Ribavin

Ribavin is an antiviral drug for systemic use. It is an artificial nucleoside analogue with a wide range of antiviral effects against RNA and DNA viruses.

The drug is effective against viruses contained in DNA: the common form of herpes (1st and 2nd subtypes), cytomegalovirus, chickenpox, adenoviruses and hepatitis type B. Among RNA viruses, sensitivity to the drug is demonstrated by influenza viruses of subtype A, HIV, measles, hepatitis types A and C, as well as mumps, as well as rotaviruses with rhinoviruses, Coxsackie, Dengue and Lassa fever. [ 1 ]

Indications Ribavin

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

Release form

The drug is released in capsules.

Pharmacodynamics

Ribavin, through various mechanisms of action, allows blocking the viral reaction. The most important, which determines the wide range of its activity, is the slowing down of the RNA cover of the virus matrix, as well as blocking the movement of genetic data. A similar effect is present in the reaction of most viruses.

Its medicinal activity is also due to its similarity in structure to guanosine, a natural nucleoside. After Ribavin is phosphorylated into 3-phosphate (bioactive form), the molecule acquires the ability to affect the enzymes of the virus associated with protein synthesis (RNA polymerase, etc.). Because of this, it demonstrates an extensive virostatic effect (relative to RNA and DNA viruses, as well as retrovirus). [ 2 ]

Ribavin inhibits herpes viral DNA polymerase, retroviral retrotranscriptase, and influenza and morbillivirus RNA polymerase. It also slows down viral replication without destroying cellular function and has a significant effect on the respiratory syncytial virus. [ 3 ]

Clinical trials have shown that the administration of the drug in monotherapy does not affect the processes of HCV RNA elimination or the improvement of liver histology after 0.5-1 year of therapy and during the subsequent six-month observation period.

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

Pharmacokinetics

• Absorption.

The drug is absorbed at high speed, but not completely, after oral administration. After oral administration of a single dose, the substance reaches Cmax values between the 1st and 2nd hour from the moment of administration.

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

• Distribution processes.

The drug is widely distributed within the body - most of it accumulates within erythrocytes with skeletal muscles, and in addition, it accumulates within the spleen, adrenal glands with kidneys and cerebrospinal fluid. Ribavin does not participate in protein synthesis processes.

The distribution volume is approximately 5000 l.

Intra-serum concentrations exceed the minimum inhibitory value for viruses sensitive to the drug.

• Exchange processes.

60% of the drug dose undergoes intrahepatic metabolism processes – via 2 pathways. The first of these is the reverse phosphorylation process, which allows the formation of 1,2,4-triazole-3-carboxamide (active metabolic processes), and the second (the decay process) involves deribosylation with amide hydrolysis to form 1,2,4-triazole-3-carboxylic acid. Intrahepatic metabolic processes are also one of the important excretion pathways.

• Excretion.

At the initial stage, the average half-life of the drug is 2 hours; the maximum average value is within 20-50 hours. When administering the 1st portion, the Tmax value is 1.5 hours.

Excretion occurs in 3 ways: 53% with urine (Ribavirin with its metabolic components), 15% with feces, and another 2% through the lungs.

Dosing and administration

Ribavin must be taken orally, with food, twice daily (in the morning and in the evening).

The portion size of the drug in combination with interferon α-2β is determined taking into account weight and is within 1-1.2 g per day. For individuals with genotype 1, the portion is divided into 2 uses:

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

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

The therapy lasts for 24-48 weeks.

• Application for children

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

Use Ribavin during pregnancy

It is prohibited to use Ribavin during pregnancy.

Contraindications

Main contraindications:

• severe intolerance associated with the components of the drug;
• breastfeeding period;
• hemoglobinopathies (including sickle cell anemia and thalassemia);
• CRF (with CC values below 50 ml per minute);
• severe depression, which includes suicidal attempts;
• severe liver dysfunction, autoimmune hepatitis and decompensated cirrhosis;
• history of thyroid disease.

Side effects Ribavin

A severe side effect of using the drug is hemolytic anemia.

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 area;
• abdominal pain, vomiting, weight loss, diarrhea, anorexia and nausea;
• thrombocyto-, neutro-, leuko- or granulocytopenia, as well as anemia;
• hemolysis-induced slight increase in indirect bilirubin and uric acid values.

Interactions with other drugs

The use of antacids weakens the therapeutic effect of Ribavin.

The drug inhibits the phosphorylation of stavudine with zidovudine. The clinical significance of this information has not yet been definitively determined.

Synergism of the drug with dideoxynazine as an HIV-inhibiting substance is noted.

Moreover, no interaction between the drug and non-nucleoside substances that inhibit proteases or reverse transcriptase is observed.

Storage conditions

Ribavin should be stored in a dark place, out of the reach of small children. Temperature indicators - maximum 30 ° C.

Shelf life

Ribavin can be used for a period of 24 months from the date of sale of the therapeutic substance.

Analogues

The analogues of the drug are Ribavirin, Livel and Ribapeg with Virazol, and also Ribba and Copegus with Moderiba. Also on the list are Virorib, Ribarin and Hepavirin, Trivorin with Rebetol, Maxvirin and Ribasphere with Ribamidil.