Pegylated interferon alfa-2b, often abbreviated as PEG-IFN alfa-2b, is a modified form of interferon alfa-2b that has been chemically linked to polyethylene glycol (PEG). This modification prolongs the half-life of interferon in the body, allowing for less frequent dosing while maintaining therapeutic levels. Interferon alfa-2b is a type of protein known as a cytokine, which is naturally produced by the body in response to viral infections, among other stimuli. It plays a vital role in regulating the immune response and has been used therapeutically in the treatment of various diseases, including certain viral infections (such as hepatitis B and C), certain cancers (such as melanoma and certain types of leukemia), and autoimmune disorders (such as multiple sclerosis).

PEGylation enhances the pharmacokinetic properties of interferon alfa-2b, allowing for sustained release and reducing the frequency of injections required for treatment. This can lead to improved patient compliance and tolerability. Pegylated interferon alfa-2b is typically administered by subcutaneous injection and is often used in combination with other medications, such as ribavirin, for the treatment of chronic hepatitis C.

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:

Pegylated Interferon Alfa-2b is a type of medicine used to treat melanoma, a serious type of skin cancer. In this treatment, the medicine is given as a shot under the skin (SubQ).

Here's how the treatment works:

• At first, the patient receives a dose of 6 micrograms (mcg) per kilogram of body weight once a week for 8 doses. This is called the initial dose.
• After that, if the treatment continues, the dose is lowered to 3 mcg per kilogram of body weight once a week. This is called the maintenance dose.
• This maintenance dose can go on for up to 5 years.

Before starting the treatment, the patient should take acetaminophen (500 to 1,000 mg by mouth) 30 minutes before the first dose. They should also take it before each subsequent dose, if needed. Acetaminophen can help reduce any side effects from the medicine, like fever or muscle aches.

It's important to follow the doctor's instructions carefully during this treatment.

Pegylated interferon-alfa 2b dose in children:

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

For treating chronic hepatitis B virus (HBV) infection, especially in adolescents who are exposed to or have HIV:

• The medication used is Pegylated Interferon Alfa-2b.
• It's given as a shot under the skin (SubQ).
• The dose is 1.5 micrograms (mcg) per kilogram of body weight once a week.
• This treatment lasts for 48 weeks.

It's essential for patients not to switch between different brands of interferon alfa therapy because different brands may have different dosages.

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

For treating chronic hepatitis C virus (HCV) infection, the dosage of Pegylated Interferon Alfa-2b varies depending on several factors such as age, presence of HIV infection, and any potential side effects.

• Non-HIV-exposed/-infected:
  • Children aged 3 years and older and Adolescents:
    • Manufacturer's labeling recommends a SubQ dose of 60 micrograms per square meter of body surface area once weekly, given in combination with ribavirin.
    • Treatment duration:
      • 48 weeks for genotype 1.
      • 24 weeks for genotypes 2 and 3.
    • Consider discontinuation of combination therapy in patients with HCV genotype 1 if a 2-log decrease in HCV-RNA has not been achieved by 12 weeks or if HCV-RNA is still detectable at 24 weeks.
• Alternate dosing (per American Association for the Study of Liver Diseases - AASLD):
  • Children aged 2 years and older and Adolescents:
    • SubQ dose of 60 micrograms per square meter of body surface area once weekly, in combination with oral ribavirin, for 48 weeks, regardless of genotype.
• HIV-exposed/-positive (coinfection):
  • Children aged 3 years and older:
    • SubQ dose of 60 micrograms per square meter of body surface area once weekly, in combination with ribavirin, for 48 weeks, regardless of genotype.
  • Adolescents:
    • SubQ dose of 1.5 micrograms per kilogram of body weight once weekly, in combination with ribavirin, for 48 weeks, regardless of genotype.

Dosage adjustments may be necessary based on toxicity:

• Depression: Dosage adjustment based on the severity of depression.
• Hematologic toxicity: Dosage adjustment based on changes in hemoglobin, white blood cell count, neutrophils, and platelets.

Severe depression or significant hematologic toxicity may require discontinuation of therapy and immediate medical consultation.

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

• Interferon alfa, a natural substance found in normal amniotic fluid, isn't found in the placenta when given externally.
• The Health and Human Services guidelines advise against using peginterferon-alfa during pregnancy due to its effects on growth and cell division, supported by animal studies showing it can cause miscarriages.
• Treating hepatitis C during pregnancy isn't recommended for either the mother's health or to prevent transmission to the baby.
• Women with hepatitis C should avoid getting pregnant until treatment is complete.
• Before starting treatment, it's important to confirm if a woman could be pregnant.
• Peginterferon Alfa-2b, especially when combined with ribavirin, is unsafe during pregnancy and even for men whose partners are pregnant due to the risk of birth defects and death to the unborn child.
• Effective contraception should be used by women of reproductive age during treatment and for at least 10 days after the last dose of peginterferon alfa2b.
• It's essential to follow all warnings regarding ribavirin and pregnancy if using it in combination therapy.

