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

Composition:1 tablet contains:
Active substance:
ribavirin - 200 mg
Excipients:
lactose monohydrate 154 mg
potato starch - 60 mg
hypromellose - 1 mg
(hydroxypropylmethylcellulose) microcrystalline cellulose - 70 mg
calcium stearate - 5 mg
Crospovidone - 10 mg
The average weight of the tablet is 500 mg

Description:Tablets are white or white with a yellowish or creamy hue of color, round, flat-cylindrical, with a facet and a risk.

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 are influenza A, B viruses, paramyxoviruses (parainfluenza, mumps, Newcastle disease), reoviruses, arenaviruses (Laos fever virus, Bolivian hemorrhagic fever), bunyaviruses (Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus), hantaviruses (haemorrhagic fever virus with renal or pulmonary syndrome), 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 the 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 1-1.5 hours. It binds to plasma proteins in insignificant quantities. The average maximum concentration of Cmax at the end of 1 week is 0.2 and 0.4 g every 8 hours - 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 the stable concentration reaches 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, 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 increase 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 IIb-III st., Myocardial infarction, renal failure with creatinine clearance less than 50 ml / min, severe anemia, severe hepatic insufficiency, decompensated liver cirrhosis, autoimmune diseases (including autoimmune hepatitis), non-treatable thyroid disease, severe depression with suicidal intent, child age (under 18), lactose intolerance, lactase deficiency or glucose-galactose malabsorption (as in to include in the tablet lactose).

Carefully:C carefully prescribe the drug to women of reproductive age (the onset of pregnancy is undesirable), with decompensated diabetes mellitus (with attacks of ketoacidosis),chronic obstructive pulmonary disease, pulmonary embolism, chronic heart failure, grade I-IIa, thyroid diseases (including hyperthyroidism), blood clotting disorders, thrombophlebitis, myelodepression, hemoglobinopathies (including thalassemia, sickle cell anemia), depression, suicidal tendencies (including in the anamnesis), accompanying HIV infection (against the background of combined high-active antiretroviral therapy-risk of lactic acidosis), in old age.
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 of platelets, determination of electrolytes, creatinine concentration, functional liver tests) should be performed before the beginning of therapy, at 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 content is lower than 110 g / l, the dose of ribavirin should be temporarily reduced by 400 mg per day, while reducing the hemoglobin content below 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 hypersensitivity is immediate (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 (treatment of patients with the genotype of virus 2 or 3 can begin without prior biopsy of the liver).
Combined therapy of ribavirin / peginterferon with azathioprine may lead to severe pancytopenia and suppression of bone marrow function. These conditions can develop 3-7 weeks after the initiation of therapy with these drugs and should serve as a reason for the cancellation of all three drugs.After restoration of the bone marrow activity (on average after 4-6 weeks of cancellation of all three drugs), the combination therapy of ribavirin / interferon should be resumed without the continuation of concomitant azathioprine therapy.

Pregnancy and lactation:The use of the drug during pregnancy and during breastfeeding is contraindicated. Data on the penetration of the drug into breast milk is not obtained. Due to the adverse effects of the drug on the baby's body, breastfeeding should be discontinued before therapy begins.

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 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 grams 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 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, suicidal tendencies, smooth muscle tone increase, tremor, paresthesia, hyperesthesia, hypesthesia, fainting .
From the cardiovascular system: decrease or increase in blood pressure, bradycardia or tachycardia, palpitations, cardiac arrest.
On the part of the blood system and hemopoiesis: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia, 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.
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: "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 breach, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection (including herpes), flu-like syndrome, sweating, lymphadenopathy, graft rejection after transplantation of the liver and kidneys.
If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:Overdose was not detected (a one-step oral administration at a dose of 10 g did not reveal the appearance of symptoms associated with an overdose).
Treatment: withdrawal of the drug, symptomatic therapy.

Interaction:Medicines containing magnesium, aluminum, and simethicone reduce the bioavailability (AUC decreases by 14%, which has no clinical significance).
When combined with interferon alpha-2b or peginterferon alfa-2b-synergism 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 lactic acidosis.
Does not affect the enzymatic activity of the liver with the participation of cytochrome P450. With the simultaneous use of ribavirin and azathioprine, the development of pancytopenia and an increased risk of azathioprine-associated myelotoxicity (neutropenia, thrombocytopenia and anemia) are possible.Patients taking this combination of drugs are advised to have a general blood test (including platelet count) weekly during the first month, twice a month for the second and third months, then monthly or more often if therapy is needed, including . change in dose.
Simultaneous food intake with a high fat content increases the bioavailability of ribavirin (AUC and Cmax increase by 70%).

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

Form release / dosage:Tablets 200 mg.

Packaging:For 10, 15, 20, 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.
By 1,2, 3, 6, 10, 14 contour squares with instructions for use in a pack of cardboard.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-001382

Date of registration:28.07.2011

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: & nbsp10.08.2015

Illustrated instructions

Instructions

Ribavirin-FPO (Ribavirin-FPO)