Peginterferon α-2b injection

Pegylated interferon-2b is a covalent conjugate of recombinant human interferon-2b and monomethoxy polyethylene glycol, with an average molecular weight of approximately 31,300 daltons. Recombinant human interferon-2b is obtained by expressing the interferon-2b gene of human leukocytes in recombinant Escherichia coli. In vitro and in vivo studies have shown that the biological activity of pegylated interferon α-2b comes from the recombinant human interferon α-2b portion of its structure. Interferon exerts its effects by binding to specific cell membrane receptors on the cell surface. Other interferon research results suggest that interferon is species-specific. In some primates, such as rhesus monkeys, there is a pharmacodynamic response after administration of human type 1 interferon. Once interferon binds to the cell membrane, it can initiate a series of complex intracellular processes, including inducing the expression of certain enzymes. This process is at least partly responsible for the cell's response to interferon, including a series of immune regulatory activities such as inhibiting viral replication, inhibiting cell proliferation, enhancing macrophage phagocytosis, and increasing lymphocyte-specific cytotoxicity to target cells in cells infected with the virus. Any or all of these reactions are related to the therapeutic effects of interferon. Recombinant human interferon-2b can inhibit viral replication both in vivo and in vitro. The mechanism of its antiviral effect is still unclear, and it may be related to changing the metabolism of host cells. This effect can inhibit viral replication, or prevent progeny viruses from leaving the cell after viral replication.

Main ingredients: Pegylated interferon α-2b Excipients: Disodium hydrogen phosphate, sodium dihydrogen phosphate, sucrose, polysorbate 80 and water for injection.

1. Chronic Hepatitis C This product is suitable for the treatment of chronic hepatitis C. Patients must be ≥18 years old and have compensated liver disease. It is now believed that the ideal treatment for chronic hepatitis C is the combination of this product and ribavirin. When this product is used in combination with ribavirin, please also refer to the product information of ribavirin. 2. Chronic Hepatitis B This product can also be used to treat HBeAg-positive chronic hepatitis B. Patients must be ≥18 years old and have compensated liver disease.

1. Chronic hepatitis C: Subcutaneous injection, once a week. For patients weighing less than 65kg, 40μg each time. For patients weighing more than 65kg, 50μg each time. Take ribavirin orally at the same time. The dosage of ribavirin is shown in the table below (150mg per tablet) (Insert PegIntron_Dosage Table_1) Treatment course: After 6 months of medication, if the viral load is still high, it is recommended to stop the medication. Dose adjustment: If severe adverse reactions and abnormal laboratory indicators occur during treatment, it is recommended to adjust the dose appropriately until the adverse reactions disappear or are alleviated. Principles for adjusting the dosage of this product (Insert PegIntron_Usage and Dosage Table_2) Methods for adjusting the dosage of this product (Insert PegIntron_Usage and Dosage Table_3) Principles for adjusting the dosage of ribavirin (Insert PegIntron_Usage and Dosage Table_4) Methods for adjusting the dosage of ribavirin (Insert PegIntron_Usage and Dosage Table_5) Specific standards for adjusting the dosage of ribavirin based on the results of indirect bilirubin test: The first dose reduction is when the indirect bilirubin is 3mg/dL (or 51μmol/L). If the indirect bilirubin is still greater than 3mg/dL after 1-2 weeks of dose reduction, the second dose reduction is performed. If the indirect bilirubin is greater than 3mg/dL for four consecutive weeks, ribavirin is discontinued. Ribavirin should be discontinued alone for at least one week and at most two weeks. If the indirect bilirubin drops to <2.5mg/dL after discontinuation of the drug, the ribavirin dose before discontinuation can be resumed. If the indirect bilirubin remains <2.5mg/dL for more than four weeks, the ribavirin dose can be adjusted to the full dose. Specific criteria for adjusting the dosage of ribavirin based on the results of hemoglobin test: the first dose reduction is when hemoglobin is <90g/L. If the hemoglobin is still below 90g/L after 1-2 weeks of dose reduction, the second dose reduction is performed. If the hemoglobin is less than 80g/L, ribavirin is discontinued. Ribavirin alone should be discontinued for at least one week and at most two weeks. If the hemoglobin is 80g/L after discontinuation, the dose of ribavirin before discontinuation can be restored. If the hemoglobin is maintained at 90g/L for more than four weeks, the dose of ribavirin can be adjusted to the full dose. For patients whose laboratory test indicators return to normal through dose adjustment, the dose should be readjusted to the full dose; for patients whose laboratory tests have not returned to normal after dose adjustment for 20 weeks, the dose after reduction should be maintained. 2. Chronic hepatitis B The currently recommended dose of this product is 1.0g/kg, once a week, subcutaneously. Course of treatment: 24 weeks. Other doses and courses of treatment have not been fully studied. Dose adjustment: Principles of dose adjustment for this product (Insert PegIntron_Usage and Dosage Table_6) Methods for dose adjustment for this product (Insert PegIntron_Usage and Dosage Table_7) Drug preparation and usage: This product is white, tablet-shaped, in one piece, or in multiple pieces, or in powder form before dissolution. Each bottle must be dissolved with 0.7ml of sterile solvent, and 0.5ml is drawn for injection. Use a sterile syringe and a long needle to draw 0.7ml of solvent, and slowly inject the solvent into the ampoule of this product along the bottle wall. It is best not to aim the solvent directly at the product, and the injection speed should not be too fast, because this will produce a lot of bubbles. Within a few minutes after dissolution, this product is cloudy or has multiple small bubbles. Gently turn the ampoule to dissolve it completely. Do not shake it vigorously. Since a small amount of this product will be lost when the dissolved product is extracted, in order to ensure that the dose of injection is consistent with the dose on the label, the actual content of this product and the solvent exceeds the content of its specification, and the 0.5ml of this product extracted is the content on the label. The concentrations of each specification of this product are: 50g/0.5ml, 80g/0.5ml, 100g/0.5ml.