Use of peginterferon during breastfeeding

• Interferon alfa, a substance naturally found in breast milk, doesn't significantly change in levels after administration.
• Breastfeeding isn't known to spread hepatitis C virus, but it's advised to avoid breastfeeding if nipples are cracked or bleeding (express and discard milk instead).
• Breastfeeding is not recommended for mothers co-infected with HIV.
• Whether to breastfeed during therapy should weigh the risks of infant exposure against the benefits of breastfeeding and treatment for the mother.
• If using interferon alfa in combination with ribavirin, all precautions regarding ribavirin and breastfeeding should be followed.
• For further details, refer to the ribavirin monograph.

Pegylated Interferon Alfa 2B Dose adjustment in renal disease:

For patients with melanoma, the dosage of pegylated interferon alfa-2b may need to be adjusted based on their kidney function:

• If the creatinine clearance (CrCl) is above 50 mL/minute/1.73 m², no adjustment is necessary.
• If CrCl is between 30 to 50 mL/minute/1.73 m², the initial dose should be reduced to 4.5 micrograms per kilogram per week, and the maintenance dose should be reduced to 2.25 micrograms per kilogram per week.
• For patients with CrCl less than 30 mL/minute/1.73 m² or those with end-stage renal disease (ESRD) on dialysis, the initial dose should be reduced to 3 micrograms per kilogram per week, and the maintenance dose should be reduced to 1.5 micrograms per kilogram per week.

In patients undergoing hemodialysis, after a single dose of 1 microgram per kilogram, peginterferon alfa-2b isn't significantly removed during hemodialysis. This means no further adjustment is necessary after hemodialysis.

Pegylated Interferon Alfa 2B Dose adjustment in liver disease:

• For patients with decompensated liver disease or autoimmune hepatitis, the use of pegylated interferon alfa-2b is not recommended due to contraindications.

• Additionally, if a patient experiences hepatic decompensation or severe (grade 3) hepatic injury during treatment, characterized by a Child-Pugh score greater than 6 (class B or C), immediate discontinuation of the treatment is advised.

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:

• Pegylated interferon alfa-2b should not be used in patients who have shown hypersensitivity reactions to peginterferon alfa-2b, interferon alfa-2b, other alfa interferons, or any component of the medication formulation.
• It's also contraindicated in patients with autoimmune hepatitis or decompensated liver disease (Child-Pugh score >6, classes B and C).
• While documentation of allergenic cross-reactivity for interferons is limited, the possibility of cross-sensitivity cannot be ruled out due to similarities in chemical structure and pharmacologic actions.
• Combination therapy with peginterferon alfa-2b and ribavirin is contraindicated in pregnancy, females who may become pregnant, males with pregnant partners, individuals with hemoglobinopathies (such as thalassemia major or sickle-cell anemia), and those with renal dysfunction (creatinine clearance less than 50 mL/minute).
• It's essential for healthcare providers to consider these contraindications and potential risks before prescribing pegylated interferon alfa-2b or combination therapy with ribavirin.

Warnings and precautions

Repression of Bone Marrow:

• Can cause bone marrow suppression and severe cytopenias.
• Use cautiously in patients who are immunosuppressed or have low blood counts.
• Combination therapy with ribavirin may enhance neutropenic effects.

Colitis

• Ulcerative or hemorrhagic/ischemic colitis may occur, typically within 12 weeks of starting treatment.
• Discontinue therapy if signs of colitis develop, such as abdominal pain, bloody diarrhea, or fever.

Dental/periodontal disorders:

• Dry mouth associated with therapy may affect teeth and mucous membranes.
• Patients should brush teeth twice daily and have regular dental exams. Rinse mouth thoroughly after vomiting.

Flu-like symptoms

• Patients commonly experience flu-like symptoms.
• Use with caution in patients with debilitating conditions.

Hypersensitivity

• Rarely, acute hypersensitivity reactions and cutaneous reactions have been reported.
• Prompt discontinuation and management are recommended.

Hypertriglyceridemia:

• May lead to high triglyceride levels, which can result in pancreatitis.
• Monitor regularly and manage appropriately. Consider discontinuation if severe.

[US Boxed Warning] Neuropsychiatric disorders

• May cause or worsen severe depression or other neuropsychiatric adverse events.
• Monitor closely and discontinue treatment if symptoms worsen or persist.

Ophthalmic Effects:

• Various eye disorders, including decreased visual acuity and blindness, have been reported.
• Ophthalmic exams are recommended before starting treatment and promptly if ocular symptoms develop.

Pancreatitis:

• Pancreatitis, including fatal cases, has been observed.
• Withhold treatment for suspected pancreatitis and discontinue for known cases.

