Ribavirin, 200 mg capsules 60 pcs

Ribavirin is a synthetic nucleoside analogue with a pronounced antiviral effect. It has a wide spectrum of activity against various DNA and RNA viruses.

Pharmacodynamics

Ribavirin easily penetrates into virus-infected cells and is quickly phosphorylated by intracellular adenosine kinase into ribavirin mono-, di- and triphosphate. These metabolites, especially ribavirin triphosphate, have pronounced antiviral activity.
The mechanism of ribavirin action is not well elucidated. However, it is known that ribavirin inhibits inosine monophosphate dehydrogenase (IMF), this effect leads to a marked decrease in intracellular guanosine triphosphate (GTP) levels, which, in turn, is accompanied by suppression of synthesis of viral RNA and virus-specific proteins. Ribavirin inhibits replication of new virions, which ensures reduction of viral load. Ribavirin selectively inhibits viral RNA synthesis without suppressing RNA synthesis in normally functioning cells.
Ribavirin is effective against many DNA and RNA viruses. The DNA viruses most sensitive to rnbavirin are: Simplex herpes virus, poks-virus, virus of Marek’s disease. The viruses insensitive to rnbavirin DNA are: Varicella Zoster, pseudorabies, cow smallpox. The most ribavirin-sensitive RNA viruses are: influenza A, B, paramyxovirus (parainfluenza, epidemic parotite, Nucasl’s illness), reoviruses, RNA tumoral viruses. RNA RNA viruses insensitive to ribavirin are: enteroviruses, rhinovirus, Semlicy Forest.
Ribavirin has activity against hepatitis C virus (HCV). The mechanism of action of ribavirin against HCV is not fully clarified. It is assumed that ribavirin triphosphate accumulates with phosphorylation and competitively inhibits formation of guanosine triphosphate, thereby reducing the synthesis of viral RNA. It is also believed that the mechanism of synergistic action of ribavirin and interferon alpha against HCV is due to increased phosphorylation of ribavirin by interferon.

Pharmacokinetics

Absorption: When administered orally, ribavirin is rapidly absorbed in the gastrointestinal tract. Its bioavailability is more than 45%.
Distribution: Ribavirin is distributed in plasma, respiratory tract mucosal secretion and erythrocytes. A large amount of ribavirin triphosphate accumulates in erythrocytes, reaching a plateau by day 4 and persisting for several weeks after administration. The half-life is 3.7 h. The volume of distribution (Vd) is 647 -802 l. When administered during a course of treatment, ribavirin accumulates in the plasma in large amounts. The ratio of bioavailability indices (AUC – area under the curve “concentration/time”) in repeated and single administration is 6. Significant concentration of ribavirin (over 67%) can be detected in cerebrospinal fluid after long-term use. It is insignificantly bound to plasma proteins.
The time of reaching of maximum concentration in plasma is from 1 to 1.5 hours.
The time of reaching of therapeutic concentration in plasma depends on the value of minute blood volume.
The average value of maximum concentration (Cmax) in plasma: about 5 μmol per liter at the end of 1 week of administration at a dose of 200 mg every 8 hours and about 11 μmol per liter at the end of 1 week of administration at a dose of 400 mg every 8 hours.
Biotransformation: ribavirin is phosphorylated in liver cells into active metabolites as mono-, di- and triphosphate, which are then metabolized to 1,2,4 – triazolecarboxamide (amide hydrolysis to tricarboxylic acid and deribosylation to form a triazole carboxyl metabolite).
Excretion: Ribavirin is excreted slowly. Elimination half-life (T½) after a single dose of 200 mg is 1 to 2 hours from plasma and up to 40 days from erythrocytes. After discontinuation of a course of administration, T½ is about 300 hours. Ribavirin and its metabolites are mainly excreted with urine. Only about 10% is excreted with feces. About 7% of ribavirin is excreted unchanged in 24 hours and about 10% – in 48 hours.
Pharmacokinetics in special clinical conditions: While taking the preparation in patients with renal insufficiency AUC and Cmax of ribavirin are increased due to the decrease of true clearance. Pharmacokinetics of ribavirin does not change in patients with hepatic insufficiency (A, B and C degree). Ribavirin pharmacokinetics changes significantly after taking a single dose with fat containing food (AUC and Cmax increase by 70%).

Indications

Orally (in combination with interferon alpha-2b or peginterferon alpha-2b):
chronic hepatitis C (in patients not previously treated with interferon alfa-2b or peginterferon alfa-2b;
in exacerbations after a course of monotherapy with interferon alfa-2b or peginterferon alfa-2b;
in patients unresponsive to interferon alfa-2b or peginterferon alfa-2b monotherapy).

