Ribavirin injection

[Drug Name]

Generic name: Ribavirin Injection

English Name: Ribavirin Injection

Chinese Pinyin: Libaweilin Zhusheye

【Certificate】

The active ingredient of this product isRibavirin, and its excipients are sodium chloride and water for injection.

Chemical name: 1-β-D-Furanosyl -1H-1, 2, 4-triazole-3-carboxamide.

Chemical structure:

Molecular formula:C₈H₁₂N₄O₅

Molecular weight: 244.21

【SexCondition】

This product is a colorless, clear liquid.

【Indications】

Antiviral drugs. Used for viral pneumonia and bronchitis caused by respiratory syncytial virus.

【Specification】1ml:100mg

【Dosage and Administration】

Intravenous infusion. Dilute with 5% glucose injection or 0.9% sodium chloride injection to make a solution containing 1mg per 1ml, and slowly infuse intravenously. For adults, the daily dose is 500 to 1000mg, and for children, it is 10 to 15mg/kg, administered in two doses. Each intravenous drip should last more than 20 minutes, with a treatment course of 3 to 7 days.

【Adverse Reactions】

The main toxicity of ribavirin is hemolytic anemia, which occurs within the first 1-2 weeks after oral treatment, characterized by a decrease in hemoglobin, red blood cells, and white blood cells. About 10% of patients may experience adverse reactions related to the heart and lungs. Hemoglobin should be frequently monitored before, during, and after treatment. This product is not recommended for patients with thalassemia or sickle cell anemia. Patients with symptoms of pancreatitis or confirmed pancreatitis should not use this product. There have been reports of patients with anemia taking this product leading to fatal or non-fatal myocardial damage, so patients with a history of heart disease or obvious heart disease symptoms should not use this product. If any symptoms of heart disease deterioration occur while using this product, it should be discontinued immediately, and appropriate treatment should be given. General systemic adverse reactions observed in clinical trials of ribavirin (including oral formulations) include fatigue, headache, weakness, malaise, chest pain, fever, chills, and flu-like symptoms.

Nervous system: dizziness;

Digestion: decreased appetite, stomach discomfort, nausea and vomiting, mild diarrhea, constipation, indigestion, etc.;

Musculoskeletal: muscle pain, joint pain;

Mental: insomnia, emotional instability, irritability, depression, attention deficit, neuroticism, etc.;

Breathing: difficulty breathing, rhinitis, etc.;

Skin appendages: hair loss, rash, itching, etc.;

It was also observed that there were abnormalities in taste and hearing.

At general doses, adverse reactions are rare, mainly reversible anemia, which can slowly recover after discontinuation; a small number of patients may experience symptoms such as thirst, loose stools, stomach pain, insomnia, and irritability; at high doses, it can inhibit hemoglobin synthesis, cause hemolysis, increase reticulocytes, pneumothorax, asphyxia, and low blood pressure. Occasionally, there may be decreased appetite, mild gastrointestinal reactions, dizziness, headaches, and rashes.

【Prohibition】

1, Those allergic to any ingredients in this product are prohibited from use. 2, Pregnant women are prohibited from use. 3, Not suitable for patients with autoimmune hepatitis. 4, Active tuberculosis is not suitable for use.

[Precautions]

1. Regularly conduct blood routine tests (hemoglobin levels, white blood cell count, platelet count), blood biochemistry (liver function, TSH) tests, especially blood drug protein tests (including before starting, at the second week of treatment, and at the fourth week). Monthly pregnancy tests for women who may be pregnant.

2Patients with severe anemia should use with caution, and this product is not recommended for patients with thalassemia or sickle cell anemia. This product should not be used by patients with symptoms of pancreatitis or those who have a confirmed diagnosis of pancreatitis. Patients with a history of heart disease or obvious heart disease symptoms should not use this product. If any symptoms of heart disease worsening occur after using this product, the medication should be stopped immediately and appropriate treatment should be given.

3, use with caution in patients with abnormal liver function. Ribavirin is not recommended for patients with a creatinine clearance of 50ml/min or less.

4, this product has certain interference with diagnosis and may cause an increase in blood bilirubin (up to 25%), and high doses may lead to a decrease in hemoglobin.

5, administer the medication as soon as possible. For respiratory syncytial virus pneumonia, medication should be given within 3 days of the onset of the disease. This product is not suitable for patients who have not been experimentally diagnosed with respiratory syncytial virus infection.

[Medication for Pregnant and Breastfeeding Women]

Sufficient animal studies have confirmed that Ribavirin has significant mutagenic and embryotoxic effects (which can occur at doses lower than 1/20 of the human dosage). This product can cause congenital malformations or fetal death. Both male and female patients taking this product should avoid pregnancy for at least 6 months before treatment, during treatment, and after discontinuation. Those who may become pregnant should use at least two effective contraceptive methods. If pregnancy occurs, they should inform their doctor immediately. This product is contraindicated in pregnant women. A small amount of the drug is excreted in breast milk, and due to the potential risks to infants, it is not recommended for breastfeeding women to take this product.

[Pediatric Medication]

Currently, there is a lack of detailed research data.

[Medication for the Elderly]

There have not been sufficient clinical studies conducted on patients aged 65 and older. The likelihood of anemia occurring in elderly patients using this product is greater than in younger patients. Elderly individuals often have decreased kidney function, which can lead to accumulation, and the use of this product is not recommended for elderly patients.

