Ribavirin

Ribavirin – drug of the expressed antiviral action, a wide range of activity against various DNA - and the RNA-containing viruses; synthetic analog of nucleosides.

Form of release and structure

• Tablets: ploskotsilindrichesky with a facet and risky, from white till yellow-white color (on 10 or 20 pieces in planimetric strip packagings, 1, 2, 5, 10, 14, 20, 28, 50 or 100 planimetric packagings in a cardboard pack; on 100 or 200 pieces in banks of polymeric, 1, 2, 4, 10, 20, 30, 50 cans in a cardboard pack; on 50 pieces in banks of polymeric, 1,2, 5, 10, 20, 30 or 50 cans in a cardboard pack; for hospitals – from 1000 to 50 000 tablets in packaging);
• Capsules: No. 0, lid and case of cream color; contents – powder or mix of granules and powder from white till yellow-white color; consolidation of contents in a form of the capsule is admissible, when pressing education breaks up (on 5 or 6 pieces in blisters, 1-10, 20, 40, 60, 80, 100, 800 blisters in a cardboard pack; on 10 pieces in containers of polymeric, 1, 5, 10, 20 containers in a cardboard pack; on 10 pieces in blisters, 2, 3, 4, 5, 6, 7, 9, 10, 20, 40, 60, 80, 100 or 800 blisters in a cardboard pack; on 10 pieces in bottles, 1, 5, 10 or 20 bottles in a cardboard pack; on 12, 18, 20, 30, 36, 40, 45, 50, 60, 100, 120, 140, 180, 200 pieces in containers of polymeric, 1, 5, 10 or 20 containers in a cardboard pack).

Structure of 1 tablet:

• Active ingredient: рибавирин – 200 mg;
• Auxiliary components: potato starch, cellulose microcrystallic, calcium stearate, povidone.

Structure of 1 capsule:

• Active ingredient: рибавирин – 200 mg;
• Auxiliary components: potato starch, cellulose microcrystallic, silicon dioxide colloid, lactoses monohydrate (milk sugar), magnesium stearate;
• Case and lid of the capsule: dye ferrous oxide yellow, titanium dioxide, gelatin – to 100%.

Indications to use

Ribavirin is shown to use at chronic hepatitis C (HGS) in the following cases:

• Complex therapy with peginterferon alpha 2b or interferon alpha 2b at the patients who were earlier not treated by these drugs;
• Exacerbation of a disease owing to a monotherapy course peginterferon alpha 2b or interferon alpha 2b;
• Immunity of patients to monotherapy by peginterferon alpha 2b or interferon alpha 2b.

Contraindications

Absolute:

• Heavy depression with suicide intentions;
• Chronic Heart Failure (CHF) of IIB-III of degree;
• Myocardial infarction;
• Heavy anemia;
• Renal failure with the clearance of creatinine (CC) less than 50 ml/min.;
• Heavy liver failure;
• Autoimmune diseases (including autoimmune hepatitis);
• Dekompensirovanny cirrhosis;
• The diseases of a thyroid gland which are not giving in to treatment;
• Pregnancy and period of breastfeeding;
• Children's and youthful age up to 18 years;
• Hypersensitivity.

Relative (Ribavirin it is necessary to take with caution):

• Dekompensirovanny diabetes mellitus, including followed by ketoacidosis attacks;
• Chronic Obstructive Pulmonary Disease (COPD);
• Thromboembolisms of a pulmonary artery;
• Degree HSN I-IIa;
• Diseases of a thyroid gland, including a thyrotoxicosis;
• Disturbances of coagulability of blood, a miyelodepressiya, thrombophlebitis, a hemoglobinopathy (including a thalassemia and a sickemia);
• Depression, tendency to a suicide (data in the anamnesis inclusive);
• HIV infection (the risk of development of lactic acidosis against the background of the combined highly active anti-retrovirus therapy is increased);
• Reproductive age at women since pregnancy approach is undesirable;
• Advanced age.

Route of administration and dosage

Tablets and capsules Ribavirin accept inside, washing down with water, not chewing, along with meal.

The recommended dosing mode: 800-1200 mg the day divided into 2 receptions (morning and evening) in a complex with interferon alpha 2b – on 3 million ME subcutaneously 3 times a week or peginterferon an alpha 2b – on 1,5 mkg/kg subcutaneously once a week.

Daily dose of a ribavirin in a combination with interferon alpha 2b, depending on the body weight of the patient:

• <75 kg – 1000 mg (400 mg in the morning and 600 mg in the evening);
• ≥75 kg – 1200 mg (600 mg in the morning and 600 mg in the evening).

Daily dose of a ribavirin in a combination with peginterferon alpha 2b, depending on the body weight of the patient:

• <65 kg – 800 mg (400 mg in the morning and 400 mg in the evening);
• 65-85 kg – 1000 mg (400 mg in the morning and 600 mg in the evening);
• ≥85 kg – 1200 mg (600 mg in the morning and 600 mg in the evening).

