Ribavirin-SZ - instructions for use, doses, side effects, contraindications

Composition:Composition per one capsule:

active substance: ribavirin - 200 mg
Excipients: lactose monohydrate (sugar milk) - 96.0 mg, silicon dioxide colloid (aerosil) -2.0 mg, magnesium stearate 2.0 mg.
Hard gelatin capsules of white color №0.
Housing: titanium dioxide, gelatin
Cap:titanium dioxide; gelatin.

Description:Capsules of white color number 0. Contents of capsules - powder white or white with a yellowish tinge.

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 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.
Ribavirin is effective against many DNA and RNA viruses. The most sensitive to ribavirin DNA viruses are:
Simplex herpes virus, poks-virus, vims of Marek's illness. Insensitive to ribavirin DNA viruses are: Varicella Zoster, pseudorabies, cow smallpox. The most sensitive to Ribavirin RNA viruses are: influenza A, B, paramyxovirus (parainfluenza, epidemic parotite, Nucasl's illness), reoviruses, RNA tumoral viruses. Insensitive to ribavirin RNA viruses are: enteroviruses, rhinovims, 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 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 is distributed in plasma, secret mucous respiratory tract and erythrocytes. 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 h. The amount of distribution (V_d) - 647 - 802 l. At course reception ribavirin accumulates in plasma in large quantities. Ratio of bioavailability (AUC - area under the curve "concentration / time") with repeated and single reception is equal to 6. A significant concentration of ribavirin (more 67 %) can be detected in the cerebrospinal fluid after prolonged use. Slightly binds to plasma proteins.

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

The time to reach a therapeutic concentration in the plasma depends on the value of the minute volume of blood.

Average maximum 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 (amide hydrolysis to tricarboxylic acid and deibosylation to form a triazole carboxyl metabolite).

Excretion: ribavirin is excreted slowly from the body. Half-life time (T_1/2) 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 by the kidneys. Only about 10 % is excreted through the intestine. Unchanged around 7% Ribavirin is excreted in 24 hours and about 10 % - behind 48 hours.

Pharmacokinetics for special clinical conditions: When taking the drug, patients with renal insufficiency AUC and C_maxRibavirin 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: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, pregnancy, lactation, chronic heart failure IIb-III art, myocardial infarction, renal failure (creatinine clearance - less than 50 ml / min), severe anemia, liver failure, decompensated cirrhosis, autoimmune diseases (including autoimmune hepatitis) are not treatable thyroid disease, severe depression with suicidal intentions, children and Youth age (up to 18).

Carefully:Women of reproductive age (the onset of pregnancy is undesirable), decompensated diabetes mellitus (with attacks of ketoacidosis); chronic obstructive pulmonary disease, thromboembolism of the pulmonary artery, chronic heart failure, thyroid disease (incl.thyrotoxicosis), bleeding disorders, thrombosis, 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 grams per day in 2 divided doses (morning and evening). Simultaneously appoint interferon alfa-2b - subcutaneously, 3 million ME 3 times a week or peginterferon alfa 2b - subcutaneously, 1.5 μg / kg 1 time per week. When combined with interferon alpha-2b at a body weight of 75 kg, the dose of ribavirin is 1 g per day (0.4 g in the morning and 0.6 g in the evening); above 75 kg -1.2 g per day (0.6 g in the morning and 0.6 g in the evening). When combined with peginterferon alfa-2b at a body weight less than 65 kg, the dose of ribavirin is 0.8 g per day (0.4 g in the morning and 0.4 g in the evening); 65-85 kg - 1 g per 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).
Duration of treatment - 24 - 48 weeks; while for previously untreated patients - not less than 24 weeks, in patients with the virus of genotype 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 side of 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: a decrease or increase in blood pressure, brady or tachycardia, palpitations, cardiac arrest.
From the hemopoiesis: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia; extremely rare - aplastic anemia.
On the part of the respiratory system: dyspnoea, cough, pharyngitis, dyspnea, bronchitis, otitis media, sinusitis, rhinitis.
On the part of the digestive system: dry mouth, decreased appetite, nausea, vomiting, diarrhea, abdominal pain, constipation, taste distortion, pancreatitis, flatulence, stomatitis, glossitis, gum bleeding, hyperbilirubinemia.
From the sense organs: lesions of the lacrimal gland, conjunctivitis, visual impairment, hearing loss / loss, tinnitus.
From the musculoskeletal system: arthralgia, myalgia.
On the part of the genitourinary system: hot flashes, 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, conjunctivitis, alopecia, hair structure disorder, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection, flu-like cider, 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:It should take into account 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 contraceptive means.
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 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.
communication with the possible deterioration of kidney function in elderly patients before using the drug, it is necessary to determine the function of the kidneys, in particular, the clearance of creatinine.

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 dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:Capsules of 200 mg.

Packaging:

10 capsules in a planar cell package.
For 30, 60 or 120 capsules in a can of polymer or a polymer vial. Each bank or vial, 3, 6, 12 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:In a dry, the dark place at a temperature of no higher than 25 0C
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:LSR-006932/10

Date of registration:21.07.2010

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Representation: & nbspNORTH STAR CJSC NORTH STAR CJSC Russia

Information update date: & nbsp12.08.2015

Illustrated instructions

Instructions

Ribavirin-SZ (Ribavirin)