Pegylated interferon α-2b injection

Mechanism of action: This product is a long-acting interferon formed by combining recombinant human interferon α2b (hereinafter referred to as ordinary interferon) with polyethylene glycol (40kDY type). Interferon can bind to specific α-interferon receptors on the cell surface, trigger complex signal transduction pathways in cells and activate gene transcription, regulate a variety of biological effects, including inhibiting viral replication in infected cells, inhibiting cell proliferation, and having immunomodulatory effects. This product has the in vitro antiviral and antiproliferative activities of non-polyethylene glycol-bound α-interferon (ordinary interferon). Pharmacodynamics: The pharmacodynamic characteristics of this product are similar to those of natural or recombinant human α-interferon, but the pharmacokinetics are very different. The structure of the polyethylene glycol (40kDY type) part directly affects the clinical pharmacological characteristics, because the size and branched structure of the polyethylene glycol part determine the absorption, distribution and elimination characteristics of the drug. Toxicological studies: Long-term toxicity test in monkeys: After administration, the body temperature, WBC, PLT, Ret, etc. of animals in each dose group showed transient changes, and no obvious drug toxicity reactions were observed in animals in each group. The dose of this product that has no obvious toxicity in crab-eating monkeys after repeated subcutaneous injection is 150µg/kg/time (300µg/kg/week). Reproductive toxicity test - teratogenic sensitive period toxicity test: Literature research results show that interferon α2b can cause abortion in pregnant primates, so this product may have a similar effect.

Active ingredient: PEGylated interferon α-2b. Source of active ingredient: This product is made of recombinant human interferon α2b expressed in yeast system and modified with polyethylene glycol (40kDY type). Excipients: sodium chloride, sodium acetate, mannitol, aspartic acid, water for injection, sodium hydroxide to adjust pH.

Colorless clear liquid.

1. Chronic Hepatitis B This product is suitable for the treatment of chronic hepatitis B in adults. Patients cannot be in the stage of liver decompensation, and chronic hepatitis B must be confirmed by serum markers (elevated transaminase, HBsAg, HBVDNA). 2. Chronic Hepatitis C This product is used to treat adult patients with chronic hepatitis C. Patients cannot be in the stage of liver decompensation. When treating this disease, this product should be used in combination with ribavirin. When this product is used in combination with ribavirin, please also refer to the product information of ribavirin. In case of intolerance or contraindications to ribavirin, this product can be used alone for treatment.

