These highlights do not include all the information needed to use RIBAVIRIN TABLETS safely and effectively. See full prescribing information for RIBAVIRIN TABLETS.
Ribavirin Tablets, oral
Initial U.S. Approval: 2002
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
See full prescribing information for complete boxed warning.
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Ribavirin monotherapy, including ribavirin tablets, is not effective for the treatment of chronic hepatitis C virus infection (Boxed Warning).
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The hemolytic anemia associated with ribavirin therapy may result in worsening of cardiac disease and lead to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with ribavirin tablets (2.3, 5.2, 6.1).
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Significant teratogenic and embryocidal effects have been demonstrated in all animal species exposed to ribavirin. Therefore, ribavirin tablets are contraindicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both female patients and in female partners of male patients who are taking ribavirin tablets therapy (4, 5.1, 8.1).
RECENT MAJOR CHANGES
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Boxed Warning |
10/2010 |
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Indications and Usage (1) |
10/2010 |
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Dosage and Administration (2.2, 2.3, 2.4, 2.5) |
10/2010 |
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Contraindications (4) |
12/2010 |
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Warnings and Precautions (5.1, 5.2, 5.3, 5.5, 5.6, 5.7, 5.8, 5.9) |
10/2010 |
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Warnings and Precautions, Hepatic Failure (5.3) |
12/2010 |
INDICATIONS AND USAGE
Ribavirin tablets are a nucleoside analogue indicated for the treatment of chronic hepatitis C (CHC) virus infection in combination with peginterferon alfa-2a in adults with compensated liver disease not previously treated with interferon alpha, and in CHC patients coinfected with HIV (1)
DOSAGE AND ADMINISTRATION
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CHC: Ribavirin tablets are administered according to body weight and genotype (2.1)
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CHC with HIV coinfection: 800 mg by mouth daily for a total of 48 weeks, regardless of genotype (2.2)
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Dose reduction or discontinuation is recommended in patients experiencing certain adverse reactions or renal impairment (2.4, 2.5)
DOSAGE FORMS AND STRENGTHS
Ribavirin tablets 200 mg (3)
CONTRAINDICATIONS
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Pregnant women and men whose female partners are pregnant (4, 5.1, 8.1)
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Hemoglobinopathies (4)
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Coadministration with didanosine (4, 7.1)
Ribavirin tablets in combination with peginterferon alfa-2a is contraindicated in patients with:
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Autoimmune hepatitis (4)
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Hepatic decompensation in cirrhotic patients (4, 5.3)
WARNINGS AND PRECAUTIONS
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Birth defects and fetal death with ribavirin: Do not use in pregnancy and for 6 months after treatment. Patients must have a negative pregnancy test prior to therapy, use at least 2 forms of contraception and undergo monthly pregnancy tests (4, 5.1, 8.1)
Peginterferon alfa-2a/ribavirin tablets: Patients exhibiting the following conditions should be closely monitored and may require dose reduction or discontinuation of therapy:
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Hemolytic anemia may occur with a significant initial drop in hemoglobin. This may result in worsening cardiac disease leading to fatal or nonfatal myocardial infarctions (5.2, 6.1)
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Risk of hepatic failure and death: Monitor hepatic function during treatment and discontinue treatment for hepatic decompensation (5.3)
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Severe hypersensitivity reactions including urticaria, angioedema, bronchoconstriction, and anaphylaxis, and serious skin reactions such as Stevens-Johnson Syndrome (5.4)
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Pulmonary disorders, including pulmonary function impairment and pneumonitis, including fatal cases of pneumonia (5.6)
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Severe depression and suicidal ideation, autoimmune and infectious disorders, suppression of bone marrow function, pancreatitis, and diabetes (5)
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Bone marrow suppression with azathioprine coadministration (5.7)
ADVERSE REACTIONS
The most common adverse reactions (frequency > 40%) in adults receiving combination therapy are fatigue/asthenia, pyrexia, myalgia, and headache (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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Nucleoside analogues: Closely monitor for toxicities. Discontinue nucleoside reverse transcriptase inhibitors or reduce dose or discontinue interferon, ribavirin or both with worsening toxicities (7.1)
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Azathioprine: Concomitant use of azathioprine with ribavirin has been reported to induce severe pancytopenia and may increase the risk of azathioprine-related myelotoxicity (7.3)
USE IN SPECIFIC POPULATIONS
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Ribavirin Pregnancy Registry: 1-800-593-2214
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Pediatrics: Safety and efficacy in patients < 18 years old have not been established (8.4)
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Renal Impairment: Do not use in patients with GFR < 50 mL/min (8.7)
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Organ transplant: Safety and efficacy have not been studied (8.10)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 4/2011
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FULL PRESCRIBING INFORMATION
WARNING: RISK OF SERIOUS DISORDERS AND RIBAVIRIN-ASSOCIATED EFFECTS
Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication.