Therapy course duration at various categories of patients:

• Earlier not treated – 24 weeks and more;
• With a hepatitis virus From a genotype of 1 - 48 weeks;
• Unreceptive to monotherapy by peginterferon alpha 2b or interferon alpha 2b, and also in case of a recurrence – of half a year about one year, depending on the clinical course of a disease and reaction to the carried-out treatment.

Side effects

• Nervous system: dizziness, headache, indisposition, general weakness, sleeplessness, depression, adynamy, concern, irritability, emotional lability, nervousness, agressive behavior, excitement, confusion of consciousness; seldom – suicide bents, a tremor, increase in a tone of unstriated muscles, paresthesias, a hypesthesia, a hyperesthesia, a faint;
• Cardiovascular system: increase or lowering of arterial pressure, bradycardia, heartbeat, tachycardia, cardiac standstill;
• Bodies of a hemopoiesis: leukopenia, hemolitic anemia, thrombocytopenia, neutropenia, granulocytopenia; extremely seldom – aplastic anemia;
• Respiratory system: pharyngitis, short wind, cough, bronchitis, sinusitis, rhinitis, average otitis;
• Alimentary system: a food faddism, a loss of appetite, dryness in a mouth, nausea, vomiting, abdominal pain, diarrhea, a lock, a meteorism, pancreatitis, stomatitis, an odontorrhagia, a glossitis, a hyperbilirubinemia;
• Sense bodys: defeat of the lacrimal gland, vision disorder, conjunctivitis, sonitus, disturbance/hearing loss;
• Musculoskeletal system: mialgiya, arthralgia;
• Urinogenital system: menorrhagia, dysmenorrhea, amenorrhea, decrease in a libido, prostatitis;
• Skin and hypodermic fatty tissue: "inflows";
• Hypersensitivity reactions: skin rash, small tortoiseshell, erythema, Quincke's disease, bronchospasm, hyperthermia, anaphylaxis, multiformny erythema, photosensitization, Lyell's disease, Stephens-Johnson's syndrome;
• Other reactions: an alopecia, disturbance of structure of hair, a hair loss, a xeroderma, a hypothyroidism, perspiration, thirst, thorax pain, mycoses, viral infections (including herpes), a grippopodobny syndrome, a lymphadenopathy.

Special instructions

It is required to consider teratogenecity of a ribavirin: men and women of reproductive age during therapy by drug and for 7 months after the end of treatment need to use effective methods of contraception.

It is recommended to conduct before therapy, on the 2 and 4 week, and further regularly next laboratory researches: clinical blood test with calculation of number of thrombocytes and a leukocytic formula, definition of functional trials of a liver, electrolytes, concentration of creatinine.

Acute manifestation of reactions of hypersensitivity (Quincke's disease, small tortoiseshell, bronchospasm, anaphylaxis) demands immediate drug withdrawal. At the same time tranzitorny rashes cannot form the basis for therapy interruption.

The maximum decrease in content in hemoglobin blood during therapy ribaviriny is preferential noted 4-8 weeks later from the beginning of a course. If a hemoglobin indicator <110 g/l, a dose of a ribavirin it is necessary to reduce temporarily by 400 mg a day; hemoglobin <100 g/l – a dose should be reduced to 50% of initial; hemoglobin of ≤85 g/l, also remains intolerance of a ribavirin after dose adjustment – administration of drug should be stopped.

Prior to treatment of hepatitis C assessment of need of histologic confirmation of the diagnosis is carried out (therapy of a virus of a genotype 2 or 3 does not demand a preliminary biopsy of a liver).

During therapy ribaviriny the patients testing drowsiness, fatigue, a disorientation are recommended to abstain from occupations potentially dangerous types of activity demanding the high speed of psychomotor reactions and the increased concentration of attention including from driving of motor transport.

Medicinal interaction

• The substances/drugs containing ions of salts of aluminum and magnesium, симетикон – reduce bioavailability of a ribavirin, reducing AUC by 14%, but this decrease clinically not significantly;
• Interferon alpha 2b or peginterferon alpha 2b – have a synergistic effect;
• The zidovudine and/or ставудин – decreases their phosphorylation, it can bring to VICh-viremii, and also demand change of the scheme of therapy;
• Fosforilirovanny metabolites of purine nucleosides (including диданозин, абакавир) – рибавирин increases their concentration owing to what the risk of development of lactic acidosis increases;
• _{P450 cytochrome} – does not exert impact on enzymatic activity of a liver;
• Food with the high content of fats – increases bioavailability of a ribavirin (_Cmax and AUC increase for 70%).

Terms and storage conditions

To store in the dry, dark place, at a temperature not above 25 °C. To protect from children.

Period of validity:

• Tablets – 4 years;
• Capsules – 3 years.