Brand name: Virazole
Drug class: Nucleosides and Nucleotides

Medically reviewed by Drugs.com on Mar 10, 2025. Written by ASHP.

Introduction

Antiviral agent with activity against a variety of RNA and DNA viruses; nucleoside derivative.

Uses for Ribavirin

Chronic HCV Infection

Oral capsules used in combination with interferon alfa-2b (Intron A; no longer available in the US) or peginterferon alfa-2b (PegIntron; no longer available in the US) for treatment of chronic HCV infection in adults and pediatric patients ≥3 years of age with compensated liver disease.

Oral tablets used in combination with peginterferon alfa-2a (Pegasys) for treatment of chronic HCV infection in adults and pediatric patients ≥5 years of age with compensated liver disease.

Oral ribavirin designated an orphan drug by FDA for treatment of chronic HCV infection in pediatric patients.

Oral ribavirin in combination with interferon or peginterferon no longer recommended for treatment of chronic HCV. Current standard of care consists of direct-acting antiviral (DAA) agents; treatment with DAA agents recommended essentially for all patients with HCV, including those coinfected with HIV.

Treatment of chronic HCV infection is complex and rapidly evolving; consult a specialist to obtain the most up-to-date information. Information from the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA) regarding diagnosis and management of HCV infection, including recommendations for initial treatment and treatment in patients from HIV/HCV coinfection, is available at [Web].

Respiratory Syncytial Virus (RSV) Infection

Ribavirin nasal and oral inhalation used for treatment of severe lower respiratory tract infections caused by RSV in hospitalized infants and young children.

Manufacturer states consider use only in 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.

AAP does not recommend routine use due to limited evidence for clinically important benefit and risk of adverse effects.

Ribavirin nasal and oral inhalation has been used for treatment of RSV infection in immunocompromised adults^{† [off-label]}, including lung transplant or hematopoietic cell transplant recipients. Manufacturer states not indicated for treatment of RSV infection in adults.

Viral Hemorrhagic Fevers

Treatment of certain viral hemorrhagic fevers^{† [off-label]}, including Lassa fever^{† [off-label]}, hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus infection^{† [off-label]}, some infections caused by New World arenaviruses^{† [off-label]}, and Crimean-Congo hemorrhagic fever^†. Designated an orphan drug by FDA for treatment of HFRS^†.

Although not commercially available, IV^† ribavirin is available for compassionate use protocols for treatment of viral hemorrhagic fevers^†. The IV^† regimen is usually preferred. 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).

Information on diagnosis and management of viral hemorrhagic fevers is available from the Viral Special Pathogens Branch of CDC. If diagnosis of viral hemorrhagic fever considered, public health officials should coordinate with CDC to ensure appropriate precautions; consult with CDC Viral Special Pathogens Branch by calling the CDC Emergency Operations Center at 770-488-7100.

Adenovirus Infections

Has been used for treatment of infections caused by adenovirus^†. Safety and efficacy not established; only limited experience to date.

Coronavirus Infections

Has been used alone or in combination with other agents for treatment of severe acute respiratory syndrome^† (SARS), Middle East respiratory syndrome^† (MERS), and coronavirus disease 2019^† (COVID-19). Findings on efficacy for the treatment of these coronaviruses are contradictory.

Hepatitis E Virus (HEV) Infection

Has been used as monotherapy for treatment of chronic HEV infection^† .

Optimal treatment of chronic HEV infection not identified.

Ribavirin Dosage and Administration

General

Pretreatment Screening

• Assess standard hematologic tests (CBC including hemoglobin, differential WBC, platelet counts) prior to initiating treatment with oral ribavirin.

• Assess blood chemistries (liver function tests and thyroid-stimulating hormone [TSH]) prior to initiating treatment with oral ribavirin.

• Verify pregnancy status in females of reproductive potential prior to treatment with oral ribavirin; a negative pregnancy test is required prior to initiating therapy.

• Assess ECG in all patients prior to initiating treatment with ribavirin capsules. Assess ECG in patients with pre-existing cardiac disease prior to initiating treatment with ribavirin tablets.

• Assess renal function in all patients prior to initiating treatment with ribavirin tablets.

• Perform an eye exam at baseline in all patients prior to initiating treatment with oral ribavirin.

