Ribavirin Information
Ribavirin () . Dosage And Administration
The recommended dose of Ribavirin () tablets is provided in . The recommended duration of treatment for patients previously untreated with Ribavirin () and interferon is 24 to 48 weeks.
The daily dose of Ribavirin () 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
Ribavirin () should be taken with food.
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 () 800 mg by mouth daily for a total duration of 48 weeks, regardless of HCV genotype.
Ribavirin () should be taken with food.
If severe adverse reactions or laboratory abnormalities develop during combination Ribavirin () /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 () /peginterferon alfa-2a therapy should be discontinued. provides guidelines for dose modifications and discontinuation based on the patient’s hemoglobin concentration and cardiac status.
Ribavirin () 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
Once Ribavirin () has been withheld due to either a laboratory abnormality or clinical manifestation, an attempt may be made to restart Ribavirin () at 600 mg daily and further increase the dose to 800 mg daily. However, it is not recommended that Ribavirin () be increased to the original assigned dose (1000 mg to 1200 mg).
See peginterferon alfa-2a full prescribing information for recommendations on peginterferon alfa-2a dose modification.
Discontinuation of peginterferon alfa-2a/ Ribavirin () therapy should be considered if the patient has failed to demonstrate at least a 2 log reduction from baseline in HCV RNA by 12 weeks of therapy, or undetectable HCV RNA levels after 24 weeks of therapy.
Peginterferon alfa-2a/ Ribavirin () therapy should be discontinued in patients who develop hepatic decompensation during treatment [see
Ribavirin () . Warnings And Precautions
Significant adverse reactions associated with Ribavirin () /peginterferon alfa-2a combination therapy include severe depression and suicidal ideation, hemolytic anemia, suppression of bone marrow function, autoimmune and infectious disorders, ophthalmologic disorders, cerebrovascular disorders, pulmonary dysfunction, colitis, pancreatitis, and diabetes.
The Peginterferon alfa-2a Package Insert should be reviewed in its entirety for additional safety information prior to initiation of combination treatment.
Ribavirin () may cause birth defects and/or death of the exposed fetus.
The primary toxicity of Ribavirin () is hemolytic anemia, which was observed in approximately 13% of all Ribavirin () /peginterferon alfa-2a- treated subjects in clinical trials. Anemia associated with Ribavirin () occurs within 1 to 2 weeks of initiation of therapy. Because the initial drop in hemoglobin may be significant, it is advised that hemoglobin or hematocrit be obtained pretreatment and at week 2 and week 4 of therapy or more frequently if clinically indicated. Patients should then be followed as clinically appropriate. Caution should be exercised in initiating treatment in any patient with baseline risk of severe anemia (e.g., spherocytosis, history of gastrointestinal bleeding) [see
Fatal and nonfatal myocardial infarctions have been reported in patients with anemia caused by Ribavirin () . Patients should be assessed for underlying cardiac disease before initiation of Ribavirin () therapy. Patients with pre-existing cardiac disease should have electrocardiograms administered before treatment, and should be appropriately monitored during therapy. If there is any deterioration of cardiovascular status, therapy should be suspended or discontinued [see Because cardiac disease may be worsened by drug-induced anemia, patients with a history of significant or unstable cardiac disease should not use Ribavirin () [see and
Before beginning peginterferon alfa-2a/ Ribavirin () combination therapy, standard hematological and biochemical laboratory tests are recommended for all patients. Pregnancy screening for women of childbearing potential must be performed. Patients who have pre-existing cardiac abnormalities should have electrocardiograms administered before treatment with peginterferon alfa-2a/ Ribavirin () .
After initiation of therapy, hematological tests should be performed at 2 weeks and 4 weeks and biochemical tests should be performed at 4 weeks. Additional testing should be performed periodically during therapy. In the clinical studies, the CBC (including hemoglobin level and white blood cell and platelet counts) and chemistries (including liver function tests and uric acid) were measured at 1, 2, 4, 6, and 8 weeks, and then every 4 to 6 weeks or more frequently if abnormalities were found. Thyroid stimulating hormone (TSH) was measured every 12 weeks. Monthly pregnancy testing should be performed during combination therapy and for 6 months after discontinuing therapy.
