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Ribavirin
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Initiation of therapy for HCV infection:[63286]
Place in therapy for HCV infection:[63286]
6 g (as 20 mg/mL solution) aerosolized over 12 to 18 hours daily for 3 to 7 days.[68199] [68200] [68202] [68203] [68208] Longer treatment may be needed for those with severe infections.[68200] [68202] [68208] Using a ribavirin solution of 20 mg/mL, the average aerosol dose for a 12-hour delivery period would be ribavirin 190 mcg/liter of air.[42030]
2 g (as 60 mg/mL solution) aerosolized over 2 to 4 hours given every 8 hours for 3 to 7 days.[68199] [68200] [68202] [68203] [68204] [68208] Longer treatment may be needed for those with severe infections.[68200] [68202] [68204] [68208]
Optimal dosing has not been established and variable dosage regimens are reported. Most common dosage regimens are a fixed dose of 800 mg PO twice daily or 600 mg PO 3 times daily or a weight-based dose of 10 mg/kg loading dose (Max: 600 mg/dose) PO on day 1, followed by 10 to 30 mg/kg/day (Usual Max: 1,800 mg/day) PO divided every 8 hours.[68199] [68208] [68211] [68212] [68214] [68215] [68224] [68238] [68239] [68240] Treatment duration is usually 5 to 10 days; however, longer treatment may be needed for those with severe infections.[68211] [68212] [68214] [68238] [68239]
Optimal dosing has not been established and variable dosage regimens are reported. Most common dosage regimens are a fixed dose of 600 mg PO 2 to 3 times daily or a weight-based dose of 10 mg/kg loading dose (Max: 600 mg/dose) PO on day 1, followed by 10 to 30 mg/kg/day (Usual Max: 1,800 mg/day) PO divided every 8 hours.[68199] [68208] [68211] [68212] [68214] [68215] [68224] [68238] [68239] [68240] Treatment duration is usually 5 to 10 days; however, longer treatment may be needed for those with severe infections.[68211] [68212] [68214] [68238] [68239]
6 g (as 20 mg/mL solution) aerosolized over 12 to 18 hours daily for 3 to 7 days.[42030] [68200] [68202] [68203] [68210] Longer treatment may be needed for those with severe infections.[68200] [68202] [68209] [68210] Using a ribavirin solution of 20 mg/mL, the average aerosol dose for a 12-hour delivery period would be ribavirin 190 mcg/liter of air.[42030] [68198]
6 g (as 20 mg/mL solution) aerosolized over 12 to 18 hours daily for 3 to 7 days.[42030] [68198] [68200] [68202] [68203] [68210] Longer treatment may be needed for those with severe infections.[68200] [68202] [68209] [68210] Using a ribavirin solution of 20 mg/mL, the average aerosol dose for a 12-hour delivery period would be ribavirin 190 mcg/liter of air.[42030]
6 g (as 20 mg/mL solution) aerosolized over 12 to 18 hours daily for 3 to 7 days.[42030] [68198] [68200] [68202] [68203] [68210] Longer treatment may be needed for those with severe infections.[68200] [68202] [68209] [68210] Using a ribavirin solution of 20 mg/mL, the average aerosol dose for a 12-hour delivery period would be ribavirin 190 mcg/liter of air.[42030]
2 g (as 60 mg/mL solution) aerosolized over 2 to 4 hours given every 8 hours for 3 to 7 days.[68198] [68200] [68203] [68210] Longer treatment may be needed for those with severe infections.[68200] [68202] [68209] [68210]
2 g (as 60 mg/mL solution) aerosolized over 2 to 4 hours given every 8 hours for 3 to 7 days.[68198] [68200] [68203] [68210] Longer treatment may be needed for those with severe infections.[68200] [68202] [68209] [68210]
15 to 25 mg/kg/day (Usual Max: 1,800 mg/day) PO divided every 8 to 12 hours has been used in high-risk pediatric oncology patients; however, data are very limited and dosing is not well established. Treatment duration is usually 7 to 10 days or until symptoms have resolved.[68214] [68218] [68219] [68220] [68221]
NOTE: Ribavirin monotherapy is not effective for hepatitis C infection.[29161] [34879]
600 mg PO in the morning and 800 mg PO in the evening for 12 weeks.[60523]
600 mg PO twice daily for 12 weeks.[60523]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[60523]
400 mg PO twice daily for 12 weeks.[60523]
600 mg PO twice daily for 12 weeks.[34879] [60523]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[34879] [60523]
400 mg PO twice daily for 12 weeks.[34879] [60523]
200 mg PO in the morning and 400 mg PO in the evening for 12 weeks.[34879] [60523]
200 mg PO twice daily for 12 weeks.[34879] [60523]
600 mg PO in the morning and 800 mg PO in the evening for 16 weeks.[60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
600 mg PO twice daily for 16 weeks.[60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 16 weeks.[60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
400 mg PO twice daily for 16 weeks.[60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
600 mg PO twice daily for 16 weeks.[34879] [60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 16 weeks.[34879] [60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
400 mg PO twice daily for 16 weeks.[34879] [60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
200 mg PO in the morning and 400 mg PO in the evening for 16 weeks.[34879] [60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
200 mg PO twice daily for 16 weeks.[34879] [60523] Guidelines recommend against use in patients with NS5A resistance-associated polymorphisms.[63286]
600 mg PO twice daily for 16 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 16 weeks.[63286]
600 mg PO twice daily for 16 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 16 weeks.[63286]
600 mg PO twice daily for 24 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks.[63286]
600 mg PO twice daily for 12 weeks.[58167]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[58167]
600 mg PO twice daily for 12 weeks.[58167]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[58167]
400 mg PO twice daily for 12 weeks.[58167]
200 mg PO in the morning and 400 mg PO in the evening for 12 weeks.[58167]
15 mg/kg/day PO given in 2 divided doses for 12 weeks.[58167]
600 mg PO twice daily for 12 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[63286]
600 mg PO twice daily for 12 weeks.[58167] Guidelines recommend without the addition of ribavirin.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[58167] Guidelines recommend without the addition of ribavirin.[63286]
600 mg PO twice daily for 12 weeks.[58167]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[58167]
400 mg PO twice daily for 12 weeks.[58167]
200 mg PO in the morning and 400 mg PO in the evening for 12 weeks.[58167]
15 mg/kg/day PO given in 2 divided doses for 12 weeks.[58167]
600 mg PO twice daily for 12 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[63286]
600 mg PO twice daily for 12 weeks.[56528]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[56528]
600 mg PO twice daily for 24 weeks when not eligible for interferon; however, this regimen may be less effective.[56528]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks when not eligible for interferon; however, this regimen may be less effective.[56528]
600 mg PO twice daily for 12 weeks.[56528]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[56528]
600 mg PO twice daily for 12 weeks.[56528]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[56528]
400 mg PO twice daily for 12 weeks.[56528]
200 mg PO in the morning and 400 mg PO in the evening for 12 weeks.[56528]
15 mg/kg/day PO given in 2 divided doses for 12 weeks.[56528]
600 mg PO twice daily for 24 weeks.[56528]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks.[56528]
600 mg PO twice daily for 24 weeks.[56528]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks.[56528]
400 mg PO twice daily for 24 weeks.[56528]
200 mg PO in the morning and 400 mg PO in the evening for 24 weeks.[56528]
15 mg/kg/day PO given in 2 divided doses for 24 weeks.[56528]
600 mg PO twice daily for up to 48 weeks or until liver transplant, whichever occurs first, to prevent post-transplant HCV infection.[56528]
400 mg PO in the morning and 600 mg PO in the evening for up to 48 weeks or until liver transplant, whichever occurs first, to prevent post-transplant HCV infection.[56528]
600 mg PO twice daily for up to 48 weeks or until liver transplant, whichever occurs first, to prevent post-transplant HCV infection.[56528]
400 mg PO in the morning and 600 mg PO in the evening for up to 48 weeks or until liver transplant, whichever occurs first, to prevent post-transplant HCV infection.[56528]
