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

Composition:1 tablet contains:
active substance: ribavirin 200 mg; Excipients: calcium hydrophosphate dihydrate 44 mg, pregelatinized starch 26 mg, magnesium stearate 3 mg, talc 3 mg, microcrystalline cellulose 34 mg.

Description:Tablets are white or almost white, round, flat-cylindrical, with a facet and a risk. Allowed a slight marbling.

Pharmacotherapeutic group:An antiviral agent.

ATX: & nbsp

J.05.A.B Nucleosides and nucleotides

J.05.A.B.04 Ribavirin

Pharmacodynamics:Ribavirin is a synthetic analogue of nucleosides active in vitro for certain RNA and DNA-containing viruses. Signs of inhibition of enzymes specific for hepatitis C virus (HCV), or suppression of hepatitis C virus replication either with ribavirin, or intracellular metabolites of ribavirin, were not detected in physiological concentrations. Monotherapy with ribavirin does not lead to the elimination of the hepatitis virus (RNA virus of hepatitis C) or to an improvement in the histological characteristics of the liver after 6-12 months of use of the drug and for 6 months of follow-up. The use of ribavirin as the sole therapeutic agent for hepatitis C, including its chronic form, is ineffective.Combined treatment with ribavirin and interferon alpha-2b or peginterferon alfa-2b in patients with hepatitis C is more effective than monotherapy with interferon alpha-2b or peginterferon alfa-2b. The mechanism by which ribavirin in combination with interferon alpha-2b or peginterferon alfa-2b shows its antiviral effect, in particular against the hepatitis C virus, is unknown.

Pharmacokinetics:Suction: Absorption is high. Bioavailability is more than 45% (there is an effect of the first passage through the liver and a linear dependence on the dose in the range from 200 to 1200 mg), the time to reach the maximum concentration in the plasma (TCmax) is 1-1.5 h. It binds to plasma proteins in small amounts. The average maximum concentration (Cmax) at the end of 1 week is about 5 μmol / L with a dose of 200 mg every 8 hours and about 11 μmol / L with a dose of 400 mg every 8 hours. Distribution: Volume distribution up to 5000 liters. Distributed in plasma, respiratory secretions and erythrocytes. A large amount of active metabolite of ribavirin triphosphate accumulates in erythrocytes, reaching a constant value 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). Metabolism occurs by reversible phosphorylation to form mono-, di- and triphosphate (active) metabolites and by cleavage (deibosylation and amide hydrolysis) to 1,2,4-triazolecarboxamide. Inactivation is carried out by de-rososylation followed by hydrolysis and rupture of the triazole ring. Excretion: Half-life (T1 / 2) with single dose: initial - 0.5-2 h from plasma and up to 40 days from erythrocytes, final - 27-36 h; when reaching a stable concentration of 151 hours. 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. Pharmacokinetics in special clinical conditions. 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 increase by 70%).

Indications:In combination with interferon alpha-2b or peginterferon alfa-2b
- treatment of patients with chronic hepatitis C, previously untreated, without signs of decompensation of liver disease, with increased activity of ALT, seropositive for RNA virus of hepatitis C, in the presence of fibrosis or severe inflammatory activity;
- treatment of patients with chronic hepatitis C in the event of relapse after treatment with interferon alpha or peginterferon alfa with a favorable response to the therapy (with normalization of ALT activity at the end of the treatment course).
In combination with only peginterferon alfa-2b
- treatment of patients with chronic hepatitis C, without signs of decompensation of liver disease, with increased ALT activity, seropositive to hepatitis C virus RNA, with fibrosis or marked inflammatory activity that has not previously been treated, including patients with clinically stable HIV infection -infection);
- treatment of patients with chronic hepatitis C without signs of decompensation of liver disease, with increased activity of ALT, seropositive to RNA of hepatitis C virus,in the presence of fibrosis or severe inflammatory activity previously treated, and in which prior therapy with interferon α (pegylated or non-pegylated) and ribavirin or interferon alpha monotherapy has proved ineffective;
- treatment of children and adolescents aged 3 years and older with chronic hepatitis C without signs of decompensation of liver disease, which had not previously been treated.

