ropeginterferon alfa 2b

Action and Spectrum

Actions and spectrum: 

ropeginterferon alfa-2b is a modified form of interferon alfa-2b, a type of immunotherapy used in the treatment of certain haematological malignancies, such as chronic myeloid leukemia (CML). It acts by modulating the immune system to inhibit division and growth of cancer cells.

ropeginterferon alfa-2b has a longer half-life compared to interferon alfa-2b, allowing for less frequent dosing. Its spectrum of action includes stimulating the immune response, promoting apoptosis of cancer cells, and interfering with the replication of viruses. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Atrial fibrillation (<10%) 

>10% 

Arthralgia (47%) 

Pruritus (45%) 

Musculoskeletal pain (41%) 

Diarrhea (33%) 

Nausea (28%) 

reaction at administration site (26%) 

Abdominal pain (20%) 

Sleep disorder (20%) 

Decreased appetite (18%) 

Edema (16%) 

Muscle spasms (16%) 

Rash (16%) 

UTI (16%) 

Vertigo (12%) 

Influenza-like illness (59%) 

Fatigue (47%) 

Nasopharyngitis (43%) 

Headache (39%) 

Hyperhidrosis (29%) 

URTI (27%) 

Dizziness (22%) 

Depression (20%) 

Leukopenia (18%) 

Alopecia (16%) 

Hypertension (16%) 

Neutropenia (16%) 

Transaminase elevations (16%) 

Thrombocytopenia (12%) 

Black Box Warning

Black Box Warning: 

ropeginterferon alfa-2b does not have a specific black box warning 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: It is contraindicated in individuals with known hypersensitivity or severe allergic reactions to ropeginterferon alfa-2b or any of its components. 
• Autoimmune Hepatitis: ropeginterferon alfa-2b is contraindicated in patients with autoimmune hepatitis due to the potential exacerbation of the underlying condition. 
• Decompensated Liver Disease: It is contraindicated in patients with decompensated liver disease, including severe liver failure, as it may further impair liver function. 
• Bone Marrow Suppression: ropeginterferon alfa-2b is contraindicated in patients with severe bone marrow suppression, including severe thrombocytopenia, neutropenia, or anemia, as it may exacerbate these conditions. 
• Pregnancy: ropeginterferon alfa-2b may cause harm to the fetus, and therefore, it is contraindicated during pregnancy.

Caution: 

• Depression and Suicidal Ideation: Treatment with ropeginterferon alfa-2b has been associated with suicidal ideation, depression, and suicidal behaviour.  
• Myelosuppression: ropeginterferon alfa-2b may cause myelosuppression, including neutropenia, thrombocytopenia, and anemia.  
• Liver Dysfunction: ropeginterferon alfa-2b can affect liver function, and periodic monitoring of liver enzymes is recommended.  
• Thyroid Dysfunction: Treatment with ropeginterferon alfa-2b can lead to thyroid dysfunction, including hypothyroidism and hyperthyroidism.  
• Cardiac Disorders: ropeginterferon alfa-2b may cause or exacerbate cardiac disorders, including arrhythmias and cardiomyopathy.  
• Pancreatitis: pancreatitis cases have been reported in patients receiving ropeginterferon alfa-2b.  
• Autoimmune Disorders: ropeginterferon alfa-2b can induce or exacerbate autoimmune disorders.

Comorbidities: 

• Hepatic Impairment: ropeginterferon alfa-2b is primarily metabolized in the liver, and patients with pre-existing hepatic impairment may be at increased risk of drug accumulation and toxicity.  
• Cardiovascular Disease: ropeginterferon alfa-2b can have cardiovascular effects, including potential cardiac toxicity.  
• Autoimmune Disorders: ropeginterferon alfa-2b has the potential to induce or exacerbate autoimmune disorders.  
• Endocrine Disorders: ropeginterferon alfa-2b can affect thyroid function, and patients with pre-existing thyroid disorders, such as hypothyroidism or hyperthyroidism, may require closer monitoring and adjustment of thyroid medications during treatment. 
• Mental Health Disorders: ropeginterferon alfa-2b has been associated with depression and other psychiatric side effects. 

Pregnancy / Lactation

Pregnancy consideration: N/A 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

• Immunomodulation: ropeginterferon alfa-2b enhances the immune response by stimulating the activity of natural killer cells, T cells, and macrophages. It promotes the production of cytokines and chemokines, which play a crucial role in regulating immune responses. 
• Antiviral Activity: ropeginterferon alfa-2b has direct antiviral effects against certain viruses. It inhibits viral replication and promotes the degradation of viral nucleic acids, thereby reducing viral load. 
• Antiproliferative Effects: ropeginterferon alfa-2b has been shown to have antiproliferative effects on various cell types, including cancer cells. It inhibits cell proliferation, induces apoptosis, and suppresses the angiogenesis that support tumor growth. 
• Induction of Cell Differentiation: ropeginterferon alfa-2b can promote the differentiation of certain cell types, particularly in hematopoietic malignancies. It helps to restore normal cell differentiation and function, which can be disrupted in cancer cells. 