Patient Monitoring

• Assess standard hematologic tests, including hemoglobin (at weeks 2 and 4 of therapy, and as clinically indicated), CBC, differential WBC count, and platelet count, periodically during treatment with ribavirin capsules.

• Assess standard hematologic tests at weeks 2 and 4 of therapy, and then periodically during treatment with ribavirin tablets.

• Assess blood chemistries (liver function tests and TSH) periodically during treatment with ribavirin capsules.

• Assess blood chemistries at 4 weeks of therapy, and then periodically during treatment with ribavirin tablets.

• Verify pregnancy status in females of reproductive potential periodically during treatment with ribavirin capsules and for 9 months after stopping treatment.

• Verify pregnancy status in females of reproductive potential periodically during treatment with ribavirin tablets and for 6 months after stopping treatment.

• Assess ECG periodically during treatment with ribavirin capsules.

• Monitor cardiovascular status in patients with pre-existing cardiac disease during treatment with oral ribavirin.

• Monitor for the development of anemia in patients with impaired renal function and those >50 years of age during treatment with ribavirin capsules.

• Monitor clinical status and hepatic function for signs and symptoms of hepatic decompensation during treatment with ribavirin tablets.

• Measure hepatitis C virus (HCV)-RNA periodically during treatment.

• Monitor respiratory function carefully during treatment with ribavirin for nasal or oral inhalation.

• In infants requiring mechanical ventilation, monitor pulmonary pressure every 2—4 hours during treatment with ribavirin for nasal or oral inhalation.

• Monitor fluid status during ribavirin inhalation therapy.

• Monitor patients with severe lower respiratory tract infection due to respiratory syncytial virus (RSV) and assess respiratory and fluid status.

Dispensing and Administration Precautions

Handling

• Ribavirin is included in the NIOSH list of hazardous drugs in healthcare settings.

Other General Considerations

• Ribavirin tablets should be administered in combination with Pegasys (peginterferon alfa-2a); ribavirin tablets should never be given as monotherapy.

• Ribavirin capsules should be administered in combination with peginterferon alfa-2b (PegIntron) or interferon alfa-2b (Intron A); however, peginterferon alfa-2b and interferon alfa-2b are no longer commercially available in the US.

• Ensure patients are well hydrated during oral ribavirin therapy, especially during initial treatment.

Administration

Administer orally or by nasal and oral inhalation. Also has been administered IV^† .

Oral Administration

Available as capsules or tablets containing 200 mg of ribavirin.

Administer ribavirin capsules or tablets with food.

Do not open, crush, or break capsules.

Per manufacturer, administer ribavirin capsules in combination with peginterferon alfa-2b (PegIntron; no longer available in the US) or interferon alfa-2b (Intron A; no longer available in the US).

Per manufacturer, administer ribavirin tablets in combination with Pegasys (peginterferon alfa-2a).

If use of ribavirin tablets considered in children ≥5 years of age, ensure child can reliably swallow the tablets.

Patients should be well hydrated, especially during initial treatment.

Nasal and Oral Inhalation

Supplied as 6 grams of lyophilized powder per 100 mL vial for aerosol administration only.

Ribavirin sterile powder must be reconstituted and diluted, and then administered as a solution only via nasal and oral inhalation using the small-particle aerosol generator (SPAG) model 2 (SPAG-2).

Prior to administration, review SPAG-2 instructions for use to assure thorough familiarity with use and operation of the SPAG-2 aerosol generator.

Do not administer using any other aerosol generator and do not administer concomitantly with other drug solutions for nebulization.

In patients not requiring mechanical ventilation, ribavirin solution for nebulization should be administered from the SPAG-2 aerosol generator via an oxygen hood. 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; 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.

When ribavirin inhalation therapy is used in patients who require mechanical ventilation, use either a pressure or volume cycle ventilator in conjunction with the SPAG-2.

Administration of aerosolized ribavirin should be undertaken only by qualified clinicians and support staff experienced with the specific ventilator and mode of administration. Give strict attention to procedures shown to minimize accumulation of ribavirin precipitates in the apparatus.

Suction the endotracheal tube every 1–2 hours; monitor pulmonary pressure frequently (every 2–4 hours). For pressure or volume cycle ventilators, use heated wire connective tubing and bacterial filters in series in the expiratory limb of the system to minimize risk of ribavirin precipitation in the system and risk of ventilator dysfunction; change the filters frequently (e.g., every 4 hours). 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.

