Please read the instruction manual carefully and use it under the guidance of a physician
[Drug Name] Common Name: Ribavirin Granules [Chinese Pinyin: Libaweilin Keli] English Name: Ribavirin Granules
Ingredients
The main component of this product is ribavirin.
Chemical name: 1- β- D-furanribosyl-1H-1,2,4-triazol-3-carboxamide
Molecular formula: C: HzN0s
Molecular weight: 244.21
【 Description 】 This product is a white or almost white soluble particle.
【 Indications 】 This product is suitable for viral pneumonia and bronchitis caused by respiratory syncytial virus, as well as skin herpes virus infection.
【 Specification 】 50mg 【 Usage and Dosage 】
This product is completely dissolved in warm water and taken orally.
1. Used for viral respiratory infections: 015g once in adults, 3 times a day, continuous use for 7 days.
2. For skin herpes virus infection: 03g once in adults, 3-4 times a day, continuous use for 7 days.
The main toxicity of ribavirin is hemolytic anemia, with a decrease in hemoglobin levels within the first 1-2 weeks after oral treatment. About 10% of patients may experience adverse cardiovascular reactions. Hemoglobin should be frequently monitored before and during treatment. Patients with thalassemia or sickle cell anemia are not recommended to use ribavirin. Patients with symptoms of pancreatitis or confirmed pancreatitis should not use ribavirin. It has been reported that taking ribavirin in patients with anemia can cause fatal or non fatal myocardial damage, so patients with a history of heart disease or obvious symptoms of heart disease should not use ribavirin. If any worsening symptoms of heart disease occur when using ribavirin, the medication should be stopped immediately and corresponding treatment should be given. The general systemic adverse reactions observed in clinical trials related to ribavirin include fatigue, headache, weakness, fatigue, chest pain, fever and chills, and flu symptoms. Neurological symptoms: Dizziness: Digestive system symptoms include decreased appetite, stomach discomfort, nausea and vomiting, mild diarrhea, constipation, indigestion, etc; Symptoms of musculoskeletal system include muscle pain and joint pain; The mental system includes insomnia, emotional state, irritability, depression, attention deficit, neuroticism, etc; Respiratory system symptoms include difficulty breathing, rhinitis, etc.: hair loss, rash, itching, etc. in the skin accessory system; Additionally, abnormal taste and hearing were observed.
Taboos
1. Prohibited for those who are allergic to any ingredients in this product.
2. Prohibited for pregnant women.
3. Prohibited for patients with autoimmune hepatitis.
【 Precautions 】
1. Regular blood routine (hemoglobin level, white blood cell count, platelet count), blood biochemistry (liver function, TSH) tests, especially hemoglobin tests (including before start, treatment 2 weeks, and 4 weeks). Conduct monthly pregnancy tests on potential pregnant women.
2. Patients with severe anemia should use it with caution. Patients with thalassemia or sickle cell anemia are not recommended to use ribavirin. Patients with symptoms of pancreatitis or confirmed pancreatitis should not use ribavirin. Patients with a history of heart disease or obvious symptoms of heart disease should not use ribavirin. If any worsening symptoms of heart disease occur after using ribavirin, the medication should be stopped immediately and corresponding treatment should be given.
3. Patients with liver and kidney dysfunction should use with caution. Ribavirin is not recommended for patients with creatinine clearance rate<50m1/min.
4. Ribavirin can interfere with diagnosis and cause an increase in blood bilirubin (up to 25%), while high doses can cause a decrease in hemoglobin.
5. Medication should be administered as early as possible, within the first 3 days of respiratory syncytial virus pneumonia. Ribavirin should not be used in patients who have not been diagnosed with respiratory syncytial virus infection in the laboratory.
【 Pregnant and lactating women's medication 】
Adequate animal research has confirmed that ribavirin has significant mutagenicity and embryotoxicity (can occur below 1/20 of human dosage). Ribavirin can cause congenital malformations or death in fetuses. Before treatment begins, during treatment, and at least 6 months after discontinuation, both males and females taking ribavirin should avoid pregnancy. Pregnant individuals should use at least two or more effective contraceptive methods, and should immediately inform a doctor once pregnant. Pregnant women are prohibited from using ribavirin. A small amount of medication is excreted through breast milk, and it is not recommended for lactating women to take ribavirin due to its potential danger to infants.
There is currently a lack of detailed research data on pediatric medication.