400 mg PO twice daily for up to 48 weeks or until liver transplant, whichever occurs first, to prevent post-transplant HCV infection.[56528]
200 mg PO in the morning and 400 mg PO in the evening for up to 48 weeks or until liver transplant, whichever occurs first, to prevent post-transplant HCV infection.[56528]
15 mg/kg/day PO given in 2 divided doses for up to 48 weeks or until liver transplant, whichever occurs first, to prevent post-transplant HCV infection.[56528]
600 mg PO twice daily for 12 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[63286]
600 mg PO twice daily for 12 weeks.[60911]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[60911]
600 mg PO twice daily for 12 weeks.[60911]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[60911]
400 mg PO twice daily for 12 weeks.[60911]
200 mg PO in the morning and 400 mg PO in the evening for 12 weeks.[60911]
15 mg/kg/day PO given in 2 divided doses for 12 weeks.[60911]
600 mg PO twice daily for 24 weeks. Recommendation includes patients who may or may not be candidates for liver transplant, including those with hepatocellular carcinoma.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks. Recommendation includes patients who may or may not be candidates for liver transplant, including those with hepatocellular carcinoma.[63286]
600 mg PO twice daily for 12 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[63286]
600 mg PO twice daily for 24 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks.[63286]
600 mg PO twice daily for 12 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[63286]
600 mg PO twice daily for 24 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks.[63286]
600 mg PO twice daily for 12 weeks.[63286]
400 mg PO in the morning and 600 mg PO in the evening for 12 weeks.[63286]
600 mg PO in the morning and 800 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2b in treatment-naive or experienced persons. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
600 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2b in treatment-naive or experienced persons. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2b in treatment-naive or experienced persons. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
400 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2b in treatment-naive or experienced persons. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
600 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
15 mg/kg/day PO given in 2 divided doses for 48 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
600 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2a. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
600 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
200 mg PO in the morning and 400 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
200 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
600 mg PO in the morning and 800 mg PO in the evening for 24 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks.[29161]
600 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks.[29161]
400 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks.[29161]
600 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
15 mg/kg/day PO given in 2 divided doses for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2a. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
600 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
200 mg PO in the morning and 400 mg PO in the evening for 24 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
200 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
600 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2a. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
600 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
400 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
200 mg PO in the morning and 400 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
200 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Maintain pediatric dosing throughout the completion of therapy if treatment is initiated prior to 18th birthday. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
600 mg PO in the morning and 800 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
600 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
400 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2b. Consider treatment discontinuation if there is not at least a 2 log10 reduction or undetectable HCV-RNA at 12 weeks or if HCV-RNA remains detectable after 24 weeks. Retreated patients who have detectable HCV-RNA at week 12 or 24 are unlikely to achieve a sustained virologic response (SVR), and treatment discontinuation should be considered.[29161]
600 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
15 mg/kg/day PO given in 2 divided doses for 24 weeks in combination with peginterferon alfa-2b. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 48 weeks in combination with peginterferon alfa-2a. Treatment is approved for patients with clinically stable HIV disease and a CD4 count more than 100 cells/mm3. Consider treatment discontinuation if the HCV-RNA is not undetectable after 24 weeks or if there is not at least a 2 log10 reduction by 12 weeks.[34879]
600 mg PO twice daily for 24 to 48 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. There are no safety or efficacy data on treatment longer than 48 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 to 48 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. There are no safety or efficacy data on treatment longer than 48 weeks.[29161]
600 mg PO twice daily for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
15 mg/kg/day PO given in 2 divided doses for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
600 mg PO twice daily for 24 to 48 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. There are no safety or efficacy data on treatment longer than 48 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 to 48 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks. There are no safety or efficacy data on treatment longer than 48 weeks.[29161]
600 mg PO twice daily for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
15 mg/kg/day PO given in 2 divided doses for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
600 mg PO twice daily for 24 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
600 mg PO twice daily for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
15 mg/kg/day PO given in 2 divided doses for 48 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
600 mg PO twice daily for 24 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
600 mg PO twice daily for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO in the morning and 600 mg PO in the evening for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
400 mg PO twice daily for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
15 mg/kg/day PO given in 2 divided doses for 24 weeks. Patients who reach their 18th birthday while on therapy should remain on the pediatric dosing regimen. Consider treatment discontinuation if an HCV-RNA value below the level of detection has not been achieved at 24 weeks.[29161]
NOTE: Ribavirin has been designated an orphan drug by the FDA for hemorrhagic fever with renal syndrome (HFRS).
A loading dose of 33 mg/kg IV, followed by 16 mg/kg IV every 6 hours for 4 days, then 8 mg/kg IV every 8 hours for 3 days (total 7 day course). Therapy may only benefit patients who have been febrile for 6 days or less.
400 mg PO twice daily for 10 days OR 600 mg PO 4 times daily for 10 days OR 10 mg/kg PO 4 times daily for 5 to 8 days in high-risk contacts. The Centers for Disease Control and Prevention (CDC) supports ribavirin for treatment of Lassa fever but does not address ribavirin prophylaxis.[46506] [58935] [58936] [58937]
600 mg PO 4 times daily for 10 days in high-risk contacts.[58936] The Centers for Disease Control and Prevention (CDC) supports ribavirin for treatment of Lassa fever but does not address ribavirin prophylaxis.[58937]
400 mg PO 4 times daily for 10 days in high-risk contacts.[58936] The Centers for Disease Control and Prevention (CDC) supports ribavirin for treatment of Lassa fever but does not address ribavirin prophylaxis.[58937]
Various regimens have been used. Typically the following has been given 33 mg/kg IV loading dose, followed by 16 mg/kg IV every 6 hours for 4 days, then 8 mg/kg IV every 8 hours for 3 to 6 days (total 7 to 10 day course). Other reports use a 35 mg/kg IV loading dose then 25 mg/kg IV every 8 hours or 15 mg/kg IV every 6 hours.