Reconstitution

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. 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.

Visually inspect the solution for particulate matter and discoloration prior to administration. 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.

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.

Parenteral Administration

Although not commercially available, parenteral ribavirin is available for compassionate use protocols for treatment of viral hemorrhagic fevers^†. Compassionate use of IV^† ribavirin can be obtained from Bausch Health; clinicians may initiate requests by contacting the Viral Special Pathogens Branch of CDC (770-488-7100).

Dosage

Pediatric Patients

Chronic HCV Infection

Must be used in conjunction with other drugs as part of a multiple-drug regimen.

Concomitant Ribavirin Capsules 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. (See Table 1.)

Recommended treatment duration is 24 weeks for HCV genotype 2 or 3 and 48 weeks for genotype 1.

In patients treated with ribavirin and interferon alfa-2b, assess virologic response at 24 weeks; consider treatment discontinuance if HCV RNA levels below the limit of detection not achieved at 24 weeks.

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.

Concomitant Ribavirin Tablets 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. (See Table 2.) If patient reaches 18th birthday during treatment, complete treatment using pediatric dosage.

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

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. The average aerosol concentration for a 12-hour delivery period is 190 mcg/L.

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

Viral Hemorrhagic Fevers†

Oral

US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommends initial loading dose of 30 mg/kg, followed by 15 mg/kg daily given in 2 divided doses for 10 days.

IV†

USAMRIID recommends initial loading dose of 30 mg/kg (maximum 2 g), followed by 16 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 for total treatment course of 10 days.

IV regimen usually preferred. 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).

Adults

Chronic HCV Infection

Must be used in conjunction with other drugs as part of a multiple-drug regimen.

Concomitant Ribavirin Capsules and Peginterferon Alfa-2b (PegIntron)

Oral

800–1400 mg daily (based on body weight) in 2 divided doses in conjunction with peginterferon alfa-2b (no longer available in the US). (See Table 3.) Duration of treatment depends on history of prior treatment, HCV genotype, and treatment response. (See Table 4.)

Concomitant Ribavirin Capsules 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 interferon alfa-2b (no longer available in the US).

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

individualize duration of treatment depending on baseline disease characteristics, response to therapy, and tolerability of regimen. In treatment-naïve adults, usual duration is 24–48 weeks; consider discontinuing if HCV RNA levels are not below the limit of detection at 24 weeks. If used in adults who relapsed after prior nonconjugated interferon monotherapy, manufacturer recommends treatment duration of 24 weeks.

Concomitant Ribavirin Tablets 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 peginterferon alfa-2a. Treatment duration depends on HCV genotype. (See Table 5.)

Adults with HCV and HIV coinfection: 800 mg daily in 2 divided doses in conjunction with peginterferon alfa-2a for 48 weeks, regardless of HCV genotype.

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

Viral Hemorrhagic Fevers†

Oral

USAMRIID recommends initial loading dose of 2 g, followed by 1.2 g 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. Duration of treatment is 10 days.

IV†

IV regimen usually preferred. 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).

Dosage Modification for Toxicity

Administer oral ribavirin with caution to patients with pre-existing cardiac disease. Evaluate patients before commencement of therapy; monitor patients appropriately during therapy. If any deterioration of cardiovascular status occurs, discontinue therapy.

Ribavirin Capsules

If severe adverse effects or laboratory changes occur during combination therapy with interferon alfa-2b or peginterferon alfa-2b, modify dosage or discontinue agent(s), if appropriate, until adverse reactions abate or decrease in severity. If intolerance persists after dosage adjustment, discontinue combination therapy.

See Table 6 for recommendations for dosage modification or treatment discontinuation based on laboratory parameters.

In pediatric patients, dosage reduction is accomplished by modifying recommended dosage from original starting dosage of 15 mg/kg daily in a 2-step process to 12 mg/kg daily, then to 8 mg/kg daily, if needed (See Table 6).

In patients with a history of stable cardiovascular disease, permanently reduce dosage if hemoglobin decreases by ≥2 g/dL during any 4-week period. If hemoglobin remains <12 g/dL after 4 weeks on reduced dosage, discontinue combination therapy.