[Elderly medication] Adequate clinical studies have not yet been conducted on elderly patients aged 65 and above. The likelihood of anemia occurring with the use of ribavirin in elderly patients is higher than that in young patients. Elderly patients often experience decreased kidney function, which can easily lead to accumulation. Therefore, it is not recommended for elderly patients to take ribavirin.
【 Drug Interaction 】 Ribavirin can inhibit the conversion of zidovudine to active zidovudine phosphate, therefore, when used together with zidovudine, it has an antagonistic effect.
Excessive medication can cause heart damage in large doses, and can lead to breathing difficulties, chest pain, and other symptoms in patients with respiratory diseases (chronic obstructive pulmonary disease or asthma).
[Pharmacology and Toxicology] Pharmacological effects
Ribavirin is a synthetic nucleoside antiviral drug. In vitro cell culture experiments have shown that Ribavirin has a selective inhibitory effect on respiratory syncytial virus (RSV). The mechanism of action of Ribavirin is not yet clear, but its in vitro antiviral activity can be reversed by guanine and xanthine nucleosides, suggesting that Ribavirin may act as a metabolic analogue of these cells.
Toxicological research
Repeated administration toxicity: Oral administration of ribavirin at doses of 30, 36, and 120 mg/kg in mice, rats, and monkeys for 4 weeks or longer can cause heart damage.
Genetic toxicity: Ribavirin concentrations of 0.015 and 0.03-5.0mg/ml, respectively, can increase cell transformation and mutation of Balb/c3T3 (fibroblasts) and L5178Y (lymphoma) in mice under conditions without metabolic activators. The concentration range is 3.75-10.0mg/ml, and under the condition of adding metabolic activators, there is a certain increase (3-4 times) in the mutation rate of L5178Y cells. The results of the mouse micronucleus test indicate that intravenous injection of ribavirin with a dosage range of 20-200mg/kg has a crack inducing effect. In the explicit lethal test, the dose range of intraperitoneal injection of ribavirin in rats was 50-200mg/kg, and there was no mutagenic effect observed for 5 consecutive days.
Reproductive toxicity: When administered to male mice at a dose range of 35-150mg/kg, it can cause significant atrophy of the seminiferous tubules, a decrease in sperm concentration, and an increase in the number of sperm with abnormal morphology. After stopping the medication for 3-6 months, the ability to produce sperm partially recovered. Several other toxicity tests also suggested that oral administration of ribavirin as low as 16mg/ko to adult rats can cause honey pill damage (atrophy of the seminiferous ducts), and no lower dose studies have been conducted. The reproductive ability of female animals has not been studied yet. Studies on animals of different species have confirmed that ribavirin has significant potential toxicity for teratogenicity and/or reduction. The single oral dose of this product to hamsters is 2.5mg/kg or higher, while the doses for home immunization or rats are 0.3mg/kg and 1.0mg/kg, respectively. The results have confirmed that teratogenic effects mainly occur in the skull, palate, eyes, limbs, jawbones, bones, and gastrointestinal tract, and the incidence and severity increase with the increase of dose. The survival rate of fetuses and offspring decreases. The dose of ribavirin causing embryonic death in rabbits and rats is 1mg/kg, and its non teratogenic dose is 0.1 and 0.3mg/kg, respectively (calculated based on surface area, equivalent to equivalent human doses of 0.015 and 0.04mg/kg, respectively).
Carcinogenicity: In rats, a dose of 16-200mg/kg of ribavirin was administered through co administration. Long term research results suggest that ribavirin may induce benign breast, pancreatic, pituitary, and adrenal tumors. The preliminary carcinogenic tests conducted in mice and rats at 18-24 months were not the final results, but these tests confirmed that the administration of ribavirin at doses of 20-75 and 10-40mg/kg, respectively, was associated with long-term administration of ribavirin. The vascular damage and retinal reductase degeneration observed in mice and rats were also associated with long-term administration of ribavirin.
Pharmacokinetics
Domestic research on human bioavailability shows that ribavirin granules are rapidly absorbed after oral administration, and the blood drug concentration can reach its peak within 60-90 minutes. After entering the body, ribavirin undergoes phosphorylation to produce an active metabolite - ribavirin monophosphate. The elimination half-life is approximately 24 hours. Ribavirin can remain in red blood cells. Mainly excreted by the kidneys, with only a small amount excreted with feces. According to the Physician's Desk Reference (54 edition), the pharmacokinetic properties of single and multiple doses of ribavirin in patients with chronic hepatitis are summarized in Table 1, which shows rapid and complete absorption of ribavirin after oral administration. However, due to the first pass effect, the average absolute bioavailability was 64% (44). There is a linear relationship between the dose of ribavirin and AUCO-t (AUC from time 0 to the final test point) within the dose range of 200-1200mg taken in a single dose. However, the relationship between dose and Cmax shows a linear curve, and tends to asymptote when a single dose is above 400-600mg. After multiple oral administration, a 6-fold accumulation of ribavirin can be observed in plasma (based on AUC12hr). Continuous oral administration of 600mg twice a day for approximately four weeks can reach steady state, with an average plasma concentration of 2200 (37%) ngm1. The average half-life measured after discontinuation is 298 (30%) hours, indicating that the product may be slowly eliminated from the non plasma portion.