Although ribavirin is recommend by the Infectious Diseases Society of America (IDSA) for SME, a specific dose has not been suggested. The guidelines do suggest that if ribavirin is administered, it should be continued for 2 to 3 weeks.[34213] In a case report, a 20 year old patient with HIV received 30 mg/kg/day IV in 3 divided doses for 1 day followed by 20 mg/kg/day in 3 divided doses for 9 days. Although this patient ultimately succumbed to SME, this was attributed to administering therapy late into the progression of the disease.[34242] In a second case report of a 4 year old with acute leukemia, the patient received 20 mg/kg/day IV in divided doses for a 3 week course and showed clinical improvement.[34242]
Although ribavirin is recommend by the IDSA for SSPE caused by the measles virus, a specific dose has not been suggested.[34213] In a study of 5 patients (ages 3 to 15 years), intrathecal ribavirin was administered to maintain CSF concentrations between 50 to 200 mcg/ml. The initial dose administered was as 1 mg/kg diluted with saline and injected as 1 to 2 ml via the Ommaya reservoir. Doses were administered 1- to 3-times daily and ranged from 1 to 9 mg/kg/day intrathecally (max of 3 mg/kg/dose). Four of the patients showed signs of clinical improvement.[34229]
Although ribavirin is recommend by the IDSA for encephalitis caused by the Nipah virus, a specific dose has not been suggested.[34213] An open label trial of 194 patients (ribavirin n=140; oral dosage n=128) received ribavirin 2 g PO on day 1, 1.2 g PO three times daily on days 2 through 4, 1.2 g PO twice daily on days 5 and 6, and 600 mg PO twice daily for another 1 to 4 days. This study suggested that ribavirin was able to reduce mortality associated with Nipah virus without serious side effects.[34230]
Although ribavirin is recommend by the IDSA for encephalitis caused by the measles virus, a specific dose has not been suggested.[34213] An open label trial of 194 patients (ribavirin n=140; IV dosage n=12) received IV ribavirin at the end of the trial (when the IV became available) for patients unable to tolerate oral ribavirin. The dosage regimen was 30 mg/kg IV as a loading dose, then 16 mg/kg IV every 6 hours for 4 days, followed by 8 mg/kg IV every 8 hours for 3 days. The authors concluded that there were too few patients that received IV therapy to make any conclusions regarding success of therapy.[34230]
The IDSA recommends against using ribavirin for West Nile encephalitis due to lack of conclusive efficacy.[34213]
NOTE: Other than supportive care, there is no established treatment for West Nile virus infection. The use of ribavirin is suggested by in vitro data only.
In one case report, a 4-year old child with lymphoma was diagnosed with West Nile virus infection based on positive IgM specific antibodies. Beginning on day 8 of admission, ribavirin 200 mg PO four times per day was given via nasogastric tube for 14 days. The WBC count gradually increased and normalized by the 12th day of admission. Slow improvement in the child's neurological status was noted at the beginning of the third week.[27073] An in vitro study has suggested that oral doses of ribavirin (2400 mg/day) are not sufficient to treat West Nile virus infection; these authors suggest using intravenous ribavirin at doses of 4 g/day in adults (e.g., 33 mg/kg IV, followed by 16 mg/kg IV every 6 hours).[27072] The Infectious Disease Society of America (IDSA) recommends against using ribavirin for West Nile encephalitis due to lack of conclusive efficacy.[34213]
Dosage not established. 400 mg IV every 8 hours OR 1.2 g PO every 8 hours OR 2 g PO loading dose followed by 1 g (less than 75 kg) or 1.2 g (75 kg or more) PO once daily has been reported.[58875] [58876] [58877]
NOTE: The use of ribavirin for hemorrhagic fever with renal syndrome (HFRS) secondary to Crimean-Congo virus is supported by in vitro data.
33 mg/kg IV loading dose, then 16 mg/kg IV every 6 hours for 4 days, then 8 mg/kg IV every 8 hours for 6 days.
2 g PO 4 times daily for 7 days OR 2 g PO loading dose, then 2 g/day PO for 4 days, then 1.2 g/day PO for 3 days OR 2 g PO loading dose, then 4 g/day PO in 4 divided doses for 4 days, then 2 g/day PO in 4 divided doses for 6 days.[58886] [58888] [58889]
Dosage adjustments for oral ribavirin therapy based on anemia:
NOTE: For dosage adjustment of interferon/peginterferon products based on adverse reactions and hematologic parameters, see interferon/peginterferon Dosage/Therapeutic Drug Monitoring.
Ribavirin tablets:[34879]
NOTE: Once ribavirin tablets have been withheld due to laboratory abnormality or clinical manifestation, therapy in adult patients may be restarted at 600 mg/day PO in divided doses and increased to 800 mg/day PO in divided doses; however, it is not recommended to increase to the original dose (1000 mg/day or 1200 mg/day PO). In children and adolescents, restarting ribavirin at one-half the full dose may be attempted.
Patients with no cardiac history and hemoglobin < 10 g/dl: In adults, reduce ribavirin dose to 600 mg PO once daily (200 mg PO in AM and 400 mg PO in PM). In children and adolescents, reduce ribavirin dose as follows based on patients weight: 60 to >= 75 kg give 600 mg/day (200 mg PO in AM and 400 mg PO in PM); 34—59 kg give 400 mg/day (200 mg PO in AM and PM); 23—33 kg give 200 mg once daily in AM.
Patients with no cardiac history and hemoglobin < 8.5 g/dl: Discontinue ribavirin therapy.
Patients with a history of stable cardiovascular disease whose hemoglobin decreases by >= 2 g/dl during any 4-week period: In adults, reduce ribavirin dose to 600 mg/day PO (200 mg PO in AM and 400 mg PO in PM). In children and adolescents, reduce ribavirin dose as follows based on patients weight: 60 to >= 75 kg give 600 mg/day (200 mg PO in AM and 400 mg PO in PM); 34—59 kg give 400 mg/day (200 mg PO in AM and PM); 23—33 kg give 200 mg once daily in AM.
Patients with a history of stable cardiovascular disease whose hemoglobin is < 12 g/dl despite 4 weeks of a reduced ribavirin dose: Discontinue ribavirin therapy.
Ribavirin capsules/solution:[29161]
For hemoglobin 8.5—10 g/dl: For adults, reduce the dose by 200 mg/day PO (except patients receiving 1400 mg/day should reduce ribavirin dose by 400 mg/day). If a second dose reduction is necessary, reduce ribavirin dose by an additional 200 mg/day PO. For pediatric patients, reduce ribavirin dose to 12 mg/kg/day PO. If a second dose reduction is necessary, reduce ribavirin dose to 8 mg/kg/day PO.
For hemoglobin < 8.5 g/dl, white blood cell count < 1 x109/L, neutrophil count < 0.5 x109/L, platelet count < 25 x109/L (adults) or < 50 x109/L (pediatric patients), or creatinine > 2 mg/dl (pediatric patients): Permanently discontinue ribavirin.
For a > 2 g/dl decrease in hemoglobin during any 4-week period in patients with a history of stable cardiovascular disease: For adults, reduce ribavirin dose by 200 mg/day and reduce Intron A/PegIntron dose by 50%. For pediatric patients, a reduced ribavirin dose, weekly evaluations, and hematology testing are advised. The first ribavirin dose reduction is to 12 mg/kg/day, and the second reduction is to 8 mg/kg/day. Permanently discontinue both ribavirin and Intron A/PegIntron if the hemoglobin concentration is < 8.5 g/dl or < 12 g/dl after four week of the reduced dose.
Dependent on route of administration and indication for therapy.
Dependent on route of administration and indication for therapy.
Dependent on route of administration and indication for therapy.
Dependent on route of administration and indication for therapy.
Dependent on route of administration and indication for therapy.
Specific guidelines for oral dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed. Safety and efficacy have not been established in patients with decompensated hepatic disease.[29161][34879]
Treatment of chronic HCV infection
Oral capsule (Rebetol):
CrCl 50 mL/minute or more: No dose adjustment needed. Closely monitor older patients (older than 50 years of age) for development of anemia.
CrCl less than 50 mL/minute: Use is contraindicated.[29161]
Oral tablet:
NOTE: If severe adverse reactions or laboratory abnormalities develop in patients with renal impairment, discontinue ribavirin therapy; further dose modifications are not recommended.[34879]
CrCl more than 50 mL/minute: No dose adjustment needed. Closely monitor older patients (older than 50 years of age) for development of anemia.
CrCl 30 to 50 mL/minute: Reduce to alternating doses of 400 mg and 200 mg PO every other day.
CrCl less than 30 mL/minute: Reduce dose to 200 mg PO daily.[34879]
Treatment of respiratory syncytial virus (RSV) infection†
Oral capsule or tablet:
NOTE: Ribavirin dosage should be adjusted for renal impairment; however, optimal dosing has not been established and variable dosage regimens are reported.[68214][68224][68239] One study reported a dose reduction to 400 mg PO twice daily (from 600 mg or 800 mg PO twice daily) for patients with mild renal impairment.[68212] Another protocol recommends the following dose adjustments based on a dose of 10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours.
CrCl 30 to 50 mL/minute: Maximum dose of 200 mg PO every 8 hours.
CrCl 10 to 29 mL/minute: Recommendations unavailable; some experts use 200 mg PO once daily under close clinical and laboratory monitoring.[68208]
If severe adverse reactions or laboratory abnormalities develop in patients with renal impairment, discontinue ribavirin therapy; further dose modifications are not recommended.[34879]
Intermittent hemodialysis
Oral capsule (Rebetol): Use is contraindicated.[29161]
Oral tablet: Reduce dose to 200 mg PO daily.[34879]
† Off-label indication
Ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a synthetic guanosine analog with antiviral activity. It has been shown to be active against many DNA and RNA viruses. Oral ribavirin monotherapy is not effective in the treatment of chronic hepatitis C; however, it can be used in combination with interferon alfa, peginterferon alfa, or a direct acting antiviral (DAA).[29161] Ribavirin has been recognized as useful in the treatment of herpes zoster and herpes genitalis infections, as well as varicella. Ribavirin is used as an aerosolized single agent and off-label as an oral agent to treat respiratory syncytial virus (RSV) infections. Intravenous ribavirin is available from the US Centers for Disease Control and Prevention for the treatment of Hantaan virus infection and Lassa fever.[29161][34879][42030]
For storage information, see the specific product information within the How Supplied section.
NOTE: A MedGuide is available for ribavirin and is to be dispensed with every prescription and prescription refill. The MedGuide discusses potential birth defects and use of birth control, risk of anemia, and ineffective use as monotherapy for the treatment of hepatitis C.
Hazardous Drugs Classification
NOTE: Ribavirin is not approved by the FDA for intravenous administration.
Preparation of 20 mg/mL aerosol solution
Preparation of 60 mg/mL aerosol solution†
Mechanically ventilated patients
Non-mechanically ventilated patients
Psychological adverse events have been reported with the use of systemic ribavirin, including suicide or suicidal ideation (< 1%). Suicidal ideation or attempts occurred more frequently among pediatric patients, primarily adolescents, compared to adult patients (2.4% versus 1%) during treatment and off-therapy follow-up. Additional psychiatric adverse events included depression (19—36%; 1—13% of pediatric patients), insomnia (26—41%; 14% of pediatric patients), irritability/anxiety/nervousness/emotional lability (4—47%; 3—16% of pediatric patients), concentration impairment (10—21%; 5% of pediatric patients), mood alteration (5%), agitation (5—8%), and anger (2% of pediatric patients). Other adverse events occurring at a frequency of < 1% included psychosis, aggression (3% of pediatric patients), drug abuse, drug overdose, psychotic disorder, and hallucinations.[29161] [34879]
Respiratory depression has been associated with the use of ribavirin aerosol in infants. This effect can occur suddenly and is more likely to occur in infants with other life-threatening conditions. The drug can cause inflammation and emphysematous changes in the lungs. Pulmonary effects can include worsening of respiratory status, bronchospasm, pulmonary edema, hypoventilation, cyanosis, dyspnea, bacterial pneumonia, pneumothorax, apnea, atelectasis, and ventilator dependence. Prolonged use of the drug or repeated courses of treatment should be avoided. [42030] Pulmonary adverse events noted in systemic ribavirin clinical trials include dyspnea (13—26%; 5% of pediatric patients), cough (7—23%), exertional dyspnea (4%), and pulmonary embolism (<1%). Pulmonary hypertension has been noted in post-marketing reports with systemic use.[29161] [34879]
The primary toxicity of oral ribavirin therapy is hemolytic anemia, which is observed in 10% to 13% of patients receiving systemic ribavirin and interferon/peginterferon during clinical trials. The anemia associated with oral ribavirin occurs within 1 to 2 weeks of initiation of therapy. The initial drop in hemoglobin may be significant; therefore, hemoglobin or hematocrit should be obtained minimally pretreatment and at weeks 2 and 4 of therapy and then as needed. Fatal and non-fatal myocardial infarction and difficulty breathing have been reported in patients with ribavirin-induced anemia. Dosage adjustments are required in some patients who develop anemia. Anemia has been reported in 11% to 67% of patients (11% of pediatric patients) during clinical trials. Pure red cell aplasia (PRCA) has been noted in postmarketing reports. Aplastic anemia has been reported in less than 1% of patients during clinical trials.[29161] [34879]
Leukopenia (5—10%; 10% of pediatric patients), neutropenia (8—31%; 1—33% of pediatric patients), lymphopenia (12—14%), and thrombocytopenia (< 1—5%) occurred during systemic ribavirin clinical trials.[29161] [34879]
Cardiac arrest, hypotension, bradycardia, digitalis toxicity, bigeminy, and sinus tachycardia have been reported with oral inhalation of ribavirin and may be dose-related since systemic toxicity is generally low. Patients with underlying congenital heart disease are more likely to experience these events.[42030] Chest pain (unspecified) has been noted in 5—9% of patients (5% of pediatric patients) during clinical trials with systemic ribavirin. Angina and arrhythmia have been reported in < 1% of patients in systemic trials.[29161]
Conjunctivitis can occur following inhalation of ribavirin. Particles of the drug in the atmosphere can cause eye discomfort. Health care workers or others exposed regularly to the patient's therapy can develop conjunctivitis, lacrimation, ocular irritation, ocular inflammation, and damage to contact lenses. Eye discomfort appears to be more severe in persons wearing contact lenses; wearing eye glasses or protective eye goggles may minimize possible side effects.[42030] Systemic ribavirin products have also been associated with conjunctivitis (4—5%) as well as blurred vision (5—6%). Oral ribavirin formulations are used in combination with alfa interferons and decrease or loss of vision, retinopathy including macular edema, retinal artery or vein thrombosis, retinal hemorrhages and cotton wool spots, optic neuritis, papilledema, and serous retinal detachment are induced or aggravated by with the use of alfa interferons. Serous retinal detachment has also been noted in post-marketing reports with systemic ribavirin. Corneal ulcer has been noted in < 1% of patients in systemic clinical trials.[29161] [34879]
Ribavirin causes teratogenesis and embryocidal effects in all animal species tested. These effects occurred at doses as low as one-twentieth of the recommended human dose. Ribavirin can be detected in human blood up to 4 weeks after dosing. Ribavirin was administered to a pregnant woman (33 weeks gestation) for influenza pneumonia complicated by respiratory failure. A normal female infant was delivered via cesarean section and is alive and well at 1 year of age.[23715] Ribavirin is known to accumulate intracellularly from where it is cleared very slowly. It is not known whether ribavirin contained in sperm will exert a potential teratogenic effect upon fertilization of the ova.[29161] [34879]