Modify or discontinue dosing in any patient whose hemoglobin level falls below 10 g/dL.

aRefer to labeling for interferon alfa-2b (Intron A) or peginterferon alfa-2b (PegIntron) for information on how and when to reduce dosage of these agents for specific laboratory parameters.

bIn adults, 1st dosage reduction of ribavirin is by 200 mg/day (except in patients receiving 1400 mg, for whom dosage reduction should be by 400 mg/day). If needed, 2nd dosage reduction of ribavirin is by an additional 200 mg/day. Patients whose dosage of ribavirin is reduced to 600 mg daily receive 200 mg in the morning and 400 mg in the evening. In pediatric patients, 1st dosage reduction of ribavirin is to 12 mg/kg daily, and 2nd dosage reduction of ribavirin is to 8 mg/kg daily.

cPediatric patients who have pre-existing cardiac conditions and experience a hemoglobin decrease ≥2 g/dL during any 4-week period during therapy should undergo weekly evaluations and hematology testing.

dPatients with a history of significant or unstable cardiac disease should not be treated with peginterferon alfa-2b/ribavirin capsules combination therapy.

Ribavirin Tablets

If serious adverse effects or laboratory changes occur during combination therapy with peginterferon alfa-2a (Pegasys), modify dosage or discontinue agent(s), if appropriate, until adverse reactions abate or decrease in severity. If intolerance persists after dosage adjustment, discontinue combination therapy. If serious adverse effects or laboratory changes occur during combination therapy with peginterferon alfa-2a (Pegasys), modify dosage or discontinue agent(s), if appropriate, until adverse reactions abate or decrease in severity. If intolerance persists after dosage adjustment, discontinue combination therapy.

See Table 7 for recommendations for dosage modification or treatment discontinuation based on patient’s hemoglobin concentration and cardiac status.

In adults, once ribavirin tablets have been withheld due to either a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart dosing at 600 mg daily and further increase dosage to 800 mg daily. However, do not increase dosage to the original assigned dosage (1–1.2 g).

In pediatric patients, upon resolution of a laboratory abnormality or clinical adverse reaction, an attempt may be made (based on physician judgment) to increase ribavirin tablet dosage to the original dosage. If ribavirin tablets have been withheld due to a laboratory abnormality or clinical adverse reaction, an attempt may be made to restart tablets at one-half the full dosage.

^aThe recommendations in this table also apply to laboratory abnormalities or adverse reactions other than decreases in hemoglobin values.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

Ribavirin tablets: Reduce dosage in adults with Cl_cr ≤50 mL/minute. For treatment of chronic HCV infection, use alternating doses of 200 mg and 400 mg every other day in adults with Cl_cr 30–50 mL/minute and use 200 mg daily in adults with Cl_cr <30 mL/minute or undergoing hemodialysis. Do not reduce dosage any further; if severe adverse effects or laboratory abnormalities occur, discontinue drug, if appropriate, until adverse reactions abate or decrease in severity. If intolerance persists after restarting ribavirin tablets, discontinue ribavirin and peginterferon alfa-2a combination therapy. Data insufficient to make dosage recommendations for pediatric patients with renal impairment.

Ribavirin capsules: Contraindicated in patients with Cl_cr <50 mL/minute.

Geriatric Patients

No specific dosage recommendations at this time.

Cautious dosage selection because of age-related decreases in renal, hepatic, and/or cardiac function. Initiate therapy at the lower end of the dosing range.

Cautions for Ribavirin

Contraindications

Oral Ribavirin

• Known hypersensitivity (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) to ribavirin or any ingredient in the formulation (capsules).

• Women who are or may become pregnant.

• Male partners of pregnant women.

• Hemoglobinopathies (e.g., thalassemia major, sickle cell anemia).

• Creatinine clearance <50 mL/minute (capsules).

• Autoimmune hepatitis (ribavirin capsules; ribavirin tablets and peginterferon alfa-2a combination therapy).

• Use of ribavirin tablets and peginterferon alfa-2a combination therapy in cirrhotic patients with chronic hepatitis C virus (HCV) monoinfection (without coexisting human immunodeficiency virus [HIV] infection) who have hepatic decompensation (Child-Pugh score >6; class B and C) prior to treatment.

• Use of ribavirin tablets 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 treatment.

Ribavirin Nasal and Oral Inhalation

• Known hypersensitivity to ribavirin or any ingredient in the formulation.

• Women who are or may become pregnant.