The entrance criteria used for the clinical studies of Ribavirin () and peginterferon alfa-2a may be considered as a guideline to acceptable baseline values for initiation of treatment:
Ribavirin () . Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In the pivotal registration trials NV15801 and NV15942, 886 patients received Ribavirin () for 48 weeks at doses of 1000/1200 mg based on body weight. In these trials, one or more serious adverse reactions occurred in 10% of CHC monoinfected subjects and in 19% of CHC/HIV subjects receiving peginterferon alfa-2a alone or in combination with Ribavirin () . The most common serious adverse event (3% in CHC and 5% in CHC/HIV) was bacterial infection (e.g., sepsis, osteomyelitis, endocarditis, pyelonephritis, pneumonia).
Other serious adverse reactions occurred at a frequency of
The percentage of patients in clinical trials who experienced one or more adverse events was 98%. The most commonly reported adverse reactions were psychiatric reactions, including depression, insomnia, irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia, headache and rigors. Other common reactions were anorexia, nausea and vomiting, diarrhea, arthralgias, injection site reactions, alopecia, and pruritus. shows rates of adverse events occurring in ≥ 5% subjects receiving pegylated interferon and Ribavirin () combination therapy in the CHC Clinical Trial, NV15801.
Ten percent of CHC monoinfected patients receiving 48 weeks of therapy with peginterferon alfa-2a in combination with Ribavirin () discontinued therapy; 16% of CHC/HIV coinfected patients discontinued therapy. The most common reasons for discontinuation of therapy were psychiatric, flu-like syndrome (e.g., lethargy, fatigue, headache), dermatologic and gastrointestinal disorders and laboratory abnormalities (thrombocytopenia, neutropenia, and anemia).
Overall 39% of patients with CHC or CHC/HIV required modification of peginterferon alfa-2a and/or Ribavirin () therapy. The most common reason for dose modification of peginterferon alfa-2a in CHC and CHC/HIV patients was for laboratory abnormalities; neutropenia (20% and 27%, respectively) and thrombocytopenia (4% and 6%, respectively). The most common reason for dose modification of Ribavirin () in CHC and CHC/HIV patients was anemia (22% and 16%, respectively).
Peginterferon alfa-2a dose was reduced in 12% of patients receiving 1000 mg to 1200 mg Ribavirin () for 48 weeks and in 7% of patients receiving 800 mg Ribavirin () for 24 weeks. Ribavirin () dose was reduced in 21% of patients receiving 1000 mg to 1200 mg Ribavirin () for 48 weeks and in 12% of patients receiving 800 mg Ribavirin () for 24 weeks.
Chronic hepatitis C monoinfected patients treated for 24 weeks with peginterferon alfa-2a and 800 mg Ribavirin () were observed to have lower incidence of serious adverse events (3% vs. 10%), hemoglobin
Common Adverse Reactions in CHC with HIV Coinfection
The adverse event profile of coinfected patients treated with peginterferon alfa-2a/Ribavirin () in Study NR15961 was generally similar to that shown for monoinfected patients in Study NV15801 (). Events occurring more frequently in coinfected patients were neutropenia (40%), anemia (14%), thrombocytopenia (8%), weight decrease (16%), and mood alteration (9%).
