Ribavirin-SZ, 200mg capsules, 60pcs

Composition

Active ingredient: ribavirin-200 mg.

Excipients: lactose (milk sugar), colloidal silicon dioxide (aerosil), magnesium stearate. Solid gelatin capsules No. 0: gelatin; purified water; dye: titanium dioxide.

Description: Capsules of white color No. 0. The contents of capsules are white or white powder with a yellowish tinge of color. Pharmacotherapeutic group: antiviral agent.

Pharmacological action

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

Pharmacodynamics .

Ribavirin easily penetrates virus-affected cells and is rapidly phosphorylated by intracellular adenosine kinase to ribavirin mono -, di-and triphosphate. These metabolites, especially ribavirin triphosphate, have a pronounced antiviral activity. The mechanism of action of ribavirin is not well understood. However, ribavirin is known to inhibit inosine monophosphate dehydrogenase (IMP); this effect leads to a marked decrease in the level of intracellular guanosine triphosphate (GTP), which, in turn, is accompanied by suppression of the synthesis of viral RNA and virus-specific proteins. Ribavirin inhibits the replication of new virions, which reduces the viral load. Ribavirin selectively inhibits viral RNA synthesis without inhibiting RNA synthesis in normally functioning cells. Ribavirin is effective against many DNA and RNA viruses. The most sensitive DNA viruses to ribavirin are: Simplex herpes virus, poks-virus, virus of Marek’s illness. Ribavirin-insensitive DNA viruses are: Varicella Zoster, pseudorabies, cow smallpox. The most sensitive RNA viruses to ribavirin are: influenza A, B, paramyxovirus (parainfluenza, epidemic parasite, Nuclear illness), reoviruses, and RNA tumoral viruses. Ribavirin-insensitive RNA viruses are: enteroviruses, rhinovirus, Semlicy Forest. Ribavirin has activity against the hepatitis C virus (HCV). The mechanism of action of ribavirin against HCV is not fully understood. It is assumed that ribavirin triphosphate accumulated during phosphorylation competitively suppresses the 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. At the same time, its bioavailability is more than 45%. Distribution: ribavirin is distributed in plasma, airway mucosal secretions, and red blood cells. A large amount of ribavirin triphosphate accumulates in red blood cells, reaching a plateau by day 4 and persisting for several weeks after use. The half-life is 3.7 h. The volume of distribution (Vd) is 647-802 liters. With a course of use, ribavirin accumulates in plasma in large quantities. The ratio of bioavailability indicators (AUC – area under the “concentration/time ” curve) with repeated and single use is 6. A significant concentration of ribavirin (more than 67%) can be detected in the cerebrospinal fluid after prolonged use. Slightly binds to plasma proteins. The time to reach the maximum concentration in plasma is from 1 to 1.5 hours. The time to reach the therapeutic plasma concentration depends on the value of the minute volume of blood. The average maximum concentration (Cmax) in plasma: about 5 mmol per liter at the end of 1 week of use at a dose of 200 mg every 8 hours and about 11 mmol per liter at the end of 1 week of use at a dose of 400 mg every 8 hours.

– Biotransformation: ribavirin is phosphorylated in liver cells to active metabolites in the form of 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).

– Elimination: ribavirin is slowly eliminated from the body. The elimination half-life (T1 / 2) after a single 200 mg dose is 1 to 2 hours from plasma and up to 40 days from red blood cells. After stopping the course of use, the T1/2 is about 300 hours. Ribavirin and its metabolites are mainly excreted from the body by the kidneys. Only about 10% is excreted through the intestines. Unchanged, about 7% of ribavirin is eliminated in 24 hours and about 10% in 48 hours. Pharmacokinetics in special clinical conditions: When taking the drug in patients with renal insufficiency, the AUC and Cmax of ribavirin increase, which is due to a decrease in true clearance. In patients with hepatic insufficiency (A, B and C degrees), the pharmacokinetics of ribavirin do not change. After taking a single dose with a food containing fats, the pharmacokinetics of ribavirin change significantly (AUC and Cmax increase by 70%).

Indications

Chronic hepatitis C (in combination with interferon Alfa-2b or peginterferon Alfa-2b): in patients not previously treated with interferon Alfa-2b or peginterferon Alfa-2b; an exacerbation after a course of monotherapy with interferon Alfa-2b or peginterferon Alfa-2b; in patients unresponsive to monotherapy with interferon Alfa-2b or peginterferon Alfa-2b.

Use during pregnancy and lactation

Ribavirin is contraindicated for use during pregnancy and lactation (breastfeeding).

Contraindications

Hypersensitivity, pregnancy, lactation, chronic heart failure IIb-III st, myocardial infarction, renal failure (creatinine clearance less than 50 ml/min), severe anemia, liver failure, decompensated cirrhosis of the liver, autoimmune diseases (including autoimmune hepatitis), untreatable thyroid diseases, severe depression with suicidal intentions, childhood and adolescence (under 18 years of age). WITH CAUTION. Women of reproductive age (pregnancy is undesirable), decompensated diabetes mellitus (with attacks of ketoacidosis); chronic obstructive pulmonary disease, pulmonary embolism, chronic heart failure, thyroid diseases (including thyrotoxicosis), blood clotting disorders, thrombophlebitis, myelodepression, hemoglobinopathy (including thalassemia, sickle cell anemia), depression, suicidal tendencies (including in the anamnesis), old age.

Side effects

From the central nervous system and peripheral nervous system:  headache, dizziness, general weakness, malaise, insomnia, asthenia, depression, irritability, restlessness, emotional lability, nervousness, agitation, aggressive behavior, confusion; rarely – suicidal tendencies, increased smooth muscle tone, tremor, paresthesia, hyperesthesia, hypesthesia, fainting.

From the cardiovascular system:  decrease or increase in blood pressure, brady or tachycardia, palpitations, cardiac arrest.

From the side of hematopoietic organs:  hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia; extremely rare – aplastic anemia.

Respiratory system disorders:  dyspnoea, cough, pharyngitis, shortness of breath, 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, gum bleeding, hyperbilirubinemia.

From the side of the senses:  lacrimal gland involvement, conjunctivitis, visual impairment, hearing impairment/loss, tinnitus.

Musculoskeletal disorders:  arthralgia, myalgia.

From the genitourinary system:  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; with intravenous use-chills.

Local reactions:  pain at the injection site.

Other services:  hair loss, alopecia, hair structure disorders, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection (including herpes), flu-like syndrome, sweating, lymphadenopathy. Medical professionals who perform inhalation may experience headache, itching, hyperemia of the eyes, or swelling of the eyelids.

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 alpha-2b – synergism of action. use 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. Increases the concentration of phosphorylated metabolites of purine nucleosides (including didanosine, abacavir) and the associated risk of lactic acidosis. It does not affect the enzymatic activity of the liver with the participation of cytochrome P450. Concomitant intake of high-fat foods increases the bioavailability of ribavirin (AUC and Cmax increase by 70%).

How to take it, course of use and dosage

Inside, without chewing and drinking water, along with a meal of 0.8-1.2 g per day in 2 doses (morning and evening). At the same time, interferon alpha-2b is prescribed subcutaneously,3 million mg each. IU 3 times a week or peginterferon alfa 2b-subcutaneously,1.5 mcg / kg 1 time a week.In combination with Interferon alfa-2b, if the body weight is less than 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, if the body weight is 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). The duration of treatment is 24-48 weeks; at the same time, for previously untreated patients – at least 24 weeks, in patients with genotype 1 virus – 48 weeks. In patients who are immune to interferon alpha 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 therapy).

Overdose

 Possible increase in the severity of side effects. Treatment: drug withdrawal, symptomatic therapy.

Special instructions

The teratogenicity of the drug should be taken into account, men and women of reproductive age should use effective contraceptives during treatment and for 7 months after the end of therapy. Laboratory tests (clinical blood analysis with calculation of the leukocyte formula and platelet count, determination of electrolytes, creatinine content, liver function tests) should be performed before the start of therapy, for 2 and 4 weeks, and then regularly. During treatment with ribavirin, the maximum decrease in hemoglobin content in most cases is noted after 4 to 8 weeks from the start of treatment. If hemoglobin decreases below 110 mg/ml, the ribavirin dose should be temporarily reduced by 400 mg / day, and 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 ensure that hemoglobin levels are restored. If hemoglobin decreases below 85 mg/ml, the drug should be discontinued. In case of acute hypersensitivity (urticaria, angioedema, bronchospasm, anaphylaxis), the drug should be discontinued immediately. Transient rashes do not serve as a reason for interrupting treatment. During treatment, people experiencing fatigue, drowsiness or disorientation should refrain from driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. Due to possible deterioration of renal function in elderly patients, it is necessary to determine renal function, in particular creatinine clearance, before using the drug.

Form of production

Capsules of 200 mg. 30 or 60 capsules in a polymer jar or in a polymer bottle. Each jar or bottle together with the instructions for use is placed in a pack of cardboard.

Storage conditions

List B. In a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date.

Active ingredient

Ribavirin

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Hepatitis