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

Teratogenic and/or embryocidal effects in all animal species studied. (See Boxed Warning.) May impair male fertility based on animal data. Exercise extreme care to avoid pregnancy in female patients and in female partners of male patients. Inform patients of potential hazard to a fetus. Do not initiate therapy until report of negative pregnancy test obtained immediately prior to initiating therapy. Perform pregnancy testing during therapy with ribavirin capsules and during 9-month period after treatment discontinuation. Perform pregnancy testing monthly during therapy with ribavirin tablets and for 6 months after treatment discontinuation. Advise female patients of reproductive potential to use effective contraception during treatment with ribavirin capsules and for 9 months post therapy. Advise male patients and their female partners of reproductive potential to use effective contraception during treatment with ribavirin capsules and for 6 months post therapy. Advise female patients of reproductive potential, and male patients and their female partners of reproductive potential, to use effective contraception (2 reliable forms) during treatment with ribavirin tablets and for 6 months post therapy.

Anemia

Hemolytic anemia reported in patients receiving oral ribavirin in conjunction with interferon alfa or peginterferon alfa; anemia usually occurs 1–2 weeks after initiation of therapy. (See Boxed Warning.) Use with caution in patients with baseline risk of severe anemia (e.g., spherocytosis, history of GI bleeding). Monitor hemoglobin or hematocrit before initiating therapy, at week 2 and 4 of therapy, or more frequently if clinically indicated. Follow patients as clinically appropriate. Fatal and nonfatal MI reported in patients with anemia due to oral ribavirin. Assess patients for underlying cardiac disease before initiating therapy. Obtain ECG in patients with known cardiac disease before therapy is initiated; monitor appropriately during therapy. Temporarily interrupt or discontinue therapy if cardiovascular status deteriorates. Not recommended in those with substantial or unstable cardiac disease.

Lack of Effectiveness with Monotherapy

Do not use oral ribavirin alone for treatment of chronic HCV infection. Oral ribavirin monotherapy not effective. (See Boxed Warning.)

Use of Aerosolized Ribavirin with Mechanical Ventilators

Use of ribavirin inhalation therapy in patients requiring mechanical ventilator assistance should be undertaken only by qualified clinicians and support staff experienced with the specific ventilator and this mode of administration. (See Boxed Warning.) Give strict attention to procedures shown to minimize accumulation of ribavirin precipitates in the apparatus, which can result in mechanical ventilator dysfunction and associated increased pulmonary pressures.

Deterioration of Respiratory Function

Use of aerosolized ribavirin in infants has resulted in sudden deterioration of respiratory function. (See Boxed Warning.) Monitor respiratory function carefully. If sudden deterioration of respiratory function occurs, discontinue therapy. Reinstitute only with extreme caution and continuous monitoring; consider concomitant administration of a bronchodilator. Optimum monitoring and attention to respiratory and fluid status needed in patients with severe lower respiratory tract infection due to RSV.

Aerosolized Ribavirin Use in Adults

Ribavirin inhalation not indicated for use in adults. (See Boxed Warning.) Patients and clinicians should be aware that ribavirin is teratogenic in animals and should not be initiated in women of childbearing potential.

Other Warnings/Precautions

Pancreatitis

Temporarily interrupt oral ribavirin in patients with manifestations of pancreatitis; discontinue in patients with confirmed pancreatitis.

Pulmonary Disorders

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

Closely monitor patients who experience pulmonary infiltrates or deterioration in pulmonary function; if appropriate, discontinue ribavirin combination therapy.

Ophthalmologic Disorders

New or worsening ophthalmologic disorders may occur.

Perform eye exam before initiating treatment with oral ribavirin.

Laboratory Test Abnormalities

Severe decreases in neutrophil and platelet counts, as well as hematologic, endocrine (e.g., TSH), and hepatic abnormalities may occur.

Complete hematology and blood chemistry testing before initiating oral therapy and then periodically thereafter.

Assess standard hematologic tests, including hemoglobin (at weeks 2 and 4 of therapy, and as clinically indicated), CBC, differential WBC count, and platelet count, periodically during treatment with ribavirin capsules. Assess blood chemistries (liver function tests, TSH) periodically during treatment with ribavirin capsules. Measure HCV-RNA periodically during treatment.

