Rebetol 200 mg Capsules

Brand name

The trade name of the drug is Rebetol. This is the registered name under which the drug is known in medical practice and is available in the pharmacy network.

International Nonproprietary Name (INN)

The international nonproprietary name is ribavirin. It denotes the active active ingredient and is used in pharmacology at the international level.

Form of release

Rebetol is available in two main forms: capsules with dosage of 200 mg, packed in blisters of 10 pieces or bottles of 70, 84, 140 or 168 capsules, and solution for oral administration with a concentration of 40 mg/mL in bottles of 100 ml with a measuring syringe. The capsules have a white or slightly yellowish color, and the solution has a clear consistency with a slight fruity taste, which facilitates its use in children or patients who have difficulty swallowing capsules.

Composition

Active substance

The main active ingredient is ribavirin. One capsule contains 200 mg of ribavirin, and 1 ml of the solution contains 40 mg.

Auxiliary components

Capsules include substances such as microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate, and the shell consists of gelatin and titanium dioxide. The solution contains sucrose, sorbitol, propylene glycol, sodium citrate, citric acid, orange flavoring, and purified water.

Pharmacologic Properties

Pharmacodynamics

Ribavirin, the active ingredient of Rebetol, is a synthetic nucleoside analog with a broad spectrum of antiviral activity. Its mechanism of action is complex and includes several pathways of hepatitis C virus suppression. After entering infected cells, ribavirin is phosphorylated to active metabolites (mono-, di-, and triphosphates) that disrupt viral RNA synthesis. The main effects include inhibition of viral RNA polymerase, disruption of viral protein synthesis, and induction of mutations in the viral genome, resulting in decreased viral viability.

In combination with interferon, ribavirin enhances the immune response by increasing T-lymphocyte activity and reducing the likelihood of viral resistance. The therapeutic effect is manifested in reduction of HCV-RNA level in blood, normalization of hepatic enzymes (ALT, AST) and improvement of liver histological picture. The full effect is achieved after 12-48 weeks of therapy, depending on the virus genotype and the patient's response. Ribavirin also has activity against other RNA viruses (e.g., influenza virus), but its primary use is limited to hepatitis C.

Pharmacokinetics

Absorption

Ribavirin is well absorbed from the gastrointestinal tract after oral administration. Maximum plasma concentration is reached in 1-2 hours for capsules and 0.5-1.5 hours for the solution. Bioavailability is about 45-65%, as the drug undergoes a first-pass effect through the liver. The ingestion of food, especially food rich in fat, increases absorption by 70%, which makes administration with food preferable.

Distribution

Ribavirin binds extensively to plasma proteins (less than 10%) but penetrates well into tissues including erythrocytes, liver and lungs. The volume of distribution is about 5000 liters, indicating extensive accumulation in cells. The drug crosses the placental barrier and is excreted into breast milk, which limits its use in pregnant and lactating women.

Metabolism

Ribavirin is metabolized in the liver and body cells by phosphorylation to active triphosphates, as well as cleavage to inactive metabolites (triazolecarboxamide and triazolecarboxamic acid). The main pathway of metabolism is degradation with the enzymes adenosine deaminase and xanthine oxidase.

Excretion

The half-life of ribavirin is about 120-170 hours due to accumulation in erythrocytes, although plasma excretion is faster (24-36 hours). The drug is excreted through the kidneys (about 61% as metabolites and 5-10% unchanged) and partially through the intestine. Complete excretion takes up to 300 hours (12-13 days).

Indications for Use

Rebetol is prescribed for the treatment of the following conditions:

• Chronic hepatitis C (genotypes 1-6) in combination with interferon alfa or pegylated interferon;
• Recurrent hepatitis C after liver transplantation (as part of combination therapy);
• Comprehensive treatment of HIV and HCV co-infection in adults.

The drug is effective in achieving sustained virologic response and preventing complications of hepatitis C.

Contraindications

The use of Rebetol is prohibited in:

• Hypersensitivity to ribavirin or auxiliary components;
• Severe anemia (hemoglobin less than 10 g/dL) or hemoglobinopathies (thalassemia, sickle cell anemia);
• Severe renal impairment (creatinine clearance less than 50 mL/min);
• Severe hepatic insufficiency (Child-Pugh class C);
• Pregnancy, lactation and in men whose partners are pregnant;
• Children under 3 years of age;
• Cardiovascular disease in decompensation stage.

With caution, prescribe in depression, diabetes mellitus, thyroid dysfunction.

Method of Administration and Dosage

How to take

Rebetol capsules are taken orally with meals, drinking water (100-150 ml) to improve absorption and reduce gastric irritation. The solution is measured by syringe and taken orally, also with food. Capsules are not chewed or opened to preserve the stability of the active ingredient.

Dosages for adults and children

Adults

Dosage depends on body weight: less than 65 kg - 800 mg/day (400 mg in the morning and evening); 65-85 kg - 1000 mg/day (400 mg in the morning, 600 mg in the evening); more than 85 kg - 1200 mg/day (600 mg in the morning and evening). The course - 24-48 weeks in combination with interferon.

Children over 3 years of age

Dosage - 15 mg/kg body weight per day, divided into 2 doses (morning and evening), maximum 1200 mg/day, in combination with interferon.

Dose adjustment for certain conditions

In renal insufficiency (creatinine clearance less than 50 ml/min) the drug is contraindicated. In hepatic insufficiency of class A-B correction is not required, but in class C the use is prohibited. In anemia (hemoglobin less than 10 g/dl) the dose is reduced by 200 mg/day.

Side Effects

Possible adverse reactions include:

• Hematopoietic system: hemolytic anemia, leukopenia, thrombocytopenia;
• Gastrointestinal system: nausea, decreased appetite, diarrhea, abdominal pain;
• Nervous system: fatigue, headache, insomnia, depression;
• Respiratory system: shortness of breath, cough;
• Allergic reactions: rash, itching, hives;
• Other: hair loss, myalgia, increased uric acid levels.

Side effects require regular blood and liver function monitoring.

Overdose

Symptoms of overdose

Doses above 2400 mg/day may cause anemia, nausea, dizziness, dyspnea, and seizures.

First aid measures

Stop taking, call an ambulance. Gastric lavage, give activated charcoal. Symptomatic treatment and hemoglobin control is required.

Drug Interactions

Influence on the effect of other drugs

Rebetalol reduces the efficacy of zidovudine and lamivudine when co-administered. Antacids decrease the absorption of ribavirin. Didanosine increases the risk of lactoacidosis.

Compatibility with alcohol and food

Alcohol increases hepatotoxicity and anemia. Food, especially fatty foods, improves absorption.

Special Precautions

Use in pregnancy and breastfeeding

Rebetol is contraindicated in pregnancy due to teratogenicity; contraception for 6 months after treatment is required. Lactation is prohibited.

Effect on driving and driving mechanisms

The drug may cause fatigue and dizziness, which requires caution when driving.

Particularities of use in elderly people and children

In the elderly, the dose is adjusted in case of impaired renal function. In children it is used with regard to body weight and under strict control.