The primary clinical toxicity of ribavirin is hemolytic anemia. The anemia associated with ribavirin therapy may result in worsening of cardiac disease and lead to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with ribavirin tablets [see Warnings and Precautions (5.2), Adverse Reactions (6.1), and Dosage and Administration (2.3)].
Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. In addition, ribavirin has a multiple dose half-life of 12 days, and it may persist in non-plasma compartments for as long as 6 months. Therefore, ribavirin, including ribavirin tablets, is contraindicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of therapy in both female patients and in female partners of male patients who are taking ribavirin therapy. At least two reliable forms of effective contraception must be utilized during treatment and during the 6-month post treatment follow-up period [see Contraindications (4), Warnings and Precautions (5.1), and Use in Specific Populations (8.1)].
1 INDICATIONS AND USAGE
Ribavirin tablets in combination with peginterferon alfa-2a is indicated for the treatment of adults with chronic hepatitis C (CHC) virus infection who have compensated liver disease and have not been previously treated with interferon alpha.
The following points should be considered when initiating ribavirin tablets combination therapy with peginterferon alfa-2a:
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This indication is based on clinical trials of combination therapy in patients with CHC and compensated liver disease, some of whom had histological evidence of cirrhosis (Child-Pugh class A), and in patients with clinically stable HIV disease and CD4 count > 100 cells/mm2.
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This indication is based on achieving undetectable HCV-RNA after treatment for 24 or 48 weeks, based on HCV genotype, and maintaining a Sustained Virologic Response (SVR) 24 weeks after the last dose.
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Safety and efficacy data are not available for treatment longer than 48 weeks.
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The safety and efficacy of ribavirin tablets and peginterferon alfa-2a therapy have not been established in liver or other organ transplant recipients, patients with decompensated liver disease, or previous non-responders to interferon therapy.
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The safety and efficacy of ribavirin tablets therapy for the treatment of adenovirus, RSV, parainfluenza or influenza infections have not been established. Ribavirin tablets should not be used for these indications. Ribavirin for inhalation has a separate package insert, which should be consulted if ribavirin inhalation therapy is being considered.
2 DOSAGE AND ADMINISTRATION
2.1 Chronic Hepatitis C Monoinfection
The recommended dose of ribavirin tablets is provided in Table 1. The recommended duration of treatment for patients previously untreated with ribavirin and interferon is 24 to 48 weeks.
The daily dose of ribavirin tablets is 800 mg to 1200 mg administered orally in two divided doses. The dose should be individualized to the patient depending on baseline disease characteristics (e.g., genotype), response to therapy, and tolerability of the regimen (see Table 1).
Ribavirin tablets should be taken with food.
Table 1. Peginterferon alfa-2a and Ribavirin Tablets Dosing Recommendations
Genotypes 2 and 3 showed no increased response to treatment beyond 24 weeks (see Table 6).
Data on genotypes 5 and 6 are insufficient for dosing recommendations. |
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Hepatitis C
Virus (HCV)
Genotype |
Peginterferon
alfa-2a
Dose* |
Ribavirin
Tablets
Dose |
Duration |
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Genotypes 1,4
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180 mcg
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<75 kg =
1000 mg |
48 weeks
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≥75 kg =
1200 mg |
48 weeks
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Genotypes 2, 3 |
180 mcg |
800 mg |
24 weeks |
2.2 Chronic Hepatitis C with HIV Coinfection
The recommended dose for treatment of chronic hepatitis C in patients coinfected with HIV is peginterferon alfa-2a 180 mcg subcutaneous once weekly and ribavirin tablets 800 mg by mouth daily for a total duration of 48 weeks, regardless of HCV genotype.
Ribavirin tablets should be taken with food.
2.3 Dose Modifications
If severe adverse reactions or laboratory abnormalities develop during combination ribavirin tablets/peginterferon alfa-2a therapy, the dose should be modified or discontinued, if appropriate, until the adverse reactions abate or decrease in severity. If intolerance persists after dose adjustment, ribavirin tablets/peginterferon alfa-2a therapy should be discontinued. Table 2 provides guidelines for dose modifications and discontinuation based on the patient’s hemoglobin concentration and cardiac status.
Ribavirin tablets should be administered with caution to patients with pre-existing cardiac disease. Patients should be assessed before commencement of therapy and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be stopped [see Warnings and Precautions (5.2)].
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