Contraindications:Hypersensitivity to ribavirin or any of the components of the drug; severe heart diseases, including unstable and uncontrolled forms that existed for at least 6 months prior to treatment; not amenable to medical correction of thyroid disease; hemoglobinopathies (for example, thalassemia, sickle cell anemia); chronic renal failure (creatinine clearance less than 50 ml / min); the need for hemodialysis; liver failure; cirrhosis of the liver with hepatic insufficiency in patients with co-infection with HCV / HIV (Child-Pugh index> 6); decompensated cirrhosis of the liver; autoimmune diseases,including autoimmune hepatitis; severe depression; suicidal thoughts or attempts, including those based on anamnesis; pregnancy and the period of breastfeeding; children under 3 years.

Carefully:Decompensated diabetes mellitus (with episodes of ketoacidosis); severe lung disease; chronic obstructive pulmonary disease; pulmonary embolism; diseases of the cardiovascular system (not related to the categories indicated in the contraindications); chronic heart failure of I-IIa degree; arrhythmias; thyroid disease (including thyrotoxicosis); bleeding disorders; thrombophlebitis; myelodepression; significant oppression of the hematopoietic function of the bone marrow; concomitant HIV infection (combined with highly active antiretroviral therapy, due to toxic effects on the mitochondrial apparatus and increased risk of lactic acidosis); elderly age.

Pregnancy and lactation:In connection with the proven teratogenic effect, the drug Ribavirin Canon is contraindicated in pregnancy. It is not known whether ribavirin with mother's milk, so breastfeeding should be discontinued before the drug is started. The drug is contraindicated in breastfeeding.

Dosing and Administration:Adults. Inside, without chewing and drinking with water, while eating 800-1400 mg per day in 2 divided doses (see Table 1). In combination with interferon alpha-2b or peginterferon alfa-2b:
concomitantly prescribe interferon alpha-2b subcutaneously for 3 million IU 3 times a week or peginterferon alfa-2b subcutaneously at 1.5 μg / kg body weight once a week. Recommended duration of treatment is up to 1 year. The individual duration of treatment depends on the clinical course of the disease, the response to the therapy and its tolerability. Patients infected with HCV genotype 1 or 4: patients who have a virologic response after 12 weeks of treatment should continue treatment for a further 9 months (a total course duration of 48 weeks). Patients with low viral load (not higher than 600 000 IU / ml) who after 4 weeks of treatment had eliminated RNA of the virus and in the subsequent period it was not detected - until 24 weeks of treatment, treatment after 24 weeks may be discontinued (total course duration 24 weeks) or continued for another 24 weeks (the total course duration is 48 weeks).However, it should be borne in mind that the risk of relapse after a 24-week course is higher than after a 48-week course. Patients infected with HCV genotype 2 or 3: the recommended duration of treatment is 24 weeks. Conducting a second course of therapy in patients who did not respond to the primary course of therapy: the recommended duration of treatment is 48 weeks, regardless of the genotype of the virus. Patients with chronic hepatitis C infected with HIV: the recommended duration of treatment is 48 weeks, regardless of the genotype of the virus.
Table 1. Recommended doses according to the patient's body weight

Body weight (kg)	The daily dose of ribavirin	Number of ribavirin tablets
<65	800 mg	2 x 200 mg in the morning 2 x 200 mg in the evening
65-85	1000 mg	2 x 200 mg in the morning 3 x 200 mg in the evening
86-105	1200 mg	3 x 200 mg in the morning 3 x 200 mg in the evening
> 105	1400 mg	3 x 200 mg in the morning 4 x 200 mg in the evening

In combination with only peginterferon alfa-2b
Children and teens
Inside, without chewing and washing with water, during meals, 15 mg / kg / day in 2 divided doses (see Table 2). At the same time, peginterferon alfa-2b is administered subcutaneously at 60 μg / m2 once a week. Patients infected with HCV genotype 1 or 4: the recommended duration of treatment is 48 weeks.Children and adolescents receiving combination therapy are advised to stop treatment if, at 12 weeks, the concentration of HCV RNA is less than 2 log (100-fold) compared to baseline, or if HCV RNA is detected within 24 weeks of treatment. Patients infected with HCV genotype 2 or 3: the recommended duration of treatment is 24 weeks. Patients who, at the time of treatment with the combination therapy Ribavirin Canon and peginterferon alfa-2b, are 18 years old must remain on the pediatric treatment regimen.
Table 2. Recommended doses according to the patient's body weight

