa (Interferons). AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 28/11/2019.

Anon. Peginterferon Alfa-2b. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/11/2019.

Buckingham R (ed). Interferon Alfa. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/11/2019.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for IFNL3 (IL28B) Genotype and PEG Interferon-α-Based Regimens. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org/. Accessed 28/11/2019.

Pegintron for Injection, for Subcutaneous Use (Schering Corporation, a subsidiary of Merck & Co., Inc.). U.S. FDA. https://www.fda.gov/. Accessed 28/11/2019.

Pegintron Injection, Powder, Lyophilized, for Solution (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/11/2019.

Sylatron (Merck Sharp & Dohme Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/11/2019.

Disclaimer: This information is independently developed by MIMS based on Peginterferon alfa-2b from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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