1. Standard dose 1.1 Chronic hepatitis B The recommended dose of this product for patients with chronic hepatitis B is 180 μg each time, once a week, for a total of 48 weeks, subcutaneously injected in the abdomen or thigh. 1.2 Chronic hepatitis C The recommended dose of this product when used alone or in combination with ribavirin is 180 μg each time, once a week, subcutaneously injected in the abdomen or thigh. Ribavirin should be taken orally at the same time during combined treatment. The dose of ribavirin combined with this product depends on the viral genotype: the dose for genotype 2 or 3 is 800 mg orally per day; the dose for genotype 1 or other genotypes is 1000 mg (<75 kg) or 1200 mg (≥75 kg) per day based on body weight. Ribavirin should be taken with meals. Treatment course of chronic hepatitis C: The treatment course of chronic hepatitis C combined with ribavirin depends on the viral genotype, 24 weeks for genotype 2 or 3, and 48 weeks for genotype 1 or other genotypes (see Table 1). Prediction of HCV response after 4 and 12 weeks of treatment For all patients who did not show a viral response within 4 weeks of treatment with this product combined with ribavirin [HCV RNA did not drop below the detection limit (15 IU/ml), or at least did not drop to less than one percent of the baseline (2log10)], the probability of not achieving a sustained viral response was about 30% [29.4% (5/17) for genotype 2/3 patients and 31.9% (46/144) for non-genotype 2/3 patients]; for all patients who showed a viral response within 4 weeks of treatment, the probability of achieving a sustained viral response exceeded 90% [90.2% (111/123) for genotype 2/3 patients and 93.6% (131/140) for non-genotype 2/3 patients, see Table 2]. For non-genotype 2/3 patients with genotype 1 who did not show an early viral response after 12 weeks of treatment with this product, it is very likely that they will not be able to achieve a sustained viral response when continuing treatment (12/13, see Table 3). Therefore, for these patients who do not achieve early viral response, treatment termination should be considered. Among the 140 patients with genotype 2/3, 137 had a viral response within 12 weeks of treatment; among the 3 patients who did not achieve a viral response, only 1 did not achieve a sustained viral response, as shown in Table 3. Therefore, patients with genotype 2/3 should be treated for 24 weeks regardless of whether they have a viral response after 12 weeks of treatment. 2. Dose adjustment in case of adverse reactions Principles of dose adjustment For patients who must adjust the dose due to moderate and severe adverse reactions (including clinical manifestations and/or abnormal laboratory indicators), the initial dose is generally reduced to 135μg, but in some cases the dose needs to be reduced to 90μg or 45μg. As adverse reactions are alleviated, it can be considered to gradually increase or return to the initial dose (see [Precautions]). 2.1 Hematological Indicators Neutrophils: When the neutrophil count (ANC) is less than 0.75×109/L, a dose reduction should be considered; when the neutrophil count is less than 0.5×109/L, temporary discontinuation of the drug should be considered until the neutrophil count recovers to greater than 1.0×109/L, then treatment can be resumed. 90μg should be used when treatment is restarted, and the neutrophil count should be monitored. Platelets: When the platelet count is less than 50×109/L, the dose of this product should be reduced to 90μg; when the platelet count is less than 25×109/L, discontinuation of the drug should be considered. Hemoglobin: Patients without obvious cardiovascular disease have hemoglobin <100g/L and ≥85g/L; or when the patient's cardiovascular disease is stable and the hemoglobin drops ≥20g/L within any 4 weeks during treatment, the ribavirin dose is reduced for the first time (by reducing the dose by 200mg/day), and rechecked after 1 to 2 weeks. When the hemoglobin returns to 100g/L, the ribavirin dose before the reduction is restored; rechecked after 2 weeks, if the hemoglobin fails to return to 100g/L (hemoglobin is still <100g/L and ≥85g/L), the dose is reduced for the second time (continue to reduce the dose by 200mg/day). If the hemoglobin of the subject after dose adjustment is >100g/L and maintained for more than 4 weeks, ribavirin can be restored to the full dose; if the hemoglobin is still <100g/L and ≥85g/L 2 weeks after the dose adjustment, ribavirin is maintained at the reduced dose. If hemoglobin is <85g/L, ribavirin should be suspended. Recheck after 1 week. When hemoglobin is >100g/L, resume the initial dose of ribavirin. When hemoglobin is <100g/L and ≥85g/L, reduce ribavirin by 200mg/day compared with the initial dose. If hemoglobin returns to 100g/L after the dose reduction, the initial dose of ribavirin can be resumed. When hemoglobin is <100g/L and ≥85g/L, reduce the dose again. If ribavirin is intolerant, monotherapy with this product can be continued (see [Dosage and Administration]). When this product is used in combination with ribavirin, please refer to the instructions for dose adjustment when adverse reactions occur with ribavirin. 2.2 Liver function Liver function often fluctuates in patients with chronic hepatitis. As with other α-interferons, elevated alanine aminotransferase (ALT) may occur after treatment with this product, including patients with improved viral response. When ALT continues to rise in patients with hepatitis C, the dose should be reduced to 135 μg. After the dose reduction, if ALT continues to rise, or if bilirubin rises or liver function decompensation occurs, drug discontinuation should be considered. Transient ALT rebound is common in patients with chronic hepatitis B. The rebound indicates immune clearance (seroconversion). If treatment continues during the ALT rebound period, consideration should be given to increasing the frequency of liver function monitoring. If the dose of this product is reduced or treatment is temporarily stopped, conventional treatment can be resumed when ALT returns to normal (see [Precautions]).