Body weight (kg)	The daily dose of ribavirin	Number of ribavirin tablets
47-59	800 mg	2 x 200 mg in the morning 2 x 200 mg in the evening
60-73	1000 mg	2 x 200 mg in the morning 3 x 200 mg in the evening
>73	1200 mg	3 x 200 mg in the morning 3 x 200 mg in the evening

All patients
In the absence of a virologic response after 6 months of therapy, a decision should be made to discontinue combination therapy with Ribavirin Canon and interferon alfa-2b or peginterferon alfa-2b. If serious adverse events or laboratory abnormalities occur during the use of Ribavirin Kanon, the dose should be adjusted or the drug should be stopped until the elimination of adverse events.
Table 3.Correction of the dosing regimen

Laboratory indicators	Dose reduction only drug Ribavirin Canon *, if:	Dose reduction only interferon alpha-2b or peginterferon alfa-2b, if:	Discontinuation of therapy if:
Hemoglobin (Hb)	<100 g / l	-	<85 g / l
Hemoglobin Adult patients with heart disease	Content Hb decreased by >20 g / l for any 4 weeks during treatment (continued use of a reduced dose)		<120 g / l
Leukocytes	-	<1.5x10⁹/ l	<1,0x10⁹/ l
Neutrophils	-	<0.75x10⁹/ l	<0.5x10⁹/ l
Platelets	-	Adults: <50x10⁹/ l	Adults: <25x10⁹/ l
Platelets		Children: <70х109 / l	Children: <50x10⁹/ l
Related bilirubin	-	-	2,5хVHN **
Free bilirubin	>5 mg / dL		Adults: >0,04 g / l
Free bilirubin	>5 mg / dL		Children: >0,04 g / l for 4 weeks
Creatinine	-	-	>0,02 g / l
Creatinine clearance			Cancel Ribavirin Canon if < 50 ml / min
Alanine aminotransferase / Aspartate aminotransferase			2 x (base value) and 10 x VGN **

* Patients who have been reduced in the dose of Ribavirin Canon to 600 mg per day should take one 200 mg tablet in the morning and two 200 mg tablets in the evening. In children and adolescents, the first reduction in the dose of Ribavirin canon is up to 12 mg / kg / day, the second reduction - up to 8 mg / kg / day.
** - the upper limit of the norm
If, after dose adjustment, the tolerability of the Ribavirin Canon preparation does not improve, the use of this drug, as well as interferon alfa-2b or peginterferon alfa-2b should be discontinued.
When Ribavirin Kanon is administered in combination with interferon alpha-2b in patients with impaired renal function and over the age of 60, patients should be carefully monitored because of the risk of anemia.

