Ribavirin Canon, 200 mg capsules 30 pcs

Hepatitis

In combination with interferon alfa2b ‑or peginterferon alfa2b ‑

The treatment of patients with chronic hepatitis C, previously untreated, without signs of decompensation of liver disease, with increased ALT activity, seropositive to hepatitis C RNA-virus, with the presence of fibrosis or marked inflammatory activity;

The treatment of patients with chronic hepatitis C with recurrence of the disease after therapy with interferon-alpha or peginterferon-alpha with favorable response to therapy (with normalization of ALT activity by the end of treatment course);

In combination with peginterferon alfa2b only ‑

– Treatment of patients with chronic hepatitis C without signs of decompensation of liver disease, with increased ALT activity, seropositive for hepatitis C virus RNA, with presence of fibrosis or expressed inflammatory activity, who have not been treated previously, including patients with clinically stable HIV infection (co-infection);

– Treatment of patients with chronic hepatitis C without signs of decompensated liver disease, with increased ALT activity, seropositive for hepatitis C virus RNA, in the presence of fibrosis or significant inflammatory activity, who have previously been treated, and in whom previous therapy with interferon α (pegylated or unpegylated) and ribavirin or interferon alfa monotherapy was ineffective;

Treatment of children and adolescents aged 3 years and older with chronic hepatitis C without signs of decompensation of liver disease who have not previously been treated.

Active ingredient

Composition

1 capsule contains:

The active ingredient:

Ribavirin 200 mg;

Associates:

calcium hydrophosphate dihydrate 51 mg,

croscarmellose sodium 6 mg,

povidone 10 mg,

/p>

Lactose monohydrate 30 mg,

Magnesium stearate 3 mg;

Capsule hard gelatin #0 – 96 mg, including:

Case – titanium dioxide 1.18 mg, gelatin 57.82 mg; cap – titanium dioxide 0.37 mg, indigo carmine dye 0.111 mg, iron oxide yellow dye 0.634 mg, gelatin 35.885 mg.

How to take, the dosage

Capsules, tablets – orally, without chewing and with water, together with a meal 0.8-1.2 g / day in 2 doses (morning and evening). Interferon alpha-2b is indicated simultaneously – once a day, 3 million IU 3 times a week or peginterferon alpha 2b – once a day, 1.5 mcg/kg once a week.
In combination with interferon alfa-2b with body weight less than 75 kg the dose of ribavirin is 1 g/day (0.4 g in the morning and 0.6 g in the evening); above 75 kg – 1.2 g/day (0.6 g in the morning and 0.6 g in the evening).
In combination with peginterferon alfa-2b the dose of ribavirin in body weight less than 65 kg is 0.8 g/day (0.4 g in the morning and 0.4 g in the evening), 65-85 kg – 1 g/day (0.4 g in the morning and 0.6 g in the evening), over 85 kg (0.6 g in the morning and 0.6 g in the evening).
Duration of treatment – 24-48 weeks; in patients not treated earlier – at least 24 weeks, in patients infected with virus genotype 1 – 48 weeks. In patients not susceptible to interferon alfa monotherapy and in case of relapse – at least 6 months to 1 year (depending on the clinical course of the disease and response to the therapy).
Concentrate for infusion solution preparation – by injection, dropwise, during 10-15 minutes, pre-dissolved in sterile water for injection, or in 5% dextrose solution or 0.9% NaCl solution. The initial loading dose is 33 mg/kg, then every 6 h – 16 mg/kg for 4 days (16 doses in total), then every 8 h – 8 mg/kg for 3 days (9 doses in total). If necessary, treatment is continued depending on the condition of the patient, but no more than 14 days.