The frequency and severity of adverse reactions of this product are similar to those of ordinary interferon. All adverse reactions that may occur with ordinary interferon α2b may occur with this product, but compared with ordinary interferon, hematological adverse reactions of this product are more common. 1. Adult patients with chronic hepatitis B This product's large-scale multicenter, randomized, open, positive drug-controlled Phase III clinical trial (B0176) compared the safety of this product and Pegasys in the treatment of adult patients with chronic hepatitis B, see Table 4. In the clinical trial of this product for the treatment of chronic hepatitis B, the safety is similar to that of the treatment of chronic hepatitis C. Most adverse reactions are mild or moderate and are not affected by treatment. The most common adverse reactions of this product include fever, fatigue, joint pain, myalgia, headache, dizziness, decreased appetite, nausea, hair loss, decreased neutrophil count, gingival bleeding, cold and heat intolerance, and increased alanine aminotransferase. Table 5 lists the most common adverse reactions (incidence ≥ 10%) of this product and Pegasys in the treatment of adult patients with chronic hepatitis B. Common adverse reactions (frequency ≥1% but 10%) that occur during the treatment of chronic hepatitis B with this drug include: (1) Blood and lymphatic system diseases: thrombocytopenia, granulocytopenia; (2) Heart organ diseases: palpitations; (3) Ear and labyrinth diseases: tinnitus; (4) Endocrine system diseases: hyperthyroidism, hypothyroidism; (5) Eye organ diseases: retinal hemorrhage, eye pain, dry eyes, retinal exudation, blurred vision, decreased visual acuity, conjunctival congestion, eye discomfort, visual fatigue; (6) Gastrointestinal system diseases: upper abdominal pain, vomiting, dry mouth, abdominal pain, abdominal distension, oral ulcers, diarrhea, abdominal discomfort; (7) Systemic abnormalities and local reactions to injection : chest discomfort, fatigue, flu-like illness, chest pain, erythema at the injection site, itching at the injection site, feeling of cold, chills, feeling of fever, local reaction at the injection site, pain at the injection site, rash at the injection site, swelling at the injection site; (8) Infections and invasive diseases: nasopharyngitis, pharyngitis; (9) Various examinations: decreased platelet count, decreased white blood cell count, increased aspartate aminotransferase; (10) Muscle, bone and connective tissue diseases: back pain, limb pain or discomfort, muscle weakness; (11) Nervous system abnormalities: insomnia, drowsiness, poor sleep quality, taste disorders, memory impairment, decreased sensation, drowsiness; (12) Psychiatric diseases: irritability, anger, mood changes, depression, Fatigue; (13) Reproductive system and breast diseases: excessive menstrual flow, decreased menstruation; (14) Respiratory, chest and mediastinal abnormalities: cough, epistaxis, oropharyngeal pain, dyspnea; (15) Skin and subcutaneous tissue abnormalities: rash, itching, night sweats, dry skin, allergic dermatitis; The following adverse reactions were also observed in clinical trials of this product for the treatment of chronic hepatitis B (frequency 1%): (1) Blood and lymphatic system diseases: lymphadenopathy, splenomegaly, neutropenia; (2) Heart organ diseases: supraventricular extrasystoles, ventricular extrasystoles, increased heart rate; (3) Ear and labyrinth diseases: ear pain, ear pruritus, vertigo; (4) Eye organ diseases: arteriosclerotic retinopathy (5) Gastrointestinal system diseases: aphthous oral mucositis, constipation, enteritis, blood in the stool, gingival pain, gingival atrophy, gingival swelling, dry lips, chapped lips, cheilitis, nausea, retching, anal pain, anal fissure, anal pruritus, functional gastrointestinal disorder, bad breath, oral discomfort, oral hypoesthesia, upper abdominal discomfort, glossitis, food poisoning, gastrointestinal disorder, gastroesophageal reflux disease, lower abdominal pain, indigestion, tooth discomfort, toothache, gingivitis, dry stool, hemorrhoids, lip erosion, belching, hunger; (6) Systemic Abnormalities and local reactions to injection: discomfort, slow reaction, high fever, thirst, pain, peripheral edema, local allergy at the injection site, and nodules at the injection site; (7) Hepatobiliary system diseases: pain in the liver area, fatty degeneration of the liver, discomfort around the liver, and jaundice; (8) Immune system diseases: decreased immune response; (9) Infections and infectious diseases: tonsillitis, molluscum contagiosum, tinea cruris, onychomycosis, conjunctivitis, oral herpes, influenza, upper respiratory tract infection, otitis externa, vulvovaginal candidiasis, gastroenteritis, pulpitis, and otitis media; (10) Various injuries, poisonings, and surgical complications: skin injuries, nail lacerations, and testicular injuries; (11) Various examinations: elevated α1-fetoprotein, elevated γ-glutamic acid, and elevated α-fetoprotein. Increased acyltransferase, increased conjugated bilirubin, positive antinuclear antibodies, increased urine output, presence of urine protein, abnormal urine test, microalbuminuria, decreased blood albumin, decreased blood thyroid stimulating hormone, increased