Side effects:Adverse events associated with combination therapy may be associated with both the use of Ribavirin Canon and interferon alfa-2b or peginterferon alfa-2b, as well as their combination.
Classification of WHO frequency of development of side effects:
Often -> 1/10 appointments (> 10%); often - from> 1/100 to <1/10 of appointments (> 1% and <10%); infrequently - from> 1/1000 to <1/100 of prescriptions (> 0.1% and <1%); rarely - from> 1/10000 to <1/1000 appointments (> 0.01% and <0.1%); rarely- <1/10000 appointments (<0.01%); frequency unknown - according to available data to establish the frequency of occurrence is not possible.
Because the ribavirin always prescribe with any interferon-alpha drug, and the above-mentioned adverse reactions also include reactions identified during post-marketing use (marked *),the exact frequency of reactions can not be determined, therefore, the frequency given below was obtained from the results of clinical studies, during which ribavirin was used in combination with interferon alpha-2b (pegylated or non-pegylated). highly Infectious and parasitic diseases: often - viral infections, pharyngitis; often - fungal infection, otitis media, infection caused by the herpes simplex virus, urinary tract infection, bacterial infections (including sepsis), influenza, respiratory tract infections; infrequently - infection at the injection site, infection of the lower respiratory tract; rarely pneumonia. Benign, malignant and unspecified neoplasms (including cysts and polyps): often - unspecified neoplasms. Violations from the blood and lymphatic system: Often - Anemia, neutropenia; often - Lakopenia, hemolytic anemia, lymphopenia, lymphadenopathy, thrombocytopenia; rarely - Aplastic anemia *; frequency unknown - true erythrocyte aplasia, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura. Immune system disorders: infrequently - Hypersensitivity, rarely - sarcoidosis *; frequency unknown - Vogt-Koyanagi-Harada syndrome, systemic lupus erythematosus, rheumatoid arthritis (first-time or worsening of the condition), acute hypersensitivity reactions, including hives, angioedema, bronchospasm, anaphylaxis. Disorders from the endocrine system: often - hypothyroidism, hyperthyroidism; rarely diabetes mellitus type II. Disorders from the metabolism and nutrition: Often anorexia; often - hyperglycemia, hyperuricemia, hypocalcemia, dehydration, increased appetite, thirst; rarely hypertriglyceridemia. Disorders from the psyche: Often - Depression, insomnia, emotional lability, anxiety; often - apathy, tearfulness, suicidal thoughts, psychosis, aggressive behavior, confusion, agitation, nervousness, sleep disorders, anxious dreams, decreased libido; infrequently panic attack, suicide attempts; rarely - hallucinations, bipolar disorder; rarely - suicide *; frequency unknown - Homicidal * thoughts, mania *, change in mental status. Impaired nervous system: Often - headache, dizziness, impaired concentration of attention; often - amnesia, memory impairment, ataxia, tremor, paresthesia, dysphonia, hypoesthesia, hyperesthesia, drowsiness, migraine, hypertonia, taste perversion; rarely - convulsive attacks (convulsions) *, peripheral neuropathy; rarely - hemorrhage in the brain *, cerebrovascular ischemia *, encephalopathy *, polyneuropathy *; frequency unknown - paralysis of the facial nerve, neuropathy (including mononeuropathy). Disorders from the side of the organ of vision: often - eye irritation, dry eyes, blurred vision, conjunctivitis, eye pain, visual impairment, lacrimal gland pathology; rarely hemorrhages in the retina *, exudates in the retina, retinopathy (including macular edema) *, retinal arterial thrombosis *, retinal vein thrombosis *, optic neuritis *, optic disc swelling *, decreased visual acuity or loss of visual fields *, foci darkening in the form of cotton wool *. Hearing disorders and labyrinthine disturbances: often - Vertigo, disorder or loss of hearing, ringing in the ears, pain in the ears. Heart Disease: often - palpitation, tachycardia; rarely - cardiomyopathy *, arrhythmia *; rarely myocardial infarction. Vascular disorders: often - lowering blood pressure, increasing blood pressure, fainting, "hot flashes"; rarely: vasculitis; rarely - ischemia of peripheral tissues *; frequency is unknown: exudative pericarditis, pericarditis. Disorders from the respiratory, thoracic and mediastinal organs: Often - shortness of breath, cough; often - sinusitis, bronchitis, epistaxis, rhinitis, respiratory disorders, edema of the nasal mucosa, rhinorrhea, unproductive cough, increased secretion of the mucous membrane of the upper respiratory tract, sore throat; rarely - pulmonary infiltrates *, pneumonitis *, interstitial pneumonitis *. Disorders from the gastrointestinal tract: Often - nausea, vomiting, dryness of the oral