Ribavirin капс. 200 mg

General characteristics. Structure:

Active agent: рибавирин – 200 mg.
Excipients: lactose (sugar milk), silicon dioxide colloid (aerosil), magnesium stearate. Capsules firm gelatinous No. 0: gelatin; the water purified; dye: titanium dioxide.

Description: Capsules of white color No. 0. Contents of capsules – powder of color, white or white with a yellowish shade. Pharmakoterapevtichesky group: antiviral means.

Pharmacological properties:

Pharmacodynamics. Ribavirin easily gets into the cells affected with a virus and is quickly phosphorylated by an intracellular adenosine kinasa in рибавирин mono - di - and triphosphate. These metabolites, especially рибавирин triphosphate, have the expressed antiviral activity. The mechanism of action of a ribavirin is found out insufficiently. However it is known what рибавирин inhibits inosine monophosphate a dehydrogenase (IMF), this effect leads to the expressed decrease in level intracellular guanine riboside of triphosphate (GTF) that, in turn, also the virus of specific proteins is followed by suppression of synthesis of virus RNA. Ribavirin inhibits replication of new virions that provides decrease in virus loading. Ribavirin selectively inhibits synthesis of virus RNA, without suppressing synthesis of RNA in normally functioning cells. Ribavirin is effective concerning many DNA and RNA of viruses. The viruses, most sensitive to DNA ribavirin, are: Simplex herpes virus, poks-virus, virus of Mareks illness. Viruses, insensitive to DNA ribavirin, are: Varicella Zoster, pseudorabies, cow smallpox. The viruses, most sensitive to a RNA ribavirin, are: influenza A, B, paramyxovirus (parainfluenza, epidemic parotite, Nucasls illness), reoviruses, RNA tumoral viruses. Viruses, insensitive to a RNA ribavirin, are: enteroviruses, rhinovirus, Semlicy Forest. Ribavirin has activity against the hepatitis C virus (HCV). The mechanism of action of a ribavirin against VGS is completely not found out. It is supposed that the triphosphate collecting in process of phosphorylation рибавирин competitively suppresses education triphosphate guanine riboside, thereby reducing synthesis of virus RNA. It is considered also that the mechanism of synergy action of a ribavirin and an alpha of interferon against VGS is caused by strengthening of phosphorylation of a ribavirin interferon.

Pharmacokinetics. Absorption: at oral administration рибавирин it is quickly soaked up in digestive tract. At the same time its bioavailability makes more than 45%. Distribution: рибавирин it is distributed in plasma, a secret mucous respiratory tracts and erythrocytes. A large number рибавирин triphosphate collects in erythrocytes, reaching the plateau by 4th day and remaining within several weeks after introduction. The period of semi-distribution makes 3,7 h. The volume of distribution (Vd) – 647 – 802 l. At course reception рибавирин collects in plasma in large numbers. The ratio of indicators of bioavailability (AUC – the area under a curve "concentration/time") at a repeated and single dose is equal to 6. Considerable concentration of a ribavirin (more than 67%) can be found in cerebrospinal liquid after prolonged use. Slightly contacts proteins of plasma. Time of achievement of the maximum concentration in plasma - from 1 to 1,5 hours. Time of achievement of therapeutic concentration in plasma depends on the size of minute volume of blood. The average size of the maximum concentration (Cmax) in plasma: about 5 µmol on liter at the end of 1 week of reception in a dose of 200 mg each 8 hours and about 11 µmol on liter at the end of 1 week of reception in a dose of 400 mg each 8 hours.
- Biotransformation: рибавирин it is phosphorylated in liver cells in active metabolites in the form of mono - di - and triphosphate which then are metabolized in 1,2,4 – триазолкарбоксамид (amide hydrolysis in trikarboksilovy acid and a deribozilirovaniye with formation of a triazolny carboxyl metabolite).
- Removal: рибавирин it is brought out of an organism slowly. Time of semi-removal (T1/2) after a single dose of a dose of 200 mg makes from 1 to 2 hours of plasma and up to 40 days of erythrocytes. After the termination of course reception of T1/2 Ribavirin makes about 300 h and his metabolites are generally brought out of an organism by kidneys. Only about 10% are removed through intestines. In an invariable look about 7% of a ribavirin are removed in 24 hours and about 10% - in 48 hours. Pharmacokinetics at special clinical states: At administration of drug by patients with a renal failure of AUC and Cmax of a ribavirin increase that is caused by decrease in true clearance. At patients with a liver failure (And, In and From degree) the pharmacokinetics of a ribavirin does not change. After reception of a single dose with the food containing fats, the pharmacokinetics of a ribavirin changes significantly (AUC and Cmax increase by 70%).

Indications to use:

Chronic hepatitis C (in a combination with interferon alpha 2b or peginterferon alpha 2b): at primary patients who were earlier not treated by interferon alpha 2b or peginterferon alpha 2b; at an aggravation after a monotherapy course interferon alpha 2b or peginterferon alpha 2b; at patients, unreceptive to monotherapy by interferon alpha 2b or peginterferon alpha 2b.

Route of administration and doses:

Inside, without chewing and washing down with water, together with meal 0.8-1.2 g a day in 2 receptions (in the morning and in the evening). At the same time appoint interferon alpha 2b - subcutaneously, on 3 million ME 3 times a week or peginterferon an alpha 2b - subcutaneously, 1.5 mkg/kg once a week. At a combination with interferon alpha 2b at body weight to 75 kg a dose of a ribavirin - 1 g a day (0.4 g in the morning and 0.6 g in the evening); it is higher than 75 kg - 1.2 g a day (0.6 g in the morning and 0.6 g in the evening). At a combination with peginterferon alpha 2b at body weight less than 65 kg a dose of a ribavirin - 0.8 g a day (0.4 g in the morning and 0.4 g in the evening); 65-85 kg - 1 g a 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). Treatment duration – 24 - 48 weeks; at the same time for earlier not treated patients - not less than 24 weeks, at patients with a virus of a genotype of 1 - 48 weeks. At patients, unreceptive to monotherapy by interferon an alpha, and also at a recurrence - not less than 6 months till 1 year (depending on the clinical course of a disease and the response to the carried-out therapy).

