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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(rye ba VYE rin)
Generic Available (U.S.)
Yes: Capsule, tablet
Index Terms
Medication Guide
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Copegus®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088576.pdf,
Rebetol®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089017.pdf
Ribasphere®: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm111342.pdf
REMS Components
Copegus®: Released from REMS requirement 5/9/2011
Rebetol®: Released from REMS requirement 4/19/2011
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Inhalation: Treatment of hospitalized infants and young children with respiratory syncytial virus (RSV) infections; specially indicated for treatment of severe lower respiratory tract RSV infections in patients with an underlying compromising condition (prematurity, cardiopulmonary disease, or immunosuppression)
Oral capsule:
In combination with interferon alfa-2b (Intron® A) injection for the treatment of chronic hepatitis C in patients with compensated liver disease who have relapsed after alpha interferon therapy or were previously untreated with alpha interferons
In combination with peginterferon alfa-2b (PEG-Intron®) injection for the treatment of chronic hepatitis C in patients with compensated liver disease who were previously untreated with alpha interferons
Oral solution: In combination with interferon alfa 2b (Intron® A) injection for the treatment of chronic hepatitis C in patients with compensated liver disease who were previously untreated with alpha interferons or patients who have relapsed after alpha interferon therapy
Oral tablet: In combination with peginterferon alfa-2a (Pegasys®) injection for the treatment of chronic hepatitis C in patients with compensated liver disease who were previously untreated with alpha interferons (includes patients with histological evidence of cirrhosis [Child-Pugh class A] and patients with clinically-stable HIV disease)
Use: Unlabeled
Inhalation: Treatment for RSV in adult hematopoietic stem cell or heart/lung transplant recipients
Used in other viral infections including influenza A and B and adenovirus
Pregnancy Risk Factor
X
Pregnancy Considerations
[U.S. Boxed Warning]: Significant teratogenic effects have been observed in all animal studies at ~0.01 times the maximum recommended daily human dose. Use is contraindicated in pregnancy. Negative pregnancy test is required before initiation and monthly thereafter. Avoid pregnancy in female patients and female partners of male patients during therapy by using two effective forms of contraception; continue contraceptive measures for at least 6 months after completion of therapy. If patient or female partner becomes pregnant during treatment, she should be counseled about potential risks of exposure. If pregnancy occurs during use or within 6 months after treatment, report to the ribavirin pregnancy registry (800-593-2214).
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to ribavirin or any component of the formulation; women of childbearing age who will not use contraception reliably; pregnancy
Additional contraindications for oral formulation: Male partners of pregnant women; hemoglobinopathies (eg, thalassemia major, sickle cell anemia); patients with autoimmune hepatitis; ribavirin tablets are contraindicated in patients with hepatic decompensation (Child-Pugh class B and C); concomitant use of didanosine
Additional contraindication for Ribasphere® capsules and Rebetrol® capsules/solution: Patients with a Clcr <50 mL/minute
Refer to individual monographs for Interferon Alfa-2b (Intron® A) and Peginterferon Alfa-2a (Pegasys®) for additional contraindication information.
Warnings/Precautions
Boxed warnings:
• Hemolytic anemia: See “Concerns related to adverse effects” below.
• Hepatitis C: See “Disease-related concerns” below.
• Inhalation: See “Dosage form specific issues” below.
• Pregnancy: See “Special populations” below.
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Hemolytic anemia: [U.S. Boxed Warning]: Hemolytic anemia is the primary toxicity of oral therapy; usually occurring within 1-2 weeks of therapy initiation; observed in ~10% to 13% of patients when alfa interferons were combined with ribavirin. Assess cardiac function before initiation of therapy. Anemia associated with ribavirin may worsen underlying cardiac disease. Avoid use in patients with significant/unstable cardiac disease. If any deterioration in cardiovascular status occurs, discontinue therapy. Patients with renal dysfunction and/or those >50 years of age should be carefully assessed for development of anemia.
Disease-related concerns:
• Hepatic impairment: Discontinue therapy if evidence of hepatic decompensation (Child-Pugh score ≥6) is observed.
• Hepatitis C: Appropriate use: [U.S. Boxed Warning]: Ribavirin monotherapy is not effective for chronic hepatitis C infection.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment or discontinuation may be required.
Concurrent drug therapy issues:
Combination therapy with alfa interferons:
• Autoimmune/infectious disorders: Have occurred with combination therapy; use with caution in patients with autoimmune disease or severe infection.
• Bone marrow suppression: Pancytopenia has occurred with combination therapy and concomitant use of azathioprine; onset occurs within 3-7 weeks; discontinue combination therapy and azathioprine if occurs; may be reversible.
• Dental and periodontal disorders: Have been reported with combination therapy; patients should be instructed to brush teeth twice daily and have regular dental exams. Xerostomia may contribute to and/or exacerbate dental disorders.
• Dermatologic reactions: Severe cutaneous reactions, including Stevens-Johnson syndrome and exfoliative dermatitis have been reported (rarely) with combination therapy; discontinue with signs or symptoms of severe skin reactions.
• Diabetes: Has occurred with combination therapy; monitor blood sugars closely.
• Hypersensitivity reactions: Acute hypersensitivity reactions (eg, anaphylaxis, angioedema, bronchoconstriction, and urticaria) have been observed (rarely) with combination therapy; discontinue with signs or symptoms of hypersensitivity reactions.
• Ophthalmologic disorders: Serious disorders (eg, retinopathy, macular edema, retinal artery/vein thrombosis, optic neuritis, retinal detachment) have occurred with combination therapy. All patients require an eye exam at baseline; those with pre-existing ophthalmologic disorders (eg, diabetic or hypertensive retinopathy) require periodic follow up. Discontinue therapy in patients with new or worsening ophthalmologic disorders.
• Pancreatitis: Has occurred with combination therapy; discontinue therapy in suspected/confirmed pancreatitis.
• Psychiatric disorders: Severe psychiatric events have occurred including depression and suicidal behavior during combination therapy. Avoid use in patients with a psychiatric history; discontinue if severe psychiatric symptoms occur.
• Pulmonary events: Pulmonary symptoms (eg, dyspnea, pulmonary infiltrates, pneumonitis, pneumonia [rarely fatal]) have been associated with combination therapy; use with caution in patients with pulmonary disease, including sarcoidosis (exacerbation reported).
Special populations:
• Elderly: Use with caution in the elderly; may be more susceptible to adverse effects
• Pediatric: Oral: In combination with peginterferon alfa-2b, ribavirin may cause a reduction in growth velocity in pediatric patients for the length of treatment. After ~ 6 months post-treatment, many patients catch up in growth, but a small percentage will not. Growth should be closely monitored in pediatric patients during therapy and post-treatment until growth catch up has occurred.
• Pregnancy: [U.S. Boxed Warning]: Significant teratogenic effects have been observed in all animal studies. A negative pregnancy test is required before initiation and monthly thereafter. Avoid pregnancy in female patients and female partners of male patients, during therapy, and for at least 6 months after treatment; two forms of contraception should be used.
Dosage form specific issues:
• Inhalation: [U.S. Boxed Warning]: Use with caution in patients requiring assisted ventilation because precipitation of the drug in the respiratory equipment may interfere with safe and effective patient ventilation; sudden deterioration of respiratory function has been observed; monitor carefully in patients with COPD and asthma for deterioration of respiratory function. Ribavirin is potentially mutagenic, tumor-promoting, and gonadotoxic. Although anemia has not been reported with inhalation therapy, consider monitoring for anemia 1-2 weeks post-treatment. Pregnant healthcare workers may consider unnecessary occupational exposure; ribavirin has been detected in healthcare workers' urine. Healthcare professionals or family members who are pregnant (or may become pregnant) should be counseled about potential risks of exposure and counseled about risk reduction strategies.
Other warnings/precautions:
• Appropriate use: Safety and efficacy have not been established in patients who have failed other alfa interferon therapy, received organ transplants, or been coinfected with hepatitis B or HIV (Copegus® may be used in HIV coinfected patients unless CD4+ cell count is <100 cells/microL). Oral products should not be used for HIV infection, adenovirus, RSV, or influenza infections.
Adverse Reactions
Inhalation:
1% to 10%:
Central nervous system: Fatigue, headache, insomnia
Gastrointestinal: Nausea, anorexia
Hematologic: Anemia
<1%: Hypotension, cardiac arrest, digitalis toxicity, conjunctivitis, mild bronchospasm, worsening of respiratory function, apnea
Note: Incidence of adverse effects (approximate) in healthcare workers: Headache (51%); conjunctivitis (32%); rhinitis, nausea, rash, dizziness, pharyngitis, and lacrimation (10% to 20%); bronchospasm and/or chest pain (case reports in individuals with underlying airway disease)
Oral (all adverse reactions are documented while receiving combination therapy with alfa interferons; percentages as reported in adults); asterisked (*) percentages are those similar to interferon therapy alone:
>10%:
Central nervous system: Fatigue (60% to 70%)*, headache (43% to 66%)*, fever (32% to 55%)*, insomnia (26% to 41%), depression (20% to 36%)*, irritability (23% to 33%), dizziness (14% to 26%), impaired concentration (10% to 21%)*, emotional lability (7% to 12%)*
Dermatologic: Alopecia (27% to 36%), pruritus (13% to 29%), rash (5% to 28%), dry skin (10% to 24%), dermatitis (≤16%)
Endocrine and metabolic: Hyperuricemia (33% to 38%)
Gastrointestinal: Nausea (25% to 47%), anorexia (21% to 32%), weight decrease (10% to 29%), vomiting (9% to 25%)*, diarrhea (10% to 22%), dyspepsia (6% to 16%), abdominal pain (8% to 13%), xerostomia (≤12%), RUQ pain (≤12%)
Hematologic: Leukopenia (6% to 45%), neutropenia (8% to 42%; grade 4: 2% to 11%; 40% with HIV coinfection), hemoglobin decreased (11% to 35%), anemia (11% to 17%), thrombocytopenia (<1% to 15%), lymphopenia (12% to 14%), hemolytic anemia (10% to 13%)
Hepatic: Bilirubin increase (10% to 32%)
Neuromuscular & skeletal: Myalgia (40% to 64%)*, rigors (25% to 48%), arthralgia (22% to 34%)*, musculoskeletal pain (19% to 28%)
Respiratory: Dyspnea (13% to 26%), cough (7% to 23%), pharyngitis (≤13%), sinusitis (≤12%)*
Miscellaneous: Flu-like syndrome (13% to 18%)*, viral infection (≤12%), diaphoresis (≤11%)
1% to 10%:
Cardiovascular: Chest pain (5% to 9%)*, flushing (≤4%)
Central nervous system: Pain (≤10%), mood alteration (≤6%; 9% with HIV coinfection), agitation (5% to 8%), nervousness (6%)*, memory impairment (≤6%), malaise (≤6%), suicidal ideation (adolescents: 2%; adults: 1%)
Dermatologic: Eczema (4% to 5%)
Endocrine & metabolic: Menstrual disorder (≤7%), hypothyroidism (≤5%)
Gastrointestinal: Taste perversion (4% to 9%), constipation (5%)
Hepatic: Hepatomegaly (4%), transaminases increased (1% to 3%), hepatic decompensation (2% with HIV coinfection)
Neuromuscular & skeletal: Weakness (9% to 10%), back pain (5%)
Ocular: Blurred vision (≤6%), conjunctivitis (≤5%)
Respiratory: Rhinitis (≤8%), exertional dyspnea (≤7%)
Miscellaneous: Fungal infection (≤6%), bacterial infection (3% to 5%)
<1%: Aggression, angina, anxiety, aplastic anemia, arrhythmia; autoimmune disorders (systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis); cerebral hemorrhage, cholangitis, colitis, coma, corneal ulcer, diabetes mellitus, drug abuse relapse/overdose, fatty liver, gastrointestinal bleeding, gout, hallucination, hepatic dysfunction, hyper-/hypothyroidism, myositis, pancreatitis, peptic ulcer, peripheral neuropathy, psychosis, psychotic disorder, pulmonary dysfunction, pulmonary embolism, suicide, thrombotic thrombocytopenic purpura, thyroid function test abnormalities
Postmarketing and/or case reports: Bone marrow suppression, dehydration, dental disorders, exfoliative dermatitis, hearing impairment/loss, hypersensitivity (including anaphylaxis, angioedema, bronchoconstriction, and urticaria), macular edema, optic neuritis, papilledema, periodontal disorders, pneumonitis, pulmonary infiltrates, pure red cell aplasia; retinal artery/vein thrombosis, retinal detachment, retinal hemorrhage, retinopathy, sarcoidosis exacerbation; skin reactions (erythema multiforme, exfoliative dermatitis, urticaria, vesiculobullous eruptions); Stevens-Johnson syndrome; transplant rejection (kidney, liver); vertigo, vision loss
Note: Incidence of anorexia, headache, fever, suicidal ideation, and vomiting are higher in children.
Metabolism/Transport Effects
None known.
Drug Interactions
AzaTHIOprine: Ribavirin may increase serum concentrations of the active metabolite(s) of AzaTHIOprine. Specifically, concentrations of potentially myelotoxic methylated metabolites may be increased, while concentrations of active 6-thioguanine nucleotides may be decreased. Management: Consider using alternative agent(s) when possible. When these drugs are used in combination, monitor patients extra closely for signs/symptoms of myelosuppression. Risk D: Consider therapy modification
Didanosine: Ribavirin may enhance the adverse/toxic effect of Didanosine. Ribavirin may increase serum concentrations of the active metabolite(s) of Didanosine. Risk X: Avoid combination
Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B) may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated). Management: Avoid anti-influenza antivirals during the period beginning 48 hours prior to and ending 2 weeks after vaccine administration. Persons receiving these agents within 2 weeks of the live intranasal spray vaccine should receive a repeat vaccine dose. Risk D: Consider therapy modification
Interferons (Alfa): May enhance the adverse/toxic effect of Ribavirin. Hemolytic anemia has been observed. Risk C: Monitor therapy
Reverse Transcriptase Inhibitors (Nucleoside): Ribavirin may enhance the hepatotoxic effect of Reverse Transcriptase Inhibitors (Nucleoside). Lactic acidosis may occur. Risk D: Consider therapy modification
Zidovudine: May enhance the adverse/toxic effect of Ribavirin. Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended for ribavirin. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Oral: High-fat meal increases the AUC and Cmax. Management: Capsule (in combination with peginterferon alfa-2b) and tablet should be administered with food. Other dosage forms and combinations should be taken consistently in regards to food.
Storage
Inhalation: Store vials in a dry place at 15°C to 30°C (59°F to 86°F).
Oral: Store at controlled room temperature of 25°C (77°F). Solution may also be refrigerated at 2°C to 8°C (36°F to 46°F).
Reconstitution
Inhalation: Do not use any water containing an antimicrobial agent to reconstitute drug. Reconstituted solution is stable for 24 hours at room temperature.
Compatibility
Inhalation: Should not be mixed with other aerosolized medication.
Mechanism of Action
Inhibits replication of RNA and DNA viruses; inhibits influenza virus RNA polymerase activity and inhibits the initiation and elongation of RNA fragments resulting in inhibition of viral protein synthesis
Pharmacodynamics/Kinetics
Absorption: Inhalation: Systemic; dependent upon respiratory factors and method of drug delivery; maximal absorption occurs with the use of aerosol generator via endotracheal tube; highest concentrations in respiratory tract and erythrocytes
Distribution: Oral capsule: Single dose: Vd: 2825 L; distribution significantly prolonged in the erythrocyte (16-40 days), which can be used as a marker for intracellular metabolism
Protein binding: Oral: None
Metabolism: Hepatically and intracellularly (forms active metabolites); may be necessary for drug action
Bioavailability: Oral: 64%
Half-life elimination, plasma:
Children: Inhalation: 6.5-11 hours
Adults: Oral:
Capsule, single dose (Rebetol®, Ribasphere®): 24 hours in healthy adults, 44 hours with chronic hepatitis C infection (increases to ~298 hours at steady state)
Tablet, single dose (Copegus®): ~120-170 hours
Time to peak, serum: Inhalation: At end of inhalation period; Oral capsule: Multiple doses: 3 hours; Tablet: 2 hours
Excretion: Inhalation: Urine (40% as unchanged drug and metabolites); Oral capsule: Urine (61%), feces (12%)
Dosage
Infants and Children: Aerosol inhalation: RSV infection: Use with Viratek® small particle aerosol generator (SPAG-2) at a concentration of 20 mg/mL (6 g reconstituted with 300 mL of sterile water without preservatives). Continuous aerosol administration: 12-18 hours/day for 3 days, up to 7 days in length
Children ≥3 years: Oral capsule or solution (Rebetol®): Chronic hepatitis C (in combination with interferon alfa-2b): Note: Oral solution should be used in children 3-5 years of age, children ≤25 kg, or those unable to swallow capsules. Recommended therapy duration (manufacturer labeling): Genotype 1: 48 weeks; genotypes 2,3: 24 weeks
Capsule/solution: 15 mg/kg/day in 2 divided doses (morning and evening)
Capsule dosing recommendations:
25-36 kg: 400 mg/day (200 mg morning and evening)
37-49 kg: 600 mg/day (200 mg in the morning and 400 mg in the evening)
50-61 kg: 800 mg/day (400 mg in the morning and evening)
>61 kg: Refer to adult dosing
Note: American Association for the Study of Liver Diseases (AASLD) guidelines recommendation: Children 2-17 years with chronic HCV infection (Ghany, 2009): Treatment of choice: Ribavirin 15 mg/kg daily in combination with SubQ peginterferon alfa-2b 60 mcg/m2 once weekly for 48 weeks
Adults:
Oral capsule (Rebetol®, Ribasphere®):
Chronic hepatitis C (in combination with interferon alfa-2b):
≤75 kg: 400 mg in the morning, then 600 mg in the evening
>75 kg: 600 mg in the morning, then 600 mg in the evening
Chronic hepatitis C (in combination with peginterferon alfa-2b): 400 mg twice daily
Tablet (Copegus®): Chronic hepatitis C (in combination with peginterferon alfa-2a):
Monoinfection, genotype 1,4:
<75 kg: 1000 mg/day in 2 divided doses for 48 weeks
≥75 kg: 1200 mg/day in 2 divided doses for 48 weeks
Monoinfection, genotype 2,3: 800 mg/day in 2 divided doses for 24 weeks
Coinfection with HIV: 800 mg/day in 2 divided doses for 48 weeks (regardless of genotype)
Note: American Association for the Study of Liver Diseases (AASLD) guidelines recommendation: Adults with chronic HCV infection (Ghany, 2009): Treatment of choice: Ribavirin plus peginterferon; clinical condition and ability of patient to tolerate therapy should be evaluated to determine length and/or likely benefit of therapy. Recommended treatment duration (AASLD guidelines): Genotypes 1,4: 48 weeks; Genotypes 2,3: 24 weeks; Coinfection with HIV: 48 weeks.
Aerosol inhalation: RSV Infection in hematopoietic cell or heart/lung transplant recipients (unlabeled use): 2 g (over 2 hours) every 8 hours
Note: Heart/lung transplant recipients also received IVIG, methylprednisolone and palivizumab. Dosage and protocol may be institution specific. (Boeckh, 2007; Chemaly, 2006; Liu, 2010).
Dosage adjustment for toxicity: Oral: Capsule, solution, tablet:
Patient without cardiac history:
Hemoglobin <10 g/dL:
Children: Decrease dose to 7.5 mg/kg/day
Adults: Decrease dose to 600 mg/day
Hemoglobin <8.5 g/dL: Children and Adults: Permanently discontinue treatment
Patient with cardiac history:
Hemoglobin has decreased ≥2 g/dL during any 4-week period of treatment:
Children: Decrease dose to 7.5 mg/kg/day
Adults: Decrease dose to 600 mg/day
Hemoglobin <12 g/dL after 4 weeks of reduced dose: Children and Adults: Permanently discontinue treatment
Dosage adjustment in renal impairment: Oral:
Rebetol® capsules/solution, Ribasphere® capsules:
Clcr ≥50 mL/minute: No dosage adjustments are recommended
Clcr <50 mL/minute: Use is contraindicated
Ribasphere® tablets:
Clcr ≥50 mL/minute: No dosage adjustments are recommended
Clcr <50 mL/minute: Use is not recommended
Copegus® tablets:
Clcr >50 mL/minute: No dosage adjustments are recommended
Clcr 30-50 mL/minute: Alternate 200 mg and 400 mg every other day
Clcr <30 mL/minute: 200 mg once daily
ESRD requiring hemodialysis: 200 mg once daily
Dosage adjustment in hepatic impairment: Hepatic decompensation (Child-Pugh class B and C): Use of ribavirin tablets is contraindicated.
Administration: Oral
Administer concurrently with interferon alfa injection. Capsule should not be opened, crushed, chewed, or broken. Capsules are not for use in children <5 years of age. Use oral solution for children 3-5 years, those ≤25 kg, or those who cannot swallow capsules.
Capsule, in combination with interferon alfa-2b: May be administered with or without food, but always in a consistent manner in regard to food intake.
Capsule, in combination with peginterferon alfa-2b: Administer with food.
Solution, in combination with interferon alfa-2b: May be administered with or without food, but always in a consistent manner in regard to food intake.
Tablet: Should be administered with food.
Administration: Inhalation
Ribavirin should be administered in well-ventilated rooms (at least 6 air changes/hour). In mechanically-ventilated patients, ribavirin can potentially be deposited in the ventilator delivery system depending on temperature, humidity, and electrostatic forces; this deposition can lead to malfunction or obstruction of the expiratory valve, resulting in inadvertently high positive end-expiratory pressures. The use of one-way valves in the inspiratory lines, a breathing circuit filter in the expiratory line, and frequent monitoring and filter replacement have been effective in preventing these problems. Solutions in SPAG-2 unit should be discarded at least every 24 hours and when the liquid level is low before adding newly reconstituted solution. Should not be mixed with other aerosolized medication.
Monitoring Parameters
Inhalation: Respiratory function, hemoglobin, reticulocyte count, CBC with differential, I & O
Oral: Clinical studies tested as follows: CBC (including hemoglobin, WBC, and platelets) and chemistries (including liver function tests and uric acid) measured at weeks 1, 2, 4, 6, and 8, and then every 4 weeks; TSH measured every 12 weeks
Baseline values used in clinical trials:
Platelet count ≥90,000/mm3 (75,000/mm3 for cirrhosis or 70,000/mm3 for coinfection with HIV)
ANC ≥1500/mm3
Hemoglobin ≥12 g/dL for women and ≥13 g/dL for men (11 g/dL for HIV coinfected women and 12 g/dL for HIV coinfected men)
TSH and T4 within normal limits or adequately controlled
CD4+ cell count ≥200 cells/microL or CD4+ cell count 100-200 cells/microL and HIV-1 RNA <5000 copies/mL for coinfection with HIV
Serum HCV RNA (pretreatment, week 12 and week 24, and 24 weeks after completion of therapy). Note: Discontinuation of therapy may be considered after 12 weeks in patients with HCV (genotypes 1,4) who fail to achieve an early virologic response (EVR) (defined as ≥2-log decrease in HCV RNA compared to pretreatment) or after 24 weeks with detectable HCV RNA. Treat patients with HCV (genotypes 2,3) for 24 weeks (if tolerated) and then evaluate HCV RNA levels (Ghany, 2009).
Pretreatment and monthly pregnancy test up to 6 months following discontinuation of therapy for women of childbearing age; pretreatment ECG in patients with pre-existing cardiac disease; dental exams; ophthalmic exam pretreatment (all patients) and periodically for those with pre-existing ophthalmologic disorders. In pediatric patients, monitor growth closely during and after treatment.
Reference Range
Rapid virological response (RVR): Absence of detectable HCV RNA after 4 weeks of treatment
Early viral response (EVR): ≥2-log decrease in HCV RNA after 12 weeks of treatment
End of treatment response (ETR): Absence of detectable HCV RNA at end of the recommended treatment period
Sustained treatment response (STR): Absence of HCV RNA in the serum 6 months following completion of full treatment course
Dietary Considerations
When used in combination with interferon alfa-2b, capsules and solution may be taken with or without food, but always in a consistent manner in regard to food intake (ie, always take with food or always take on an empty stomach). When used in combination with peginterferon alfa-2b, capsules should be taken with food. Tablets should be taken with food.
Patient Education
For oral administration, take capsules with food and solution with or without food. Do not allow pregnant women or women of childbearing age to come in any contact with this medication. If prescribed in conjunction with other medications, maintain schedule as directed. Maintain adequate hydration, unless instructed to restrict fluid intake. You will need regular blood tests while taking this drug. You may experience increased susceptibility to infection. May cause dental or periodontal disorders. You may be required to have regular ophthalmic exams during therapy. May cause confusion, dizziness, insomnia, impaired concentration, emotional liability, headache, nausea, vomiting, anorexia, extreme fatigue, diarrhea, loss of hair (reversible), or dermatitis. Report chest pain or palpitations; unusual cough or difficulty breathing; rash; signs of infection (fever, chills, unusual bleeding or bruising, infection, or unhealed sores or white plaques in mouth); tingling, weakness, or pain in extremities; CNS changes (suicide ideation, fatigue, insomnia, irritability, depression, impaired concentration); or changes in vision.
Geriatric Considerations
No specific recommendations are necessary in the elderly; however, in patients with creatinine clearance <50 mL/minute, the oral route not recommended; dosage adjustment or discontinuation may be necessary. Many elderly will fall into this category.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and taste perversion.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
When used in combination with interferon alfa-2A or alfa-2b: Dizziness and drowsiness are common; may rarely cause delirium. Severe psychiatric disorders, including depression and suicidal behavior, have been associated with the use of some interferons. Careful neuropsychiatric monitoring is recommended.