mucosa, abdominal pain, diarrhea; often - Ulcerative stomatitis, stomatitis, colitis, pain in the right upper quadrant of the abdomen, dyspepsia,gastrointestinal reflux disease *, glossitis, bleeding gums, gingivitis, loosening of taste, loose stools, constipation, flatulence, bloating, cheilitis; infrequently - pain in the oral cavity; rarely - Pancreatitis *; rarely - ischemic colitis *, ulcerative colitis *; frequency unknown - violations from the periodontal, dental disorders. Disorders from the liver and bile ducts: often - hepatomegaly, jaundice, hyperbilirubinemia *; rarely - hepatotoxicity (including fatal outcome) *. Disturbances from the skin and subcutaneous tissues: Often - alopecia, itching, dry skin, rash; often - night sweats, hyperhidrosis, erythema *, psoriasis, current deterioration of already existing psoriasis, eczema, photosensitivity reaction, maculopapular rash, erythematous rash, dermatitis, acne, furunculosis *, disorders of the skin, bruising, excessive sweating, impaired the structure of hair, disorders from the nails *; rarely - sarcoidosis of the skin; rarely -sindrom Stevens-Johnson *, toxic epidermal necrolysis *, erythema multiforme and exudative *. Disturbances from the osteomuscular and connective tissue: Often - Arthralgia, myalgia, pain in muscles and bones; often - Arthritis, back pain, muscle spasms; infrequently: muscle weakness; rarely rhabdomyolysis *, myositis *. Disorders from the kidneys and urinary tract: often - frequent urination, polyuria; rarely - impaired renal function *, renal failure *; rarely -nonephritic syndrome. Violations of the genitals and mammary glands: often - Women: menstrual cycle disorders, menorrhagia, amenorrhea, hypermenorrhea, dysmenorrhea, pain in the mammary glands, ovarian dysfunction, vaginal dysfunction; men: erectile dysfunction, impotence, prostatitis, sexual dysfunction (without specifying an exact diagnosis) *. General disorders and disorders at the site of administration: Often - fatigue, chills, fever, flu-like symptoms, asthenia, irritability; often - pain in the chest, swelling of the face, peripheral edema. Laboratory instrumental data: Often - weight loss; often - heart murmur, disturbances in urine analysis (increased bilirubin concentration).In some cases, an increase in the concentration of uric acid and indirect bilirubin, due to hemolysis. These indicators are normalized within 4 weeks after the end of therapy. Only a small number of patients with elevated uric acid concentrations had clinical gout symptoms that did not require dose adjustment or treatment withdrawal.
In HIV-infected patients with chronic hepatitis C who received complex therapy with ribavirin in combination with peginterferon alfa-2b, there were also other side effects that were not recorded in patients with a monoinfection: with a frequency> 5%, the following side effects were identified: oral candidiasis (14%), acquired lipodystrophy (13%), decreased appetite (8 %), an increase in the concentration of gamma-glutamyl transpeptidase (9 %), pain in the back area (5 %), an increase in the concentration of amylase in the blood (6 %), an increase in the concentration of lactic acid in the blood (5 %), cytolytic hepatitis (6 %), increasing the concentration of lipase (6 %) and pain in the upper and lower extremities (6 %). Toxic effect on mitochondria. In HIV-infected patients with chronic hepatitis C who received nucleoside reverse transcriptase inhibitors in combination with ribavirin, mitochondrial toxicity and lactic acidosis were observed. Laboratory indicators in patients with co-infection with HCV / HIV. In most cases anemia, leukopenia, neutropenia, granulocytopenia and thrombocytopenia are moderately expressed (according to WHO criteria). Although neutropenia, thrombocytopenia and anemia were more common in HIV-infected patients with chronic hepatitis C, in most cases, blood changes were possible
to eliminate by reducing the dose, so they rarely led to early termination of treatment. When treated with ribavirin in combination with peginterferon alfa-2b blood changes developed more often than with ribavirin and interferon alfa-2b: decrease in the absolute number of neutrophils <500 / mm³, a decrease in the number of platelets <50000 / mm³, anemia (Hb <9,4 g / dL). Reduction in concentration Cd4-lymphocytes. Treatment with ribavirin in combination with peginterferon alfa-2b accompanied by a reversible decrease in the absolute number Cd4 + cells during the first 4 weeks, which was not combined with a decrease in the percentage of these cells. Number Cd4 + cells increased after a dose reduction or discontinuation of therapy. Combination therapy with ribavirin and peginterferon alfa-2b It did not exert a clear negative influence on the concentration of HIV RNA both during treatment and after its completion. Data on