Ribavirin

Aka: Ribavirin, Virazole, Rebetol

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II. Indications

  1. Hepatitis C
    1. See Hepatitis C Treatment with Interferon and Ribavirin
    2. Largely replaced in the U.S. by other Hepatitis C Antiviral Regimens, with the exception of a few Genotypes
  2. Respiratory Syncytial Virus (RSV)
    1. Aerosolized Ribavirin (Virazole) used in high risk infants
  3. Acute Hemorrhagic Fever (Intravenous or Oral Ribavirin, not FDA approved)
    1. Arenavirus (Lassa Fever, AHF, BHF, VHF)
    2. Bunyaviridae (e.g. Hantavirus, Rift Valley Fever)
  4. Severe Influenza infection (not FDA approved)
    1. Intravenous or aerosolized

III. Contraindications

  1. Pregnancy
  2. Hemoglobinopathy
  3. Unstable cardiovascular disease
  4. Autoimmune Hepatitis
  5. Cirrhosis with Decompensation
    1. Child-Pugh Score >6 if HCV Infection only
    2. Child-Pugh Score >5 if HCV Infection and HIV Infection

IV. Pharmacokinetics

  1. Half-Life after single dose: >40 hours
  2. Half life after multiple doses: ~300 hours
    1. Extremely long half life >12 days
    2. Elimination over 5 half-lives is 60 days

V. Mechanism

  1. Synthetic antiviral Nucleoside analog of guanosine
  2. Ribavirin incorporates into viral RNA, substituting guanosine, and resulting in mutations and blocking viral replication
  3. Activity against both RNA viruses (e.g. Hepatitis CVirus) as well as DNA viruses

VI. Adverse Effects

  1. Hemolytic Anemia
    1. Increased risk in age >50 years, Renal Insufficiency
  2. Teratogenic (Pregnancy Class X)
    1. Women need to avoid conception for 6 months (2 forms of Contraception)
    2. Men should use barrier protection for 6 months

VII. Dosing: Chronic Hepatitis C

  1. Used in combination with Interferon
    1. See Hepatitis C Treatment with Interferon and Ribavirin
  2. Adult weight <75 kg
    1. Dose 400 mg orally each morning, and 600 mg orally each evening
  3. Adult weight >75 kg
    1. Dose 600 mg orally twice daily
  4. Hemolytic Anemia
    1. Dose 300 mg orally twice daily
  5. Renal Dosing
    1. eGFR 30 to 50 ml/min
      1. Alternate 200 mg with 400 mg every other day
    2. eGFR <30 ml/min
      1. Dose 200 mg orally daily

VIII. Dosing: Respiratory Syncytial Virus (RSV)

  1. Aerosolized Ribavirin (Virazole) 12 to 18 hours per day for 3 to 7 days
  2. Risk of exposure to Caregivers (avoid exposing pregnant women)

IX. Safety

  1. Pregnancy Category X
  2. Avoid in Lactation

X. Monitoring

  1. Complete Blood Count (CBC)
    1. Obtain at baseline, 2 weeks, 4 weeks and then periodically
  2. Other testing as indicated
    1. Baseline Pregnancy Test and then periodically afterward for up to 6 months after last dose
    2. Baseline Electrocardiogram if preexisting cardiac disorder

XI. Drug Interactions

  1. Warfarin
    1. May decrease INR
    2. Increased INR monitoring for 4 weeks after starting and stopping Ribavirin
  2. Nucleoside Reverse Transcriptase Inhibitor (nRTI)
    1. Lactic Acidosis risk
    2. Avoid Zidovudine and Didanosine
  3. Azathioprine
    1. Neutropenia risk
    2. Monitor CBC weekly for 1 month, every other week for 2 months and then monthly

XII. Resources

  1. Ribavirin Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eee304d0-c2ea-44f4-97d9-92a414d31b6c
  2. Ribavirin Powder for Aerosolization Solution
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=39723ea2-780c-4266-954a-869723b144c4

XIII. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. (1999) Med Lett Drugs Ther 41(1054):53-4 [PubMed]

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