Mental Health: Effects on Psychiatric Treatment
When used in combination with interferon alfa-2A or alfa-2b: May cause leukopenia; use caution with clozapine and carbamazepine; concurrent use with psychotropics may produce additive sedation and dry mouth
Nursing: Physical Assessment/Monitoring
Note specific cautions for healthcare professionals' exposure risks with inhalation formulation. Evaluate patient health status and history for contraindications and use cautions prior to beginning therapy. Evaluate weight on a regular basis throughout therapy. Monitor for headache; fatigue; irritability; impaired concentration; nausea, vomiting, or anorexia; anemia; or deterioration of hepatic, respiratory, or cardiac status on a regular basis.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 200 mg
Rebetol®: 200 mg
Ribasphere®: 200 mg
Combination package, oral [dose-pack/each package contains]:
Ribasphere® RibaPak®: Tablet: 400 mg (7s) [medium blue tablets] and Tablet: 600 mg (7s) [dark blue tablets] (14s, 56s)
Powder for solution, for nebulization:
Virazole®: 6 g [reconstituted product contains ribavirin 20 mg/mL]
Solution, oral:
Rebetol®: 40 mg/mL (100 mL) [contains propylene glycol, sodium benzoate; bubblegum flavor]
Tablet, oral: 200 mg
Copegus®: 200 mg
Ribasphere®: 200 mg, 400 mg, 600 mg
Tablet, oral [dose-pack]:
Ribasphere® RibaPak®: 400 mg [14s]
Ribasphere® RibaPak®: 400 mg [56s]
Ribasphere® RibaPak®: 600 mg [14s]
Ribasphere® RibaPak®: 600 mg [56s]
Pricing: U.S. (www.drugstore.com)
Capsules (Rebetol)
200 mg (60): $554.02
Capsules (Ribasphere)
200 mg (30): $135.61
Capsules (Ribavirin)
200 mg (56): $260.01
Solution (Rebetol)
40 mg/mL (100): $223.98
References
American Academy of Pediatrics Committee on Infectious Diseases, “Reassessment of the Indications for Ribavirin Therapy in Respiratory Syncytial Virus Infections,” Pediatrics, 1996, 97(1):137-40.
American Academy of Pediatrics Committee on Infectious Diseases, “Use of Ribavirin in the Treatment of Respiratory Syncytial Virus Infection,” Pediatrics, 1993, 92(3):501-4.
Barry M, Russi M, Armstrong L, et al, “Brief Report: Treatment of a Laboratory-Acquired Saria Virus Infection,” N Engl J Med, 1995, 333(5):294-6.
Boeckh M, Englund J, Li Y, et al, “Randomized Controlled Multicenter Trial of Aerosolized Ribavirin For Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients,” Clin Infect Dis, 2007, 44(2):245-9.
Chemaly RF, Ghosh S, Bodey GP, et al, “Respiratory Viral Infections in Adults With Hematologic Malignancies and Human Stem Cell Transplant Recipients: A Retrospective Study at a Major Cancer Center,” Medicine (Baltimore), 2006, 85(5):278-87.
Davis GL, Esteban-Mur R, Rustgi V, et al, “Interferon Alfa-2b Alone or in Combination With Ribavirin for the Treatment of Relapse of Chronic Hepatitis C. International Hepatitis Interventional Therapy Group,” N Engl J Med, 1998, 339(21):1493-9.
Dienstag JL and McHutchinson JG, “American Gastroenterological Association Medical Position Statement on the Management of Hepatitis C,” Gastroenterology, 2006, 130(1):225-30.
Englund JA, Piedra PA, Ahn YM, et al, “High-Dose, Short-Duration Ribavirin Aerosol Therapy Compared With Standard Ribavirin Therapy in Children With Suspected Respiratory Syncytial Virus Infection,” J Pediatr, 1994, 125:635-41.
Ghany MG, Nelson DR, Strader DB, et al, “An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guideline by the American Association for the Study of Liver Diseases,” Hepatology, 2011, 54(4):1433-44.
Ghany MG, Strader DB, Thomas DL, et al, “Diagnosis, Management And Treatment Of Hepatitis C: An Update,” Hepatology, 2009, 49(4):1335-74.
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Last full review/revision March 2012
Content last modified March 2012
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