Interaction

Drugs containing magnesium and aluminum compounds, simethicone decrease the bioavailability of the drug (AUC decreases by 14%, has no clinical significance). When concomitant use with interferon alpha-2b or peginterferon alpha-2b – synergism. Administration of ribavirin during treatment with zidovudine and/or stavudine is accompanied by a decrease in their phosphorylation, which may lead to HIV viremia. If plasma concentrations of HIV RNA are elevated, the use of Ribavirin Canon in combination with reverse transcriptase inhibitors should be reconsidered. In addition, concomitant use of ribavirin and zidovudine is not recommended due to an increased risk of anemia. Increases the concentration of phosphorylated purine nucleoside metabolites (including didanosine, abacavir) and the associated risk of lactate acidosis. There is no effect on hepatic enzymatic activity involving cytochrome P450. Concomitant use of ribavirin and azathioprine may lead to pancytopenia and increased risk of azathioprine-associated myelotoxicity (neutropenia, thrombocytopenia and anemia). Patients who are simultaneously infected with hepatitis C virus and HIV and receive highly active antiretroviral therapy (HAART) may develop lactate acidosis. Increased caution should be exercised when using combination therapy with Ribavirin Canon in addition to HAART.

Special Instructions

Safety and efficacy of combination therapy have only been studied when ribavirin is used in combination with interferon alpha-2b or peginterferon alpha-2b. There are no data on the efficacy and safety of ribavirin in combination with interferons other than alpha-2b. It is also recommended that you read the instructions for use for interferon alpha-2b or peginterferon alpha-2b that accompany each of these drugs before you prescribe combination therapy.

The therapy with Ribavirin Canon should not be started until a negative pregnancy test has been obtained, which should be done immediately before starting treatment. Female patients of childbearing age as well as their male partners should use effective contraception during treatment and for 6 months after it ends. Because ribavirin causes sperm changes at doses below therapeutic levels, male patients should use condoms during treatment and for at least 6 months after treatment ends.

Disorders of hematopoiesis. Due to the high risk of myelotoxicity with combined therapy of ribavirin and azathioprine, patients taking this combination of drugs are recommended to have a total blood count (including platelet count) weekly during the first month, twice a month during months 2 and 3, then monthly or more frequently if changes in therapy, including changes in dose are necessary. In most cases anemia (Hb less than 94 g/l), neutropenia (absolute number of neutrophils less than 50000/m3) and thrombocytopenia (platelet count is less than 50000/m3) are moderately expressed, corrected by dose lowering and rarely lead to early discontinuation of therapy.

Mental and CNS disorders.The drug should be used with caution in patients with a history of mental disorders. Mental and/or CNS side effects are usually quickly reversible after discontinuation of therapy, but in some cases it took up to 3 weeks for their complete reversal. If symptoms of mental disorders do not regress or worsen, it is recommended that treatment with Ribavirin Canon and interferon alfa-2b be discontinued and a psychiatrist consulted. Children and adolescents with current or history of severe psychiatric disorders should not receive ribavirin in combination with peginterferon alfa-2b. A higher incidence of suicidal ideation and suicide attempts has been observed with combination therapy with interferon alfa-2b than in adults, both during treatment and in the following 6 months.

Hemolysis is the main toxic effect of ribavirin. However, a decrease in hemoglobin alone is not usually a reason to discontinue therapy. Most laboratory abnormalities are corrected by adjusting the dose.

Lung diseases. There are reports of the development of pneumonitis, infiltrative lung diseases (some cases of fatal pneumonia have been observed), development or exacerbation of pulmonary sarcoidosis against the background of combined therapy with ribavirin and alpha interferon. In case of appearance of such symptoms as dyspnea, dyspnea should be reported to a physician. If the above mentioned diseases are diagnosed, combined therapy should be discontinued.

Disorders of the cardiovascular system. Although Ribavirin Canon has no direct effect on the cardiovascular system, anemia associated with taking the drug may cause worsening of heart failure and/or exacerbation of coronary heart disease symptoms. Therefore, therapy with Ribavirin Canon should be administered to patients with these diseases only after appropriate evaluation. In case of any deterioration of the cardiovascular system, treatment should be discontinued. Patients with cardiovascular abnormalities detected before the start of this therapy are recommended to undergo electrocardiographic examination before and during therapy. Cardiac rhythm disturbances (mainly supraventricular arrhythmias) usually respond well to conventional therapy, but withdrawal of antiviral therapy may be required in individual cases.

Pancreatic disorders. Patients should be informed of the possible development of symptoms of pancreatitis. If the diagnosis is confirmed, combined therapy should be discontinued.

