Pegylated Interferon Alfa 2B is a type of recombinant interferon that is marketed by the brand name of Pegintron among others.

Indications of Pegylated Interferon Alfa 2B:

• Melanoma (adjuvant therapy):

  • Sylatron:

    • It is used for adjuvant treatment of melanoma with microscopic or gross nodal involvement within 84 days of definitive surgical resection with complete lymphadenectomy.
  • Note: Indications in the manufacturer's labeling may not reflect current clinical practices.

Pegylated Interferon Alfa 2B dose in adults:

Note: PegIntron Redipen and PegIntron 80 mcg, 120 mcg, and 150 mcg vials have been discontinued in the US for more than 1 year.

Pegylated interferon-alpha 2b dose in the treatment of Melanoma (adjuvant therapy):

• Initial: 6 mcg/kg/week subcutaneous for 8 doses.
• Maintenance: 3 mcg/kg/week for up to 5 years.
• Note:
  • Premedicate with acetaminophen (500 to 1,000 mg orally) half-hour before to the first dose and as needed for subsequent doses thereafter.

Pegylated interferon-alfa 2b dose in children:

Note: Due to differences in dosage, patients should not change brands of interferon alfa therapy.

Pegylated Interferon Alfa 2B dose in the treatment of chronic hepatitis B virus infection (HIV-exposed/-positive):

• Adolescents:
  • PegIntron:1.5 mcg/kg subcutaneous once weekly for 48 weeks.

Pegylated Interferon Alfa 2B dose in the treatment of chronic hepatitis C virus infection:

Non-HIV-exposed/-infected:

• Manufacturer's labeling:

  • Children ≥3 years and Adolescents:
    • PegIntron:
      • 60 mcg/m² subcutaneous once weekly concurrently with ribavirin.
    • Treatment duration:
      • 48 weeks (genotype 1); 24 weeks (genotypes 2 and 3).
      • Therapy should be stopped in patients with HCV (genotype 1) at 12 weeks if a 2 log decrease in HCV-RNA is not achieved or if HCV-RNA is still detectable at 24 weeks.
  • Note: Adolescents who reach their 18th birthday during treatment should remain on the pediatric regimen.

• Alternate dosing:

  • American Association for the Study of Liver Diseases recommendations:
    • Children ≥2 years and Adolescents: PegIntron:60 mcg/m subcutaneous once weekly concurrently with oral ribavirin for 48 weeks (all genotypes).

HIV-exposed/-positive (co-infection):

• Children ≥3 years:

  • PegIntron:60 mcg/m² subcutaneous once weekly concurrently with ribavirin.
  • Treatment duration: 48 weeks, regardless of genotype.

• Adolescents:

  • PegIntron: 1.5 mcg/kg subcutaneous once weekly concurrently with ribavirin.
  • Treatment duration: 48 weeks, regardless of genotype.

Pegylated Interferon Alfa 2B dose adjustment for toxicity:

• Chronic hepatitis C:

  • Dosage adjustment for depression (severity based upon DSM-IV criteria):

  • Mild depression:

    • No dosage adjustment required; evaluate once weekly.
    • If depression remains stable, continue weekly visits.
    • If depression improves, resume normal visit schedule. For worsening depression, see “Moderate depression” below.

  • Moderate depression:

    • Evaluate once weekly with an office visit at least every other week.
    • If depression remains stable, consider a psychiatric evaluation and continue with reduced dosing.
    • If symptoms improve and remain stable for 4 weeks, resume normal visit schedule;
    • continue reduced dose or return to the normal dose.
    • Therapy should be immediately stopped worsening or severe depression and obtain immediate psychiatric consultation.
    • Utilize followup psychiatric therapy as needed.

    • Children and Adolescents:

      • Decrease to 40 mcg/m² once weekly, may further decrease to 20 mcg/m once weekly if needed.

  • Severe depression:

    • Children and Adolescents:

      • Discontinue peginterferon alfa-2b and ribavirin permanently. Obtain immediate psychiatric consultation.

• Chronic hepatitis C: Dosage adjustment in hematologic toxicity:

  • Hemoglobin decrease >2 g/dL in any 4 weeks in patients with stable cardiac disease:

    • 50% dose reduction of peginterferon alfa-2b;
    • monitor and evaluate weekly.
    • Peginterferon alfa 2b and ribavirin should be permanently stopped if the hemoglobin remains <12 g/dL after 4 weeks of dose reduction.

