Ribavirin is aimed at combating viruses and to help cells with illness become healthy. Metabolites as ribavirin triphosphates, are active antiviral medicine by their nature (Jardins & Burton, 2019). The effect of this medication can be described by the suppression of viral RNA synthesis, which accompanies the decrease in intracellular guanosinetrophosphate. Viral load is significantly reduced due to the suppression of new virion division (Gardenshire, 2019). Ribovirin acts only on sick cells and does not stop the synthesis of healthy cells. Among the DNA viruses most vulnerable to the drug are herpes virus, smallpox virus, and Marek’s disease (Jardins & Burton, 2019).
Ribavirin is also effective against RNA viruses among others. Among such viruses as the most sensitive are reoviruses and influenza species A and B. There are also diseases that are invulnerable to the drug, among which pseudorabies, cowpox and Varicella-Zoster stand out. One of the most common and dangerous diseases against which Ribavirin is actively used is hepatitis C. In the case of RNA viruses, Ribavirin works by competitively suppressing the released guanosine triphosphate. This is due to the triphosphate of the drug itself, which accumulates in action and thus stops the synthesis of viral RNA. (Jardins & Burton, 2019).
Ribavirin is an antiviral medicine available under different brand names: Rebetol, Ribasphere, RibaPak, Copegus, Virazole, and Moderiba (Gardenshire, 2019). Rapidly penetrates cells and acts inside virus-infected cells (Gardenshire, 2019). Intracellularly, ribavirin is readily phosphorylated by adenosine kinase to mono-, di- and triphosphate metabolites (Jardins & Burton, 2019). Ribavirin triphosphate is a potent competitive inhibitor of inosine monophosphate dehydrogenase, influenza virus RNA polymerase, and guanylyl RNA information transferase, the latter manifested by inhibiting the informational RNA envelope coating process. These various effects lead to a significant decrease in the amount of intracellular guanosine triphosphate and suppression of viral RNA and protein synthesis (Jardins & Burton, 2019). Ribavirin inhibits the replication of new virions, which reduces viral load and selectively inhibits viral RNA synthesis without inhibiting RNA synthesis in normally functioning cells.
It is most active against DNA viruses – respiratory syncytial virus, Herpes simplex viruses type 1 and 2, adenoviruses, CMV, smallpox viruses, Marek’s disease. Also RNA viruses – influenza A, B, paramyxoviruses (parainfluenza, epidemic parotitis, Newcastle disease), reoviruses, arenaviruses (Lassa fever virus, Bolivian hemorrhagic fever virus), bunyaviruses (Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus), hantaviruses (hemorrhagic fever virus with the renal or pulmonary syndrome) paramyxoviruses, oncogenic RNA viruses (Gardenshire, 2019). The treatment of hemorrhagic fever with renal syndrome decreases disease severity, reduces the duration of symptoms (fever, oliguria, pains in the lumbar region, abdomen, headache), improves laboratory indexes of renal function, and reduces the risk of hemorrhagic complications and unfavorable disease outcome. (Jardins & Burton, 2019) DNA viruses – Varicella zoster, pseudorabies virus, natural cowpox are not sensitive to ribavirin (Gardenshire, 2019). RNA viruses – enteroviruses, rhinoviruses, Semliki forest encephalitis virus are immune to medicine (Gardenshire, 2019).
Indications for Use and Routes of Administration
Oral: treatment of chronic hepatitis C in adults (in combination with Interferon alpha-2b or pegInterferon alpha-2b) (Bennett & Dolin & Blaser, 2019).
Parenteral: hemorrhagic fever with renal syndrome.
Combination of therapies: skin and mucous membrane infections caused by Herpes simplex viruses of types 1 and 2, various localizations, including genital area; herpes zoster (as part of complex therapy) (Bennett & Dolin & Blaser, 2019).
Duration of treatment – 24 to 48 weeks; with at least 24 weeks for previously untreated patients, and 48 weeks for patients with genotype 1 virus. In patients unresponsive to Interferon alfa 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 ongoing therapy) (Bennett & Dolin & Blaser, 2019). The recommended dose is 0.8-1.2 g/day in two doses (morning and evening).
CNS and peripheral nervous system: headache, dizziness, general weakness, malaise, insomnia, asthenia, depression, irritability, anxiety, emotional lability, nervousness, agitation, aggressive behavior, confused consciousness; rarely – suicidal tendency, increased smooth muscle tone, tremor, paresthesia, hyperesthesia, hypoesthesia, syncope (Bennett & Dolin & Blaser, 2019).