the safety of therapy in HIV-infected patients with hepatitis C with a number Cd4 + cells <200 / μl are limited. Children and adolescents the profile of adverse reactions was the same as in adults, but children also had a growth retardation and a decrease in body weight. Infectious and parasitic diseases: Often - viral infection, pharyngitis; often - bacterial infections, lung infections, tooth abscess, influenza, infections caused by the herpes simplex virus, vaginitis, fungal infection, otitis media, streptococcal pharyngitis, nasopharyngitis, sinusitis; infrequently - pneumonia, ascariasis, enterobiasis, shingles, cellulitis, urinary tract infections, gastroenteritis. Benign, malignant and unspecified neoplasms: often: unspecified neoplasms. Violations of the blood and lymphatic system: Often - anemia, leukopenia, neutropenia; often - lymphadenopathy, thrombocytopenia. Disorders from the endocrine system: often - hypothyroidism, hyperthyroidism, virilism. Disorders from the metabolism and nutrition: highly often - anorexia, increased appetite; often hypertriglyceridemia, hyperuricemia. Disorders from the psyche: often - suicidal thoughts, confusion, agitation, somnambulism, sleep disturbance, apathy, depression, aggressive behavior, insomnia, emotional lability, anger, agitation, anxiety, mood changes, anxiety, nervousness; infrequently - behavioral disorders, depressed mood, emotional disorders, fear, anxious dreams. Impaired nervous system: Often - headache, dizziness; often - hyperkinesia, dysphonia, hyperesthesia, dysgeusia, syncope, impaired concentration, drowsiness, poor sleep quality; infrequently - Neuralgia, lethargy, paresthesia, hypoesthesia, psychomotor agitation, tremor. Disorders from the side of the organ of vision: often - pain in the eyes, visual impairment, lacrimal gland disorders, conjunctivitis; infrequently - blurred vision, hemorrhage in the conjunctiva, itching in the eyes, keratitis, blurred vision, photophobia. Hearing disorders and labyrinthine disturbances: often - Vertigo. Heart Disease: often - a feeling of palpitations, tachycardia. Vascular disorders: often - "tides"; infrequently - lowering blood pressure, increasing blood pressure, pallor.
Disturbances from the respiratory, thoracic and mediastinal organs: often - cough, shortness of breath, rapid breathing, nasal congestion, epistaxis, pain in the pharynx; infrequently - sneezing, discomfort in the nose, rhinorrhea. Disorders from the gastrointestinal tract: Often - nausea, vomiting, abdominal pain, pain in the upper abdomen; often - ulcerative stomatitis, cheilosis, pain in the oral cavity, toothache, dental abnormalities, glossitis, gastroesophageal reflux, stomach discomfort, rectal disorders, constipation, loose stools, diarrhea; infrequently - dyspepsia, gingivitis.
Disorders from the liver and bile ducts: often - abnormal liver function; infrequently - hepatomegaly. Disturbances from the skin and subcutaneous tissues: Often - alopecia, itching, dry skin; often - Sweating, discoloration of the skin, dry skin, redness, bruising, skin diseases, eczema, acne, multiforme and exudative erythema, impaired nail structure; infrequently - photosensitivity reaction, maculopapular rash, skin peeling, pathological pigmentation, atopic dermatitis, skin discoloration. Disturbances from the musculoskeletal and connective tissue: Often - arthralgia, myalgia; often - pain in the muscles and bones, pain in the limbs, back pain; infrequently - Muscular contractures, muscle twitching. Disorders from the kidneys and urinary tract: often - enuresis, urination disorders, urinary incontinence; infrequently - proteinuria. Violations of the genitals and mammary glands: often - Women: amenorrhea, menorrhagia, menstrual irregularity, violations of the vagina; men: pain in the testicle; infrequently - dysmenorrhea. General disorders and disorders at the site of administration: Often - fast fatigue, chills, fever, flu-like symptoms, asthenia, pain, malaise, irritability; often - swelling, a feeling of cold; infrequently - pain in the chest, discomfort in the chest, pain in the face. Laboratory and instrumental data: Often - decreased body weight; often - increased concentration of TSH, increasedwconcentration of thyroglobulin; infrequently - positive antibodies to the thyroid gland. Trauma, intoxication and complications of manipulation: infrequently - contusion. Reducing the concentration of hemoglobin, the number of leukocytes, platelets and neutrophils, an increase in the concentration of bilirubin may require a dose reduction or cancellation of therapy (see "Method of administration and dose"). The changes in laboratory parameters detected in the clinical trial in patients who received ribavirin and peginterferon alfa-2b, returned to baseline values within a few weeks after the end of therapy.