Ribavirin is a nucleoside analog that has produced positive findings in multiple in vitro and animal in vivo genotoxicity assays (i.e., causes clastogenesis), and should be considered a potential carcinogen. Ribavirin demonstrated increased incidences of mutation and cell transformation in multiple assays. Further studies are ongoing to assess the carcinogenic potential of ribavirin.[29161] [34879]
Post-marketing reports with systemic ribavirin have included hearing disorder (hearing loss and tinnitus), hearing impairment, and vertigo.[29161][34879]
Injection site reaction occurred in 5—58% (19% of pediatric patients) during ribavirin / peginterferon clinical trials. This included injection site inflammation (6—25%; 24% of pediatric patients) and injection site erythema (29% of pediatric patients) [29161] [34879]
Fever / pyrexia (21—46%; 61—80% of pediatric patients, rigors (25—48%; 25% of pediatric patients) and chills (36—39%; 21% of pediatric patients) occurred in systemic ribavirin clinical trials. Flushing occurred in 3—4% of patients in trials.[29161] [34879]
Metabolic and nutritional adverse events reported in systemic ribavirin clinical trials included anorexia (21—32%; 29—51% of pediatric patients), weight loss (10—29%; 19% of pediatric patients), and decreased appetite (22 of pediatric patients).[29161] [34879]
In systemic ribavirin clinical trials, gastrointestinal adverse events included nausea (25—47%; 18—33% of pediatric patients), vomiting (9—29%; 27—42% of pediatric patients), diarrhea (10—22%), abdominal pain (8—13%; 21% of pediatric patients), dyspepsia (5—16%; < 1% of pediatric patients), constipation (5%), gastrointestinal bleeding (< 1%), and peptic ulcer (< 1%).[29161] [34879] Oral ribavirin tablets are used in combination with peginterferon alfa-2a and dehydration has been associated with the use of peginterferon alfa-2a in postmarketing reports.[34879]
Fatigue (60—70%; 30—58% of pediatric patients), asthenia (9—68%; 5—15% of pediatric patients), malaise (4—6%), and peripheral neuropathy (< 1%) were reported during clinical trials for systemic ribavirin.[29161] [34879]
Musculoskeletal adverse events reported in systemic ribavirin clinical trials included arthralgia (21—34%; 15—17% in pediatric patients), myalgia (22—64%; 17—32% in pediatric patients), back pain (5%), musculoskeletal pain (19—28%; 21% in pediatric patients), and myositis (< 1%). Additional adverse events included right upper quadrant pain (6—12%) and unspecified pain (9—13%).[29161] [34879]
Skin and soft tissue adverse events that occurred during systemic ribavirin clinical trials included rash (5% to 29%; 17% of pediatric patients), alopecia (17% to 36%; 17% to 23% of pediatric patients), pruritus (13% to 29%; 12% of pediatric patients), dermatitis (13% to 16%), dry skin (10% to 13%), increased sweating (5% to 11%), eczema (4% to 5%), and thrombotic thrombocytopenic purpura (TTP) (less than 1%). Stevens-Johnson syndrome and toxic epidermal necrolysis have been noted in postmarketing reports.[29161] [34879] Rash has also been reported in patients receiving inhaled ribavirin.[42030]
Headache (41—66%; 62—69% of pediatric patients), dizziness (13—26%; 14—20% of pediatric patients), and memory impairment (5—6%) have been reported in clinical trials of systemic ribavirin.[29161] [34879] Cases of headache have been reported in health care workers exposed to aerosolized ribavirin.[42030]
Infectious or inflammatory adverse reported during systemic ribavirin clinical trials include pharyngitis (12—13%), rhinitis (6—8%), sinusitis (5—12%; < 1% in pediatric patients), viral infection (12%), fungal infection (1—6%), and influenza-like symptoms (13—18%; 31% in pediatric patients).[29161] [34879]
Xerostomia was noted in 4—12% of systemic ribavirin patients. Dental and periodontal disorders have been reported in patients receiving ribavirin and interferon combination therapy. As dry mouth can have a damaging effect on teeth and oral mucous membranes, advise patients to thoroughly brush their teeth twice daily, to have regular dental examinations, and to rinse their mouths if they vomit. Taste perversion (dysgeusia) was also noted in 4—9% of patients (< 1% of pediatric patients).[29161] [34879]
Data from an open-label trial of patients ages 3 to 17 years suggest that oral ribavirin may be associated with growth inhibition in pediatric patients. Weight and height gain of pediatric patients treated with peginterferon alfa-2b plus ribavirin capsules/solution lags behind predicted normal growth based on population data for the entire length of treatment. Six months after treatment, patients' weight gain rebounded to reach their predicted average; however, six months after treatment, height gain stabilized at less than the average predicted growth. Severely inhibited growth velocity (< 3rd percentile) was observed in 70% of patients while on treatment, and 20% of those patients had continued inhibited growth velocity after 6 months. Girls ages 3 to 11 years who were treated for 48 weeks had the largest average drop in height and weight.[29161]
Hypothyroidism was reported in 4—5% of patients in systemic ribavirin clinical trials. Other autoimmune phenomena were reported in < 1% of patients in trials, including hyperthyroidism, sarcoidosis, systemic lupus erythematosus, and rheumatoid arthritis.[29161] [34879]
Menstrual disorder / menstrual irregularity was noted in 6—7% of systemic ribavirin patients during clinical trials.[29161]
Systemic ribavirin is administered with alfa interferons. Chronic hepatitis C patients with cirrhosis may be at risk for hepatic decompensation (hepatic failure) and death when treated with alfa interferons (see Contraindications). Hepatomegaly (4%), cholangitis (< 1%), hepatic dysfunction (< 1%), and fatty liver (< 1%) have been reported in patients during systemic ribavirin clinical trials. Additionally, liver and renal graft rejection has been noted in post-marketing reports.[29161] [34879]
Diabetes mellitus has been noted in < 1% of patients during systemic ribavirin clinical trials and in post-marketing reports.[29161] [34879]
Cerebral hemorrhage and coma both occurred in < 1% of patients during systemic ribavirin clinical trials.[29161] [34879]
Pancreatitis has been reported in < 1% of patients during systemic ribavirin clinical trials. Therapy should be suspended in patients with signs and symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis.[29161] [34879]
Ribavirin may be used in combination with either interferon alfa-2b or peginterferon alfa-2b. Alfa interferons may cause or aggravate fatal or life-threatening neuropsychiatric disorders, such as depression, suicidal ideation, suicide attempts, completed suicides, homicidal ideation, and aggression towards others. Patients with pre-existing history of substance abuse (e.g., alcoholism), depression, or severe psychiatric disorder may be at increased risk; thus, interferon therapy must be administered with extreme caution to these patients. In addition, pediatric drug recipients (primarily adolescents) are more likely to experience suicidal ideation or attempts as compared to adults (2.4% vs. 1%). Instruct all patients to immediately report any symptoms of depression or suicidal ideation to their health care provider. Closely monitor patients for depression and other psychiatric symptoms during treatment and for 6 months after the last alfa interferon dose. Patients experiencing persistent or worsening psychiatric symptoms should be immediately discontinued from combination therapy and closely followed with appropriate medical management. Although, interferon dose reduction or cessation of combination therapy may lead to resolution of the symptoms, depression may persist and suicides have occurred after withdrawing therapy. Full resolution of symptoms may take up to 3 weeks in severe cases.[29161][29627][47391]
Ribavirin may be used in combination with alpha interferons. Patients receiving interferon alpha have developed hyperglycemia, hypoglycemia, and diabetes mellitus. Patients with preexisting diabetes mellitus may experience alterations in glucose control if given combination ribavirin; interferon therapy.[29161]
Aerosolized ribavirin therapy requires an experienced clinician. Aerosolized ribavirin use in patients with respiratory insufficiency or respiratory depression requiring mechanical ventilation should be done only by clinicians and support staff familiar with the specific ventilator being used and the administration of aerosolized ribavirin.[42030] Ribavirin can precipitate in the respiratory apparatus which can cause additional difficulty in ventilation. Strict adherence to guidelines for minimizing accumulation of ribavirin must be followed. If worsening of respiratory function occurs, aerosolized ribavirin should be withdrawn. Aerosolized ribavirin is not for use in adults.
Health care workers or others subjected to regular ocular exposure to aerosolized ribavirin can develop ocular irritation. Eye discomfort appears to be more severe in persons wearing contact lenses; wearing eye glasses or protective eye goggles may minimize possible side effects.
Ribavirin is contraindicated for use during pregnancy, in females of childbearing potential who may become pregnant, or in males whose female partners are pregnant. The drug has been associated with birth defects (including male-mediated teratogenicity) and death of the exposed fetus (intrauterine fetal death). Available data from the Ribavirin Pregnancy Registry, show a higher rate of birth defects among live birth from directly exposed mother (9.09%, n = 88) and indirectly exposed mother (by a male partner; 6.12%, n = 98) compared to a background birth defect rate of 2.72%. Animal studies indicate teratogenic (e.g., malformations of skull, palate, eye, jaw, limbs, skeleton, and gastrointestinal tract) or embryocidal properties in all species tested. The incidence and severity of these effects increased with increasing ribavirin dose. Health care workers who are pregnant or trying to get pregnant should avoid contact with patients receiving aerosolized ribavirin; however, no reports of teratogenesis in babies of mothers who were exposed to aerosolized ribavirin during pregnancy have been confirmed. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients if ribavirin is prescribed. The health care provider must be informed right away if a female patient becomes pregnant while taking ribavirin or within 9 months after discontinuing treatment. Similarly, the provider must be notified if the sexual partner of a male patient becomes pregnant during or within 6 months of treatment with ribavirin. The drug recipient or the sexual partner of the drug recipient that becomes pregnant should be apprised of the potential hazard to the fetus.[29161]
Ribavirin should be used with caution in males because animal studies have shown that ribavirin-induced testicular degeneration and infertility may occur. Testicular degeneration appears to be reversible after stopping ribavirin with recovery occurring within 1 or 2 spermatogenesis cycles.
It is not known if ribavirin is excreted in the breast milk, although it has been shown to be toxic to nursing animals. According to the manufacturer, a decision must be made whether to discontinue nursing or discontinue treatment with ribavirin. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.[29161] [34879]
Oral ribavirin should be used with caution in patients with anemia. The major clinical toxicity of ribavirin is hemolytic anemia. Decreases in hemoglobin occur within 1—2 weeks of initiating ribavirin therapy. It is recommended that a CBC be obtained in patients prior to beginning therapy, at weeks 2 and 4 of therapy and as needed. Dosage reductions are recommended for patients who experience drops in hemoglobin to < 10 g/dl; ribavirin therapy should be discontinued in patients with hemoglobin < 8.5 g/dl (see Dosage). The anemia associated with ribavirin therapy may result in deterioration in cardiac function and/or exacerbation of the symptoms of coronary artery disease or cerebrovascular disease. Patients with history of cardiac disease should be assessed before initiation of therapy and should be appropriately monitored during therapy. If there is any deterioration in cardiac status, therapy should be suspended or discontinued (see Dosage). Because cardiac disease (e.g., angina or congestive heart failure) may be worsened by drug-induced anemia, patients with a history of significant or unstable cardiac disease should not use ribavirin therapy. Those patients with a history of myocardial infarction and/or previous or current cardiac arrhythmias should be closely monitored; fatal and nonfatal myocardial infarctions have been reported in patients with ribavirin-induced anemia.
Ribavirin may be used in combination with alpha interferons and should be given with caution to patients with bone marrow suppression, patients receiving other myelosuppressive therapy including radiation therapy, or patients with a history of neoplastic disease (cancer). Patients with preexisting infections should be treated prior to starting ribavirin; interferon therapy. It is recommended that a complete blood count (CBC) with differential be obtained in patients prior to beginning combination therapy, at weeks 2 and 4 of therapy and as needed. Combination therapy should be reduced or discontinued in patients who develop leukopenia, (white blood cell count less than 1,500/mm3), neutropenia (absolute neutrophil count less than 750/mm3) or thrombocytopenia (platelet count less than 80,000 or 50,000/mm3 depending upon dosage).[29161]
Oral ribavirin is contraindicated in patients with any hemoglobinopathy (e.g., thalassemia major, sickle cell disease).
In general, oral ribavirin should be administered to geriatric patients cautiously, starting at the lower end of the dosing range, reflecting the greater frequency of decreased renal, hepatic and/or cardiac function, and of concomitant disease or other drug therapy. In clinical trials, elderly subjects had a higher frequency of anemia (67%) than did younger patients (28%). Aerosolized ribavirin is not indicated for use in elderly patients.
