Ribavin

Ribavirin is an antiviral medication for systemic use. It is an artificial nucleoside analogue with a wide range of antiviral effects on RNA and DNA viruses.

The drug effectively acts against viruses contained in DNA: the common form of herpes (1st and 2nd subtypes), cytomegalovirus, chickenpox, adenoviruses and hepatitis type B. Among RNA viruses, influenza viruses of subtype A, HIV, measles, hepatitis A and C, and mumps, and in addition rotaviruses with rhinoviruses, Coxsackie, Dengue and Lassa fever. [1]

Indications Ribavirin

It is used for the viral form of hepatitis C (chronic) - in combination with recombinant interferon α-2β.

Release form

The production of drugs is realized in capsules - 42 pieces inside a polyethylene bottle.

Pharmacodynamics

Ribavirin, using different mechanisms of action, allows you to block the viral reaction. The most important, which determines the wide range of its activity, is the deceleration of the RNA cover of the virus matrix, as well as the blocking of the movement of genetic data. A similar effect is present in the reaction of most viruses.

The drug activity is also due to its similarity in structure to guanosine, a natural nucleoside. After ribavirin is phosphorylated to 3-phosphate (bioactive form), the molecule acquires the ability to act on viral enzymes associated with protein synthesis (RNA polymerase, etc.). Because of this, it exhibits an extensive virostatic effect (relative to RNA and DNA of viruses, as well as retrovirus). [2]

Ribavirin inhibits herpes viral DNA polymerase, retroviral retrotranscriptase, and also RNA polymerase of influenza and morbilliviruses. At the same time, it slows down the repeated viral division without destroying cellular function, and demonstrates a pronounced effect relative to the syncytial respiratory virus. [3]

Clinical tests revealed that the introduction of drugs in monotherapy does not affect the processes of elimination of HCV RNA or the improvement of hepatic histology after 0.5-1 years of therapy and during the next six months of observation.

The combined use of the drug with interferon-α has demonstrated the safety and efficacy of therapy in individuals with hepatitis C subtype (chronic form); with such a combination, a synergistic drug effect is noted.

Pharmacokinetics

Absorption.

The medication is at high speed, but not fully absorbed after oral administration. After oral administration of a 1-time portion, the substance reaches Cmax values between the 1st and 2nd hours from the moment of administration.

Bioavailability values are about 45-65%. Food increases this figure to 70%. When eating fatty foods, the average plasma level Cmax also increases.

Distribution processes.

The drug is widely distributed inside the body - most of it accumulates inside erythrocytes with skeletal muscles, and in addition accumulates inside the spleen, adrenal glands with kidneys and cerebrospinal fluid. Ribavirin is not involved in protein synthesis.

The distribution volume indicator is about 5000 liters.

Intra-serum concentrations exceed the minimum retardation rate for viruses that are sensitive to drugs.

Exchange processes.

The processes of intrahepatic exchange undergo 60% of the dose of the drug - through 2 ways. The first of them is the process of reverse phosphorylation, which allows the formation of 1,2,4-triazole-3-carboxamide (active metabolic processes), and the second (decomposition process) contains deribosylation with amide hydrolysis to form 1,2,4-triazole-3 -carboxylic acid. Intrahepatic metabolic processes are also one of the important routes of excretion.

Excretion.

At the initial stage, the average half-life of a drug is 2 hours; the limiting average is in the range of 20-50 hours. With the introduction of the 1st portion, the Tmax is 1.5 hours.

Excretion is carried out in 3 ways - 53% with urine (ribavirin with its metabolic components), 15% - with feces, and another 2% - through the lungs.

Dosing and administration

It is necessary to use Ribavirin orally, together with food - every day in 2 applications (in the morning and also in the evening).

The portion size of the drug when combined with interferon α-2β is determined taking into account the weight and is in the range of 1-1.2 g per day. For persons with a genotype, 1 serving is divided into 2 uses:

• weight below 75 kg: 0.4 g (corresponds to 2 capsules) in the morning, as well as 0.6 g (corresponds to 3 capsules) in the evening;
• weight over 75 kg: 0.6 g in the morning, as well as 0.6 g in the evening.

People with genotypes 2 or 3 need to inject 0.8 g of the substance per day (in 2 applications).

Therapy lasts for 24-48 weeks.

• Application for children

There is not enough information regarding the medicinal effect and safety of the use of drugs in pediatrics, which is why it is not prescribed to persons under the age of 18.

Use Ribavirin during pregnancy

It is forbidden to use Ribavirin during pregnancy.

Contraindications

The main contraindications:

• severe intolerance associated with the elements of the drug;
• GW period;
• hemoglobinopathies (among them sickle cell type anemia and thalassemia);
• CRF (with CC indicators below 50 ml per minute);
• severe depression, in which suicidal attempts are observed;
• severe hepatic dysfunction, autoimmune hepatitis and decompensated cirrhosis;
• a history of thyroid disease.

Side effects Ribavirin

A severe side effect when using drugs is anemia of the hemolytic type.

Sometimes the following violations occur:

• fatigue, headaches, sleep disorders (drowsiness or insomnia), asthenia and a general feeling of malaise;
• weakening of vision and pain in the sternum;
• abdominal pain, vomiting, weight loss, diarrhea, anorexia and nausea;
• thrombocyto-, neutro-, leuko- or granulocytopenia, as well as anemia;
• a slight increase in the values of indirect bilirubin with uric acid caused by hemolysis.

Interactions with other drugs

The use of antacids weakens the therapeutic effect of Ribavirin.

The drug inhibits the phosphorylation of stavudine with zidovudine. It has not yet been possible to conclusively determine the clinical significance of this information.

There is a synergism of the drug with dideoxinazine as a substance that inhibits HIV.

In this case, there is no interaction between the drug and non-nucleoside substances that slow down proteases or reverse transcriptase.

Storage conditions

Ribavirin must be kept out of the reach of small children, in a dark place. Temperature readings - maximum 30 ° С.

Shelf life

Ribavirin can be used for a 24-month term from the moment the therapeutic substance is marketed.

Analogs

The analogues of the medication are the drugs Ribavin, Livel and Ribapeg with Virazol, and in addition, Ribba and Copegus with Moderiba. Also on the list are Virorib, Ribarin and Gepavirin, Trivorin with Rebetol, Maxvirin and Ribasfer with Ribamidil.