  • Hemoglobin 8.5 to <10 g/dL in patients without a history of cardiac disease:

    • No dosage adjustment for peginterferon alfa-2b. Decrease ribavirin dose.

  • WBC 1000 to <1500/mm³, neutrophils 500 to <750/mm³ , or platelets 50,000 to <70,000/mm³:

    • Reduce peginterferon alfa-2b dose to 40 mcg/m once weekly;
    • may further reduce to 20 mcg/m once weekly.

  • Hemoglobin <8.5 g/dL, WBC <1000/mm³ , neutrophils <500/mm³ , or platelets <50,000/mm³ :

    • Permanently discontinue peginterferon alfa-2b and ribavirin.

Pregnancy Risk Factor: C (X in combination with Ribavirin)

• Interferon alpha is not able to cross the placental boundary, but it can be used as an endogenous amniotic fluid.
• Animal studies have shown that abortifacients can disrupt normal menstrual cycles.
• Health and Human Services Perinatal HIV Guidelines advise against using HIV in pregnancy because of its antigrowth and proliferative effects.
• It is not advised to use HCV during pregnancy.
• To reduce the chance of HCV transmission, HCV-infected women should not get pregnant before treatment is completed.
• Females should use effective contraception during treatment, and for at least 10 days after receiving the last dose of peginterferon alfa 2b.
• Peginterferon Alfa-2b and ribavirin combination therapy is not recommended for pregnant women and men whose partners are pregnant, as it can cause birth defects or death in unborn children.

Use of peginterferon during breastfeeding

• Interferon alfa can be added to breast milk endogenously.
• Interferon alfa can be found in breast milk, and the administration of the medication did no significant affect endogenous levels.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks and benefits to the infant as well as the benefits to the mother.
• Hepatitis C virus can be transmitted to breastfeeding. However, it is not recommended that you breastfeed if your nipples are broken or bleeding.
• However, mothers with HIV should not breastfeed.
• For more information, refer to the ribavirin monograph.

Pegylated Interferon Alfa 2B Dose adjustment in renal disease:

•  Melanoma:

  • Creatinine clearance >50 mL/minute/1.73 m² :

    • No dosage adjustment is necessary.

  • Creatinine clearance 30 to 50 mL/minute/1.73 m² :

    • Reduce initial dose to 4.5 mcg/kg/week; reduce maintenance dose to 2.25 mcg/kg/week.

  • Creatinine clearance <30 mL/minute/1.73 m² and ESRD on dialysis:

    • Reduce initial dose to 3 mcg/kg/week; reduce maintenance dose to 1.5 mcg/kg/week.

  • Hemodialysis:

    • Following a single 1 mcg/kg/ dose, no clinically meaningful amount of peginterferon alfa-2b was removed during hemodialysis.

Pegylated Interferon Alfa 2B Dose adjustment in liver disease:

• Decompensated liver disease or autoimmune hepatitis:

  • Use is contraindicated.

• Hepatic decompensation or severe hepatic injury during treatment (Child-Pugh score >6 [class B or C]):

  • Discontinue immediately.

Antiviral:

Common Side effects of Pegylated Interferon Alfa 2B:

• Central Nervous System:

  • Headache
  • Fatigue
  • Depression
  • Anxiety
  • Emotional Lability
  • Irritability
  • Insomnia
  • Rigors
  • Dizziness

• Dermatologic:

  • Alopecia
  • Pruritus

• Endocrine & Metabolic:

  • Weight Loss

• Gastrointestinal:

  • Nausea
  • Anorexia
  • Diarrhea
  • Abdominal Pain

• Infection:

  • Viral Infection

• Local:

  • Inflammation At Injection Site
  • Injection Site Reaction

• Neuromuscular & Skeletal:

  • Myalgia
  • Weakness
  • Musculoskeletal Pain
  • Arthralgia

• Miscellaneous:

  • Fever

Rare Side Effects Of Pegylated Interferon Alfa 2B:

• Cardiovascular:

  • Chest Pain
  • Flushing

• Central Nervous System:

  • Lack Of Concentration
  • Right Upper Quadrant Pain
  • Malaise
  • Nervousness
  • Agitation
  • Suicidal Ideation

• Dermatologic:

  • Diaphoresis
  • Skin Rash

• Endocrine & Metabolic:

  • Hypothyroidism
  • Menstrual Disease
  • Hyperthyroidism

• Gastrointestinal:

  • Vomiting
  • Dyspepsia
  • Xerostomia
  • Constipation

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Neutropenia

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Hepatomegaly

• Immunologic:

  • Antibody Development

• Local:

  • Pain At Injection Site

• Ophthalmic:

  • Conjunctivitis
  • Blurred Vision

• Respiratory:

  • Pharyngitis
  • Cough
  • Sinusitis
  • Dyspnea
  • Rhinitis

Antineoplastic:

Common Side Effects Of Pegylated Interferon Alfa 2B:

• Central Nervous System:

  • Fatigue
  • Headache
  • Chills
  • Depression
  • Dizziness
  • Neuropathy
  • Paresthesia

• Dermatologic:

  • Exfoliative Dermatitis
  • Alopecia

• Endocrine & Metabolic:

  • Weight Loss

• Gastrointestinal:

  • Anorexia
  • Nausea
  • Dysgeusia
  • Diarrhea
  • Vomiting

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase
  • Increased Serum Alkaline Phosphatase

• Immunologic:

  • Antibody Development

• Local:

  • Injection Site Reaction

• Neuromuscular & Skeletal:

  • Myalgia
  • Arthralgia

• Miscellaneous:

  • Fever

Rare Side Effects Of Pegylated Interferon Alfa 2B:

• Cardiovascular:

  • Bundle Branch Block
  • Myocardial Infarction
  • Supraventricular Cardiac Arrhythmia
  • Ventricular Tachycardia

• Endocrine & Metabolic:

  • Increased Gamma-Glutamyl Transferase

• Genitourinary:

  • Proteinuria

• Hematologic & Oncologic:

  • Anemia

• Respiratory:

  • Dyspnea
  • Cough

Contraindications to Pegylated Interferon-alpha 2B:

• Hypersensitivity can include anaphylaxis and angioedema as well as urticaria, Steven-Johnson Syndrome, and toxic epidermal necrosis to peginterferon, other alfa Interferons, or any component in the formulation.
• Autoimmune hepatitis
• Decompensated liver disease (Child–Pugh score>6, classes B, and C).
• Combination therapy is contraindicated
• Thalassemia major/sickle cells anemia
• Renal dysfunction
• Contraindicated: Pregnancy and willingness to conceive (combination therapy).
• Females who are pregnant with their partners.

Warnings and precautions

• Repression of Bone Marrow:

  • Cytopenias can be life-threatening and severe with interferon.
  • Ribavirin could increase the severity of hematologic toxicities associated with interferon, and anemia (hemolytic toxicity).
  • It is also associated with anemia.
  • Cytopenias should not be treated. In some cases, colony stimulating factors may be helpful.

• Colitis

  • Interferon has been linked to ischemic and ulcerative colitis.
  • If the patient develops fever, abdominal pain, or bloody diarrhea, it is important to stop treatment. This could indicate that they have hemorhagic/ischemic bowel disease.
  • It will typically take between 1 and 3 weeks for symptoms to disappear.

• Dental/periodontal disorders:

  • Therapy can lead to dry mouth, damaged teeth, and other disorders of the mucous membranes.
  • It is important to brush your teeth twice daily and have regular dental examinations.
  • After vomiting, it is important to thoroughly wash your mouth.

• Flu-like symptoms

  • Interferons can be associated with flu-like symptoms so it is important to use them sparingly.

• Hypersensitivity

  • In the event of acute hypersensitivity reactions, such as angioedema or bronchoconstriction, supportive measures should be taken.

• Hypertriglyceridemia:

  • If you have persistent hypertriglyceridemia greater than 1000 mg/dL, and if you have symptoms that favor pancreatitis, peginterferon should not be used.

• [US Boxed Warning] Neuropsychiatric disorders

  • Interferon therapy may cause aggression, depression and hallucinations as well as psychosis, homicidal ideastion, suicidal behavior/ideation or bipolar disorder.
  • Encephalopathy can be caused by higher doses of alcohol in the elderly.
  • In the event of persistent or worsening depression, or other neuropsychiatric disorders, treatment should be stopped.
    • Patients with substance abuse and other mental disorders should be screened for drugs before starting treatment. A periodic health assessment is also recommended.
    • Patients should be checked for depression, pneumonitis and dyspnea before melanoma treatment.
    • Combination therapy should be discontinued if there is pulmonary infiltrate/impaired lung function.