Assess standard hematologic tests at weeks 2 and 4 of therapy, and then periodically during treatment with ribavirin tablets. Assess blood chemistries at 4 weeks of therapy, and then periodically during treatment with ribavirin tablets.

Dental and Periodontal Disorders

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

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

Bone Marrow Suppression and Concomitant Use of Azathioprine

Pancytopenia and bone marrow suppression reported within 3—7 weeks of concomitant administration of pegylated interferon/ribavirin and azathioprine. Myelotoxicity reversible within 4—6 weeks upon withdrawal of both HCV antiviral therapy and concomitant azathioprine; did not recur upon reintroduction of either treatment alone.

Discontinue pegylated interferon, ribavirin, and azathioprine if pancytopenia occurs; do not reintroduce pegylated interferon/ribavirin with concomitant azathioprine.

Impact on Growth in Pediatric Patients

Weight loss and growth inhibition reported in pediatric patients with ribavirin capsule combination therapy; long-term growth inhibition (reduced adult height) reported in some patients. Growth impairment also reported with ribavirin tablet combination therapy in pediatric patients.

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. 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.

Closely monitor clinical status and hepatic function. Discontinue ribavirin tablets plus peginterferon alfa-2a combination therapy immediately if decompensation occurs.

Sensitivity Reactions

Severe acute hypersensitivity reactions (e.g., urticaria, angioedema, bronchoconstriction, anaphylaxis) reported with ribavirin plus alpha interferon combination therapy. If such a reaction occurs, discontinue combination therapy immediately and institute appropriate medical therapy.

Serious skin reactions, including vesiculobullous eruptions, reactions in the spectrum of Stevens-Johnson syndrome with varying degrees of skin and mucosal involvement and exfoliative dermatitis, reported in patients receiving peginterferon with or without oral ribavirin. If signs or symptoms of severe skin reactions occur, discontinue therapy.

Specific Populations

Pregnancy

May cause fetal toxicity and/or death based on findings from animal studies. Teratogenic and/or embryocidal in almost all animal species tested to date at dosages well below recommended human dosage.

Data from pregnancy registry insufficient to identify drug-associated risk of birth defects, miscarriage, or adverse maternal or fetal outcomes in humans.

Oral ribavirin contraindicated in women who are or may become pregnant; also contraindicated in male partners of such women.

Exercise extreme care to avoid pregnancy in female patients and in female partners of male patients receiving ribavirin. Inform patients of potential fetal hazard.

Do not initiate oral ribavirin until negative pregnancy test obtained immediately prior to initiating therapy. Perform periodic pregnancy testing during treatment with ribavirin capsules and during the 9-month period after treatment discontinuation. Perform pregnancy testing monthly during therapy with ribavirin tablets and for 6 months after treatment discontinuation.

Ribavirin nasal and oral inhalation contraindicated in women who are or may become pregnant. Manufacturer encourages hospitals to perform training to minimize potential occupational exposure to ribavirin because of animal evidence of teratogenic potential. Pregnant health-care personnel should consider avoiding direct care of patients being treated with aerosolized ribavirin; if close patient contact cannot be avoided, take precautions to limit exposure. Refer to the NIOSH recommendations for additional information to minimize environmental exposures.

Lactation

Toxic to lactating animals and their offspring. Not known whether distributed into human milk. No data on effects on breast-fed infant or on milk production.

Discontinue nursing or discontinue ribavirin, taking into account the importance of therapy to mother. Consider benefits of breast-feeding along with mother’s clinical need for ribavirin and any potential adverse effects on breast-fed child from drug or from underlying maternal condition.

Females and Males of Reproductive Potential

May cause fetal harm when administered during pregnancy. May impair male fertility based on animal data; effects were mostly reversible within few months after drug cessation.

Perform pregnancy testing in females of reproductive potential prior to initiating treatment with ribavirin capsules, and periodically during therapy and for 9 months post therapy.

Perform pregnancy testing in females of reproductive potential prior to initiating treatment with ribavirin tablets, and monthly during therapy and for 6 months post therapy.

Advise female patients of reproductive potential to use effective contraception during treatment with ribavirin capsules and for 9 months post therapy. Advise male patients and their female partners of reproductive potential to use effective contraception during treatment with ribavirin capsules and for 6 months post therapy.

Advise female patients of reproductive potential, and male patients and their female partners of reproductive potential, to use effective contraception (2 reliable forms) during treatment with ribavirin tablets and for 6 months post therapy.