blood thyroid stimulating hormone, increased blood bilirubin, decreased hemoglobin, increased blood alkaline phosphatase, abnormal funduscopy, decreased free thyroxine, increased free thyroxine, decreased free triiodinated thyroxine, increased free triiodinated thyroxine; (12) Metabolic and nutritional diseases: hunger, decreased food intake, increased appetite, weight loss; (13) Muscle, bone and connective tissue diseases: bone pain, muscle spasms, myositis, spinal pain, neck pain, costochondritis, coccyx pain, chest Musculoskeletal pain, axillary lumps, herniated disc; (14) Benign, malignant and unspecified tumors (including cysts and polyps): ocular hemangioma; (15) Nervous system diseases: hypoesthesia, migraine, postural dizziness, head discomfort, nystagmus, decreased level of consciousness, tremor, attention disorder, intraspinal meningeal cyst; (16) Psychiatric diseases: eccentricity, agitation, anxiety, tension, psychogenic vomiting, emotional volatility, high spirits, difficulty falling asleep, sleep disorders, decreased libido, depression, irritability, abnormal dreams; (17) Kidney and urinary system diseases: urgency, frequency, difficulty urinating, pigmenturia, nocturia; (18) Reproductive system and breast diseases: erectile dysfunction disorders, pelvic pain, breast pain, breast hyperplasia, vaginal bleeding, frequent menstruation, menstrual disorders, delayed menstruation; (19) respiratory, chest and mediastinal abnormalities: dry nose, rhinorrhoea, nasal congestion, dysphonia, allergic rhinitis, shortness of breath, hemoptysis, sputum, increased sputum, pharyngeal diseases, dry throat, hiccups; (20) skin and subcutaneous tissue abnormalities: hyperhidrosis, general itching, cold sweat, hair color change, pityriasis rosea, skin pain, dermatitis, itchy rash, seborrhea, papules, neurodermatitis, eczema, dandruff, petechiae, nail lesions, purpura, urticaria, nail necrosis, herpes, acne; (21) vascular and lymphatic diseases: pallor, flushing, facial flushing, peripheral coldness. 2. Adult patients with chronic hepatitis C This large-scale multicenter, randomized, open, positively controlled Phase III clinical trial (C0158) compared the safety of this product with that of Pegasys combined with ribavirin in the treatment of adult patients with chronic hepatitis C, see Table 6. When this product is used in combination with ribavirin, most adverse reactions are mild or moderate and the treatment is not affected. The most common adverse reactions of this product include fever, fatigue, arthralgia, myalgia, headache, dizziness, decreased appetite, nausea, hair loss, rash, itching, decreased neutrophil count, decreased hemoglobin, etc. Table 7 lists the most common adverse reactions (incidence ≥ 10%) of this product and Pegasys combined with ribavirin in the treatment of adult patients with chronic hepatitis C. Common adverse reactions (frequency ≥1% but 10%) of this product combined with ribavirin for the treatment of chronic hepatitis C in adult patients include: (1) Blood and lymphatic system diseases: anemia; (2) Cardiac abnormalities: palpitations; (3) Ear and labyrinth diseases: tinnitus; (4) Endocrine system diseases: hyperthyroidism, hypothyroidism; (5) Eye diseases: retinal hemorrhage, eye pain, dry eyes, eye discomfort, increased tearing, blurred vision, decreased visual acuity, retinal exudation; (6) Oral and gastrointestinal system diseases: dry mouth, abdominal discomfort, upper abdominal pain, diarrhea, vomiting, abdominal distension, gingival bleeding, constipation, indigestion, abdominal pain, oral ulcers, toothache, hard stools; (7) Systemic abnormalities and local reactions to injection: erythema at the injection site, chest pain, itching at the injection site, high fever, local reactions at the injection site, intolerance to cold and heat, dryness at the injection site, bleeding at the injection site, rash at the injection site, influenza-like illness, fatigue; (8) Hepatobiliary system diseases: Perihepatic discomfort, jaundice; (9) Infections and invasive diseases: nasopharyngitis, oral herpes; (10) Laboratory tests: decreased white blood cell count, positive antinuclear antibodies, decreased thyroid-stimulating hormone, increased free thyroid hormone, increased alanine aminotransferase, increased blood bilirubin; (11) Metabolic and nutritional diseases: weight loss; (12) Musculoskeletal and connective tissue diseases: back pain, limb pain, musculoskeletal discomfort, joint pain, muscle weakness; (13) Nervous system abnormalities: poor sleep quality, drowsiness, decreased sensation, sleepiness, taste disorders, memory impairment; (14) Mental system abnormalities: irritability, anger, mood changes; (15) Reproductive system and breast diseases: oligomenorrhea, frequent menstruation, excessive menstruation, delayed menstruation; (16) Respiratory, chest and mediastinal abnormalities: cough, dry throat, oropharyngeal pain, dyspnea, rhinorrhea, epistaxis, sputum; (17) Skin and subcutaneous tissue abnormalities: dry skin, herpes, itching, allergic dermatitis. The following adverse reactions were also observed in clinical trials (frequency 1%): (1) Blood and lymphatic system diseases: bone marrow failure, megaloblastic anemia, granulocytopenia, lymphadenitis, autoimmune hemolytic anemia; (2) Cardiac