Overdose:

Single-dose ribavirin intake in a dose 10 g and subcutaneous administration of interferon alfa-2b in a dose 39 million ME did not reveal any undesirable phenomena associated with overdose. Antidote is unknown, hemodialysis and peritoneal dialysis are not effective, treatment is symptomatic.

Interaction:

Drugs 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 - synergy of action. The use 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. Therefore, careful monitoring of plasma HIV RNA concentrations in patients treated with Ribavirin Canon in combination with one of the two drugs is recommended. Ribavirin increases the concentration of phosphorylated metabolites of purine nucleosides (including didanosine, abacavir) and the associated risk of developing lactic acidosis. Simultaneous use is not recommended. Not has an effect on 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. In patients infected with the hepatitis virus at the same time C and HIV and those receiving highly active antiretroviral therapy (HAART), lactate acidosis may develop.When prescribing a combination therapy with Ribavirin Canon, in addition to HAART, caution should be exercised.

Special instructions:

The safety and effectiveness of combination therapy was investigated only when ribavirin was used in combination with interferon alpha-2b or peginterferon alfa-2b. Data on the efficacy and safety of ribavirin in combination with other interferons (not alpha-2b) not available. Before the appointment of a combination therapy is also recommended to read the instructions for the use of interferon alfa-2b or peginterferon alfa-2b, attached to each of these drugs.