Pediatric Use

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

Ribavirin capsules: Safety and efficacy in conjunction with peginterferon alfa-2b for treatment of chronic HCV infection not established in children <3 years of age. When deciding whether to use ribavirin capsules in conjunction with interferon alfa-2b in HCV-infected children, consider evidence of disease progression (hepatic inflammation, fibrosis), prognostic factors for response, HCV genotype, and viral load. Weigh benefits against adverse effects reported in pediatric patients.

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

Suicidal ideation or attempts reported more frequently during or after oral ribavirin in pediatric patients (primarily adolescents) than in adults receiving the drug. Other adverse psychiatric effects (depression, emotional lability, somnolence), anemia, and neutropenia reported as in adults. Growth inhibition/impairment reported with oral ribavirin combination therapy in pediatric patients.

Geriatric Use

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

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.

Substantially eliminated by kidneys; risk of adverse effects increased in patients with renal impairment. Monitor renal function and consider age-related decreases in renal function when selecting dosage.

Hepatic Impairment

Do not use in patients with autoimmune hepatitis. Monitor liver function tests before and during therapy.

Capsules: 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.

Tablets: Effect of hepatic impairment on pharmacokinetics not evaluated.

Renal Impairment

Capsules: Contraindicated in patients with Cl_cr <50 mL/ minute.

Tablets: Use reduced dosage in adults with Cl_cr ≤50 mL/minute.

Capsules: AUC increased twofold or threefold in non-HCV-infected individuals with Cl_cr 30–60 or 10–30 mL/minute, respectively.

Tablets: In patients with Cl_cr ≤50 mL/minute, apparent clearance was approximately 30% of values observed in those with normal renal function. In HCV-infected individuals with end-stage renal disease requiring hemodialysis who were receiving ribavirin tablets 200 mg daily, plasma exposures about 20% lower than exposures achieved with 1–1.2 g daily in individuals with normal renal function.

Organ Transplant Recipients

Safety and efficacy of oral ribavirin in conjunction with interferon or peginterferon for treatment of HCV not established in patients with liver or other transplantations.

HIV or HBV Co-infection

Safety and efficacy of ribavirin capsules in conjunction with peginterferon alfa-2b or interferon alfa-2b not established in chronic HCV patients coinfected with HIV or HBV.

Common Adverse Effects

Oral capsules plus peginterferon alfa-2b or interferon alfa-2b (≥40%), adults: Injection site reaction, fatigue/asthenia, headache, rigors, fevers, nausea, myalgia, anxiety/emotional lability/irritability. Hemolytic anemia occurred in >10% of adults.

Oral capsules plus peginterferon alfa-2b or interferon alfa-2b (>25%), pediatric patients: Pyrexia, headache, neutropenia, fatigue, anorexia, injection site erythema, vomiting.

Oral tablets plus peginterferon alfa-2a (>40%), adults: Fatigue/asthenia, pyrexia, myalgia, and headache. Similar effects seen in pediatric patients.

Nasal and oral inhalation: Respiratory and cardiovascular effects.

Drug Interactions

Does not inhibit CYP isoenzymes 2C9, 2C19, 2D6, or 3A4; not a substrate for CYP450 isoenzymes. Interactions with drugs metabolized by CYP enzymes unlikely.

Studies not performed to evaluate drug interactions between ribavirin inhalation and other drugs concomitantly used to treat respiratory syncytial virus infections (e.g., digoxin, bronchodilators, anti-infectives, antimetabolites, other antiviral agents). Effect of ribavirin inhalation on laboratory tests not evaluated.

The following drug interactions are based on studies using oral ribavirin. When oral ribavirin is used in combination with peginterferon alfa-2a, peginterferon alfa-2b (no longer available in the US), or interferon alfa-2b (no longer available in the US), consider interactions associated with the interferon; refer to full prescribing information for interferon drug interactions.

Specific Drugs

Ribavirin Pharmacokinetics

Absorption

Bioavailability

Following oral administration, absorbed rapidly and extensively from GI tract. Peak plasma concentrations achieved within 1–3 hours following administration of oral capsules; peak plasma concentrations achieved in 2 hours following administration of oral tablets.

Bioavailability is 64% following oral administration.