Pharmacodynamics: 

• Activation of JAK/STAT Pathway: ropeginterferon alfa-2b binds to cell surface receptors, leading to the activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway. This activation triggers the phosphorylation of STAT proteins, which translocate to nucleus and regulate gene expression.  
• Immunomodulatory Effects: ropeginterferon alfa-2b enhances the immune response by increasing the production of various cytokines, including interferon-gamma (IFN-γ), interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-α). These cytokines stimulate the activity of immune cells thereby promoting immune surveillance and defense against infections and tumor cells. 
• Antiviral Effects: ropeginterferon alfa-2b exhibits direct antiviral activity against certain viruses. It inhibits viral replication by inducing the expression of antiviral proteins, interfering with viral protein synthesis, and enhancing the degradation of viral RNA. 
• Antiproliferative and Proapoptotic Effects: ropeginterferon alfa-2b has antiproliferative effects on various cell types, including cancer cells. It inhibits cell proliferation and promotes cell cycle arrest. Additionally, ropeginterferon alfa-2b induces apoptosis (programmed cell death) in cancer cells, contributing to its potential antitumor activity. 
• Differentiation Induction: ropeginterferon alfa-2b can promote the differentiation of certain cell types, particularly in hematopoietic malignancies. It helps restore normal cell differentiation and function, which can be disrupted in cancer cells.

Pharmacokinetics: 

Absorption 

ropeginterferon alfa-2b is administered via subcutaneous injection. After injection, it is slowly and gradually absorbed into the bloodstream. The absorption rate may vary depending on factors such as injection site, formulation, and individual patient characteristics. 

Distribution 

Once in the bloodstream, ropeginterferon alfa-2b is distributed throughout the body. It binds to specific receptors on cell surfaces, including immune cells, and exerts its pharmacological effects. The distribution of ropeginterferon alfa-2b is expected to be widespread but may be influenced by factors such as protein binding and tissue permeability. 

Metabolism 

ropeginterferon alfa-2b is a protein-based therapeutic agent and undergoes metabolic degradation in various tissues. It is primarily metabolized by proteolytic enzymes, such as peptidases and proteases, which break down the protein structure into smaller peptides and amino acids. The exact metabolic pathways and metabolites of ropeginterferon alfa-2b have not been extensively characterized. 

Elimination and excretion 

The elimination of ropeginterferon alfa-2b occurs through renal clearance. After metabolism and breakdown, the resulting peptides and amino acids are eliminated from the body via urine. The exact elimination half-life of ropeginterferon alfa-2b has not been clearly established. 

Adminstartion

Administration: 

• Preparation: Follow the instructions provided by the healthcare professional or the manufacturer on how to properly prepare the medication for injection. This may involve reconstitution of a lyophilized powder with a diluent provided in the package. 
• Injection site: Choose a clean area on the upper arm, thigh, or abdomen for the subcutaneous injection. Rotate injection sites to minimize injection site reactions and to ensure proper absorption. 
• Injection technique: Use a sterile syringe and needle appropriate for subcutaneous injections. Pinch the skin at the chosen injection site to create a fold or tent. Insert the needle at 45 to 90-degree angle into the fold of skin, and slowly inject the medication. The depth of injection may depend on the needle length and patient’s body habitus. 
• Dose and frequency: The specific dose and frequency of ropeginterferon alfa-2b will be determined by the healthcare professional based on the patient’s condition. Follow the prescribed dose and administration schedule exactly as instructed. 
•  Post-injection care: After injection, remove the needle and apply pressure gently to the injection site with a sterile cotton ball or gauze pad. Do not rub the injection site. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ropeginterferon alfa 2b 

Pronounced: (roh-peh-jin-ter-FEER-on al-fa).  

Why do we use ropeginterferon alfa 2b? 

• Polycythemia Vera: It is used in the treatment of polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea, which is another medication used in the management of this condition. 
• Essential Thrombocythemia: It is indicated for the treatment of adults with essential thrombocythemia who are at high risk of thromboembolic complications such as blood clots and have had an inadequate response to or are intolerant of hydroxyurea. 
• Chronic Myeloid Leukemia: In some cases, ropeginterferon alfa-2b is also used as a treatment plan for certain patients with chronic myeloid leukemia (CML), either as initial therapy or after failure of other treatments.