1. Single medication: 1.1 According to foreign clinical trials, most adverse reactions are mild or moderate and are not affected by treatment. According to reports, most patients may experience headaches and muscle pain. The most common adverse reactions (≥10% of patients) include injection site pain/inflammation, fatigue, chills, fever, depression, joint pain, nausea, hair loss, skeletal muscle pain, irritability, flu-like symptoms, insomnia, diarrhea, abdominal pain, weakness, pharyngitis, weight loss, anorexia, anxiety, attention disorders, dizziness and injection site reactions. Common adverse reactions (≥2% of patients) are pruritus, dry skin, discomfort, increased sweating, pain in the right upper quadrant of the body, neutropenia, leukopenia, anemia, rash, vomiting, dry mouth, emotional lability, nervousness, dyspnea, viral infection, drowsiness, thyroid dysfunction, chest pain, dyspepsia, flushing, paresthesia, cough, agitation, sinusitis, hypertonia, hyperesthesia, blurred vision, impaired consciousness, flatulence, decreased libido, skin erythema, eye pain, apathy, hypoesthesia, loose stools, conjunctivitis, nasal congestion, constipation, dizziness, menorrhagia, and menstrual disorders. Psychiatric symptoms are uncommon. Life-threatening psychiatric symptoms rarely occur. These reactions include suicide, attempted suicide, suicidal ideation, irritability, aggressive behavior, and hallucinations. 5 The incidence of hypothyroidism is 5%, and the incidence of hyperthyroidism is 3%. In patients treated with 0.5µg/kg or 1.0µg/kg of this product, the incidence of granulocytopenia (0.75×109/L) was 4% and 7%, respectively, and the incidence of thrombocytopenia (70×109/L) was 1% and 3%, respectively. 1.2 Clinical trials of chronic hepatitis B conducted in China showed that adverse reactions were similar to those of ordinary interferons, and no unexpected adverse events occurred. This is close to the data reported abroad. The total incidence of adverse events in the treatment group of this product was 74.78%, and the total incidence of adverse events in the control group was 75.65%. Drug-related adverse events mainly manifested as flu-like symptoms, decreased white blood cells and platelets, etc. The degree of reaction was mostly mild to moderate, and it could be relieved by itself after continuing the medication or adjusting the dosage, without special treatment. The proportion of serious adverse events was 0.87% in the treatment group of this product, while it was 3.48% in the control group. 2. Combined use: 2.1 When this product is used in combination with ribavirin, in addition to the adverse reactions that occur when the above drugs are used alone, the following adverse reactions have also been reported: 5% to 10% adverse reactions: tachycardia, rhinitis and abnormal taste. 2% to 5% adverse reactions reported: hypotension, syncope, hypertension, tear gland disorders, tremor, gingival bleeding, glossitis, gastritis, gastric ulcer, hearing loss/loss, tinnitus, palpitations, thirst, aggressive behavior, fungal infection, prostatitis, otitis media, bronchitis, abnormal breathing, epistaxis, eczema, abnormal hair quality, photosensitivity reaction and lymphadenopathy. Rare adverse reactions include spasms, pancreatitis, hypertriglyceridemia, arrhythmia, diabetes and peripheral neuropathy. Aplastic anemia is rare when interferon α-2b is used in combination with ribavirin. 2.2 Other adverse reactions include the following adverse reactions when this product is used alone or in combination with ribavirin: Rare adverse reactions related to α-interferon include: ophthalmic disorders including retinopathy (including macular edema), retinal hemorrhage, retinal artery or vein thrombosis, cotton-wool exudates, loss of visual acuity and visual field, optic neuritis and papilledema (see Precautions). Patients with a history of cardiovascular disease or who have been treated with cardiotoxic drugs may experience adverse events of the cardiovascular system, especially arrhythmia. There are reports of cardiomyopathy in patients with no history of cardiovascular disease after using α-interferon, but it is a rare adverse reaction and returns to normal after stopping the drug. Rare adverse reactions reported for this product after marketing are as follows: rhabdomyolysis, myositis, renal insufficiency and renal failure. Very rare adverse reactions reported include myocardial ischemia, myocardial infarction, cerebrovascular ischemia, cerebrovascular hemorrhage, encephalopathy, ulcerative and ischemic colitis, sarcoidosis or exacerbation of sarcoidosis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrosis, and injection site necrosis. Diabetes, diabetic ketoacidosis, and hypertriglyceridemia have been reported. A variety of autoimmune diseases, or immune-mediated diseases, have been reported to be associated with alpha-interferon therapy, and rare occurrences of autoimmune and indirect immune diseases include idiopathic thrombocytopenic purpura, rheumatoid arthritis, systemic lupus erythematosus, and Vogt-Koyanagi-Harada syndrome. Cases of acute allergic reactions including anaphylaxis, urticaria, and angioedema have been reported. Asthenic conditions (including weakness, malaise, and fatigue), dehydration, facial paralysis, migraine, homicidal ideation, bacterial infections including sepsis, hypothyroidism, hyperthyroidism, and psoriasis have been reported.