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

Bioavailability following nasal and oral inhalation not determined but may depend on method of drug delivery during nebulization (i.e., oxygen hood, face mask, oxygen tent).

Food

Administration with a high-fat meal increases oral bioavailability.

Peak plasma concentration and AUC increases following administration of tablets or capsules with high-fat meal.

Special Populations

Following a single dose of ribavirin (capsules), 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.

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

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

Distribution

Extent

Ribavirin and/or its metabolites accumulate in erythrocytes.

Not known whether distributes into milk in humans.

Plasma Protein Binding

Not bound.

Elimination

Metabolism

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

Elimination Route

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

Half-life

Capsules: 43.6 hours (single dose) and 298 hours (multiple doses).

Tablets: 120–170 hours (single dose).

Special Populations

Clearance reduced in patients with renal impairment.

Stability

Storage

Nasal and Oral Inhalation

For Inhalation Solution

25°C (excursions permitted between 15–30°C); store in dry place.

Following reconstitution, store solution under sterile conditions at 20–30°C for up to 24 hours.

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

Oral

Capsules

20–25°C (excursions permitted between 15–30°C).

Tablets, Film-Coated

20–25°C (excursions permitted between 15–30°C). Keep bottle tightly closed.

Actions and Spectrum

• Synthetic nucleoside antiviral agent (purine analogue); broad spectrum of antiviral activity against both RNA and DNA viruses.

• Exact mechanism of antiviral activity against HCV not fully elucidated; increases mutation frequency in genomes of several RNA viruses and ribavirin triphosphate inhibits HCV polymerase.

• Active in vitro against many RNA viruses, including respiratory syncytial virus (RSV).

• Inhibitory activity for RSV is selective; precise mechanism of action unknown. Reversal of antiviral activity by guanosine or xanthosine suggests that ribavirin may act as analogue of these cellular metabolites.

• Active in vitro against influenza A and B viruses and herpes simplex virus but clinical importance unknown.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).

• Advise patients that the most common adverse event associated with oral ribavirin is anemia, which may be severe. Inform patients that laboratory tests are required prior to starting oral ribavirin therapy and periodically thereafter. Advise patients that it is important to be well hydrated, especially during the initial stages of ribavirin therapy. Advise patients to avoid driving or operating machinery if they develop dizziness, confusion, somnolence, or fatigue.

• Advise patients to take ribavirin capsules or tablets with food.

• Ask patients about prior history of drug abuse before initiating combination therapy with ribavirin/peginterferon alfa-2a, since relapse of drug addiction and drug overdoses have been reported in patients treated with interferons.

• Advise females of reproductive potential and pregnant women of the risk of embryocidal and teratogenic effects with ribavirin. Advise patients to notify their clinician immediately in the event of a pregnancy during treatment with oral ribavirin.

• Advise females of reproductive potential that they must have a negative pregnancy test prior to initiating treatment with ribavirin capsules, and pregnancy tests will be performed periodically during therapy and for 9 months post therapy.

• Advise females of reproductive potential that they must have a negative pregnancy test prior to initiating treatment with ribavirin tablets, and pregnancy tests will be performed monthly during therapy and for 6 months post therapy.

• Advise female patients of reproductive potential to use effective contraception during treatment with ribavirin capsules and for 9 months post therapy. Advise male patients and their female partners of reproductive potential to use effective contraception during treatment with ribavirin capsules and for 6 months post therapy.

• Advise female patients of reproductive potential, and male patients and their partners of reproductive potential, to use effective contraception (2 reliable forms) during treatment with ribavirin tablets and for 6 months post therapy.

• Advise patients not to drink alcohol, as alcohol may exacerbate chronic HCV infection.

• In the event of a missed dose of ribavirin capsules or tablets, instruct patients to take the missed dose as soon as possible during the same day. Instruct patients not to double the next dose and to contact their clinician if they have any questions.

• Inform patients that the effect of ribavirin/peginterferon alfa-2a on transmission of HCV during treatment of HCV infection is unknown, and it is important to take appropriate precautions to prevent HCV transmission during treatment or in the event of treatment failure.

• Advise patients to brush their teeth thoroughly twice daily and have regular dental examinations during treatment with ribavirin capsules. If vomiting occurs, advise patients to rinse out their mouth thoroughly afterwards.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise patients to inform clinicians if they plan to breast-feed during treatment with oral ribavirin.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

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