Composition, form of production and packaging
Capsules of white color, size в„–0; the contents of the capsules are granules of white or white with a yellowish tint of color.
1 caps.
ribavirin 200 mg
[PRING] potato starch, microcrystalline cellulose, aerosil, magnesium stearate.
The composition of the capsule shell: gelatin, titanium dioxide.
6 pcs. - packings cellular planimetric (5) - packs cardboard.
6 pcs. - packings cellular planimetric (7) - packs cardboard.
6 pcs. - packings cellular planimetric (10) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (6) - packs cardboard.
30 pcs. - polymer cans (1) - packs of cardboard.
60 pcs. - polymer cans (1) - packs of cardboard.
Tablets are white or white with a yellowish tint of color, flat-cylindrical.
1 tab.
ribavirin 200 mg
[PRING] lactose, corn starch, microcrystalline cellulose, sodium croscarmellose, magnesium stearate.
6 pcs. - packings cellular planimetric (5) - packs cardboard.
6 pcs. - packings cellular planimetric (7) - packs cardboard.
6 pcs. - packings cellular planimetric (10) - packs cardboard.
10 pieces. - packings cellular planimetric (3) - packs cardboard.
10 pieces. - packings cellular planimetric (6) - packs cardboard.
10 pieces. - packings cellular planimetric (9) - packs cardboard.
30 pcs. - polymer cans (1) - packs of cardboard.
60 pcs. - polymer cans (1) - packs of cardboard.
90 pcs. - polymer cans (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
Antiviral drug, a synthetic analogue of nucleosides with a pronounced antiviral effect. Has a wide spectrum of activity against various DNA and RNA-containing viruses.
Ribavirin easily penetrates into virus-infected cells and is rapidly phosphorylated by intracellular adenosine kinase to ribavirin mono-, di- and triphosphate. These metabolites, especially ribavirin triphosphate, have a pronounced antiviral activity.
The mechanism of action of ribavirin has not been elucidated. It has been established that ribavirin inhibits inosine monophosphate dehydrogenase, this effect leads to a marked decrease in the level of intracellular guanosine triphosphate, which in turn is accompanied by suppression of the synthesis of viral RNA and virus-specific proteins. Ribavirin inhibits the replication of new virions, which reduces viral load, selectively inhibits the synthesis of viral RNA, without affecting the synthesis of RNA in normally functioning cells.
Ribavirin is active against many DNA and RNA viruses. The most sensitive to ribavirin DNA-containing viruses are: Herpes simplex virus, poks virus, Marek's disease virus. Insensitive to ribavirin, DNA-containing viruses are Varicella zoster, pseudorabies viruses, vaccinia viruses. The most sensitive to ribavirin RNA-containing viruses are: influenza A, B viruses, paramyxoviruses (parainfluenza, mumps, Newcastle disease), reoviruses, RNA-containing tumor viruses. Insensitive to ribavirin RNA-containing viruses are enteroviruses, rhinoviruses, Semlicy Forest.
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 synergistic action of ribavirin and interferon alpha against HCV is due to the increased phosphorylation of ribavirin by interferon.
PHARMACOKINETICS
Suction
After taking the drug, ribavirin is rapidly absorbed from the digestive tract. Bioavailability is more than 45%. The time to reach C max is from 1 to 1.5 hours. The time to reach a therapeutic concentration in the plasma depends on the value of the minute volume of blood. The average plasma C max value of about 5 Ојmol / L at the end of the 1 week dose at a dose of 200 mg every 8 hours and about 11 Ојmol / L at the end of the 1 week dose at a dose of 400 mg every 8 hours.
Distribution
Ribavirin is distributed in plasma, the secretion of the mucosa of the respiratory tract and red blood cells. A large amount of ribavirin triphosphate accumulates in erythrocytes, reaching a plateau by day 4 and persisting for several weeks after administration. The half-distribution period is 3.7 hours. V d - 647-802 l. When taking a course ribavirin accumulates in plasma in large quantities. The ratio of AUC for repeated and single administration is 6. A significant concentration of ribavirin (> 67%) can be detected in the cerebrospinal fluid after prolonged use. Binding to plasma proteins is negligible.
Metabolism
Ribavirin is phosphorylated in liver cells into active metabolites in the form of mono-, di-, and triphosphate, which are then metabolized to 1,2,4-triazolecarboxamide (amide hydrolysis to tricarboxylic acid and deribozylation to form a triazole carboxyl metabolite).
Excretion
Ribavirin is excreted slowly from the body. T 1/2 after a single dose of 200 mg is from 1 to 2 hours from the plasma and up to 40 days from the erythrocytes. After stopping the course of admission T 1/2 is about 300 h. Ribavirin and its metabolites are mainly excreted from the body with urine. Only about 10% is excreted with feces. In unchanged form, about 7% of ribavirin is excreted in 24 hours and about 10% in 48 hours.
Pharmacokinetics in special clinical cases
In patients with renal insufficiency, AUC and C max ribavirin increase, which is due to a decrease in true clearance.