abnormalities: complete atrioventricular block, arrhythmia; (3) Ear and labyrinth diseases: ear pruritus, ear pain, hearing loss, motion sickness; (4) Endocrine system diseases: subacute thyroiditis; (5) Eye diseases: cataract, vitreous opacity, eye pruritus, hypertensive retinopathy, amaurosis, macular degeneration, macular lesions, conjunctival hemorrhage, chorioretinopathy, visual impairment, retinal vascular disease, dark circles under the eyes, eye swelling, eyelid edema, eyelid erosion, eyelid edema, eyelid pruritus, conjunctival congestion, conjunctivitis, retinal Diseases, photophobia, blepharitis; (6) Oral and gastrointestinal system diseases: gingival pain, dry lips, cheilitis, large intestine bleeding, abdominal distension, retching, bad breath, increased bowel movement frequency, tongue ulcers, tongue coating, glossitis, gastric ulcers, gastroesophageal reflux disease, hyperacidity, gastritis, lip ulcers, blood in the stool, upper abdominal discomfort, dry tongue, hemorrhoids; (7) Systemic abnormalities and local reactions to injection: fever, coldness, chills, local swelling, thirst, peripheral edema, axillary pain, mucosal discoloration, discoloration at the injection site, injection site papules, injection site pain, injection site atrophy, injection site induration, injection site swelling, discomfort, injection site necrosis; (8) Hepatobiliary system diseases: abnormal liver function, liver disease; (9) Immune system diseases: decreased immune response; (10) Infections and infective diseases: lung infection , tuberculous pleurisy, conjunctivitis, local infection, folliculitis, urinary tract infection, sepsis, impetigo, upper respiratory tract infection, pharyngitis, otitis media; (11) various examinations: elevated aspartate aminotransferase, elevated blood thyroid stimulating hormone, abnormal funduscopy, elevated free triiodinated thyronine, inverted electrocardiogram T wave, elevated blood glucose; (12) metabolic and nutritional diseases: hypokalemia, hyponatremia; (13) musculoskeletal and connective tissue diseases: skeletal muscle pain, neck pain, chest musculoskeletal pain, limb discomfort; (14) nervous system abnormalities: hypoesthesia, tremor, syncope; (15) mental system abnormalities: cramps, anxiety, mental abnormalities, depression, fatigue, difficulty falling asleep, depressed mood, irritability, schizophrenia-like disorder, schizophrenia; (1 6) Kidney and urinary system diseases: frequent urination, pigmenturia; (17) Reproductive system and breast diseases: decreased menstruation, menstrual disorders, irregular menstruation, vaginal discharge; (18) Respiratory, chest and mediastinal abnormalities: nasal congestion, tonsillar hypertrophy, shortness of breath, pharyngeal erythema, throat irritation, oropharyngeal discomfort, increased upper respiratory tract secretions, increased sputum; (19) Skin and subcutaneous tissue abnormalities: alopecia areata, macules, macular rash, lichen planus, night sweats, hyperhidrosis, erythema, erythema nodosum, skin peeling, skin tightness, skin erosion, dermatitis, itchy rash, papules, itchy generalized skin, generalized rash, pigmentation abnormalities, eczema, blisters, lichenoid keratosis, petechiae, seborrheic dermatitis, purpura, urticaria, scabs, psoriasis; (20) Vascular and lymphatic diseases: hot flashes, facial flushing. Anti-interferon antibodies In the Phase II and Phase III clinical trials of this product for the treatment of chronic hepatitis B, the production rate of interferon-α binding antibodies was 2.0% (12/614) for this product and 3.3% (10/303) for Pegasys, with no significant difference between the two (P=0.2103); the production rate of interferon-α neutralizing antibodies was 0.0% (0/614) for this product and 1.0% (3/303) for Pegasys, with a significant difference between the two (P=0.0358). None of the subjects with baseline and newly added interferon-α neutralizing antibody positive achieved HBeAg seroconversion, and the situation of Pegasys and Pegasys was similar. The production of interferon-α neutralizing antibodies did not affect the safety of this product and Pegasys. In the Phase II and Phase III clinical trials of this product combined with ribavirin for the treatment of chronic hepatitis C, among patients with negative baseline anti-interferon α binding antibodies, the production rate of new binding antibodies was 5.8% (35/608) for this product and 8.8% (26/296) for Pegasys, with no significant difference between the two (P=0.089); the production rate of new neutralizing antibodies against interferon α was 0.5% (3/608) for this product and 4.1% (12/296) for Pegasys, with a significant difference between the two (P=0.0003). The newly generated neutralizing antibodies against interferon α did not affect the efficacy or safety of this product and Pegasys, and the baseline neutralizing antibodies against interferon α significantly affected the response of HCV RNA in the treatment of chronic hepatitis C by this product and Pegasys. Since the results of antibody detection are affected by multiple factors such as background disease, detection method, sample collection time and sample processing, and concomitant medication, it is necessary to be cautious when comparing the antibody incidence in different trials.