Laboratory Test Abnormalities
Anemia due to hemolysis is the most significant toxicity of Ribavirin () therapy. Anemia (hemoglobin
The following adverse reactions have been identified and reported during post-approval use of peginterferon alfa-2a/Ribavirin () combination therapy. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System disorders
Pure red cell aplasia
Ear and Labyrinth disorders
Hearing impairment, hearing loss
Eye disorders
Serous retinal detachment
Immune disorders
Liver and renal graft rejection
Metabolism and Nutrition disorders
Dehydration
Skin and Subcutaneous Tissue disorders
Stevens-Johnson Syndrome (SJS)
Toxic epidermal necrolysis (TEN)
Ribavirin () . Drug Interactions
In vitro
In Study NR15961 among the CHC/HIV coinfected cirrhotic patients receiving NRTIs cases of hepatic decompensation (some fatal) were observed [see
Patients receiving peginterferon alfa-2a/Ribavirin () and NRTIs should be closely monitored for treatment associated toxicities. Physicians should refer to prescribing information for the respective NRTIs for guidance regarding toxicity management. In addition, dose reduction or discontinuation of peginterferon alfa-2a, Ribavirin () or both should also be considered if worsening toxicities are observed, including hepatic decompensation (e.g., Child-Pugh ≥ 6) [see and
Didanosine
Co-administration of Ribavirin () and didanosine is contraindicated. Didanosine or its active metabolite (dideoxyadenosine 5’-triphosphate) concentrations are increased when didanosine is co-administered with Ribavirin () , which could cause or worsen clinical toxicities. Reports of fatal hepatic failure, as well as peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis have been reported in clinical trials [see
Zidovudine
In Study NR15961, patients who were administered zidovudine in combination with peginterferon alfa-2a/Ribavirin () developed severe neutropenia (ANC
ID62
In vitro
Ribavirin () . Use In Specific Populations
Pregnancy: Category X [see
Ribavirin () produced significant embryocidal and/or teratogenic effects in all animal species in which adequate studies have been conducted. Malformations of the skull, palate, eye, jaw, limbs, skeleton, and gastrointestinal tract were noted. The incidence and severity of teratogenic effects increased with escalation of the drug dose. Survival of fetuses and offspring was reduced [see
In conventional embryotoxicity/teratogenicity studies in rats and rabbits, observed no-effect dose levels were well below those for proposed clinical use (0.3 mg/kg/day for both the rat and rabbit; approximately 0.06 times the recommended daily human dose of Ribavirin () ). No maternal toxicity or effects on offspring were observed in a peri/postnatal toxicity study in rats dosed orally at up to 1 mg/kg/day (approximately 0.01 times the maximum recommended daily human dose of Ribavirin () ).
Treatment and Post treatment: Potential Risk to the Fetus
Ribavirin () is known to accumulate in intracellular components from where it is cleared very slowly. It is not known whether Ribavirin () is contained in sperm, and if so, will exert a potential teratogenic effect upon fertilization of the ova. However, because of the potential human teratogenic effects of Ribavirin () , male patients should be advised to take every precaution to avoid risk of pregnancy for their female partners.
Ribavirin () should not be used by pregnant women or by men whose female partners are pregnant. Female patients of childbearing potential and male patients with female partners of childbearing potential should not receive Ribavirin () unless the patient and his/her partner are using effective contraception (two reliable forms) during therapy and for 6 months post therapy [see
Ribavirin () Pregnancy Registry
A Ribavirin () Pregnancy Registry has been established to monitor maternal-fetal outcomes of pregnancies of female patients and female partners of male patients exposed to Ribavirin () during treatment and for 6 months following cessation of treatment. Healthcare providers and patients are encouraged to report such cases by calling 1-800-593-2214.
Pharmacokinetic evaluations in pediatric patients have not been performed.
Safety and effectiveness of Ribavirin () have not been established in patients below the age of 18.
No clinically significant differences in the pharmacokinetics of Ribavirin () were observed between male and female subjects.
Ribavirin () pharmacokinetics, when corrected for weight, are similar in male and female patients.
Ribavirin () . Overdosage
No cases of overdose with Ribavirin () have been reported in clinical trials. Hypocalcemia and hypomagnesemia have been observed in persons administered greater than the recommended dosage of Ribavirin () . In most of these cases, Ribavirin () was administered intravenously at dosages up to and in some cases exceeding four times the recommended maximum oral daily dose.
Ribavirin () . Description
Ribavirin () is a nucleoside analogue with antiviral activity. The chemical name of Ribavirin () is 1-β-Dribofuranosyl--1,2,4-triazole-3-carboxamide and has the following structural formula:
The molecular formula of Ribavirin () is CHNO and the molecular weight is 244.2. Ribavirin () is a white to off-white powder. It is freely soluble in water and slightly soluble in anhydrous alcohol.
Each film-coated Ribavirin () tablet intended for oral administration contains 200 mg or 400 mg or 500 mg or 600 mg of Ribavirin () . In addition, each tablet contains the following inactive ingredients: crospovidone, hypromellose, iron oxide red, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, silicon dioxide, talc and titanium dioxide.