• Autoimmune disease: [US-Boxed Warning]

  • Interferon therapy can be used to treat thyroiditis, thrombotic angiopathy, immune-thrombocytopenia and rheumatoid arthritis.
  • If symptoms worsen, it is best to stop treatment. The condition could reverse.

• Cardiovascular disease

  • It can cause hypotension, tachycardia and arrhythmia.
  • Patients should be monitored closely and have an ECG taken before starting combination treatment with Ribavirin.
  • Combination therapy should not be used with severe or unstable heart disease.
  • It should be stopped permanently for new-onset ventricular arrhythmias or cardiovascular decompensation.

• Diabetes:

  • Hyperglycemia and new-onset type 1 diabetes mellitus can both occur.
  • Patients at high risk for diabetic ketoacidosis should not use it.

• Hepatic impairment

  • It is not recommended for patients with autoimmune liver disease or hepatic decompensation.
  • You should stop treatment immediately if you have evidence of severe hepatic injuries or Child-Pugh score>6.
  • Hepatic decompensation can be caused by alcohol, chronic liver disease C with cirrhosis, and the human immunodeficiency viruses.
  • If there is a transient rise in ALT (between 2 and 5 times the baseline), but it is not associated to liver dysfunction, close monitoring can be used.

• Infectious disorders: [US Boxed Warning]:

  • Flu-like symptoms and fever are common side effects of interferon therapy.
  • If there are persistent signs and symptoms, it can lead to or exacerbate infectious disorders.

• Ischemic disorders: [US Boxed Warning]:

  • This may cause or aggravate hemorhagic and ischemic cerebrovascular events. It is important to monitor closely, stop the treatment, and seek appropriate therapy.

• Renal impairment

  • Patients with kidney impairment (CrCl 50mL/minute), should be cautious.
  • Be on the lookout for signs of interferon toxicemia.
  • For chronic hepatitis, dose reduction is necessary in cases of moderate to severe renal impairment.
  • Combination therapy with Ribavirin is not recommended if creatinine clearance is 50mL/minute.
  • Children with serum creatinine greater than 2 mg/dL should not use it.
  • When treating melanoma associated with renal impairment, dosage reduction is necessary.

• Thyroid disorders:

  • Patients with hypothyroidism should not use it. It is also not recommended for patients with uncontrolled thyroid disorders, despite the fact that they are being treated with medication.

Monitoring parameters:

• CBC
• Liver function tests
• Renal function tests
• Lipid profile
• Blood glucose levels
• Baseline and periodic TSH (for patients with melanoma, obtain baseline within 4 weeks before treatment initiation, and then at 3 and 6 months, and every 6 months thereafter during treatment).
• Pregnancy status
• Ophthalmic examination regularly
• ECG monitoring
• Evaluation of depression and other psychiatric symptoms.

How to administer Pegylated Interferon Alfa 2B?

• The injection site should be rotated for subcutaneous administration.
• The weekly dose may be administered at bedtime to reduce flu-like symptoms.

Mechanism of action of Pegylated Interferon-alpha 2B:

• Alpha interferons, which are produced by nucleated cells, are proteins that have immune-regulating, antiproliferative and viral activity.
• There are 16 types of alpha interferons. Interferons interact with cells through high-affinity cell surface receptors. Interferons are activated by activating cells and exhibit a variety of actions, including inhibition of cell growth and interfering in oncogene transcription, increasing macrophage activity and cellular differentiation, alteration or cellular differentiation, gene transcription, augmentation of cytotoxicity and the stimulation of lymphocytes for target tissues.

Bioavailability:

• Increases with chronic dosing.

Half-life elimination:

• CHC: ~40 hours (range: 22 to 60 hours)
• Melanoma: ~43 to 51 hours

Time to peak:

• CHC: 15 to 44 hours

Excretion:

• Urine (~30%); clearance reduced in renal impairment by 17% in moderate dysfunction, 44% in severe dysfunction

Pegylated Interferon Alfa 2B brand names (International):

• Peg-Intron Redipen Pak 4
• Peg-Intron Redipen
• PegIntron
• Sylatron
• Alphapeg
• Peg Intron
• Peg-Intron
• PEG-Intron
• Pegintron
• PegIntron
• Pegtron
• ViraFeronPEG

Pegylated Interferon Alfa 2B Brands in Pakistan: