Ribavirin

Pronunciation

Class: Nucleosides and Nucleotides
VA Class: AM800
Chemical Name: 1-β-D-Ribofuranosyl-1H-1,2,4-triazole-3 carboxamide
CAS Number: 36791-04-5
Brands: Copegus, Rebetol, Ribasphere, Virazole

Warning(s)

  • Oral Ribavirin
  • Ribavirin not effective alone for treatment of chronic HCV infection; do not use ribavirin monotherapy for this indication.349 377 402 403

  • Principal toxicity of oral ribavirin is hemolytic anemia which may result in worsening of cardiac disease and has resulted in fatal and nonfatal MI.349 377 402 403 Do not use ribavirin in patients with a history of clinically important or unstable cardiac disease.349 377 402 403

  • Teratogenic and/or embryocidal effects demonstrated in all animal species exposed to ribavirin.349 377 402 403 Ribavirin has a long half-life (12 days after multiple doses) and may persist in nonplasma compartments for as long as 6 months.349 377 402 403

  • Contraindicated in pregnant women and male partners of pregnant women.349 377 402 403 Extreme care must be used to avoid pregnancy during and for 6 months following ribavirin therapy in female patients and female partners of male patients receiving ribavirin.349 377 402 403 Must use at least 2 reliable forms of contraception during and for 6 months following completion of treatment.349 377 402 403

  • Ribavirin Nasal and Oral Inhalation
  • Aerosolized ribavirin (ribavirin for nasal and oral inhalation) should be used in patients requiring mechanical ventilator assistance only if clinicians and support staff are familiar with this mode of administration and the specific ventilator being used.1 Strict attention must be directed to procedures that minimize accumulation of drug precipitate, which can result in mechanical ventilator dysfunction and associated increased pulmonary pressure.1

  • Initiation of aerosolized ribavirin in infants has resulted in sudden deterioration of respiratory function.1 Monitor respiratory function carefully during treatment.1 If sudden deterioration of respiratory function occurs, discontinue the drug.1 Reinstitute only with extreme caution and continuous monitoring; consider concomitant administration of a bronchodilator.1

  • Ribavirin for nasal and oral inhalation is not indicated in adults.1

Introduction

Antiviral agent; nucleoside derivative.1 4 6 7 9 11 22 166

Uses for Ribavirin

Chronic HCV Infection

Treatment of chronic HCV infection in adults and pediatric patients with compensated liver disease.96 119 342 349 362 377 402 403 419 420 421 422 Used in conjunction with peginterferon alfa (peginterferon alfa-2a, peginterferon alfa-2b)119 342 349 362 377 387 388 402 403 419 420 421 422 423 or, less frequently, with nonconjugated interferon alfa-2b.323 324 325 326 331 332 333 338 339 340 349 362 403 428

Treatment of chronic HCV genotype 1 infection in adults with compensated liver disease; used in conjunction with peginterferon alfa (alfa-2a or alfa-2b) and an HCV nonstructural 3/4A (NS3/4A) protease inhibitor (i.e., boceprevir, telaprevir).119 121 184 185 388

Do not use alone for treatment of chronic HCV infection.349 377 402 403

Goal of antiviral therapy is sustained suppression of HCV replication and prevention of HCV-related complications (e.g., necroinflammation, fibrosis, cirrhosis, hepatocellular carcinoma) and death.96 120 When making decisions regarding treatment, consider severity of liver disease, HCV genotype, treatment history, potential for serious adverse reactions, likelihood of treatment response, presence of coexisting conditions, and patient’s readiness for treatment.96 119 120 121

American Association for the Study of Liver Diseases (AASLD) and other experts state peginterferon alfa used in conjunction with oral ribavirin is the standard of care for treatment of HCV infection (genotypes 2, 3, 4, 5, 6) in treatment-naive patients (have not previously received interferon alfa therapy) and also is recommended for previously treated patients following failure of prior therapy (nonconjugated interferon alfa monotherapy, concomitant nonconjugated interferon alfa and oral ribavirin).96 119 120 121

For initial treatment of chronic HCV genotype 1 infection in treatment-naive adults, AASLD and other experts state that an NS3/4A protease inhibitor (i.e., boceprevir, telaprevir) in conjunction with peginterferon alfa and oral ribavirin is the standard of care.119 121 This regimen also recommended for retreatment in adults who had virologic relapse or were partial responders after prior treatment with other regimens (nonconjugated interferon alfa or peginterferon alfa with or without ribavirin).119 121

Slideshow: Sovaldi and The Evolving Course of Hepatitis C Therapy

Safety and efficacy of ribavirin tablets (Copegus, Ribasphere) used in conjunction with peginterferon alfa-2a not established in patients who are previous nonresponders to interferon therapy.377 402

Safety and efficacy of oral ribavirin in conjunction with peginterferon alfa not established for treatment of chronic HCV infection in patients with decompensated liver disease,349 377 402 403 HBV coinfection,349 403 or liver or other organ transplants.349 377 387 402 403

Oral ribavirin in conjunction with peginterferon alfa-2a (Pegasys) is used for treatment of chronic HCV infection in adults with compensated liver disease who are coinfected with HIV and have clinically stable HIV disease and CD4+ T-cell counts >100 cells/mm3.96 120 121 190 377 387 423 Safety and efficacy not established in HCV and HIV coinfected patients with CD4+ T-cell counts <100 cells/mm3.377 402

Manufacturers state safety and efficacy of oral ribavirin used in conjunction with peginterferon alfa-2b (PegIntron) or interferon alfa-2b (Intron A) not established in patients with HCV and HIV coinfection.349 403

Treatment of chronic HCV infection is complex and rapidly evolving; consult a specialist to obtain the most up-to-date information regarding patient selection criteria and preferred regimens.96 119 120 121

Respiratory Syncytial Virus (RSV) Infection

Ribavirin nasal and oral inhalation used for treatment of severe lower respiratory tract infections (i.e., bronchiolitis, pneumonia) caused by RSV in hospitalized infants and young children.1 16 41 45 75 76 89 90 91 100 101 105 196 197 202 277 278 405 410 411 412 413 414 415 416 417 418

Should be considered only for infants and small children with severe RSV lower respiratory tract infections; use in mechanically ventilated patients only if clinicians and support staff are familiar with the mode of administration and specific ventilator being used.1

AAP states ribavirin nasal and oral inhalation therapy should not be used routinely in children with bronchiolitis, but may be considered in children with documented severe RSV bronchiolitis that is potentially life-threatening and in those at risk for severe disease (e.g., immunocompromised, hemodynamically important cardiopulmonary disease).105 405

Not indicated for treatment of RSV infection in adults.1

Viral Hemorrhagic Fevers

Treatment of viral hemorrhagic fevers, including Lassa fever, Hantavirus infections, infections caused by New World arenaviruses, and Crimean-Congo hemorrhagic fever.105 337 343 344 351 389 392

Only antiviral identified to date that exhibits potential efficacy for management of viral hemorrhagic fevers; however, ribavirin provides benefit only in some (not all) of these infections.343 344 351 Has some activity against Arenaviridae and Bunyaviridae, but is inactive against Filoviridae and most Flaviviridae.343 344 351

Considered the drug of choice for treatment of Lassa fever.59 104 105 177 179 219 257 258 343 351 Previously recommended for postexposure prophylaxis of Lassa fever in high-risk contacts,219 but CDC no longer recommends such prophylaxis.397 Instead, exposed individuals or contacts should be placed under medical surveillance for 21 days and treated presumptively with ribavirin if clinical evidence of viral hemorrhagic fever develops.397

Treatment of hemorrhagic fever with renal syndrome (HFRS)105 270 271 272 276 (designated an orphan drug by FDA for this use).273

Treatment of Crimean-Congo hemorrhagic fever (CCHF).105 347 389 392 Although experience limited, CDC states use of ribavirin to treat the disease and prevent infection in high-risk contacts is reasonable based on in vitro susceptibility data for this and other Bunyaviridae.219

Treatment of clinically evident viral hemorrhagic fever in the context of biologic warfare or bioterrorism when the disease is caused by Arenavirus (e.g., Lassa fever, New World hemorrhagic fever) or Bunyavirus (e.g., Rift Valley fever) or is of unknown etiology.343 351 357 Preemptive administration of ribavirin or postexposure prophylaxis with ribavirin not recommended following known or presumed exposure to hemorrhagic fever virus in the context of biologic warfare or bioterrorism.351 Those with known or presumed exposure, including high-risk contacts (i.e., individuals with mucous membrane contact with infected patient) and close contacts (i.e., individuals who live with, shake hands or hug, process laboratory specimens from, or care for infected patients [prior to initiation of appropriate precautions]) should be placed under medical surveillance for 21 days and treated presumptively with ribavirin if fever ≥38.3°C develops.351

Information on diagnosis and management of viral hemorrhagic fevers is available from Special Pathogens Branch of CDC at or at 404-639-1115 or 404-639-2888.337 397 Clinicians should immediately notify CDC's Special Pathogens Branch of any suspected cases of viral hemorrhagic fever occurring in individuals residing in or requiring evacuation to the US.337 In addition, state health departments should notify Division of Global Migration and Quarantine (DGMQ) at CDC regarding possible travel-related exposures to ensure that prompt risk assessments, notifications, and appropriate containment measures are implemented for exposed travelers.397

Adenovirus Infections

Has been used for treatment of infections caused by adenovirus in immunocompromised adults and children, including bone marrow or stem cell transplant recipients, solid organ transplant recipients (e.g., liver, kidney), and patients with leukemia or severe combined immunodeficiency.393 394 395 396

Safety and efficacy not established;349 377 only limited experience to date.393 394 395 396

Generally has been used in critically ill patients with severe adenovirus infections (e.g., hemorrhagic cystitis, nephritis, respiratory tract infections, GI infections, disseminated disease) who received multiple treatment modalities.393 395 396 Not all patients respond;393 394 396 unlikely to be of benefit if initiated late in the course of severe infections.393

Has been used for preemptive therapy in immunocompromised patients who were asymptomatic but had clinical cultures positive for adenovirus.395 Possible benefits and risks in such patients not determined; asymptomatic adenovirus infections often resolve spontaneously.395

Severe Acute Respiratory Syndrome (SARS)

Has been used empirically in some adults and a limited number of children with severe acute respiratory syndrome (SARS), alone or in conjunction with systemic corticosteroids; 367 368 369 370 371 373 380 381 382 clinical benefit of the various anti-infective regimens employed to date, including ribavirin, have been disappointing.368 369 373

Ribavirin Dosage and Administration

Administration

Administer orally349 377 402 403 or by nasal and oral inhalation.1 Also has been administered IV.105 270 271 272 276 389 393 394 395 396 397

Oral Administration

Administer ribavirin capsules,349 403 tablets,377 402 and oral solution349 with food.

Do not open, crush, or break capsules.349 403

Oral solution containing 40 mg of ribavirin per mL recommended (instead of capsules) in children ≥3 years of age weighing <47 kg.349 The oral solution may be used in any patient ≥3 years of age, regardless of weight.349

Patients should be well hydrated, especially during initial treatment.349 377 402 403

Nasal and Oral Inhalation

Ribavirin sterile powder (Virazole) must be reconstituted and diluted and administered as a solution only via nasal and oral inhalation using the Valeant small-particle aerosol generator (SPAG) Model SPAG-2 available from the manufacturer.1 162 Do not administer using any other aerosol generator and do not administer concomitantly with other drug solutions for nebulization.1

Consult the SPAG-2 manual for detailed administration instructions.1 162

In patients not requiring mechanical ventilation, ribavirin solution for nebulization should be administered from the SPAG-2 aerosol generator via an oxygen hood.1 162 If an oxygen hood cannot be used, the solution may be administered from the SPAG-2 aerosol generator via a face mask or oxygen tent;1 162 because the volume and condensation area of the solution for nebulization are larger in an oxygen tent, this may alter delivery dynamics of the drug.1

When ribavirin inhalation therapy is used in patients who require assisted ventilation, constantly monitor the patient and apparatus (e.g., in an intensive care setting).182 183 Use either a pressure or volume cycle ventilator in conjunction with the SPAG-2.1 For pressure or volume cycle ventilators, heated wire connective tubing and bacterial filters in series in the expiratory limb of the system must be used to minimize the risk of ribavirin precipitation in the system and risk of ventilator dysfunction; the filters should be changed frequently (e.g., every 4 hours).1 Water column pressure release valves should be used in the ventilator circuit for pressure cycle ventilators and may be used in the ventilator circuit for volume cycle ventilators.1 The endotracheal tube should be suctioned every 1–2 hours; monitor pulmonary pressure frequently (every 2–4 hours).1

Reconstitution and Dilution

Add a minimum of 75 mL of sterile water for injection or inhalation (additive free) to the vial containing 6 g of ribavirin; shake well.1 162 Transfer reconstituted solution to the sterile 500-mL reservoir of the SPAG-2 aerosol generator; further dilute with sterile water for injection or inhalation (additive free) to a final volume of 300 mL to provide a solution containing 20 mg/mL.1 162

Solutions that have been placed into the SPAG-2 reservoir should be discarded at least every 24 hours and prior to the addition of freshly reconstituted solution whenever the amount of solution remaining in the reservoir is low.1 162

Rate of Administration

When 20-mg/mL solution is delivered using the SPAG-2 aerosol generator according to the manufacturer's instructions, the average aerosol concentration for a 12-hour delivery period is 190 mcg/L.1

Administer the 20-mg/mL solution via the SPAG-2 aerosol generator at a rate of about 15 L/minute when using an oxygen hood or tent or about 12 L/minute when using a face mask.162

Parenteral Administration

Although not commercially available, parenteral ribavirin is available for compassionate use protocols for treatment of viral hemorrhagic fevers such as Lassa fever, Hantavirus infections, and Congo-Crimean hemorrhagic fever.337 To obtain IV ribavirin for emergency use, contact FDA for compassionate use authorization and also contact the manufacturer (Valeant Pharmaceuticals) at 800-548-5100.337

Dosage

Pediatric Patients

Treatment of Chronic HCV Infection

Must be used in conjunction with peginterferon alfa or nonconjugated interferon alfa.349 377 403

Concomitant Ribavirin Capsules (Rebetol, Ribasphere) or Oral Solution (Rebetol) and Peginterferon Alfa-2b (PegIntron) or Interferon Alfa-2b (Intron A)
Oral

Children 3–17 years of age: 15 mg/kg daily in 2 divided doses in conjunction with sub-Q peginterferon alfa-2b or interferon alfa-2b.349 403 (See Table 1.) Use oral solution in those weighing <47 kg.349 If patient reaches 18th birthday during treatment, complete treatment using pediatric dosage.349 403

Recommended treatment duration is 24 weeks for HCV genotype 2 or 3 and 48 weeks for genotype 1.349 403

With the exception of HCV genotypes 2 and 3, consider discontinuing HCV treatment if HCV RNA levels have not decreased ≥2 log10 from baseline at week 12 or remain detectable after 24 weeks of treatment.349 403

Table 1. Pediatric Dosage of Ribavirin Capsules (Rebetol, Ribasphere) or Oral Solution (Rebetol) for Concomitant Use with Peginterferon Alfa-2b (PegIntron) or Nonconjugated Interferon Alfa-2b (Intron A)349403

Weight

Ribavirin Dosage (Capsules, Oral Solution)

<47 kg

15 mg/kg daily, given as oral solution in 2 divided doses

47–59 kg

400 mg in morning and 400 mg in evening

60–73 kg

400 mg in morning and 600 mg in evening

>73 kg

600 mg in morning and 600 mg in evening

Concomitant Ribavirin Tablets (Copegus) and Peginterferon Alfa-2a (Pegasys)
Oral

Children ≥5 years of age: Approximately 15 mg/kg daily in 2 divided doses in conjunction with sub-Q peginterferon alfa-2a.377 (See Table 2.) If patient reaches 18th birthday during treatment, complete treatment using pediatric dosage.377

Recommended treatment duration is 24 weeks for HCV genotype 2 or 3 and 48 weeks for other HCV genotypes.377

Table 2. Pediatric Dosage of Ribavirin Tablets (Copegus) for Concomitant Use with Peginterferon Alfa-2a (Pegasys)377

Weight

Copegus Dosage (Tablets)

23–33 kg

200 mg in morning and 200 mg in evening

34–46 kg

200 mg in morning and 400 mg in evening

47–59 kg

400 mg in morning and 400 mg in evening

60–74 kg

400 mg in morning and 600 mg in evening

>75 kg

600 mg in morning and 600 mg in evening

Dosage Modification for Toxicity
Oral

If serious adverse effects or laboratory changes occur when oral ribavirin used in conjunction with peginterferon alfa or nonconjugated interferon alfa, modify dosage of one or both drugs, if appropriate, until adverse effects abate.349 377 403 If intolerance persists after dosage adjustment, discontinue both drugs.349 377 403

Concomitant ribavirin capsules or oral solution (Rebetol, Ribasphere) and peginterferon alfa-2b or nonconjugated interferon alfa-2b in children 3–17 years of age: If hemoglobin <10 g/dL, decrease ribavirin dosage from 15 mg/kg daily to 12 mg/kg daily and, if needed, to 8 mg/kg daily.349 403 If hemoglobin <8.5 g/dL, leukocyte count <1000/mm3, neutrophil count <500/mm3, or platelet count <50,000/mm3, permanently discontinue both drugs.349 403 In pediatric patients with preexisting cardiac conditions, closely monitor with weekly hematology evaluations if hemoglobin decreases by ≥2 g/dL during any 4-week period; discontinue if hemoglobin concentration <8.5 g/dL (or <12 g/dL after 4 weeks of reduced dosage).349

Concomitant ribavirin tablets (Copegus) and peginterferon alfa-2a in children ≥5 years of age without cardiac disease: If hemoglobin <10 g/dL, decrease ribavirin dosage to 200 mg daily (200 mg in morning) in those weighing 23–33 kg, 400 mg daily (200 mg in morning and 200 mg in evening) in those weighing 34–59 kg, or 600 mg daily (200 mg in morning and 400 mg in evening) in those weighing ≥60 kg.377 If hemoglobin <8.5 g/dL, discontinue both drugs.377

Concomitant ribavirin tablets (Copegus) and peginterferon alfa-2a in children ≥5 years of age with history of stable cardiac disease: If hemoglobin decreases by ≥2 g/dL during any 4-week period, decrease ribavirin dosage to 200 mg daily (200 mg in morning) in those weighing 23–33 kg, 400 mg daily (200 mg in morning and 200 mg in evening) in those weighing 34–59 kg, or 600 mg daily (200 mg in morning and 400 mg in evening) in those weighing ≥60 kg.377 If hemoglobin <12 g/dL after 4 weeks of reduced dosage, discontinue both drugs.377

Consult manufacturer's information for more specific recommendations regarding dosage modification for hematologic or other adverse effects.349 377 403

Treatment of Respiratory Syncytial Virus (RSV) Infection
Inhalation

Using a solution containing 20 mg/mL and SPAG-2 aerosol generator with an oxygen hood, face mask, or oxygen tent, deliver mist continuously for 12–18 hours daily for 3–7 days.1 162 Manufacturer recommends mist be delivered at a rate of about 15 L/minute when using an oxygen hood or tent or about 12 L/minute when using a face mask.162 The average aerosol concentration for a 12-hour delivery period is 190 mcg/L.1

Dose and administration schedule for infants requiring mechanical ventilation is the same as that for infants not requiring assisted ventilation.1

Viral Hemorrhagic Fevers
Treatment of Viral Hemorrhagic Fevers in Context of Biologic Warfare or Bioterrorism
Oral

US Army Medical Research Institute of Infectious Diseases (USAMRIID) and US Working Group on Civilian Biodefense recommend initial loading dose of 30 mg/kg, followed by 15 mg/kg daily given in 2 divided doses.343 351 Duration of treatment is 10 days.343 351

IV regimen usually preferred.343 351 Oral regimen may be used when parenteral preparation cannot be obtained or would be impractical (e.g., when large numbers of individuals require treatment in a mass casualty setting).343 351

IV

US Working Group on Civilian Biodefense recommends initial loading dose of 30 mg/kg (maximum 2 g), followed by 15 mg/kg (maximum 1 g) every 6 hours for 4 days and then 8 mg/kg (maximum 500 mg) every 8 hours for 6 days.351

IV regimen recommended for contained casualty settings if parenteral preparation can be obtained.351

Treatment of Adenovirus Infections
IV

Severe infections in immunocompromised children: 25 mg/kg daily in 3 divided doses on day 1 followed by 15 mg/kg daily in 3 divided doses on days 2–10 has been used.393 Alternatively, 15 mg/kg daily for 10 days has been used.396

Adults

Treatment of Chronic HCV Infection

Must be used in conjunction with peginterferon alfa or nonconjugated interferon alfa.349 377 402 403

Concomitant Ribavirin Capsules (Rebetol, Ribasphere) and Peginterferon Alfa-2b (PegIntron)
Oral

800–1400 mg daily (based on body weight) in 2 divided doses in conjunction with sub-Q peginterferon alfa-2b.349 403 (See Table 3.) Duration of treatment depends on history of prior treatment, HCV genotype, and treatment response.349 403 (See Table 4.)

Table 3. Adult Dosage of Ribavirin Capsules (Rebetol, Ribasphere) for Concomitant Use with Peginterferon Alfa-2b (PegIntron) for Chronic HCV Infection.349403

Weight

Total Daily Dosage of Ribavirin (Capsules)

Recommended Ribavirin Dosage Regimen (Capsules)

≤65 kg

800 mg

400 mg in morning and 400 mg in evening

66–80 kg

1 g

400 mg in morning and 600 mg in evening

81–105 kg

1.2 g

600 mg in morning and 600 mg in evening

>105 kg

1.4 g

600 mg in morning and 800 mg in evening

Table 4. Duration of Treatment with Ribavirin Capsules (Rebetol, Ribasphere) and Peginterferon Alfa-2b (PegIntron) in Adults for Chronic HCV Infection.349403

Patient Type and Response

HCV Genotype

Duration

Considerations

Treatment-naive

1

48 weeks

Consider discontinuing HCV treatment if HCV RNA has not decreased ≥2 log10 by week 12 or remains detectable after 24 weeks of treatment349 403

Treatment-naive

2,3

24 weeks

Prior failure

Any

48 weeks

Consider discontinuing HCV treatment if HCV RNA still detectable at week 12 or remains detectable after 24 weeks of treatment349 403

Concomitant Ribavirin Capsules (Rebetol, Ribasphere) and Interferon Alfa-2b (Intron A)
Oral

Adults weighing ≤75 kg: 1 g daily (400 mg in morning and 600 mg in evening) in conjunction with sub-Q interferon alfa-2b.349 403

Adults weighing >75 kg: 1.2 g daily (600 mg in morning and 600 mg in evening) in conjunction with sub-Q interferon alfa-2b.349 403

Duration of treatment depends on history of prior treatment, HCV genotype, and treatment response.349 403 In treatment-naive adults, usual duration is 24–48 weeks; consider discontinuing if HCV RNA levels are not below the limit of detection at 24 weeks.349 403 If used in adults who relapsed after prior nonconjugated interferon monotherapy, manufacturers recommend treatment duration of 24 weeks.349 403

Concomitant Ribavirin Tablets (Copegus, Ribasphere) and Peginterferon Alfa-2a (Pegasys)
Oral

Adults with HCV monoinfection (without coexisting HIV infection): 800–1200 mg daily in 2 divided doses in conjunction with sub-Q peginterferon alfa-2a.377 402 Treatment duration depends on HCV genotype.377 402 (See Table 5.)

Table 5. Adult Dosage of Ribavirin Tablets (Copegus, Ribasphere) for Concomitant Use with Peginterferon Alfa-2a (Pegasys) for Chronic HCV Monoinfection377402

HCV Genotype

Ribavirin Dosage (Tablets)

Duration

1,4

1 g daily (500 mg twice daily) in those weighing <75 kg

48 weeks

 

1.2 g daily (600 mg twice daily) in those weighing ≥75 kg

 

2,3

800 mg daily (400 mg twice daily)

24 weeks

5,6

Data insufficient to make dosage recommendations

Adults with HCV and HIV coinfection: 800 mg daily in 2 divided doses in conjunction with sub-Q peginterferon alfa-2a for 48 weeks, regardless of HCV genotype.377 402 Some experts suggest HIV-infected adults with HCV coinfection types 1, 4, 5, or 6 receive weight-based ribavirin dosage: 1 g daily (600 mg in morning and 400 mg in evening) for those weighing <75 kg or 1.2 g daily (600 mg in morning and 600 mg in evening) for those weighing ≥75 kg.190

Consider discontinuing HCV treatment if HCV RNA levels have not decreased ≥2 log10 from baseline at week 12 or are still detectable after 24 weeks of treatment.377 402

Manufacturer states safety and efficacy beyond 48 weeks of therapy not established.377 402

Dosage Modification for Toxicity
Oral

If serious adverse effects or laboratory changes occur when oral ribavirin used in conjunction with peginterferon alfa or nonconjugated interferon alfa, modify dosage of one or both drugs, if appropriate, until adverse effects abate.349 377 402 403 If intolerance persists after dosage adjustment, discontinue both drugs.349 377 402 403

Ribavirin capsules (Rebetol, Ribasphere) and peginterferon alfa-2b or interferon alfa-2b in adults: If hemoglobin decreases to <10 g/dL, decrease ribavirin dosage by 200 mg daily (or by 400 mg daily in those originally receiving 1.4 g daily); an additional dosage reduction of 200 mg daily may be used if needed.349 403 If hemoglobin <8.5 g/dL, leukocyte count <1000/mm3, neutrophil count <500/mm3, or platelet count <25,000/mm3, permanently discontinue both drugs.349 403 In those with history of stable cardiovascular disease, decrease ribavirin dosage by 200 mg daily if hemoglobin decreases by ≥2 g/dL during any 4-week period; discontinue if hemoglobin <8.5 g/dL (or <12 g/dL after 4 weeks of reduced dosage).349

Ribavirin tablets (Copegus, Ribasphere) and peginterferon alfa-2a in adults: In those without cardiac disease, decrease ribavirin dosage to 600 mg daily (200 mg in morning and 400 mg in evening) if hemoglobin decreases to <10 g/dL; discontinue the drug if hemoglobin decreases to <8.5 g/dL.377 402 In those with history of stable cardiac disease, decrease ribavirin dosage to 600 mg daily (200 mg in morning and 400 mg in evening) if hemoglobin decreases by ≥2 g/dL during any 4-week period; discontinue the drug if hemoglobin decreases to <12 g/dL after 4 weeks of reduced dosage.377 402 If ribavirin tablets have been withheld and toxicity resolves or decreases in severity, may attempt reinitiation using ribavirin dosage of 600 mg daily; may then increase ribavirin dosage to 800 mg daily if tolerated.377 402 Do not resume usual maximum recommended adult dosage of 1–1.2 g daily (see Table 5).377 402

Consult manufacturer's information for more specific recommendations regarding dosage modification for hematologic or other adverse effects.349 377 402 403

Viral Hemorrhagic Fevers
Treatment of Lassa Fever
IV

CDC and USAMRIID recommend initial loading dose of 30 mg/kg (up to 2 g), followed by 16 mg/kg (up to 1 g) every 6 hours for 4 days and then 8 mg/kg (up to 500 mg) every 8 hours for 6 days for total treatment duration of 10 days.219 343

Treatment of Hantavirus Infections
IV

Hemorrhagic fever with renal syndrome (HFRS): Initial loading dose of 33 mg/kg, followed by 16 mg/kg every 6 hours for 4 days and then 8 mg/kg every 8 hours for 3 days for a total treatment duration of 7 days has been used.270 271 276

Treatment of Crimean-Congo Hemorrhagic Fever
Oral

Initial loading dose of 30 mg/kg, followed by 15 mg/kg every 6 hours for 4 days and then 7.5 mg/kg every 8 hours for 6 days has been used.392

IV

CDC and USAMRIID recommend initial loading dose of 30 mg/kg (up to 2 g), followed by 16 mg/kg (up to 1 g) every 6 hours for 4 days and then 8 mg/kg (up to 500 mg) every 8 hours for 6 days for a total treatment duration of 10 days.219 343

Treatment of Viral Hemorrhagic Fevers in Context of Biologic Warfare or Bioterrorism
Oral

USAMRIID and US Working Group on Civilian Biodefense recommend initial loading dose of 2 g, followed by 1.2 daily given in 2 divided doses for those weighing >75 kg or 1 g daily (400 mg in morning and 600 mg in evening) for those weighing ≤75 kg.343 351 Duration of treatment is 10 days.343 351

IV regimen usually preferred.343 351 Oral regimen may be used when parenteral preparation cannot be obtained or would be impractical (e.g., when large numbers of individuals require treatment in a mass casualty setting).343 351

IV

USAMRIID and US Working Group on Civilian Biodefense recommend initial loading dose of 30 mg/kg (maximum 2 g), followed by 15 mg/kg (maximum 1 g) every 6 hours for 4 days and then 8 mg/kg (maximum 500 mg) every 8 hours for 6 days.343 351

IV regimen recommended for contained casualty settings if parenteral preparation can be obtained.343 351

Treatment of Adenovirus Infections
IV

Severe infections in immunocompromised adults: Initial 33-mg/kg loading dose followed by 16 mg/kg every 6 hours for 4 days and then 8 mg/kg every 8 hours for another 3 days or longer until relevant cultures are negative for adenovirus.394 396

Special Populations

Hepatic Impairment

Effect of hepatic impairment on pharmacokinetics of oral ribavirin not fully evaluated;349 377 402 403 peak concentrations are increased depending on severity of hepatic impairment.349 403 (See Pharmacokinetics.)

Renal Impairment

Ribavirin tablets (Copegus): Reduce dosage in adults with Clcr ≤50 mL/minute.377 For treatment of chronic HCV infection, use alternating doses of 200 mg and 400 mg every other day in adults with Clcr 30–50 mL/minute and use 200 mg daily in adults with Clcr <30 mL/minute or undergoing hemodialysis.377 Do not reduce dosage any further; if severe adverse effects or laboratory abnormalities occur, discontinue drug.377 Data insufficient to make dosage recommendations for pediatric patients with renal impairment.377

Ribavirin capsules (Rebetol, Ribasphere),349 403 tablets (Ribasphere),402 oral solution (Rebetol) and peginterferon alfa-2b or interferon alfa-2b therapy:349 Contraindicated in adults with Clcr <50 mL/minute.349 402 403

Pediatric patients with renal impairment: Discontinue ribavirin capsules or oral solution (Rebetol) and peginterferon alfa-2b or interferon alfa-2b if Scr concentrations >2 mg/dL.349

Geriatric Patients

Cautious dosage selection because of age-related decreases in renal, hepatic, and/or cardiac function.349 403 Initiate therapy at the lower end of the dosing range.349 403 (See Geriatric Precautions under Cautions.)

Cautions for Ribavirin

Contraindications

  • Oral Ribavirin
  • Hypersensitivity to ribavirin or any ingredient in the formulation.349 377 402 403 (See Sensitivity Reactions under Cautions.)

  • Women who are or may become pregnant.349 377 402 403 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Male partners of pregnant women.349 377 402 403

  • Patients with hemoglobinopathies (e.g., thalassemia major, sickle cell anemia).349 377 402 403

  • Concomitant use with didanosine.349 377 402 403 (See Interactions.)

  • Use of ribavirin capsules (Rebetol, Ribasphere), tablets (Ribasphere), and oral solution (Rebetol) in patients with Clcr <50 mL/minute.349 402 403

  • Use of concomitant oral ribavirin and peginterferon alfa in patients with autoimmune hepatitis.349 377 402 403

  • Use of concomitant oral ribavirin tablets (Copegus, Ribasphere) and peginterferon alfa-2a in cirrhotic patients with chronic HCV monoinfection (without coexisting HIV infection) who have hepatic decompensation (Child-Pugh score >6; class B and C) prior to or during treatment.377 402

  • Use of concomitant oral ribavirin tablets (Copegus, Ribasphere) and peginterferon alfa-2a in cirrhotic patients with chronic HCV infection who are coinfected with HIV and have hepatic decompensation (Child-Pugh score ≥6) prior to or during treatment.377 402

  • Ribavirin Nasal and Oral Inhalation
  • Hypersensitivity to ribavirin or any ingredient in the formulation.1 (See Sensitivity Reactions under Cautions.)

  • Women who are or may become pregnant.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Warnings/Precautions

Warnings

Concomitant Peginterferon Alfa or Interferon Alfa

Must not be used alone for treatment of chronic HCV infection.349 377 402 403

When used in conjunction with peginterferon alfa or interferon alfa, consider cautions, precautions, and contraindications associated with both oral ribavirin and peginterferon alfa or interferon alfa.349 377 402 403

When used in conjunction with peginterferon alfa and an HCV NS3/4A protease inhibitor (i.e., boceprevir, telaprevir), also consider cautions, precautions, and contraindications associated with the HCV NS3/4A protease inhibitor.184 185 If serious skin reaction occurs during oral ribavirin, peginterferon alfa, and telaprevir therapy, immediately discontinue all 3 drugs and promptly refer patient for urgent medical care.14 184

Ribavirin in conjunction with peginterferon alfa or interferon alfa is associated with substantial adverse effects including severe depression and suicidal ideation, hemolytic anemia, bone marrow suppression, autoimmune and infectious disorders, pulmonary dysfunction, pancreatitis, and diabetes.349 377 402 403 Review prescribing information and medication guide prior to initiation of therapy.349 377 402 403

Respiratory Effects

Use of aerosolized ribavirin for treatment of RSV in infants has resulted in sudden deterioration of respiratory function.1 Monitor respiratory function carefully.1 If sudden deterioration of respiratory function occurs, discontinue therapy.1 Reinstitute with extreme caution and continuous monitoring; consider concomitant administration of a bronchodilator.1

Optimum monitoring and attention to respiratory and fluid status needed in patients with severe lower respiratory tract infection due to RSV.1

Use of oral ribavirin has been associated with adverse pulmonary effects, including dyspnea, pulmonary infiltrates, pulmonary hypertension, pneumonitis, and pneumonia (sometimes fatal).349 377 402 403 Sarcoidosis or exacerbation of sarcoidosis reported rarely with oral ribavirin.349 377 402 403

Closely monitor patients who experience pulmonary infiltrates or deterioration in pulmonary function; if appropriate, discontinue ribavirin.349 377 402 403

Mechanically Ventilated Patients

Administer aerosolized ribavirin under the supervision of and by qualified clinicians and support staff experienced with the specific ventilator and mode of administration.1 (See Nasal and Oral Inhalation under Dosage and Administration.)

Fetal/Neonatal Morbidity and Mortality

Teratogenic and/or embryocidal.349 377 402 403 Exercise extreme care to avoid pregnancy in female patients and in female partners of male patients.349 377 402 403 Women of childbearing potential and men must use 2 forms of effective contraception during therapy and for 6 months following completion of therapy.349 377 402 403

Do not initiate therapy until a report of a negative pregnancy test has been obtained; the pregnancy test should be performed immediately prior to initiating therapy.349 377 402 403 Perform pregnancy testing monthly during therapy and for 6 months after therapy is completed.349 377 402 403

If pregnancy occurs in a patient or in the partner of a patient during oral ribavirin therapy or during the 6 months following completion of therapy, report such cases to the pregnancy registry at 800-593-2214.349 377 402 403

Hematologic Effects

Hemolytic anemia reported in patients receiving oral ribavirin in conjunction with interferon alfa; anemia usually occurs 1–2 weeks after initiation of therapy.349 377 402 403 Use with caution in patients with baseline risk of severe anemia (e.g., spherocytosis, history of GI bleeding).377 402

Monitor hemoglobin or hematocrit before initiating therapy, at week 2 and 4 (or more frequently if needed), and during therapy as appropriate.349 377 402 403 Dosage modification may be necessary.349 377 402 403 (See Treatment of Chronic HCV Infection under Dosage and Administration.)

Cardiovascular Effects

Fatal and nonfatal MI reported in patients with anemia due to oral ribavirin.349 377 402 403

Assess patient for cardiac disease before initiating therapy and monitor during therapy.349 377 402 403 Obtain an electrocardiogram in patients with known cardiac disease.349 377 402 403

Temporarily interrupt or discontinue therapy if cardiovascular status deteriorates.349 377 402 403 Dosage modification may be necessary.349 377 402 403 (See Treatment of Chronic HCV Infection under Dosage and Administration.)

Not recommended in those with substantial or unstable cardiac disease.349 377 402 403

Hepatic Failure

Patients with chronic HCV infection and cirrhosis may be at risk of hepatic decompensation and death during interferon alfa (including peginterferon alfa) therapy.349 377 402 403 Such patients who are coinfected with HIV and receiving highly active antiretroviral therapy (HAART) in conjunction with interferon alfa-2a therapy (with or without ribavirin) appear to be at increased risk for development of hepatic decompensation compared with patients not receiving HAART.349 377 402 403

Closely monitor clinical status and hepatic function.349 377 402 403 Decrease dosage or immediately discontinue peginterferon alfa if decompensation (Child-Pugh score ≥6) occurs.349 377 402 403

Sensitivity Reactions

Serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme, reported in patients receiving peginterferon with or without oral ribavirin.349 377 402 403

If acute hypersensitivity reactions (urticaria, angioedema, bronchoconstriction, anaphylaxis) occur, discontinue immediately and initiate appropriate medical intervention.377 402

General Precautions

Other Viral Infections

Safety and efficacy of oral ribavirin in the treatment of HIV infection, adenovirus infection, RSV infection, parainfluenzae virus infection, or influenza virus infection have not been established; oral ribavirin should not be used for these indications.349 377 402 403

Pancreatitis

Temporarily interrupt oral ribavirin in patients with manifestations of pancreatitis; discontinue in patients with confirmed pancreatitis.349 377 402 403

Dental and Periodontal Disorders

Dental and periodontal disorders reported in patients receiving oral ribavirin in conjunction with peginterferon alfa or interferon alfa; dry mouth may contribute to damage of teeth and oral mucous membranes during long-term treatment.349 403

Advise patients to have regular dental examinations during treatment, brush their teeth thoroughly twice daily, and rinse their mouth thoroughly after vomiting.349 403

Environmental Exposure of Health-care Personnel and Visitors

The potential risks, particularly for long-term and cumulative effects, associated with environmental exposure to aerosolized ribavirin by health-care personnel and visitors while in contact with patients undergoing inhalation therapy with the drug have not been elucidated; acute effects do not appear to be substantial.187 188 189 192 195 206 216 217 227 228 229 234 235 236 237 238 239 240 241 242 243 247 261 266 267 Exposure of pregnant women187 188 216 217 218 226 227 228 234 238 239 240 241 242 243 244 247 263 265 267 and possibly those who may become pregnant187 188 216 265 may represent a risk to the fetus. Consult specialized sources (e.g., National Institute for Occupational Safety and Health [NIOSH]) for recommended procedures to minimize environmental exposure.

Specific Populations

Pregnancy

Category X.1 349 377 402 403 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Pregnancy Registry at 800-593-2214 to monitor pregnancy outcomes of female patients and female partners of male patients exposed to ribavirin.349 377 402 403

Lactation

Not known whether ribavirin is distributed into human milk.349 377 402 403 Discontinue nursing or delay or discontinue the drug.349 377 402 403

Pediatric Use

Nasal and oral inhalation: Safety and efficacy established for treatment of RSV infection in infants and young children.1

Ribavirin oral capsules (Rebetol, Ribasphere) and oral solution (Rebetol): Safety and efficacy in conjunction with peginterferon alfa-2b or nonconjugated interferon alfa-2b for treatment of chronic HCV infection not established in children <3 years of age.349 403 When deciding whether to use such regimens in HCV-infected children, consider evidence of disease progression (hepatic inflammation, fibrosis), prognostic factors for response, HCV genotype, and viral load.349 403 Weigh benefits against adverse effects reported in pediatric patients.349 403 Do not use concomitant ribavirin capsules or oral solution (Rebetol) and peginterferon alfa-2b or nonconjugated interferon alfa-2b in pediatric patients with Scr >2 mg/dL.349

Ribavirin tablets (Copegus): Safety and efficacy in conjunction with peginterferon alfa-2b for treatment of chronic HCV infection not established in children <5 years of age.377

Ribavirin tablets (Ribasphere): Safety and efficacy not established in patients <18 years of age.402

Adverse effects reported with oral ribavirin in pediatric patients generally similar to those reported in adults.349 377 Suicidal ideation or attempts reported more frequently during or after oral ribavirin in pediatric patients (primarily adolescents) than in adults receiving the drug.349 Other adverse psychiatric effects (depression, emotional lability, somnolence), anemia, and neutropenia reported as in adults.349

Decreased weight and height for age z-scores as well as percentiles of the normative population reported in pediatric patients receiving peginterferon alfa and oral ribavirin therapy;349 377 403 generally return to baseline normative growth curve percentiles for weight and height at end of 2-year follow-up after completion of treatment.349 377 403

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.349 377 402 403 Higher incidence of anemia reported in geriatric patients compared with younger adults.349 403

Caution advised; start at the lower end of the dosing range due to greater frequency of decreased renal, hepatic, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.349 403

Substantially eliminated by kidneys; risk of adverse effects increased in patients with renal impairment.349 403 Monitor renal function and consider age-related decreases in renal function when selecting dosage.349 403 (See Renal Impairment under Dosage.)

Hepatic Impairment

Do not use in patients with autoimmune hepatitis or hepatic decompensation.349 377 402 403 (See Contraindications under Cautions.)

Monitor liver function before and during therapy.349 377 402

Renal Impairment

Capsules (Rebetol, Ribasphere),349 403 tablets (Ribasphere),402 oral solution (Rebetol)349 : Contraindicated in patients with Clcr <50 mL/minute.349 403

Tablets (Copegus): Use reduced dosage in adults with Clcr <50 mL/minute.377 (See Renal Impairment under Dosage.)

Common Adverse Effects

Oral: Fatigue/asthenia, headache, fever, rigors, nausea, myalgia, emotional lability/irritability.349 377 402 403

Nasal and oral inhalation: Respiratory and cardiovascular effects.1

Interactions for Ribavirin

Does not inhibit and is not a substrate for CYP450 isoenzymes.349 377 Interactions with drugs affecting or metabolized by CYP enzymes unlikely.349 377

Specific Drugs

Drug

Interaction

Comments

Antacids containing magnesium, aluminum, and simethicone (Mylanta)

Decreased ribavirin concentrations349

Clinical importance unknown349

Antiretrovirals, nucleoside reverse transcriptase inhibitors (NRTIs)

Possible increased risk of potentially fatal hepatic decompensation in cirrhotic patients with chronic HCV coinfected with HIV who are receiving peginterferon alfa (with or without ribavirin) and antiretroviral regimens that include NRTIs377 387

Didanosine: Fatal hepatic failure, peripheral neuropathy, pancreatitis, symptomatic hyperlactatemia/lactic acidosis reported349 377

Zidovudine: Possible increased risk of severe neutropenia (ANC <500/mm3) and severe anemia (hemoglobin <8 g/dL) if used concomitantly with peginterferon alfa and ribavirin377 387

Ribavirin can reduce phosphorylation of lamivudine, stavudine, and zidovudine; no evidence of pharmacokinetic or pharmacodynamic interaction when ribavirin used concomitantly with these drugs in patients coinfected with HCV and HIV349 377

Stavudine and zidovudine: In vitro evidence of antagonistic antiretroviral effects; possibility of increased risk of adverse effects173 222 279 349 352 353 354 377

If used in patients coinfected with HIV who are receiving NRTIs, closely monitor for toxicities;377 387 if worsening toxicities are observed, consider discontinuing or reducing dosage of peginterferon and/or ribavirin;377 387 if decompensation occurs (Child-Pugh score ≥6), discontinue387

Didanosine: Concomitant use contraindicated200 349 377 402 403

Stavudine: Use concomitantly with caution220 349 377 402 403

Zidovudine: Avoid concomitant use or use with caution and increased monitoring200 222 349 377 402 403

Azathioprine

Severe pancytopenia and bone marrow suppression reported in patients receiving peginterferon alfa and oral ribavirin;349 377 402 403 may be due to interaction with ribavirin which may increase accumulation of azathioprine metabolite associated with myelotoxicity349 377 402 403

If used concomitantly with oral ribavirin and peginterferon alfa, perform CBCs (including platelet counts) weekly for first month, twice monthly during second and third months, and then monthly or more frequently if necessary349 377 402 403

If pancytopenia develops, discontinue all 3 drugs (azathioprine, ribavirin, peginterferon alfa) and do not reinitiate peginterferon alfa and ribavirin concomitantly with azathioprine349 377 402 403

Interferons (interferon alfa, peginterferon alfa)

Hepatic decompensation, including some fatalities, reported in cirrhotic HCV patients coinfected with HIV receiving ribavirin, peginterferon alfa, and NRTIs349 377 402 403

Ribavirin may potentiate hematologic effects of interferons (anemia, neutropenia, lymphocytopenia);387 388 no evidence of pharmacokinetic interaction377

Ribavirin Pharmacokinetics

Absorption

Bioavailability

Absorbed rapidly from GI tract; peak plasma concentrations achieved within 1–3 hours.349 377 Bioavailability is 64%.349

Following nasal and oral inhalation, absorbed systemically from the respiratory tract.1 Concentrations achieved in respiratory tract secretions are likely to be substantially greater than those achieved in plasma.1 4 16

Food

Administration with a high-fat meal increases oral bioavailability.349 377

Special Populations

Mean peak plasma concentrations increased with severity of hepatic impairment; mean AUCs in individuals with mild, moderate, or severe hepatic impairment similar to AUCs in controls.349

Following a single oral dose of ribavirin, AUC increased twofold or threefold in non-HCV-infected individuals with Clcr 30–60 or 10–30 mL/minute, respectively.349

In HCV-infected individuals with end-stage renal disease requiring hemodialysis, ribavirin 200 mg daily (Copegus tablets) produced plasma exposures about 20% lower than exposures achieved with 1–1.2 g daily in individuals with normal renal function.377

Distribution

Extent

Ribavirin and/or its metabolites accumulate in erythrocytes.1 4 16 22 61 132 133 138 149 193

Distributes slowly into CSF.78 169 CSF concentrations approximately 70% of concurrent plasma concentrations reported in HIV-infected patients.78

Not known whether ribavirin crosses the placenta158 or distributes into milk in humans.1

Plasma Protein Binding

Not bound.349

Elimination

Metabolism

Undergoes reversible phosphorylation in nucleated cells and deribosylation and amide hydrolysis.349

Elimination Route

Following oral administration, eliminated in urine (61%) and feces (12%) as metabolites and unchanged drug (17%).349

Half-life

Rebetol capsules: 43.6 hours (single dose) and 298 hours (multiple doses).349

Copegus tablets: 120–170 hours (single dose).377

Special Populations

Clearance reduced in patients with renal impairment.349

Stability

Storage

Nasal and Oral Inhalation

For Inhalation Solution

25°C (may be exposed to 15–30°C).1 Following reconstitution, store solution under sterile conditions at 20–30°C for up to 24 hours.1

After placement in SPAG-2 reservoir, discard unused solution within 24 hours and prior to adding any newly reconstituted solution (e.g., when remaining amount of solution in reservoir is low).1

Oral

Capsules

25°C (may be exposed to 15–30°C).349 403

Oral solution

2–8°C or 25°C (may be exposed to 15–30°C).349

Tablets

25°C (may be exposed to 15–30°C).377 402

Actions and Spectrum

  • Exact mechanism of antiviral activity not fully elucidated,1 3 4 but appears to interfere with RNA3 7 21 28 34 35 140 149 166 and DNA synthesis3 7 35 38 39 140 149 166 and subsequently inhibit protein synthesis21 28 and viral replication.3 15 18 28 33 148 157

  • Antiviral activity appears to depend principally on intracellular conversion to ribavirin-5′-triphosphate3 4 6 7 16 20 22 24 140 149 161 and -monophosphate.3 4 7 16 24 29 140 149 161

  • Ribavirin is active in vitro against many RNA viruses including respiratory syncytial virus (RSV);1 44 60 61 64 many strains of influenza A1 7 16 22 31 40 44 50 55 56 58 61 66 69 70 166 and B1 7 16 22 31 40 44 50 55 56 61 66 69 166 viruses; measles virus;7 16 18 22 31 44 46 69 82 141 166 subacute sclerosing panencephalitis virus;16 18 22 31 61 69 82 166 parainfluenzae viruses;7 16 22 31 44 46 50 61 62 69 82 166 mumps virus;7 40 61 65 69 enterovirus 72 (formerly hepatitis A virus);43 148 human rhinoviruses;7 16 22 31 40 69 82 166 human reovirus 1,7 40 46 2,40 and 3;40 human rotavirus;7 Colorado tick fever virus;57 61 human immunodeficiency virus (HIV);15 48 49 54 175 195 Crimean-Congo hemorrhagic fever virus;219 Junin virus (causes Argentine hemorrhagic fever);68 185 186 various hantaviruses (including those causing Korean hemorrhagic fever and hantavirus pulmonary syndrome);164 165 yellow fever virus;68 Lassa fever virus;81 and Machupo virus (causes Bolivian hemorrhagic fever).68 The drug also has antiviral activity in vivo against hantavirus,51 68 163 Lassa fever virus,16 22 40 51 61 71 81 and Rift Valley fever virus.40 51 68 71 Some viruses, including arboviruses,7 31 40 68 71 144 rhinoviruses,7 and rotaviruses,7 40 144 that are inhibited in vitro by ribavirin may not be inhibited in vivo.

  • Ribavirin has antiviral activity in vitro against many DNA viruses including herpes simplex types 1 (HSV-1)16 22 31 40 46 50 61 63 67 69 82 166 and 2 (HSV-2);7 16 22 31 40 50 52 61 67 69 82 166 human cytomegalovirus;7 16 22 31 40 67 69 166 and human adenovirus.7 16 22 31 40 50 67 69 82 166 Cytomegalovirus may not be susceptible to the drug in vivo.7 31 40 144 In vitro, ribavirin has some activity against variola virus,383 vaccinia virus7 16 22 31 39 40 50 67 69 82 85 166 178 383 and other orthopoxviruses including camelpox,85 cowpox,85 383 and monkeypox.85 383 Although ribavirin was active against cowpox virus in a mouse model, the in vivo activity of the drug against poxvirus infections (including smallpox) in humans has not been evaluated to date.176

Advice to Patients

  • Advise patient of the benefits and risks of therapy for chronic HCV infection.349 377 402 403 Importance of reading the medication guide.349 377 402 403

  • Effect of therapy on transmission of HCV unknown; appropriate precautions to prevent transmission should be used.349 377

  • Possibility of anemia; necessity of laboratory monitoring.349 377 402 403

  • Importance of adequate hydration, especially during the initial phase of therapy.349 377 402 403

  • Importance of taking ribavirin as instructed; importance of taking with food.349 377 402 403

  • Potential for the drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual known.377 402

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.349 377

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.349 377 402 403 Advise men and women of importance of using effective contraception during and for 6 months after ribavirin therapy.349 377 402 403 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  • Importance of advising patients of other important precautionary information.349 377 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ribavirin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Nasal and Oral Inhalation

For inhalation solution

6 g

Virazole

Valeant

Oral

Capsules

200 mg*

Rebetol

Merck

Ribasphere

Kadmon

Ribavirin Capsules

Solution

40 mg/mL

Rebetol

Merck

Tablets, film-coated

200 mg*

Copegus

Genentech

Ribasphere

Kadmon

Ribavirin Tablets

400 mg*

Ribasphere

Kadmon

Ribavirin Tablets

600 mg*

Ribasphere

Kadmon

Ribavirin Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Rebetol 200MG Capsules (SCHERING): 60/$554.02 or 180/$1,633.06

Rebetol 40MG/ML Solution (SCHERING): 100/$223.98 or 300/$614.94

Ribasphere 200MG Capsules (KADMON PHARMACEUTICALS): 30/$135.61 or 90/$360.96

Ribavirin 200MG Capsules (SANDOZ): 56/$260.01 or 168/$776.02

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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