Features of use:

It is necessary to consider teratogenecity of drug, the man and woman of reproductive age during treatment and within 7 months after the end of therapy have to use effective contraceptive remedies. Laboratory researches (clinical blood test with calculation of a leukocytic formula and number of thrombocytes, definition of electrolytes, contents of creatinine, functional trials of a liver) need to be conducted before therapy, on 2 and 4 weeks, and further it is regular. In the course of treatment ribaviriny the maximum decrease in a hemoglobin content is in most cases noted after 4 – 8 weeks from an initiation of treatment. At decrease in hemoglobin lower than 110 mg/ml it is necessary to reduce temporarily a dose of a ribavirin by 400 mg a day, at decrease in hemoglobin lower than 100 mg/ml it is necessary to reduce a dose to 50% of initial. In most cases the recommended changes of a dose provide recovery of level of hemoglobin. At decrease in hemoglobin lower than 85 mg/ml administration of drug should be stopped. At acute manifestation of hypersensitivity (a small tortoiseshell, a Quincke's disease, a bronchospasm, an anaphylaxis) use of drug should be stopped immediately. Tranzitorny rashes do not form the basis for treatment interruption. During treatment the persons testing fatigue, drowsiness or a disorientation need to abstain from driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions. Due to the possible deterioration in function of kidneys at elderly patients before use of drug definition of function of kidneys, in particular clearance of creatinine is necessary.

Side effects:

- From a nervous system: a headache, dizziness, the general weakness, an indisposition, sleeplessness, an adynamy, a depression, irritability, concern, emotional lability, nervousness, excitement, an agressive behavior, the confused consciousness; seldom - suicide bent, increase in a tone of unstriated muscles, a tremor, paresthesias, a hyperesthesia, a hypesthesia, a faint.
- From cardiovascular system: decrease or increase in arterial pressure, bradi-or tachycardia, heartbeat, cardiac standstill.
- From bodies of a hemopoiesis: hemolitic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia; extremely seldom - aplastic anemia.
- From respiratory system: диспноэ, cough, pharyngitis, short wind, bronchitis, average otitis, sinusitis, rhinitis.
- From the alimentary system: dryness in a mouth, a loss of appetite, nausea, vomiting, diarrhea, abdominal pain, a lock, a food faddism, pancreatitis, a meteorism, stomatitis, a glossitis, an odontorrhagia, a hyperbilirubinemia.
- From sense bodys: defeat of the lacrimal gland, conjunctivitis, vision disorder, disturbance/hearing loss, sonitus.
- From a musculoskeletal system: arthralgia, mialgiya.
- From urinogenital system: inflows, decrease libido, dysmenorrhea, amenorrhea, menorrhagia, prostatitis.
- Allergic reactions: skin rash, erythema, small tortoiseshell, hyperthermia, Quincke's disease, bronchospasm, anaphylaxis, photosensitization, multiformny erythema, Stephens-Johnson's syndrome, toxic epidermal necrolysis.
- Other: hair loss, conjunctivitis, alopecia, disturbance of structure of hair, xeroderma, hypothyroidism, thorax pain, thirst, fungal infection, viral infection, grippopodobny cider, perspiration, lymphadenopathy.

Interaction with other medicines:

The medicines containing compounds of magnesium and aluminum симетикон reduce bioavailability of drug (AUC decreases by 14%, has no clinical value). At combined use with interferon alpha 2b or peginterferon alpha 2b - an action synergism. Purpose of a ribavirin during treatment by a zidovudine and/or stavudiny is followed by decrease in their phosphorylation that can bring to VICh-viremii and demand change of the scheme of treatment. Increases concentration of fosforilirovanny metabolites of purine nucleosides (including a didanozina, an abakavira) and the related risk of development of milk acidosis. Does not exert impact on enzymatic activity of a liver with P450 cytochrome participation. The concomitant use of food with the high content of fats increases bioavailability of a ribavirin (AUC and Cmax increase by 70%).

Contraindications:

Hypersensitivity, pregnancy, the lactation period, chronic heart failure of IIB-III of St, myocardial infarction, renal failure (clearance of creatinine - less than 50 ml/min.), the heavy anemia, a liver failure, dekompensirovanny cirrhosis, autoimmune diseases (including autoimmune hepatitis) which are not giving in to treatment of a disease of a thyroid gland, a heavy depression with suicide intentions, children's and youthful age (up to 18 years).

With CARE. Women of reproductive age (approach of pregnancy is undesirable), a dekompensirovanny diabetes mellitus (with ketoacidosis attacks); a chronic obstructive pulmonary disease, a thrombembolia of a pulmonary artery, chronic heart failure, diseases of a thyroid gland (including a thyrotoxicosis), disturbances of coagulability of blood, thrombophlebitis, a miyelodepressiya, a hemoglobinopathy (including a thalassemia, a sickemia), a depression, tendency to a suicide (including in the anamnesis), advanced age.

Overdose:

Strengthening of expressiveness of side effect is possible. Treatment: drug withdrawal, symptomatic therapy.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Capsules on 200 mg. On 30 or 60 capsules in bank polymeric or in a bottle polymeric. Each can or a bottle together with the application instruction are placed in a pack from a cardboard.