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

Composition:1 capsule contains:
Active substance:
Ribavirin - 200 mg;
Excipients:
lactose monohydrate - 12.8 mg;
potato starch - 24.6 mg;
hypromellose - 6.0 mg;
cellulose microcrystalline - 14.0 mg;
calcium stearate - 2.6 mg;
Capsules hard gelatinous (body: titanium dioxide 2%, dye blue patented 0.0115%, dye diamond black 0.0066%, gelatin - up to 100% lid: titanium dioxide 2%, dye blue patented 0,0766%, dye diamond black 0.0008%, dye Ponso 4R 0.0101%, dye azorubin 0.0055%, gelatin - up to 100%)
The average mass of the contents is 260 mg of the goat capsule.

Description:Capsules number 1 with a casing of blue color and a lid of blue color. The contents of capsules are granules of white or almost white color.

Pharmacotherapeutic group:An antiviral agent.

ATX: & nbsp

J.05.A.B Nucleosides and nucleotides

J.05.A.B.04 Ribavirin

Pharmacodynamics:An antiviral agent. Quickly penetrates into the cells and acts inside the virus-infected cells. Intracellularly ribavirin it is easily phosphorylated by adenosine kinase to mono-, di- and triphosphate metabolites. Ribavirin triphosphate is a strong competitive inhibitor of inosine monophosphate dehydrogenase, RNA polymerase of influenza virus and guanylyltransferase of matrix RNA, the latter being manifested by inhibition of the capping of matrix RNA.These various effects lead to a significant decrease in the amount of intracellular guanosine triphosphate, as well as suppression of the synthesis of viral RNA and protein. Ribavirin inhibits the replication of new virions, which reduces the viral load, selectively inhibits the synthesis of viral RNA, without suppressing the synthesis of RNA in normally functioning cells.
The activity of ribavirin with respect to hepatitis C virus has been revealed. Although the mechanism of action is completely unclear, it is assumed that ribavirin triphosphate accumulating in the course of phosphorylation competitively suppresses the formation of guanosine triphosphate, thereby reducing the synthesis of viral RNAs.
It is also believed that the mechanism of synergistic action of ribavirin and interferon alfa-2b or peginterferon alfa-2b against hepatitis C virus is due to increased interferon phosphorylation of ribavirin.
The most sensitive to ribavirin DNA viruses are herpes simplex virus, adenoviruses, cytomegaloviruses, smallpox viruses, Marek's diseases; RNA viruses - influenza A, B viruses, paramyxoviruses (parainfluenza, mumps, Newcastle disease), reoviruses, arenaviruses (Lassa fever virus, Bolivian hemorrhagic fever),bunyaviruses (Rift Valley fever virus, hemorrhagic fever Crimean Congo virus), hantaviruses (hemorrhagic fever virus with renal or pulmonary syndrome), paramyxoviruses, oncogenic RNA viruses.
When treating hemorrhagic fever with kidney syndrome reduces the severity of the disease, reduces the duration of symptoms (fever, oliguria, pain in the lumbar region, abdomen, headache), improves laboratory indicators of kidney function (reduces the concentration of creatinine and urea in the blood plasma), reduces the risk of developing haemorrhagic complications and an unfavorable outcome of the disease. Ribavirin-insensitive DNA viruses - Varicella zoster, pseudorabies virus, cowpox virus; RNA viruses - enteroviruses, rhinoviruses, encephalitis virus of the forest Semliki.

Pharmacokinetics:Absorption is high; bioavailability - 45-65% (has the effect of first passage through the liver and linear dependence on the dose in the range from 200 to 1200 mg), the time to reach the maximum plasma concentration (TCmax) is l-1.5 h. It binds to plasma proteins in small amounts. The average value of the maximum concentration of Cmax at the end of 1 week 0.2 and 0.4 g every 8 hours is 5 and 11 μmol / l, respectively. The volume of distribution is 647-802 to 5000 liters.Distributed in plasma, respiratory secretions and erythrocytes. A large amount of the active metabolite of ribavirin triphosphate accumulates in the erythrocytes, reaching a constant level after about 4 days and remaining in them for several weeks after application. Significant concentration (after long-term use) can be detected in cerebrospinal fluid (67% of that in plasma).
Metabolized by reversible phosphorylation to form mono-, di- and triphosphate (active) metabolites; is also metabolized to 1,2,4-triazolecarboxamide. Inactivation is carried out by de-rososylation followed by hydrolysis and rupture of the triazole ring. Elimination half-life (T1 / 2) with single dose: initial - 0.5-2 h from plasma and up to 40 days from erythrocytes; the final - 27-36 h; when stable concentration is reached - 151 h.
It is excreted by the kidneys: 7% unchanged for 24 hours; 10% unchanged for 48 hours. The metabolite 1,2,4-triazolecarboxamide is also characterized by a renal excretion pathway. Through the intestine, 10% is excreted.
It is not excreted by hemodialysis. In patients with renal failure, the ratio of bioavailability (AUC-area under the concentration / time curve) and Cmax of ribavirin increases,which is due to a decrease in true clearance; in patients with hepatic insufficiency pharmacokinetics 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 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 (XCH) IIb-III art, myocardial infarction, renal failure with creatinine clearance (KK) of less than 50 ml / min, severe anemia, severe hepatic failure, decompensated cirrhosis, autoimmune diseases ( including autoimmune hepatitis) are not treatable thyroid disease, severe depression with suicidal intentions, children's age (18 years), lactose intolerance, lactase deficiency or glucose-galactose malabsorption ( since the tablet contains lactose).