In patients with hepatic insufficiency (class A, B and C on the Child-Pugh scale), the pharmacokinetics of ribavirin does not change.
With a single admission with food containing fats, the pharmacokinetics of ribavirin varies significantly (AUC and C max are increased by 70%).
INDICATIONS
- chronic hepatitis C (for primary therapy of previously untreated interferon alfa patients, with exacerbation after a course of interferon alfa monotherapy, in patients not susceptible to interferon alfa monotherapy), treatment is performed in combination with interferon alpha.
DOSING MODE
The drug is taken orally, without chewing and washing with water, while eating.
The dose of the drug is set at the rate of 15 mg / kg body weight, which corresponds to 800-1200 mg / day (2-3 capsules or morning tablets and 2-3 capsules or tablets in the evening). The average recommended dose for patients weighing less than 75 kg is 1 g / day (2 capsules or in the morning and 3 capsules or in the evening),patients with a body weight of more than 75 kg should take 1.2 g / day (3 capsules or in the morning and 3 capsules or in the evening).
The duration of the combination therapy with ribavirin with interferon alpha is usually 24-48 weeks. (for previously untreated patients - not less than 24 weeks, and in patients with a genotype virus 1-48 weeks). If immunity to monotherapy with interferon alfa or relapse of the disease duration of the course is at least 6 months.
SIDE EFFECT
From the side of the central nervous system: headache, insomnia, asthenic syndrome, depression.
From the cardiovascular system: lowering blood pressure, bradycardia, cardiac arrest.
From the hemopoietic system: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia.
On the part of the digestive system: decreased appetite, nausea, hyperbilirubinemia.
Allergic reactions: urticaria, angioedema, bronchospasm, anaphylaxis, skin rash.
Other: hair loss.
CONTRAINDICATIONS
- chronic heart failure IIB-III stage;
- myocardial infarction;
- renal failure (CC less than 50 ml / min);
- severe anemia;
- liver failure;
Decompensated cirrhosis of the liver;
- autoimmune diseases (including autoimmune hepatitis);
- non-treatable thyroid disease;
- severe depression with suicidal intentions;
- children's and adolescence under 18;
- Pregnancy;
- lactation period;
- Hypersensitivity to the drug.
Caution is prescribed for women of reproductive age (pregnancy is undesirable), with decompensated diabetes mellitus (with attacks of ketoacidosis), chronic obstructive pulmonary disease, pulmonary embolism, chronic heart failure, thyroid disorders (including thyrotoxicosis), disorders blood coagulation, thrombophlebitis, myelodepression, hemoglobinopathies (including thalassemia, sickle cell anemia), patients with depression, suicidal tendencies (including anamneze).
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated for use in renal failure (CC less than 50 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated for use in liver failure.
SPECIAL INSTRUCTIONS
Men and women of reproductive age during therapy and within 7 months after the end of treatment should use effective contraceptive means (considering teratogenicity of ribavirin).
Against the background of ribavirin therapy, the maximum reduction in hemoglobin in most cases is observed after 4-8 weeks. from the beginning of treatment. With a decrease in hemoglobin below 110 mg / ml, the dose of ribavirin should be temporarily reduced by 400 mg / day, with a decrease in hemoglobin below 100 mg / ml, the dose should be reduced by 50% of the initial 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 case of acute manifestations of hypersensitivity reactions (hives, angioedema, bronchospasm, anaphylaxis), the drug should be stopped immediately. Transient rashes do not serve as a basis for interrupting treatment.
Control of laboratory indicators
Clinical analysis of blood counting the leukocyte count and number of platelets, determination of electrolytes, creatinine content, functional liver samples should be performed before the start of therapy, for 2 and 4 weeks. reception and then regularly.
In connection with the possible deterioration in the function of the kidneys in the elderly, the use of the drug should be monitored by the function of the kidneys (including KK).
Influence on the ability to manage motor vehicles and work with mechanisms
During the period of application of the drug to patients experiencing fatigue, drowsiness or disorientation, it is necessary to refrain from engaging in potentially dangerous activities requiring an increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: may increase the severity of side effects.
Treatment: discontinuation of the drug; if necessary, conduct symptomatic therapy.
DRUG INTERACTION
With the combined use of ribavirin and interferon alfa, synergy of their action is noted.
In the clinical use of various drugs in therapeutic doses in combination with ribavirin, no significant interaction was found.
The administration of ribavirin during the administration of zidovudine and / or stavudine to patients with concomitant HIV infection is accompanied by a decrease in the phosphorylation of these drugs, which leads to HIV viremia and requires a change in the treatment regimen. There was no interaction between ribavirin and non-nucleoside reverse transcriptase inhibitors or protease inhibitors. Therefore, the combined use of ribavirin and these drugs for the treatment of patients with co-infection with HIV and hepatitis C is possible.
With simultaneous use of drugs containing magnesium and aluminum compounds, simethicone reduce the bioavailability of the drug.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored in a dry, protected from light, out of reach of children, at a temperature of no higher than 25 В° C. Shelf life - 3 years.