The following patients are contraindicated: Allergic to pegylated interferon-2b or any interferon or excipients Pregnant women. Do not start the combination therapy of this product and ribavirin before obtaining a negative pregnancy reaction result Male patients whose spouses are pregnant cannot use this product and ribavirin in combination therapy Autoimmune hepatitis or a history of autoimmune diseases Decompensated liver function Patients with severe renal insufficiency (creatinine clearance 50ml/min) when using the drug in combination

No pharmacokinetic interaction between this product and ribavirin was found in multiple-dose pharmacokinetic studies. The results of single-dose pharmacokinetic studies of this product showed that it had no effect on the activity of cytochrome P450 enzymes CYP1A2, CYP2C8/9, CYP2D6, CYP3A4 or liver N-acetyltransferase. In addition, there are literature reports that when CYP1A2 substrates (such as theophylline) are used with other interferons, their clearance is reduced by 50%. Therefore, care should be taken when this product is used with drugs related to CYP1A2 metabolism. If the patient is infected with HIV and receives highly active antiretroviral therapy (HAART) at the same time, the possibility of lactic acidosis will increase. This product and ribavirin should be used with caution in patients receiving HAART.

Must be stored at 2-8oC, not frozen. Keep away from children. The prepared solution must be used within 24 hours at 2-8oC. Unused solution must be discarded. Do not use if the solution changes color. Do not use after the expiration date.

80μg/vial