Carefully:C care prescribers women of reproductive age (pregnancy undesirable), decompensated diabetes (with ketoacidosis episodes); chronic
obstructive pulmonary disease (COPD), pulmonary embolism, XCH I-IIa extent, thyroid diseases (including hyperthyroidism), blood clotting disorders, thrombophlebitis, mielodepression, hemoglobinopathies (including thalassemia, sickle-cell anemia ), depression, suicidal tendencies (incl disease), HIV co-infection (against the background of a combination highly active antiretroviral therapy - the risk of lactic acidosis), 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 administered interferon alfa-2b - subcutaneously at 3 million ME 3 times a week or less. peginterferon alfa-2b - subcutaneously, 1.5 mcg / kg once a 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). In combination with peginterferon alfa-2b at a body weight less than 65 kg dose of Ribavirin - 0.8 g per day (0.4 g in the morning and evening, 0.4 g); 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 is 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 during 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.
On the part of the blood system and hemopoiesis: Hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia; extremely rare is aplastic anemia.
On the part of 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.
On the part of the senses: lesions of the lacrimal gland, conjunctivitis, visual impairment, hearing impairment / loss, tinnitus.
From the musculoskeletal system: arthralgia, myalgia.
From 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, alopecia, hair structure disorder, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection (including herpes), flu-like syndrome, sweating, lymphadenopathy.

Overdose:It is not revealed (one-stage oral administration in a dose of 10 g did not reveal the appearance of symptoms associated with overdose).
Treatment: withdrawal of the drug, symptomatic therapy.

Interaction:Medicines (LS) containing magnesium, aluminum, and simethicone reduce the bioavailability (AUC decreases by 14%, which has no clinical significance).
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 nucleoside (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.
The use of ribavirin and azathioprine may potentiate the development of severe pancytopenia and increase the risk of azathioprine-associated myelotoxicity.
Simultaneous high-fat meals increases the bioavailability of ribavirin (AUC and Cmax increase by 70%).

Special instructions:Men and women of reproductive age during treatment and within 7 months after the end of therapy should use effective contraceptives.
Laboratory tests (clinical blood count with counting of leukocyte count and number
platelets, determination of electrolytes, creatinine concentration, functional liver tests) should be performed before the start of therapy, at 2 and 4 weeks and then regularly.
During treatment with ribavirin, the maximum reduction in hemoglobin in most
of cases occurs after 4-8 weeks from the start of treatment. If the hemoglobin content is lower than 110 g / l, the dose of ribavirin should be temporarily reduced by 400 mg per day, when the hemoglobin content is lower than 100 g / l, the dose should be reduced to 50% of the initial dose. If the intolerance of ribavirin remains intact after dose adjustment, and if the hemoglobin content falls below 85 g / l, the drug should be discontinued.
If immediate-type hypersensitivity occurs (hives, angioedema, bronchospasm, anaphylaxis), the drug should be discontinued immediately. Transient rashes
Do not serve as a basis for interrupting treatment.
Before the initiation of hepatitis C therapy, the need for histological confirmation of the diagnosis should be assessed (dividing patients with genotype 2 or 3 can be started without a prior liver biopsy).
The efficacy and safety of ribavirin in patients after organ transplantation has not been studied.

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

Form release / dosage:Capsules of 200 mg.

Packaging:10 capsules per contour cell package. For 1, 2, 3, 4, 5, 6, 7, 8, or 9 contour mesh packages together with the instruction for use are placed in a cardboard box.

Storage conditions:List B. In a dry, the dark place at a temperature of no higher than 250C. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004161/10

Date of registration:11.05.2010

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Representation: & nbspOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCOBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSCRussia

Information update date: & nbsp13.08.2015

Illustrated instructions

Instructions

Ribavirin-FPO® (Ribavirin-FPO®)