The combination of ribavirin and peginterferon alfa-2a is contraindicated in patients with autoimmune hepatitis as this can cause a worsening of the hepatitis. Additionally, the combination of ribavirin and peginterferon alfa-2a are contraindicated in the treatment of cirrhotic chronic hepatitis C in patients who experience hepatic decompensation or hepatic disease (Child-Pugh score greater than 6; class B and C) before or during treatment, or in cirrhotic patients with hepatitis C and HIV coinfection. The safety and efficacy of oral ribavirin therapy have not been established in patients with liver or other organ transplant, decompensated hepatic disease, concurrent hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection, or in patients who are non-responders to interferon monotherapy. The safety and efficacy of oral ribavirin monotherapy for the treatment of certain viral infections including HIV infection, adenovirus, early RSV infection, parainfluenza, or influenza have not been established. Ribavirin capsules should not be used for such viral infection. In addition, monotherapy with ribavirin capsules is not effective in the treatment of hepatitis C; the safety and efficacy of ribavirin capsules have only been established when used as combination therapy with interferon alfa.[34879] HIV treatment guidelines recommend all adult and adolescent patients presenting with HIV infection undergo routine screening for hepatitis C virus (HCV). Additionally, perform HCV screening in any child whose mother is known to have HCV infection. For HCV seronegative individuals who are at continued high risk of acquiring hepatitis C, specifically men who have sex with men (MSM) or persons who inject drugs, additional HCV screening is recommended annually or as indicated by clinical presentation (e.g., unexplained ALT elevation), risk activities, or exposure. Similarly, the AASLD/IDSA HCV guidelines and the CDC preexposure prophylaxis (PrEP) guidelines recommend HCV serologic testing at baseline and every 12 months for MSM, transgender women, and persons who inject drugs. Use an FDA-approved immunoassay licensed for detection of HCV antibodies (anti-HCV); in settings where acute HCV infection is suspected or in persons with known prior infection that cleared spontaneously or after treatment, use of nucleic acid testing for HCV RNA is recommended. If hepatitis C and HIV coinfection is identified, consider treating both viral infections concurrently. It is recommended to use a fully suppressive antiretroviral therapy and an HCV regimen in all patients with coinfection regardless of CD4 count, as lower CD4 counts do not appear to compromise the efficacy of HCV treatment. In most patients, a simplified pangenotypic HCV regimen (i.e., glecaprevir; pibrentasvir or sofosbuvir; velpatasvir) may be an appropriate choice; however, these regimens are NOT recommended for use in persons with HCV and HIV coinfection who: are treatment-experience with HCV relapse (reinfection after successful therapy is not an exclusion); have decompensated cirrhosis; on a tenofovir disoproxil fumarate containing regimen with eGFR less than 60 mL/minute; on efavirenz, etravirine, nevirapine, or boosted protease inhibitor; have untreated chronic hepatitis B; are pregnant. Patients with HCV and HIV coinfection who meet these exclusion criteria should be treated for HCV following standard approaches as described in the AASLD/IDSA HCV guidelines. Treatment of HCV infection in children younger than 3 years is not usually recommended; however, treatment should be considered for all children 3 years and older with HCV and HIV coinfection who have no contraindications to treatment. Instruct patients with coinfection to avoid consuming alcohol, limit ingestion of potentially hepatotoxic medications, avoid iron supplementation in the absence of documented iron deficiency, and receive vaccinations against hepatitis A and hepatitis B as appropriate.[34361] [34362] [46638] [63286]
In infants, initiation of aerosolized ribavirin therapy has been associated with a sudden deterioration of respiratory function. Carefully monitor respiratory function. If a sudden deterioration of respiratory function occurs, treatment should be stopped and should be restarted with extreme caution; continuous monitoring is necessary and consideration should be given to concomitant administration of bronchodilators. The safety and efficacy of oral ribavirin therapy in children have only been established when used concomitantly with interferon alfa-2b for the treatment of chronic hepatitis C. In addition to other serious adverse events (generally similar in children compared to adults) that should be taken into consideration prior to initiating therapy in a pediatric patient, suicidal ideation or attempts occurred more frequently among pediatric patients, primarily adolescents, compared to adult patients (2.4% vs. 1%) during treatment and off-therapy follow-up. Monitor for the potential for growth inhibition in children and adolescents receiving peginterferon alfa-2b and ribavirin. Data from an open-label trial of patients ages 3 to 17 years show that weight and height gain of pediatric patients treated with peginterferon alfa-2b plus ribavirin capsules or solution lags behind predicted normal growth based on population data for the entire length of treatment. Six months after treatment, patients' weight gain rebounded to reach their predicted average; however, six months after treatment, height gain stabilized at less than the average predicted growth. Severely inhibited growth velocity (less than 3rd percentile) was observed in 70% of patients while on treatment, and 20% of those patients had continued inhibited growth velocity after 6 months. Girls ages 3 to 11 years who were treated for 48 weeks had the largest average drop in height and weight. In another study, pediatric patients receiving 48 weeks of treatment with peginterferon alfa-2a plus ribavirin tablets also demonstrated delays in weight and height increases. At the end of treatment, 43% of peginterferon alfa-2a/ribavirin treated pediatric patients experienced weight percentile decreases of at least 15 percentiles and 25% experienced height percentile decreases of at least 15 percentiles on normative growth curves. Of note most patients had returned to baseline normative growth curve percentiles by the end of the 2 year follow-up after treatment. At 2 years post-treatment, only 16% and 11% of patients were more than 15 percentiles below their baseline for weight and height, respectively. At 6 years post-treatment, post-treatment recovery in growth at 2 years had been maintained for most patients, although data were limited to 38 patients. The available longer term data is too limited to determine the risk of reduced adult height in some patients. Safety and efficacy of ribavirin capsules and solution have not been established in neonates, infants, or children younger than 3 years of age. Safety and efficacy of ribavirin tablets have not been established in neonates, infants, or children younger than 5 years or less than 23 kg.[29161] [34879]
Oral ribavirin therapy should be suspended in patients with signs and symptoms of pancreatitis and discontinued in patients with confirmed pancreatitis. Fatal and non-fatal pancreatitis has been reported in patients treated with the combination of interferon alfa and ribavirin.
Oral ribavirin therapy should not be used in patients with significant renal impairment (creatinine clearance < 50 ml/min). The mean AUC value of ribavirin was three-fold greater in patients with creatinine clearance between 10—30 ml/min than controls. Ribavirin is not removed by hemodialysis and should not be given to patients with renal failure or patients receiving dialysis.
Ribavirin may be used in combination with alpha interferons and must not be given to patients with thyroid disease (e.g., hyperthyroidism or hypothyroidism) whose thyroid function cannot be maintained in the normal range by medication. Testing of TSH levels in these patients is recommended at baseline and every 3 months following initiation of interferon alfa-2b therapy. Also, the development or exacerbation of an autoimmune thyroid disease (e.g., Graves' disease, thyroiditis) has been observed in patients receiving alpha interferons. Interferon alfa-2b should be used with caution in these patients and only if the potential benefit justifies the risk.[29627]
Females of childbearing potential must undergo pregnancy testing immediately prior to starting ribavirin therapy and periodically while being treated and for 9 months after treatment is discontinued. Due to the reproductive risk, contraception requirements exist for males and females of childbearing potential in whom ribavirin is prescribed. For females of reproductive potential, effective contraception is required during treatment and for 9 months post-therapy. For male patients and their female partners, effective contraception is required during treatment and for 6 months post-therapy.[29161]
The antiviral effect of ribavirin is not fully understood. It is phosphorylated intracellularly to mono-, di-, and triphosphate metabolites. Once phosphorylated, ribavirin disrupts cellular purine metabolism by inhibiting inosine monophosphate dehydrogenase, which leads to a decrease in guanosine triphosphate.[24689] It has been suggested that ribavirin acts as a potent RNA virus mutagen and increases the mutation rate of RNA viruses leading to 'error catastrophe.' Typically, RNA viruses have a high mutation rate that enables the virus to evolve rapidly and escape host immune mechanisms; however, the high mutation rate is also associated with the production of nonviable virions. In one virus strain, the increased mutation rate induced by ribavirin correlated with reduced formation of genomic viral RNA and decreased the infectivity of new virions. Thus, ribavirin increases the natural mutation rate beyond the limit where viable virions can be produced.[23548] Antiviral activity can be reversed by adenosine or guanosine. At high concentrations, ribavirin has some cytotoxicity within host cells.
