Ribavin - instructions for use, doses, side effects, contraindications

Composition:Active substance: Ribavirin (USA) - 100 mg or 200 mg.
Excipients: lactose, microcrystalline cellulose, povidone K-30, sodium lauryl sulfate, magnesium stearate.

Description:Capsules of 100 mg: hard gelatin capsules, size "2", with a green casing and a green lid, with the inscription "RIBAVIN" on the body and lid.
Capsules of 200 mg: hard gelatin capsules, size "1", with a blue body and a blue lid, with the inscription "RIBAVIN" on the body and lid.

Pharmacotherapeutic group:An antiviral agent.

ATX: & nbsp

J.05.A.B Nucleosides and nucleotides

J.05.A.B.04 Ribavirin

Pharmacodynamics:Ribavirin - a synthetic analogue of nucleosides with a pronounced antiviral effect. Has a wide spectrum of activity against various DNA and RNA viruses.
Ribavirin readily penetrates into the cells affected by the virus and is rapidly phosphorylated by intracellular adenosine kinase in 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. However, it is known that ribavirin inhibits inosine monophosphate dehydrogenase (IMP), this effect leads to a marked decrease in the level of intracellular guanosinetriphosphate (GTP), which, in turn, is accompanied by suppression of the synthesis of viral RNA and the virus of specific proteins. Ribavirin inhibits the replication of new virions, which ensures a reduction in viral load. Ribavirin selectively inhibits the synthesis of viral RNA, without suppressing the synthesis of RNA in normally functioning cells.
Ribavirin is effective against many DNA and RNA viruses. The most susceptible to ribavirin DNA viruses are: Simplex herpes virus, poks-virus, virus of Marek's illness. Insensitive to ribavirin DNA viruses are: Varicella Zoster, pseudorabies, cow smallpox in rhinotracheitis. The most sensitive to Ribavirin RNA viruses are: influenza A, B, paramyxovirus (parainfluenza, epidemic paratite, Nucasl's illness), reoviruses, RNA tumoral viruses. Insensitive to ribavirin RNA viruses are: enteroviruses, rhinovirus, 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 proceeds ribavirin triphosphate competitively inhibits the formation of guanosine triphosphate, thereby reducing the synthesis of viral RNA. It is also believed that the mechanism of synergistic action of ribavirin and alpha interferon against HCV is due to the increased phosphorylation of ribavirin by interferon.

Pharmacokinetics:

Absorption: when administered orally ribavirin quickly absorbed in the gastrointestinal tract. At the same time, its bioavailability is more than 45%.

Distribution: ribavirin distributed in the plasma, the secretion of the respiratory tract and red blood cells. A large number of ribavirin triphosphate accumulates in erythrocytes, reaching a plateau to 4 day and remaining for several weeks after the administration. The half-distribution period is 3.7 hours. Volume of distribution (V_d) - 647 - 802L. At course reception ribavirin accumulates in plasma in large quantities. Ratio of bioavailability (AUC - the area under the curve "concentration / time") with repeated and single administration is equal to 6. A significant concentration of ribavirin (more 67 %) can be detected in the cerebrospinal fluid after prolonged administration.

Binding to proteins: slightly binds to plasma proteins.

Time to reach the peak concentration in plasma from 1 before 1 ,5 hours.

Time to reach the therapeutic concentration in plasma depends on the amount of minute volume of blood. The concentration in the secretion of the respiratory tract is much higher than in the plasma.

Average peak concentration (C_max) in plasma: about 5 μMol per liter at the end 1 Weeks of admission in a dose 200 mg every 8 hours and about 11 μMol per liter at the end 1 Weeks of admission in a dose 400 mg every 8 hours.

Biotransformation: ribavirin phosphorylated in liver cells into active metabolites in the form of mono-, di- and triphosphate, which are then metabolized in 1,2,4 triazolecarboxamide. The second pathway of metabolism involves amide hydrolysis to tricarboxylic acid and de-bosylation to form a triazole carboxyl metabolite.

Excretion: ribavirin is excreted slowly from the body. Half-life (T₁_/₂) after a single dose 200 mg is from 1 before 2 hours from plasma to 40 days from erythrocytes. After the termination of course reception 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. Unchanged around 7 % of ribavirin is excreted in 24 hours and about 10 % - behind 48 hours.

Pharmacokinetics in special clinical conditions: when taking the drug 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 (A, B and C degree) the pharmacokinetics of ribavirin does not change. After taking a single dose with food containing fats, the pharmacokinetics of ribavirin varies significantly (AUC and C_max increase by 70%).

Indications:Treatment of chronic hepatitis C (in combination with alpha interferon).

Contraindications:Hypersensitivity, pregnancy, lactation, hepatic and / or renal failure, severe anemia.

Carefully:women of reproductive age (the onset of pregnancy is undesirable), decompensated diabetes mellitus (with the phenomenon of ketoacidosis); pulmonary embolism, thromboembolism of the pulmonary artery, heart failure, thyroid disease (including thyrotoxicosis), hemoglobinopathy (including thalassemia, sickle cell disease), depression, suicidal tendencies (including history) autoimmune hepatitis, childhood and adolescence (up to 18 years).

Dosing and Administration:The drug is taken orally without chewing and washing with water, along with a meal.
Patients with hepatitis C are recommended to take ribavirin from the calculation of 15 mg per 1 kg of body weight, which corresponds to 800-1200 mg per day, i.e. 2-3 capsules in the morning and 2-3 capsules in the evening.Usually the recommended dosage for patients with a body weight less than 75 kg is 1000 mg per day (2 capsules in the morning and 3 capsules in the evening), patients with a body weight of more than 75 kg are recommended to take 1200 mg per day (3 capsules in the morning and 3 capsules in the evening).
The duration of the combination therapy with ribavirin with alpha-interferon is usually 24 to 48 weeks. At the same time for previously untreated patients, the duration of the course is at least 24 weeks, and in patients with the virus of genotype 1, the course duration is 48 weeks. In patients who are not susceptible to monotherapy with alpha interferon, and if the disease recurs, the course duration is at least 6 months.

Side effects:From the nervous system: headache, insomnia, asthenic syndrome.
From the cardiovascular system: lowering blood pressure, bradycardia, cardiac arrest.
On the part of hemopoiesis: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia.
On the part of the respiratory system: pneumothorax, dyspnoea, bronchospasm, pulmonary edema, hypoventilation syndrome, lung atelectasis, apnea (with inhalations).
On the part of the digestive system: decreased appetite, nausea, hyperbilirubinemia.
Allergic reactions: skin rash, etc.

Overdose:Perhaps an increase in the severity of side effects.
Treatment: withdrawal of the drug, symptomatic therapy.

Interaction:With the combined use of ribavirin and alpha interferon, synergy is noted.
In the clinical use of various drugs in therapeutic doses in combination with ribavirin, no significant interactions were found.
The appointment of ribavirin during treatment with zidovudine and / or stavudine 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.
Medicines containing magnesium and aluminum compounds, simethicone reduce bioavailability.

Special instructions:It is used only in a hospital with a specialized resuscitation department.
Medical staff working with the drug should take into account its teratogenicity. Men and women of reproductive age during treatment and within 7 months after the end of therapy should use effective contraceptives.
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. With a decrease in hemoglobin below 11 g / dL, the dose of ribavirin should be temporarily reduced by 400 mg per day, with a decrease in hemoglobin below 10 g / dL, the dose should be reduced to 50% of the initial dose. In most cases, recommended dose changes ensure the recovery of hemoglobin. However, while maintaining ribavirin intolerance after dose adjustment, as well as with a drop in hemoglobin below 8.5 g / dsl, the drug should be discontinued.
In case of acute allergic reactions, the drug should be discontinued and appropriate treatment should be prescribed.
Ribavirin should be administered with caution after appropriate examination for patients with heart disease, chronic obstructive pulmonary disease, diabetes mellitus, for clotting disorders, thrombophlebitis, myelodepression.
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.
Safety of the drug in the treatment of children and adolescents is not established, so its use in patients under 18 years is not recommended.

Form release / dosage:Capsules of 100 mg and 200 mg.

Packaging:For 4 capsules in a blister of PVC / aluminum foil.
One blister is placed in an envelope of thick paper together with instructions for use. 10
such envelopes are placed in a cardboard box.
10 blisters are placed in a cardboard box together with instructions for use.
At packing at the enterprise ZAO "FarmFirma Soteks" (Russia)
One blister is placed in an envelope made of cardboard together with instructions for use. 10
such envelopes are placed in a cardboard box.
10 blisters are placed in a cardboard box together with instructions for use.

Storage conditions:List B. In a dry place at a temperature of no higher than 30 C.
Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N 015584/01

Date of registration:24.03.2009

The owner of the registration certificate:Lupine Co., Ltd.Lupine Co., Ltd. India

Manufacturer: & nbsp

LUPIN, Ltd. India

Information update date: & nbsp16.08.2015

Illustrated instructions

Instructions

Ribavin® (Ribavin®)