Ribavirin is a manufactured simple of nucleosides with an articulated antiviral impact. Has a wide range of action against different DNA and RNA infections.
Ribavirin promptly enters into the cells influenced by the infection and is quickly phosphorylated by intracellular adenosine kinase to ribavirin monophosphate and triphosphate. These metabolites, particularly ribavirin triphosphate, have an articulated antiviral action.
The system of activity of ribavirin has not been explained. In any case, it is realized that ribavirin hinders inosine monophosphate dehydrogenase (IMP), this impact prompts a checked reduction in intracellular guanosine triphosphate (GTP), which thusly is joined by concealment of the union of viral RNA and the infection of particular proteins. Ribavirin represses the replication of new dreams, which lessens the viral load. Ribavirin specifically represses the combination of viral RNA, without smothering the amalgamation of RNA in regularly working cells.
Ribavirin is effective against many DNA and RNA viruses. The most sensitive to ribavirin DNA viruses are Simplex herpes virus, pox-virus, The virus of Marek’s illness. Insensitive to ribavirin DNA viruses are Varicella Zoster, pseudorabies, cow smallpox. The most sensitive to Ribavirin RNA viruses are: influenza A, B, paramyxovirus (parainfluenza, epidemic parotitis, Nucasl’s illness), reverses, RNA tumor viruses.
Ribavirin has activity against the hepatitis C virus (HCV). The mechanism of action of ribavirin against HCV is not fully elucidated. It is assumed that accumulating as phosphorylation, ribavirin triphosphate competitively suppresses the formation of guanosine triphosphate, thereby reducing the synthesis of viral RNAs. It is also believed that the mechanism of the synergistic effect of ribavirin and interferon alfa vs HCV is due to the increased phosphorylation of ribavirin by interferon.
Indications for use
Chronic hepatitis C (in combination with interferon alpha-2b or peginterferon alfa-2b): in primary patients previously untreated with interferon alpha-2b or peginterferon alfa-2b; when exacerbated after a course of monotherapy with interferon alpha-2b or peginterferon alfa-2b; in patients not susceptible to monotherapy with interferon alpha-2b or peginterferon alfa-2b.
Hypersensitivity, pregnancy, lactation, chronic heart failure II6-III st, myocardial infarction, renal failure (creatinine clearance less than 50 ml / min), severe anemia, hepatic insufficiency, decompensate liver cirrhosis, autoimmune diseases (incl. autoimmune hepatitis), non-treatable thyroid disease, severe depression with suicidal intent, children and adolescents (under 18 years of age).
Women of reproductive age (the onset of pregnancy is undesirable), decompensated diabetes mellitus (with attacks of ketoacidosis); chronic obstructive pulmonary disease, pulmonary embolism, chronic heart failure, thyroid diseases (including thyrotoxicosis), blood clotting disorders, thrombophlebitis, myelodepression, hemoglobinopathy (including thalassemia, sickle cell anemia), depression, propensity to suicide (including in the anamnesis), elderly age.
Dosing and Administration
Inside, without chewing and washing down with water, along with a meal of 0.8-1.2 grams per day in 2 divided doses (morning and evening). Simultaneously appoint interferon alfa-2b – subcutaneously, 3 million ME 3 times a week or peginterferon alfa 2b – subcutaneously, 1.5 μg / kg 1 time per week. When combined with interferon alpha-2b at a body weight of 75 kg, the dose of ribavirin is 1 g per day (0.4 g in the morning and 0.6 g in the evening); above 75 kg – 1.2 g per day (0.6 g in the morning and 0.6 g in the evening). When combined with peginterferon alfa-2b at a body weight less than 65 kg, the dose of ribavirin is 0.8 g per day (0.4 g in the morning and 0.4 g in the evening); 65-85 kg – 1 g per day (0.4 g in the morning and 0.6 g in the evening); more than 85 kg (0.6 g in the morning and 0.6 g in the evening).
Duration of treatment – 24 – 48 weeks; while for previously untreated patients – not less than 24 weeks, in patients with the virus of genotype 1 – 48 weeks. In patients who are not susceptible to monotherapy with interferon alpha, and also in case of relapse, at least 6 months to 1 year (depending on the clinical course of the disease and response to ongoing therapy).
From the nervous system: a headache, dizziness, general weakness, malaise, insomnia, asthenia, depression, irritability, anxiety, emotional lability, nervousness, agitation, aggressive behavior, confused consciousness; rarely – suicidal tendencies, increased smooth muscle tone, tremor, paresthesia, hyperesthesia, hypoesthesia, fainting.
It is possible to increase the severity of side effects. Treatment: withdrawal of the drug, symptomatic therapy.
Interaction with other medicines
Drugs containing magnesium and aluminum compounds simethicone reduce the bioavailability of the drug (AUC decreases by 14%, has no clinical significance).
When combined with interferon alpha-2b or peginterferon alfa-2b – synergism of action.
The appointment of ribavirin during treatment with zidovudine and/or stavudine is accompanied by a decrease in their phosphorylation, which can lead to HIV viremia and require a change in the treatment regimen.
Increases the concentration of phosphorylated metabolites of purine nucleosides (including didanosine, Abacavir) and the associated risk of developing dairy acidosis.
Does not affect the enzymatic activity of the liver with the participation of cytochrome P450.
Simultaneous food intake with a high-fat content increases the bioavailability of ribavirin (AUC and C max are increased by 70%).
It should take into account the teratogenicity of the drug, men, and women of reproductive age during treatment and for 7 months after the end of therapy should use effective contraceptive means.
Laboratory tests (clinical analysis of blood counting the leukocyte formula and number of platelets, determination of electrolytes, creatinine content, functional liver tests) should be performed before the start of therapy, for 2 and 4 weeks, and then regularly.
During treatment with ribavirin, the maximum reduction in hemoglobin in most cases occurs after 4-8 weeks from the start of treatment. If the hemoglobin falls below 110 mg/ml, the dose of ribavirin should be temporarily reduced by 400 mg per day, with a decrease in hemoglobin below 100 mg/ml, the dose should be reduced to 50% of the original dose. In most cases, recommended dose changes ensure the recovery of hemoglobin. With a decrease in hemoglobin below 85 mg/ml, the drug should be discontinued.
In an acute manifestation of hypersensitivity (hives, angioedema, bronchospasm, anaphylaxis), the drug should be discontinued immediately. Transient rashes do not serve as a basis for interrupting treatment
During treatment, people who are tired, drowsy or disoriented should refrain from driving vehicles and be practicing potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.
In connection with the possible deterioration in the function of the kidneys in elderly patients, before using the drug, it is necessary to determine the function of the kidneys, in particular, creatinine clearance.
List B. In a dry, dark place at a temperature of no higher than 25 ° C. In a place inaccessible to children.