Ribavirin canon therapy should not be started until a negative pregnancy test result is obtained, which should be performed immediately before the start of treatment. Female patients of childbearing age, as well as their male partners, should use effective contraceptives during treatment and during 6 months after its completion. Due to ribavirin causes changes in sperm in doses lower than therapeutic, male patients during treatment, and also for at least 6 months after the end of the day, condoms should be used. Violation of hematopoiesis. Due to the high risk of myelotoxicity in combination therapy with ribavirin and azathioprine, patients taking this combination of drugs are recommended to perform a general blood test (including platelet count) weekly for the first month, twice a month for 2 and 3 months, then monthly or more often if therapy is needed, incl. change in dose. In most cases, anemia (Hb less 94 g / l), neutropenia (the absolute number of neutrophils is less than 500 / m³) and thrombocytopenia (platelet count less than 50,000 / m³) are moderately expressed, are adjusted by dose reduction and rarely lead to early termination of therapy. Disorders from the psyche and the central nervous system. It should be used with caution in patients with psychiatric disorders in history. Side effects from the psyche and / or the CNS are usually rapidly reversible after discontinuation of therapy, however, in some cases, up to 3 weeks for their full reverse development. If the symptoms of a mental disorder do not regress or worsen, it is recommended to stop Ribavirin Kanon and interferon alfa-2b and consult a psychiatrist.Children and adolescents with severe mental disorders should not, at present or in the past, be prescribed ribavirin in combination with peginterferon alfa-2b. When combined therapy with interferon alpha-2b there was a higher incidence of suicidal thoughts and suicide attempts than in adults, both during treatment and subsequent 6 months. Hemolysis - the main toxic effect of ribavirin. However, a decrease in hemoglobin content by itself does not usually cause a cessation of therapy. The majority of deviations of laboratory parameters are corrected by means of selection of a dose. Diseases of the lungs. There are reports of the development of pneumonitis, infiltrative lung disease (there have been isolated cases of fatal pneumonia), development or exacerbation of lung sarcoma in combination with ribavirin and alpha interferon. When symptoms such as dyspnoea appear, dyspnea should be reported to the doctor. When diagnosing the above listed diseases, the combination therapy should be discontinued. Disorders from the cardiovascular system. Although Ribavirin Canon does not have a direct effect on the cardiovascular system, anemia associated with taking the drug may cause increased heart failure and / or worsening of symptoms of coronary heart disease. In this regard, therapy with Ribavirin Canon should be prescribed to patients with these diseases only after an appropriate examination. In the event of any worsening of the cardiovascular system, treatment should be discontinued. Patients who had cardiovascular abnormalities before the beginning of this therapy are recommended to perform an electrocardiographic study before and during therapy. Cardiac arrhythmias (mainly supraventricular arrhythmias) usually respond well to relief by conventional means, but in some cases, antiviral therapy may need to be canceled. Disturbance of the pancreas. It is necessary to inform patients about the possible development of symptoms of pancreatitis. If the diagnosis is confirmed, the combination therapy should be discontinued. Acute hypersensitivity. In case of acute hypersensitivity (hives, angioedema, bronchospasm, anaphylaxis), the use of Ribavirin Canon should be stopped immediately and appropriate treatment should be prescribed. Transient skin rashes do not serve as a basis for interrupting treatment. Function of the kidneys. Regardless of age before the use of the drug Ribavirin Kanon it is necessary to determine the state of kidney function. Function of the liver. All patients who have severe liver function abnormalities should receive careful monitoring. Treatment should be discontinued if the patient has an increase in clotting time and changes in other parameters of the blood coagulation system, which may indicate a decompensation of the liver. In HIV-infected patients, patients with chronic hepatitis C, liver function on the Child-Pugh scale should be evaluated periodically. At the onset of decompensation of liver function, therapy with drugs against viral hepatitis should be stopped immediately. Disorders from the teeth and periodontal. Dryness of the oral cavity under long-term combined therapy with ribavirin and interferon alfa-2b can contribute to damage to the teeth and mucous membranes of the oral cavity, so it is recommended that you regularly check with a dentist. Disorders from the side of the organ of sight. All patients before starting therapy this drug should be ophthalmologic examination. If a patient experiences a new ophthalmologic disorder or the condition of an existing disease worsens, then combined therapy with interferons alpha should be abolished. Disorders from the thyroid gland. Before the start of therapy with peginterferon alfa-2b it is necessary to determine the concentration of thyrotropic hormone (TSH). If there is a symptom on the background of possible thyroid dysfunction, the concentration of TSH should be determined. In case of thyroid dysfunction, combined therapy with Ribavirin Canon and peginterferon alfa-2b can be continued if it is possible to medically maintain the concentration of TSH within the limits of normal values.If it is not possible to achieve medical compensation for the impaired thyroid function, combined therapy should be abolished. In children and adolescents, every 3 months should investigate the function of the thyroid gland. Laboratory research. Before starting treatment, all patients should undergo a clinical blood test, electrolyte analysis, determination of serum creatinine and uric acid content, functional liver tests. The normal values at which you can start therapy with Ribavirin Canon are: Hb ≥ 120 g / l (women), ≥130 g / l (male), ≥ 110 g / l (girls), ≥120 g / l (boys); platelets ≥100000 / mm³, neutrophils ≥ 1500 / mm³. Then, laboratory tests are recommended at the 2nd, 4th and 8th weeks of treatment and then regularly, as needed. Periodically, the concentration of HCV RNA should be determined during treatment. Use in children and adolescents. Against the background of a course of treatment of up to 48 weeks in patients aged from 3 before 17 years, there was often a loss of body weight and stunting. If possible, treatment should be carried out after puberty growth.Data on the long-term effects on puberty are absent. It is necessary to carefully weigh the expected benefits of treatment, taking into account the safety data for children and adolescents. It is important to consider that combination therapy causes growth retardation, the reversibility of which remains unclear. Risk should be weighed against the characteristics of the disease in the child, such as the progression of the disease (especially fibrosis), concomitant diseases that can accelerate the progression of the main, as well as prognostic response factors to treatment (HCV genotype, viral load).

Effect on the ability to drive transp. cf. and fur:

In the period of treatment with Ribavirin Canon, people who are tired, drowsy or disoriented should refrain from driving vehicles and practicing potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Pills 200 mg.

Packaging:

By 10 or 30 tablets into a contour mesh box made of polyvinyl chloride film and aluminum foil printed lacquered. By 2, 3, 6, 9, 12 contour cell packs for 10 tablets or 1, 2, 3, 4 contourcell packings by 30 Tablets together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, dark place at a temperature of not more than 25 FROM.

Keep out of the reach of children.

Shelf life:

4 of the year. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-002521

Date of registration:23.12.2011

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp07.08.2015

Illustrated instructions

Instructions

Ribavirin Canon (Ribavirin)