Producer: JSC VEROPHARM Russia
Code of automatic telephone exchange: J05AB04
Release form: Firm dosage forms. Capsules.
General characteristics. Structure:
Acting substance: one capsule contains 0,2 g of a ribavirin as active agent. Excipients: aerosil, potato starch, magnesium stearate, cellulose microcrystallic. Description: capsules, cream-yellow color.
Antiviral drug. Synthetic analog of nucleosides. in vitro concerning some RNA - and the DNA-containing viruses is active. рибавирин, intracellular nucleotide metabolites of a ribavirin in physiological concentration had no inhibiting effect on the enzymes specific to a hepatitis C virus, and suppressed replication of a virus of hepatitis C.
Data of clinical trials showed that use of a ribavirin as monotherapy at hepatitis C, in t. h at its chronic form, inefficiently. However the combination therapy ribaviriny and interferon alpha 2b at the patients with hepatitis C who had a disease recurrence against the background of monotherapy by interferon alpha 2b was by 10 times of more effective, than monotherapy interferon alpha 2b and approximately by 3 times of more effective at the patients who were earlier not treated by interferon alpha 2b.
The mechanism of antiviral action of a ribavirin in a combination with interferon alpha 2b, in particular, concerning a hepatitis C virus, is unknown.
Absorption. After intake рибавирин easily and almost it is completely soaked up from a GIT. At reception in a single dose time of achievement of Cmax of a ribavirin in a blood plasma makes 1,5 h. Absolute bioavailability makes about 45-65% that, apparently, is connected with metabolism at "the first passing" through a liver. Between a dose and an indicator of bioavailability (AUC) there is a linear dependence.
After achievement of Cmax рибавирин it is quickly distributed in an organism. Vd makes about 5000 l. Ribavirin does not contact proteins of plasma.
At course introduction рибавирин collects in plasma in large numbers; the ratio of an indicator of bioavailability (AUC12h) at a repeated and single dose is equal to 6. At intake in a dose of 600 mg of 2 times/days of Css of a ribavirin in plasma it was reached by the end 4 weeks and made about 2200 ng/ml.
Metabolism. Metabolism of a ribavirin is carried out by reversible phosphorylation and by splitting — a deribozilirovaniye and amide hydrolysis with formation of a triazolny carboxyl metabolite.
Removal of a ribavirin from an organism slow. After a single dose in T1/2 makes 79 h. After the termination of course use of T1/2 of a ribavirin makes about 298 h of an organism that, apparently, demonstrates its slowed-down removal from other body tissues, except plasma. Ribavirin and his metabolites — триазолкарбоксамид and triazolcarboxylic acid — are brought out of an organism with urine. Only about 10% of a dose are removed with a stake.
Pharmacokinetics in special clinical cases
At patients with a renal failure the pharmacokinetics of a ribavirin at a single dose inside changes — Cmax and AUC increase in comparison with control (KK> of 90 ml/min.). Concentration of a ribavirin in plasma at a hemodialysis significantly does not change. The pharmacokinetics of a ribavirin at introduction of a single dose does not change at the patients having a liver failure irrespective of its expressiveness (types, And, In or With on classification of Chayld-Pyyu). After intake of a single dose with food with the high content of fats bioavailability of a ribavirin increased (indicators of AUC and Cmax increased by 70%). Apparently, it is caused by delay of transport of a ribavirin or change рН gastric contents. Value of this phenomenon for clinic is not defined. Nevertheless, for the purpose of achievement of the maximum concentration of a ribavirin in a blood plasma it is recommended to accept drug together with food.
Indications to use:
- the recurrence of chronic hepatitis C at patients is more senior than 18 years which were earlier receiving treatment by interferon an alpha with positive effect (normalization of ALT by the end of a medical course);
- the chronic hepatitis C confirmed histologically earlier not treated, without signs of a decompensation of function of a liver, with the raised ALT, a seropozitivnost to a hepatitis C RNA virus, in the presence of fibrosis or the expressed inflammatory activity.
- drug is used only in a combination with interferon alpha 2b.
Route of administration and doses:
Ribavirin accept inside in the dose of 1000-1200 mg a day divided into two receptions (in the morning and in the evening). The recommended doses of a ribavirin depend on the body weight of the patient:
- at the body weight of 75 kg and below the patient has to receive a day 1000 mg of drug in two steps: two capsules on 200 mg in the morning and three capsules on 200 mg in the evening;
- weighing over 75 kg the patient has to receive a day 1200 mg of drug in two steps: three capsules on 200 mg in the morning and three capsules on 200 mg in the evening.
Duration of treatment depends on the clinical course of a disease. The recommended duration of a course of treatment for patients with a disease recurrence after the previous treatment — 6 months, and for not treated patients — at least 24 weeks. In the latter case treatment should be prolonged for 24 weeks ( in total up to 48 weeks) to patients with a virus of a genotype 1 at whom before an initiation of treatment high virus loading was defined (concentration of a RNA virus of hepatitis C in blood), and by the end of the first 24 weeks of treatment the RNA virus of hepatitis C ceased to come to light.
Features of use:
Safety and efficiency of a combination therapy is studied only at use of a ribavirin with interferon alpha 2b.
Decrease in a hemoglobin content to level below 10 g/dl was observed at 14% of the patients receiving рибавирин during clinical tests. Though direct influence on cardiovascular system is not characteristic of a ribavirin, the anemia connected with administration of drug can cause aggravation of heart failure and/or an aggravation of symptoms of a heart disease. In this regard patients with heart diseases рибавирин should appoint with care and only after the corresponding inspection.
During treatment by such patient special observation is required. At emergence of symptoms of deterioration from cardiovascular system treatment should be stopped.
Ribavirin it is necessary to apply with care at patients with a serious illness of lungs (in particular, chronic obstructive diseases of lungs) or a diabetes mellitus with the ketoacidosis phenomena.
With care it is necessary to use drug at patients with disturbances of coagulability of blood (in t. h at thrombophlebitis, an embolism of a pulmonary artery) or the expressed miyelodepressiya.
At acute reactions of hypersensitivity (a small tortoiseshell, a Quincke's disease, a bronchospasm, an anaphylaxis) рибавирин it is necessary to cancel and appoint the corresponding treatment immediately. Tranzitorny skin rashes are not the basis for treatment interruption.
As with age functionality of kidneys and a liver can decrease, at elderly patients prior to use of a ribavirin it is necessary to define their function.
Control of laboratory indicators
Laboratory researches (clinical blood test with calculation of a leukocytic formula and number of thrombocytes, the analysis of electrolytes, determination of content of creatinine in blood serum, functional trials of a liver) should be conducted before an initiation of treatment, then on the 2 and 4 week of treatment, and further it is regular, as required.
At emergence of the serious undesirable phenomena or deviations in laboratory indicators during use of drug it is necessary to correct a dose or to stop administration of drug before the termination of the undesirable phenomena.
Use in pediatrics
Safety and efficiency of drug at treatment of children and teenagers is not established. Therefore use for patients aged up to 18 years is not recommended.
Influence on ability to driving of motor transport and to control of mechanisms
The persons testing fatigue, drowsiness or a disorientation at treatment should recommend to refuse driving of the car or control of mechanisms.
Pregnant women and the feeding women cannot appoint drug. Women of childbearing age have to use effective contraceptive remedies during treatment and within 6 months after treatment.
It is necessary to be careful also in case of disturbance of coagulability of blood or considerable oppression of marrow.
From system of a hemopoiesis: reduction of a hemoglobin content owing to hemolysis — the main toxic effect of a ribavirin which with high probability can be corrected by means of the recommended changes of a dose during treatment; slight anemia, a leukopenia, neutropenia, granulocytopenia, thrombocytopenia are possible.
From endocrine system: dysfunction of a thyroid gland — change of maintenance of TTG is possible (the corresponding therapy was required at 3% of the patients who did not have earlier such disturbances).
Allergic reactions: skin rash, a small tortoiseshell, a Quincke's disease, a bronchospasm, an anaphylaxis are possible.
Others: arterial hypotension, changes of laboratory indicators are possible. By-effects are expressed generally poorly or moderately and do not influence the treatment course.
Hypersensitivity reactions, a lowering of arterial pressure, changes of laboratory indicators are noted. The most part of the undesirable phenomena poorly or are moderately expressed.
Interaction with other medicines:
Medicinal interaction of a ribavirin only with interferon alpha 2b and antacids is studied.
Bioavailability of a ribavirin in a dose of 600 mg decreased at a concomitant use of the antiacid drug containing compounds of magnesium and aluminum or симетикон; the indicator of AUC decreased by 14%. It is possible that decrease in bioavailability in this research was caused by delay of transport of a ribavirin or change рН gastric contents. It is represented that this interaction is not clinically significant.
At simultaneous use of a ribavirin and interferon alpha 2b medicinal interaction is not revealed.
Ribavirin of in vitro inhibits phosphorylation of a zidovudine and stavudin. The clinical importance of these data is not finalized. However, they give the grounds to believe that simultaneous use of a ribavirin with a zidovudine or stavudiny can lead to increase in concentration of RNK-VICh in a blood plasma. Therefore careful monitoring of indicators of concentration of RNK-VICh in plasma at patients to whom treatment ribaviriny is carried out to combinations with one of these two means is recommended. At increase in level of concentration of RNK-VICh in plasma use of a ribavirin in combination with inhibitors of the return transcriptase should be reconsidered. Proofs of interaction of a ribavirin with nenukleozidny inhibitors of the return transcriptase or inhibitors of proteases are not available. Therefore рибавирин it is possible to appoint together with the specified means for treatment of patients with the combined infection of HIV and a viral hepatitis of Page.
The possibility of medicinal or other type of interaction with ribaviriny can remain up to two months (5 periods of T1/2 of a ribavirin) after the termination of its use in connection with the slowed-down removal.
Enzymes of P450 cytochrome do not participate in metabolism of a ribavirin. Ribavirin is not inhibitor of enzymes of system of P450 cytochrome. Toxicological researches do not give the grounds to believe what рибавирин stimulates fermental activity of a liver. Thus, the interaction connected with participation of enzymes of system of P450 cytochrome is improbable.
- the serious illness of heart (including forms, unstable and steady against therapy) preceding treatment, at least, within 6 months;
- diseases of a thyroid gland steady against therapy;
- hemoglobinopathies (including thalassemia, sickemia);
- chronic renal failure (KK <50 ml/min.);
- a heavy depression, suicide thoughts or attempts of a suicide (in t. h in the anamnesis);
- the expressed abnormal liver function or dekompensirovanny cirrhosis;
- autoimmune diseases (including autoimmune hepatitis);
- period of a lactation (breastfeeding);
- hypersensitivity to a ribavirin and other components of drug.
Cases of overdose are noted.
In dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C. Period of validity 2 years. It is not necessary to use drug after expiry date.
According to the recipe
On 10 capsules in a blister strip packaging. On 3, 6 blister strip packagings or on 30 capsules in bank of orange glass together with the application instruction in a pack.