Cardiovascular system: decrease or increase in BP, Brady- or tachycardia, palpitations, cardiac arrest (Bennett & Dolin & Blaser, 2019).
Blood organs: hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia and rarely – aplastic anemia (Bennett & Dolin & Blaser, 2019).
Respiratory system: dyspnea, cough, pharyngitis, bronchitis, otitis media, sinusitis, rhinitis (Bennett & Dolin & Blaser, 2019).
Digestive system: dry mouth, decreased appetite, nausea, diarrhea, abdominal pain, constipation, pancreatitis, flatulence, stomatitis, glossitis, bleeding gums, hyperbilirubinemia (Bennett & Dolin & Blaser, 2019).
Sensory organs: lacrimal gland involvement, conjunctivitis, visual impairment, hearing impairment, tinnitus (Bennett & Dolin & Blaser, 2019).
Musculoskeletal system: arthralgia, myalgia.
Genitourinary system: hot flashes, decreased libido, dysmenorrhea, prostatitis (Bennett & Dolin & Blaser, 2019).
Allergic reactions: skin rash, erythema, hyperthermia, angioedema, bronchospasm, anaphylaxis, photosensitization, Stevens-Johnson syndrome, toxic epidermal necrolysis (Bennett & Dolin & Blaser, 2019).
Local reactions: pain at the injection site.
Other: hair loss, alopecia, hair texture disorders, dry skin, hypothyroidism, chest pain, thirst, fungal infection, viral infection (including herpes), flu-like syndrome, sweating, lymphadenopathy. Medical personnel performing inhalation administration may suffer from headache, itching, eye hyperemia or swollen eyelids (Bennett & Dolin & Blaser, 2019).
Contraindications to Use
The use of the drug is contraindicated if the patient has chronic heart failure stage, myocardial infarction, renal failure, severe anemia, severe hepatic insufficiency, decompensated cirrhosis, autoimmune diseases, untreatable thyroid disease, and severe depression with suicidal tendencies (Bennett & Dolin & Blaser, 2019). Also prohibited to children and adolescents under 18 years old, pregnant women, and individuals with lactation, and hypersensitivity to ribavirin.
Can be used only in case of hospitalization with specialized intensive care unit. Ribavirin can be used in patients who require resuscitation only by specialists experienced in resuscitation measures. Use with caution in women of reproductive age (pregnancy is undesirable), in patients with decompensated diabetes mellitus (with episodes of ketoacidosis), COPD, pulmonary embolism, chronic heart failure, thyroid disease (including thyrotoxicosis), clotting disorders, thrombophlebitis, myelosuppression, hemoglobinopathy (including thalassemia, sickle cell anemia), depression, suicidal tendencies (including history), concomitant HIV infection (with combined highly active antiretroviral therapy – risk of lactacidosis), elderly patients. Medical personnel using ribavirin should take into account its teratogenicity. The allowable period of preservation of drug interaction usually refers to a period of up to two months, which is explained by the long and slow elimination of the substance from the body. Therapeutic efficacy is increased when concomitantly used with Interferon. Co-administration with ribavirin may decrease the efficacy of stavudine and zidovudine.
In the absence of signs of respiratory failure and symptoms of developing laryngospasm, the Ribavirin inhalation solution may be used. In experimental studies in a model of macaque rhesus infected with MERS-CoV, the effectiveness of using a combination of Ribavirin and Interferon-α2b (IFN-α2b) was shown, which allowed the authors to conclude that this method of MERS-CoV treatment is promising (Bennett & Dolin & Blaser, 2019).
Combination therapy with these two drugs was used to treat 5 patients with MERS-CoV (Bennett & Dolin & Blaser, 2019). Ribavirin was used in doses of up to 2,000 mg daily (400-600 mg every 8 hours) in combination with administration of IFN-α2b in a dose of 100 mcg twice daily subcutaneously. However, therapy with ribavirin combined with IFN-α2b was started at a late stage of the disease (on average, on 19 days from the disease onset), when all 5 patients were already in extremely serious condition with severe respiratory failure (Bennett & Dolin & Blaser, 2019). Despite the lack of effect of therapy, timely treatment started early in the course of the disease can lead to positive therapeutic results.
Bennett, J. E., Dolin, R., Blaser, M. J. (2019). Mandell, Douglas, and Bennett’s principles and practice of infectious diseases e-book. Elsevier Health Sciences.
Gardenshire, D. S. (2019). Rau’s respiratory care pharmacology. Elsevier – Health Sciences Division.
Jardins, T. D., Burton, G. G. (2019). Clinical manifestations & assessment of respiratory disease e-book. Elsevier Health Sciences.