Ribavirin also increases the production of antiviral cytokines, such as interleukin (IL)—2, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma, by Type 1 CD4 and CD8 T-cells. Type 1 T-cells are responsible for cell-mediated immunity, especially helper T-cell-mediated cytotoxic T-cell response to viral pathogens. In addition, it inhibits Type 2 T-cell-mediated immune responses. Type 2 T-cells produce IL-4, IL-5, IL-10, enhance antibody production and shift the cytokine profile from Type 1 to Type 2, which may promote viral disease progression in some cases. The ability of ribavirin to increase Type 1 and decrease Type 2 T-cell immune responses is a dose-dependent and occurs at concentrations less than those required for its antiproliferative effects.[25605]
Revision Date: 04/29/2024, 02:01:00 AMRibavirin is given by nasal/oral inhalation or orally.
Ribavirin does not bind to plasma proteins. Ribavirin has a large volume of distribution (2825 L). This may be due to extensive transport of ribavirin into cells, including erythrocytes. Transport of ribavirin into non-plasma compartments appears to take place via an e(S)-type equilibrative nucleoside transporter, which is present on virtually all cell types and may explain the extensive volume of distribution of ribavirin. Concentrations in erythrocytes continue to rise for about 4 days, while plasma concentrations decline. Concentrations in CSF are approximately 70% of plasma concentrations following prolonged administration. Data are limited on whether the drug crosses the human placenta or is excreted into breast milk; however, ribavirin is teratogenic in animal models. Ribavirin undergoes metabolism by a reversible phosphorylation pathway in nucleated cells and a degradative pathway involving deribosylation and amide hydrolysis to yield a triazole carboxylic acid metabolite. Ribavirin undergoes little or no cytochrome P450 enzyme mediated metabolism. The elimination half-life of ribavirin following a single oral dose of 600 mg is 43.6 hours; following multiple doses of ribavirin 600 mg twice daily, the elimination half-life is 298 hours, which probably reflects elimination from non-plasma compartments. Ribavirin and its triazole carboxamide and triazole carboxylic acid metabolites are extensively renally eliminated.
Ribavirin is extensively and rapidly absorbed following oral administration. Tmax following oral administration is 1 hour for the oral solution following a single dose, 1.7 hours for the capsules following a single dose, and 3 hours for the capsules following multiple dosing. Pharmacokinetic parameters for ribavirin oral solution are slightly greater than for the capsules following a single dose; ribavirin Cmax is approximately 870 ng/ml for the oral solution and 780 ng/ml for the capsules; the ribavirin AUC is approximately 14,100 ng x hr/ml for the oral solution and 13,400 ng x hr/ml for the capsules. In a single dose pharmacokinetic study, the AUC and Cmax of ribavirin are increased by 70% when ribavirin capsules are administered with a high-fat meal. There are insufficient data to address the clinical relevance of this study; however, in clinical trials with interferon alfa-2b, ribavirin was administered without regard to meals. Ribavirin undergoes extensive first-pass metabolism resulting in an absolute bioavailability of 64%. Steady state plasma levels are reached in approximately 4 weeks following oral doses of 600 mg twice daily.
Following nasal and oral inhalation the amount of ribavirin absorbed into respiratory tract secretions vary depending on method of delivery, concentration of drug in solution, and length of time of delivery. Peak concentrations in respiratory tract secretions are generally achieved at the end of the inhalation period and are greater than plasma concentrations. A small amount of systemic absorption occurs following nasal inhalation. Following inhalation, the elimination half-life is about 9.5 hours and appears to take place in a biphasic manner.
Following single doses of oral ribavirin, there was no significant difference in mean AUC values in patients with varying degrees hepatic dysfunction when compared to controls. However, the mean Cmax values increased with the severity of hepatic dysfunction and was 2-fold greater in patients with severe hepatic dysfunction (Child-Pugh Class C) as compared to controls. The multiple-dose pharmacokinetic parameters of ribavirin capsules are similar in adult and pediatric (5—16 years of age) patients when ribavirin is administered with interferon alfa for chronic hepatitis C infection.
In patients with renal dysfunction, the mean AUC values of oral ribavirin were 3-fold greater in patients with creatinine clearance values between 10—30 ml/min and 2-fold greater in patients with creatinine clearance of 30—60 ml/min as compared to control patients with creatinine clearances of > 90 ml/min. Ribavirin is not removed by hemodialysis.
The multiple-dose pharmacokinetic parameters of ribavirin capsules are similar in adult and pediatric (5—16 years of age) patients when ribavirin is administered with interferon alfa for chronic hepatitis C infection. Complete pharmacokinetic characteristics of ribavirin oral solution have not been determined in pediatric patients, although Cmin values were similar following administration of the oral solution or capsules during 48 weeks of therapy in pediatric patients aged 3—16 years. Studies evaluating the pharmacokinetic parameters of ribavirin tablets in pediatric patients have not been performed; safety and efficacy of ribavirin tablets have not been established in patients < 5 years of age.[34879]
Ribavirin is contraindicated for use during pregnancy, in females of childbearing potential who may become pregnant, or in males whose female partners are pregnant. The drug has been associated with birth defects (including male-mediated teratogenicity) and death of the exposed fetus (intrauterine fetal death). Available data from the Ribavirin Pregnancy Registry, show a higher rate of birth defects among live birth from directly exposed mother (9.09%, n = 88) and indirectly exposed mother (by a male partner; 6.12%, n = 98) compared to a background birth defect rate of 2.72%. Animal studies indicate teratogenic (e.g., malformations of skull, palate, eye, jaw, limbs, skeleton, and gastrointestinal tract) or embryocidal properties in all species tested. The incidence and severity of these effects increased with increasing ribavirin dose. Health care workers who are pregnant or trying to get pregnant should avoid contact with patients receiving aerosolized ribavirin; however, no reports of teratogenesis in babies of mothers who were exposed to aerosolized ribavirin during pregnancy have been confirmed. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients if ribavirin is prescribed. The health care provider must be informed right away if a female patient becomes pregnant while taking ribavirin or within 9 months after discontinuing treatment. Similarly, the provider must be notified if the sexual partner of a male patient becomes pregnant during or within 6 months of treatment with ribavirin. The drug recipient or the sexual partner of the drug recipient that becomes pregnant should be apprised of the potential hazard to the fetus.[29161]
It is not known if ribavirin is excreted in the breast milk, although it has been shown to be toxic to nursing animals. According to the manufacturer, a decision must be made whether to discontinue nursing or discontinue treatment with ribavirin. Consider the benefits of breast-feeding, the risk of infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.[29161] [34879]
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