Hypersensitivity to the active ingredient, interferon-α or any excipient of this product; autoimmune chronic hepatitis; severe liver dysfunction or decompensated cirrhosis; history of severe heart disease, including unstable or uncontrolled heart disease within 6 months (see Precautions); severe mental illness or history of severe mental illness, mainly depression; pregnancy and breastfeeding; severe renal insufficiency when used in combination. When this product is used in combination with ribavirin, please also refer to the [Contraindications] section in the ribavirin instructions.

Precautions for children: The use of this drug in patients under 18 years of age has not been adequately studied. Precautions for pregnancy and lactation: There is no data on the use of this product in pregnant women. The potential risk of this product to human pregnancy is unknown. This product is contraindicated during pregnancy (see [Contraindications]). Patients should take effective contraceptive measures during treatment with this product. Ribavirin causes significant teratogenicity and embryotoxicity in all animal species. Ribavirin is contraindicated for pregnant women or males whose sexual partners are pregnant. Female patients treated with ribavirin and sexual partners of male patients should pay special attention to avoid pregnancy. Any contraceptive measure may fail, so it is crucial that women of childbearing age and their sexual partners take two effective contraceptive measures during treatment and within 6 months after the end of treatment. When combined with ribavirin, please also refer to the instructions for ribavirin (especially [Contraindications], [Precautions], and [Use in Pregnant and Lactating Women]). It is not clear whether this product and its excipients are excreted in human milk, so the decision to stop breastfeeding or treatment should be based on the importance of drug treatment to the mother. Elderly precautions: Use of this drug in elderly patients has not been adequately studied.

Adequate drug interaction studies have not been performed.

Sealed, protected from light, stored and transported at 2-8°C. Do not freeze or violently shake. Keep out of reach of children.

135 micrograms (500,000 U)/0.5 ml/tube (prefilled)

Tentative 36 months

Xiamen Amoytop Biotech Co., Ltd.

• Founded in:

  1996-08-07

• Address:

  No. 330, Wengjiao Road, Xinyang Industrial Zone, Haicang, Xiamen

• Tax NO.:

  913502002600603688

• Registered Funds:

  406.8 million yuan

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