Contraindications

Hypersensitivity to ribavirin or any of the drug components; severe heart disease, including unstable and uncontrolled forms that have existed for at least 6 months, preceding treatment; thyroid disease not amenable to drug correction; hemoglobinopathies (e.g., thalassemia, sickle cell anemia); chronic renal failure (creatinine clearance less than 50 mL/min), need for hemodialysis; liver failure; cirrhosis with liver failure in patients with HCV/HIV co-infection (Child-Pugh index > 6); decompensated cirrhosis; autoimmune diseases, including autoimmune hepatitis; severe depression; suicidal thoughts or attempts, including a history; lactase deficiency, lactose intolerance and glucose-galactose malabsorption; pregnancy and breastfeeding period; children under
3 years old.

With caution

Women of reproductive age (pregnancy is undesirable); decompensated diabetes mellitus (with episodes of ketoacidosis); severe lung diseases, including chronic obstructive pulmonary disease; pulmonary embolism; chronic heart failure of I-IIa degree; arrhythmias; cardiovascular diseases (not included in the categories listed in the contraindications); thyroid disease (including thyrotoxicosis); blood clotting disorders; thrombophlebitis; myelodepression; concomitant HIV infection (against the background of combined highly active antiretroviral therapy – risk of lactate acidosis); older age.

Side effects

Adverse events during combination therapy may be associated with both Ribavirin Canon and interferon alfa-2b or peginterferon alfa-2b or a combination of the two.

WHO classification of the incidence of side effects:

very common (≥1/10),

frequent (≥1/100 to < 1/10),

frequently- (1/1000 to < 1/100),

frequently (≥1/10000 to < 1/1000),

very rarely(< 1/10000),

frequency unknown – the frequency of occurrence cannot be determined from the available data.

Because ribavirin is always administered with an interferon alfa drug, and the adverse reactions listed also include those identified during post-marketing use (indicated by *), the exact frequency of reactions cannot be determined, therefore, the frequency listed below was derived from clinical studies in which ribavirin was used in combination with interferon alfa-2b (pegylated or unpegylated).

Infectious and parasitic diseases: very often – viral infections, pharyngitis; frequently – fungal infection, otitis media, infection caused by herpes simplex virus, urinary tract infection, bacterial infections (including sepsis), influenza, respiratory tract infections; infrequent – infections at the injection site, lower respiratory tract infection; seldom – pneumonia*.

Benign, malignant and unspecified neoplasms (including cysts and polyps):often – unspecified neoplasms.

Disorders of the blood and lymphatic system:very often – anemia, neutropenia; frequently – leukopenia, hemolytic anemia, lymphopenia, lymphadenopathy, thrombocytopenia; very rarely – aplastic anemia*; frequency unknown – true erythrocytic aplasia, idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura.

Disorders of the immune system: frequently – hypersensitivity, very rarely – sarcoidosis*; frequency unknown – Vogt-Koyanagi-Harada syndrome, systemic lupus erythematosus, rheumatoid arthritis (first occurrence or worsening), acute hypersensitivity reactions including urticaria, angioneurotic edema, bronchospasm, anaphylaxis.

Endocrine system disorders: often hypothyroidism, hyperthyroidism; frequently – diabetes mellitus type II.

Disorders of metabolism and nutrition:very often – anorexia, decreased appetite; often – hyperglycemia, hyperuricemia, hypocalcemia, dehydration, increased appetite, thirst; very rarely – hypertriglyceridemia*.

Mental disorders:very common – depression, insomnia, emotional lability, anxiety; frequent – apathy, tearfulness, suicidal thoughts, psychosis, aggressive behavior, confusion, agitation, nervousness, sleep disorders, disturbing dreams, apathy, reduced libido; infrequent – panic attack, suicide attempts;rarely – hallucinations, bipolar disorder; very rarely – suicide*; frequency unknown – homicidal* thoughts, mania*, change in mental status.

Nervous system disorders: very often – headache, dizziness, concentration disorders; frequently – amnesia, memory impairment, ataxia, tremor, paresthesias, dysphonia, hypoesthesia, hyperesthesia, somnolence, migraine, hypertonicity, perversions of taste; frequently

Overdose

Single administration of oral ribavirin at a dose of 10 g and subcutaneous injection of interferon alfa-2b at a dose of 39 million IU showed no adverse events associated with overdose. Antidote is unknown, hemodialysis and peritoneal dialysis are not effective, treatment is symptomatic.

Similarities