The effect of food on the absorption of ribavirin: In single dose drug studies, when ribavirin was consumed together with a high-fat diet (841 kcal, 53.8 g fat, 31.6 g protein, and 57.4 g carbohydrates), AUCtf and Cmax increased by 70%. There is not yet sufficient data to confirm the clinical relevance of these results. There was no explanation regarding food consumption during clinical efficacy studies. (See Usage and Dosage)
The effect of antacids on the absorption of ribavirin: Taking an antacids containing magnesium, aluminum, and dimethyl silicone oil while taking ribavirin can lead to a 14% decrease in the average AUCtf of ribavirin. The clinical relevance of single dose study results is unknown. [See Table 1]
Ribavirin can enter red blood cells and has been confirmed to enter through ES type nucleoside carriers. In essence, this type of carrier exists in all types of cells and can lead to an expansion of distribution volume. Ribavirin binds less to plasma proteins.
Ribavirin has two metabolic pathways: () reversible phosphorylation in nucleated cells, and () metabolic pathways that include ribosylation and amine hydrolysis to produce a tripyrrole carboxylate metabolite. Ribavirin and its metabolites of tripyrrole amide and tripyrrole carboxylic acid are excreted through the kidneys. After oral administration of 600mg 14C ribavirin, approximately 61% and 12% of the samples were eliminated in urine and feces within 336 hours, respectively. Among them, only 17% were untransformed ribavirin.
The results of in vitro metabolism studies on human and rat liver microsomes indicate that ribavirin is rarely or almost not metabolized through cytochrome P450, with only a small amount of potential enzyme drug interactions. Special population
Renal dysfunction: After oral administration of a single dose (400mg) of ribavirin to HCV infected patients with varying degrees of renal dysfunction, the AUCtf value of patients with creatinine clearance values between 10-30m1/min was three times higher than that of the control group (creatinine clearance>90m1/min), and twice higher than that of patients with creatinine clearance values between 30-60m1/min, all of which were due to the decrease in clearance rate and the reduction in drug elimination. It is difficult to predict the pharmacokinetic parameters of ribavirin after multiple administration. Hemodialysis cannot effectively clear ribavirin. Patients with creatinine clearance rate<50m1/min. It is not recommended to use ribavirin (see precautions).
Liver dysfunction: Patients with mild, moderate, and severe liver dysfunction (classified as ABC according to Chai1d pugh) who received a single dose (600mg) of ribavirin orally were compared with those who did not
There is no significant difference in the average AUCtf value compared to the control group. However, the average Cmax value increases with the severity of liver dysfunction, and patients with severe liver dysfunction have Cmax twice as large as the control group.
Pediatric patients: Detailed pharmacokinetic studies have not yet been conducted on pediatric patients. Elderly patients: Pharmacokinetic studies have not yet been conducted on elderly patients
Gender: No significant gender pharmacokinetic differences were found in single dose studies conducted on 18 male and 18 female patients.
【 Storage 】 Sealed and stored in a dry place. 
[Packaging] Packaging material: Medicinal composite film
Packaging specifications: 18 bags/box
【 Validity 】 24 months
[Implementation Standards] Part 2 of the 2020 edition of the Chinese Pharmacopoeia
[Approval Number] National Pharmaceutical Approval Letter H20083309
Listing permit holder: Guizhou Liangji Pharmaceutical Co., Ltd
Address of Listing Permit Holder: Gujiao Town Pharmaceutical Industrial Park, Longli County, Qiannan Buyi and Miao Autonomous Prefecture, Guizhou Province
Production enterprise: Guizhou Liangji Pharmaceutical Co., Ltd
Production address: Medical Industry Park, Gujiao Town, Longli County, Qiannan Buyi and Miao Autonomous Prefecture, Guizhou Province
Postal Code: 551206
Phone number: (0854) 5670149
Fax number: (0854) 5670556
Website: wwwlangjiyaoye.com