Pulmonary Effects:

• May cause or worsen respiratory conditions, leading to respiratory failure.
• Monitor closely and use with caution in patients with existing pulmonary disease.

Autoimmune disease: [US-Boxed Warning]

• May cause or exacerbate autoimmune disorders.
• Monitor closely and discontinue treatment if symptoms worsen or persist.

Cardiovascular disease

• Use with caution in patients with or at risk of cardiovascular disease.
• Monitor closely and discontinue treatment for new-onset cardiac issues.

Diabetes:

• Diabetes mellitus and hyperglycemia have been reported.
• Discontinue if diabetes cannot be effectively managed with medication.

Hepatic impairment

• Contraindicated in severe liver disease.
• Discontinue immediately for hepatic decompensation or severe hepatic injury.

Infectious disorders: [US Boxed Warning]:

• May cause or worsen infectious disorders.
• Monitor closely and discontinue treatment if symptoms worsen.

Ischemic disorders: [US Boxed Warning]:

• May cause or worsen cerebrovascular events.
• Monitor closely and discontinue treatment if ischemia persists.

Renal impairment

• Use with caution in patients with renal impairment.
• Monitor closely for signs of toxicity and adjust dosage as necessary.

Thyroid disorders:

• Use with caution in patients with thyroid disorders.
• Discontinue if thyroid disease cannot be controlled with medication.

Monitoring parameters:

• Thyroid Function:
  • Baseline and periodic thyroid-stimulating hormone (TSH) monitoring is recommended.
  • For patients with melanoma, obtain baseline TSH within 4 weeks prior to treatment initiation, then at 3 and 6 months, and every 6 months thereafter during treatment.
• Complete Blood Count (CBC) and Platelets:
  • Regular CBC with differential and platelet counts should be conducted.
• Liver Function:
  • Monitor serum bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, and lactate dehydrogenase (LDH).
  • For patients with melanoma, monitor these parameters at 2 and 8 weeks, and 2 and 3 months following initiation, then every 6 months during therapy.
• Renal Function and Triglycerides:
  • Regular assessment of renal function and triglyceride levels is recommended.
• Serum Glucose or HbA1c:
  • Monitor serum glucose or hemoglobin A1c (HbA1c) levels in patients with diabetes mellitus.
• Pregnancy Evaluation:
  • Evaluate pregnancy status prior to use in females of reproductive potential, regardless of indication.
• Psychiatric Symptoms:
  • Assess for depression and other psychiatric symptoms before and after initiation of therapy.
  • For patients being treated for melanoma, monitor for depression and psychiatric symptoms every 3 weeks during the first eight weeks of treatment, then every 6 months thereafter. Continued monitoring for 6 months after the last dose is recommended.
• Ophthalmic Examination:
  • Conduct baseline ophthalmic eye examination.
  • Perform periodic ophthalmic exams, especially in patients with diabetic or hypertensive retinopathy.
• Cardiac Evaluation:
  • Consider baseline electrocardiogram (ECG) in patients with cardiac disease.

These monitoring guidelines aim to ensure the safety and efficacy of pegylated interferon alfa-2b therapy and to detect any potential adverse effects or complications early on.

How to administer Pegylated Interferon Alfa 2B?

• Rotate Injection Site:
  • Rotate the injection site with each dose to minimize discomfort and reduce the risk of injection site reactions.
• Administration Timing:
  • The weekly dose may be administered at bedtime to help reduce flu-like symptoms, which are common side effects of pegylated interferon alfa-2b therapy.

These administration guidelines aim to optimize patient comfort and minimize side effects associated with SubQ pegylated interferon alfa-2b administration.

Mechanism of action of Pegylated Interferon-alpha 2B:

• Alpha interferons are a group of proteins made by certain cells in the body, which have roles in fighting viruses, controlling cell growth, and regulating the immune system.
• There are 16 different types of alpha interferons.
• These proteins interact with cells through specific receptors on their surface, leading to various effects such as activating genes and inhibiting cellular growth.
• They also change how cells differentiate, affect the expression of certain genes related to cancer, alter the presentation of antigens on cell surfaces, boost the ability of immune cells to engulf pathogens, and enhance the killing ability of immune cells against infected or abnormal cells.

Bioavailability:

• Increases with repeated or chronic dosing, meaning the body absorbs more of the medication over time.

Half-life Elimination:

• For chronic hepatitis C (CHC), the half-life is approximately 40 hours, ranging from 22 to 60 hours.
• For melanoma treatment, the half-life ranges from approximately 43 to 51 hours.

Time to Peak:

• For CHC, it takes between 15 to 44 hours for the medication to reach its peak concentration in the body.

Excretion:

• About 30% of the drug is excreted through urine.
• Clearance of the medication is reduced in cases of renal impairment, with a reduction of 17% in moderate dysfunction and 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: