Vero-Ribavirin - instructions for use, dose, side effects, contraindications

Excipients: silicon dioxide colloid (aerosil), magnesium stearate, potato starch, microcrystalline cellulose; capsules are hard gelatinous (titanium dioxide, iron oxide yellow, gelatin).

Description:Cream-yellow capsules number 0. Capsule contents - powder from white to white with a yellowish tint of color.

Pharmacotherapeutic group: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 guanosine triphosphate (GTP), which in turn is accompanied by a 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.

The most sensitive to ribavirin DNA viruses are herpes simplex virus, adenoviruses, cytomegaloviruses, smallpox viruses, Marek's diseases; RNA viruses - influenza viruses A, B, paramyxoviruses (parainfluenza, mumps, Newcastle disease), reoviruses, arenaviruses (Lassa fever virus, Bolivian hemorrhagic fever), bunyaviruses (valley fever virus Rift, Crimean-Congo hemorrhagic fever viruses), hantaviruses (hemorrhagic fever virus with renal or pulmonary syndrome) paramyxoviruses, oncogenic RNA viruses.

Ribavirin-insensitive DNA viruses - Varicella zoster, pseudorabies virus, cowpox; RNA viruses-enteroviruses, rhinoviruses, encephalitis virus of the forest Semiliki.

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 the synergistic effect of ribavirin and interferon alfa vs HCV is due to the increased phosphorylation of ribavirin by interferon.

Pharmacokinetics:Absorption: for oral use 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 mucosa of the respiratory tract and erythrocytes. A large number 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. The volume of distribution (Vd) is 647 - 802 l. At course reception ribavirin accumulates in plasma in large quantities. The ratio of bioavailability indicators (AUC is the area under the concentration / time curve) with repeated and single administration is 6. A significant concentration of ribavirin (more than 67%) can be detected in cerebrospinal fluid after prolonged use. Slightly binds to plasma proteins.Time to reach the maximum concentration in the plasma - from 1 to 1.5 hours. The time to achieve a therapeutic concentration in the plasma depends on the value of the minute volume of blood.

The mean maximum plasma concentration (Cmax) is about 5 μmol per liter at the end of 1 week of 200 mg dose every 8 hours and about 11 μmol per liter at the end of 1 week of 400 mg dose every 8 hours.

Biotransformation: 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 of tricarboxylic acid and deribozylation to form a triazole carboxyl metabolite).

Excretion: ribavirin is excreted slowly from the body. The half-life (Tl / 2) after a single dose of 200 mg is from 1 to 2 hours from plasma and up to 40 days from erythrocytes. After the termination of the course reception T1 / 2 is about 300 hours. Ribavirin and its metabolites are mainly excreted from the body by the kidneys. Only about 10% is excreted through the intestine. In an unchanged form, about 7% of ribavirin is excreted in 24 hours and about 10% in 48 hours.

Pharmacokinetics for special clinical conditions: When the drug is administered to patients with renal insufficiency, AUC and Cmax ribavirin are increased,which is due to a decrease in true clearance. In patients with hepatic insufficiency (A, B and C degrees), the pharmacokinetics of ribavirin does not change. After taking a single dose with food containing fats, the pharmacokinetics of ribavirin varies significantly (AUC and Cmax are increased by 70%).

Indications: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.

Contraindications:Hypersensitivity to the drug components, pregnancy, lactation, chronic heart failure IIb-III st, acute myocardial infarction, renal failure (creatinine clearance less than 50 ml / min), severe anemia, severe hepatic insufficiency, decompensated liver cirrhosis, autoimmune diseases including autoimmune hepatitis), resistant to the therapy of thyroid disease, severe depression with suicidal intent, children and adolescence (under 18 years).

Carefully:Women of childbearing age (must use effective contraception), decompensated diabetes (ketoacidosis with attacks), chronic obstructive pulmonary disease, pulmonary embolism, chronic heart failure, thyroid disease (including hyperthyroidism), bleeding disorders, thrombophlebitis , mielodeprescia, hemoglobinopathies (including thalassemia, sickle-cell anemia), depression, suicide (including history), advanced age.

Dosing and Administration:Inside, without liquid and squeezed water, along with a meal of 0.8-1.2 g per day in 2 divided doses (morning and evening).

Simultaneously administered interferon alfa-2b - subcutaneously, 3 mln.ME 3 times a week or peginterferon alfa 2b - subcutaneously 1.5 mg / kg 1 time a week.

When combined with interferon alpha-2b at a body weight of 75 kg, the dose of ribavirin is 1 g per day (400 mg in the morning and 600 mg in the evening); above 75 kg - 1.2 grams per day (600 mg in the morning and 600 mg in the evening).

When combined with peginterferon alfa-2b with a body weight less than 65 kg, the dose of ribavirin is 800 mg per day (400 mg in the morning and 400 mg in the evening); 65-85 kg - 1 g per day (400 mg in the morning and 600 mg in the evening); more than 85 kg (600 mg in the morning and 600 mg in the evening).

Duration of treatment - 24 - 48 weeks; while for previously untreated patients - not less than 24 weeks, in patients with genotype virus 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).

Side effects:From the nervous system: 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.

From the cardiovascular system:decrease or increase in blood pressure, brady- or tachycardia, palpitations, cardiac arrest.

From the hematopoiesis: Hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia; extremely rare - aplastic anemia.

From the respiratory system: dyspnoea, cough, pharyngitis, dyspnea, bronchitis, otitis media, sinusitis, rhinitis.

From the digestive system: dry mouth, decreased appetite, nausea, vomiting, diarrhea, abdominal pain, constipation, taste distortion, pancreatitis, flatulence, stomatitis, glossitis, bleeding from the gums, hyperbilirubinemia.

From the sense organs: lesions of the lacrimal gland, conjunctivitis, visual impairment, hearing impairment / loss, tinnitus.

From the musculoskeletal system: arthralgia, myalgia.

From the genitourinary system: tides, decreased libido, dysmenorrhea, amenorrhea, menorrhagia, prostatitis.

Allergic reactions: skin rash, erythema, urticaria, hyperthermia, angioedema, bronchospasm, anaphylaxis, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Other: hair loss, alopecia, hair structure disorder, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection, flu-like syndrome, sweating, lymphadenopathy.

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

Interaction:Medicines 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%).

Special instructions:Given 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 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. 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 case of 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.

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.

Effect on the ability to drive transp. cf. and fur:During treatment, people who are tired, drowsy or disoriented should refrain from driving vehicles and practicing potentially hazardous activities,requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Capsules of 200 mg.

Packaging:6 or 10 capsules in a planar cell package.

30 capsules in a can of orange glass.

Each bank or 2, 3, 6 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:List B. Store at a temperature not higher than 250C, in a dry place, protected from light and inaccessible to children.

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

Terms of leave from pharmacies:On prescription

Registration number:P N001159 / 01

Date of registration:19.11.2007 / 08.10.2015

Expiration Date:Unlimited

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp01.02.2017

Illustrated instructions

Instructions

Vero-Ribavirin (Vero-Ribavirin)