[Drug Interactions]

This product has an antagonistic effect when used with Zidovudine, as this product can inhibit the conversion of Zidovudine into its active form, zidovudine triphosphate.

[Drug Overdose]

High doses can cause cardiac damage and may lead to difficulty breathing, chest pain, etc., in patients with respiratory diseases (such as chronic obstructive pulmonary disease or asthma).

【Pharmacology and Toxicology】

Pharmacological effectsBroad-spectrum antiviral drug. It has the ability to inhibit the growth of various viruses in vitro, including respiratory syncytial virus, influenza virus, hepatitis A virus, adenovirus, etc., although its mechanism is not fully understood. This product does not alter virus adsorption, invasion, or uncoating, nor does it induce the production of interferons. After the drug enters the virus-infected cells, it is rapidly phosphorylated, and its products act as competitive inhibitors of viral synthesis enzymes, inhibiting inosine monophosphate dehydrogenase, influenza virus RNA polymerase, and mRNA guanylate transferase, leading to a reduction in intracellular guanosine triphosphate, damaging viral RNA and protein synthesis, thereby suppressing viral replication and transmission. It may also have immune effects and neutralizing antibody effects against respiratory syncytial virus.

Toxicological studiesRepeated dose toxicity: Mice, rats, and monkeys administered this product orally at doses of 30, 36, and 120mg/kg, for a duration of 4 weeks or longer, may cause cardiac damage.

Genotoxicity: At concentrations of 0.015 and 0.03-5.0mg/ml, this product can increase the cell transformation and mutation of mouse Balb/c3T3(fibroblasts)L5178Y (lymphoma) under conditions without metabolic activation. At a concentration range of 3.75-10.0mg/ml, there is a certain increase in the mutation rate of L5178Y cells when metabolic activators are added (by 3-4 times). Results from the mouse micronucleus test suggest that intravenous injection of this product at doses ranging from 20-200mg/kg has a clastogenic effect. In the dominant lethal test, intraperitoneal injection of this product in rats at doses ranging from 50-200mg/kg for 5 consecutive days did not show mutagenic effects.

Reproductive toxicity: When male mice are given doses ranging from 35-150mg/kg, it can lead to significant atrophy of the seminiferous tubules, a decrease in sperm concentration, and an increase in the number of abnormally shaped sperm. After discontinuation of the drug for 3-6 months, spermatogenic capacity partially recovers.

Other toxicity tests also suggest that adult rats given this product orally at doses as low as 16mg/kg can cause testicular damage (atrophy of the seminiferous tubules), and no studies have been conducted at lower doses. The reproductive capacity of male animals has not been studied. Research on different animal species has confirmed that this product has significant potential teratogenic and/or embryotoxic effects. Hamsters given a single oral dose of this product at 2.5mg/kg or higher, and rabbits and rats at doses of 0.3 and 1.0mg/kg respectively, have all confirmed teratogenic effects. Malformations primarily occur in the skull, palate, eyes, limbs, jaw, skeleton, and gastrointestinal tract, with the incidence and severity increasing with higher doses. The survival rate of fetuses and offspring is reduced. The dose of this product that causes embryonic lethality in rabbits and rats is 1mg/kg, with no teratogenic effects observed at doses of 0.1 and 0.3mg/kg (calculated based on body surface area, equivalent to human equivalent doses of 0.015 and 0.04mg/kg).

Carcinogenicity: Long-term studies in rats with doses of 16-200mg/kg of this product suggest that it may induce benign tumors of the breast, pancreatic duct, pituitary gland, and adrenal gland. Preliminary carcinogenic tests in mice and rats over 12-18 months are not final results, but these tests confirm that doses of 20-75 and 10-40mg/kg administered to mice and rats, respectively, are associated with vascular damage and retinal aldehyde reductase degeneration related to long-term administration of this product.

Pharmacokinetics

30Intravenous administration of Ribavirin 800mg within 30 minutes, the plasma concentration (μg/ml) after 5 minutes is 17.8±5.5, and the plasma concentration after 30 minutes is 42.3±10.4. Ribavirin enters the body and rapidly distributes to various parts, with concentrations in respiratory secretions mostly higher than blood drug concentrations. It can cross the blood-brain barrier, and after long-term use, the drug concentration in cerebrospinal fluid can reach 67% of the simultaneous blood drug concentration. This product can accumulate in red blood cells for several weeks, can cross the placenta, and enter breast milk. It binds almost not at all to plasma proteins. It is metabolized in the liver and mainly excreted through the kidneys. During intravenous administration within a 0-48 hour interval, 16.7%±10.3% of the drug is excreted unchanged in urine, with 6.2%±1.7% excreted as metabolites. The elimination from the body is slow, and even after 4 weeks of discontinuation, it cannot be completely cleared from the body.

【Storage】 Sealed preservation.

【Packaging】 Ampoule packaging, 10 pieces/ box

【Validity Period】 24 months

[Implementation Standard] 'Pharmaceutical Standards of China' 2020 Edition, Volume Two

【Approval Number】 National Medicine Standard CodeH20067579

【Drug Marketing Authorization Holder】/【Manufacturing Enterprise】

Name:Guizhou Tiandi Pharmaceutical Co., Ltd.

Address: No. 6, Baokang Road, Hongxing Pharmaceutical Industry Park, Dingxiao Town, Xingyi City, Qiannan Buyei and Miao Autonomous Prefecture, Guizhou Province

postal code：562400

tel：0859-3119928

Fax number: 0859-3118152

Website: www.gztiandi.com