Active ingredient

Composition

Active ingredient: ribavirin 200 mg

How to take, the dosage

Orally, without chewing and drinking water, along with meals 0.8-1.2 g per day in 2 doses (morning and evening). Simultaneously interferon alfa-2b – subcutaneously, 3 million ME three times a week or peginterferon alfa 2b – subcutaneously, 1.5 mcg/kg once a week is prescribed. In combination with interferon alfa-2b in case of body weight less than 75 kg a dose of ribavirin – 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 with 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); over 85 kg (0.6 g in the morning and 0.6 g in the evening).
Duration of treatment – 24 – 48 weeks; at least 24 weeks for patients not previously treated; 48 weeks for patients with genotype 1 virus. In patients resistant to interferon alfa monotherapy, as well as in case of relapse – at least 6 months to 1 year (depending on the clinical course of the disease and the response to the therapy).

Interaction

Medicinal products containing magnesium and aluminum compounds, simethicone reduce the bioavailability of the drug (AUC decreases by 14%, has no clinical significance).
When used together with interferon alpha-2b or peginterferon alpha-2b – synergism of action.

The administration of ribavirin during treatment with zidovudine and/or stavudine is accompanied by a decrease in their phosphorylation, which may lead to HIV viremia and require a change in the treatment regimen.

It increases the concentration of phosphorylated metabolites of purine nucleosides (including didanosine, abacavir) and the associated risk of lactic acidosis.
Has no effect on liver enzymatic activity involving cytochrome P450.
Simultaneous intake of food with high fat content increases the bioavailability of ribavirin (AUC and Cmax increase by 70%).

Special Instructions

The teratogenicity of the drug should be taken into account; men and women of reproductive age should use effective contraception during treatment and for 7 months after the end of therapy.

Laboratory studies (clinical blood count with leukocyte count and platelet count, determination of electrolytes, creatinine content, liver function tests) should be performed before the start of therapy, at 2 and 4 weeks, and regularly thereafter.

In treatment with ribavirin the maximum decrease in hemoglobin is in most cases observed after 4-8 weeks from the start of treatment. If hemoglobin decreases below 110 mg/ml, the dose of ribavirin should be temporarily reduced by 400 mg per day; if hemoglobin decreases below 100 mg/ml, the dose should be reduced to 50% of the initial dose. In most cases, the recommended dose changes provide hemoglobin recovery. If hemoglobin drops below 85 mg/ml, the drug should be stopped.

In case of acute manifestation of hypersensitivity (urticaria, angioedema, bronchospasm, anaphylaxis) the drug should be stopped immediately. Transient rashes are not grounds for discontinuation of treatment.

When using the drug, those who are tired, drowsy or disoriented should refrain from driving and engaging in potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

With regard to possible worsening of renal function in elderly patients, renal function, particularly creatinine clearance, should be determined before using the drug.

Contraindications

Hypersensitivity, pregnancy, lactation, chronic heart failure stage II6-III, myocardial infarction, renal failure (creatinine clearance less than 50 ml/min), severe anemia, liver failure, decompensated liver cirrhosis, autoimmune diseases (including autoimmune hepatitis), untreatable thyroid diseases, severe depression and suicidal intentions.autoimmune diseases (including autoimmune hepatitis), untreatable thyroid disorders, severe depression with suicidal tendencies, childhood and adolescence (under 18 years).

With caution: women of childbearing age (pregnancy is undesirable), decompensated diabetes (with episodes of ketoacidosis); chronic obstructive pulmonary disease, pulmonary embolism, chronic heart failure, thyroid disease (including thyrotoxicosis).Thyrotoxicosis), blood clotting disorders, thrombophlebitis, myelodepression, hemoglobinopathy (including thalassemia, sickle cell anemia), depression, suicidal tendencies (including in anamnesis), elderly age.

Side effects

Nervous system disorders: headache, dizziness, general weakness, malaise, insomnia, asthenia, depression, irritability, anxiety, emotional lability, nervousness, agitation, aggressive behavior, confusion; rarely – suicidal tendency, increased smooth muscle tone, tremor, paresthesia, hyperesthesia, hypoesthesia, fainting.

Cardiovascular system disorders: decreased or increased blood pressure, brady or tachycardia, palpitations, cardiac arrest.

Hematopoietic disorders: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia; very rarely – aplastic anemia.

Respiratory system disorders: dyspnea, cough, pharyngitis, dyspnea, bronchitis, otitis media, sinusitis, rhinitis.

Digestive system disorders: dry mouth, decreased appetite, nausea, vomiting, diarrhea, abdominal pain, constipation, perversion of taste, pancreatitis, flatulence, stomatitis, glossitis, gum bleeding, hyperbilirubinemia.

Sensory organs: lacrimal gland involvement, conjunctivitis, visual impairment, hearing impairment/loss, tinnitus.

Musculoskeletal disorders: arthralgia, myalgia.

Urogenital system disorders: hot flashes, decreased libido, dysmenorrhea, amenorrhea, menorrhagia, prostatitis.

Allergic reactions: skin rash, erythema, urticaria, hyperthermia, angioedema, bronchospasm, anaphylaxis, photosensitization, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Other: hair loss, conjunctivitis, alopecia, hair texture disorders, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection, flu-like syndrome, sweating, lymphadenopathy.

Overdose

The severity of side effects may increase.

Treatment: drug withdrawal, symptomatic therapy.

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