Ribavirin () . Clinical Pharmacology
Multiple dose Ribavirin () pharmacokinetic data are available for HCV patients who received Ribavirin () in combination with peginterferon alfa-2a. Following administration of 1200 mg/day with food for 12 weeks mean±SD (n=39; body weight > 75 kg) AUC was 25,361±7110 ng·hr/mL and C was 2748±818 ng/mL. The average time to reach C was 2 hours. Trough Ribavirin () plasma concentrations following 12 weeks of dosing with food were 1662±545 ng/mL in HCV infected patients who received 800 mg/day (n=89), and 2112±810 ng/mL in patients who received 1200 mg/day (n=75; body weight > 75 kg).
The terminal half-life of Ribavirin () following administration of a single oral dose of Ribavirin () is about 120 to 170 hours. The total apparent clearance following administration of a single oral dose of Ribavirin () is about 26 L/h. There is extensive accumulation of Ribavirin () after multiple dosing (twice daily) such that the C at steady state was four-fold higher than that of a single dose.
Effect of Food on Absorption of Ribavirin ()
Bioavailability of a single oral dose of Ribavirin () was increased by co-administration with a high-fat meal. The absorption was slowed (T was doubled) and the AUC and Cincreased by 42% and 66%, respectively, when Ribavirin () was taken with a high-fat meal compared with fasting conditions [see and
Elimination and Metabolism
The contribution of renal and hepatic pathways to Ribavirin () elimination after administration of Ribavirin () is not known. studies indicate that Ribavirin () is not a substrate of CYP450 enzymes.
Mechanism of Action
The mechanism by which Ribavirin () contributes to its antiviral efficacy in the clinic is not fully understood. Ribavirin () has direct antiviral activity in tissue culture against many RNA viruses. Ribavirin () increases the mutation frequency in the genomes of several RNA viruses and Ribavirin () triphosphate inhibits HCV polymerase in a biochemical reaction.
Antiviral Activity in Cell Culture
In the stable HCV cell culture model system (HCV replicon), Ribavirin () inhibited autonomous HCV RNA replication with a 50% effective concentration (EC) value of 11 to 21 mcM. In the same model, PEG-IFN α-2a also inhibited HCV RNA replication, with an EC value of 0.1 to 3 ng/mL. The combination of PEG-IFN α-2a and Ribavirin () was more effective at inhibiting HCV RNA replication than either agent alone.
Resistance
Different HCV genotypes display considerable clinical variability in their response to PEG-IFN-α and Ribavirin () therapy. Viral genetic determinants associated with the variable response have not been definitively identified.
Cross-resistance
Cross-resistance between IFN α and Ribavirin () has not been observed.
Ribavirin () . Nonclinical Toxicology
Carcinogenesis
In a p53 (+/-) mouse carcinogenicity study up to the maximum tolerated dose of 100 mg/kg/day, Ribavirin () was not oncogenic. Ribavirin () was also not oncogenic in a rat 2 year carcinogenicity study at doses up to the maximum tolerated dose of 60 mg/kg/day. On a body surface area basis, these doses are approximately 0.5 and 0.6 times the maximum recommended daily human dose of Ribavirin () , respectively.
Mutagenesis
Ribavirin () demonstrated mutagenic activity in the mouse lymphoma assay. No clastogenic activity was observed in an mouse micronucleus assay at doses up to 2000 mg/kg. However, results from studies published in the literature show clastogenic activity in the mouse micronucleus assay at oral doses up to 2000 mg/kg. A dominant lethal assay in rats was negative, indicating that if mutations occurred in rats they were not transmitted through male gametes. However, potential carcinogenic risk to humans cannot be excluded.
Impairment of Fertility
In a fertility study in rats, Ribavirin () showed a marginal reduction in sperm counts at the dose of 100 mg/kg/day with no effect on fertility. Upon cessation of treatment, total recovery occurred after 1 spermatogenesis cycle. Abnormalities in sperm were observed in studies in mice designed to evaluate the time course and reversibility of Ribavirin () -induced testicular degeneration at doses of 15 to 150 mg/kg/day (approximately 0.1 to 0.8 times the maximum recommended daily human dose of Ribavirin () ) administered for 3 to 6 months. Upon cessation of treatment, essentially total recovery from Ribavirin () -induced testicular toxicity was apparent within 1 or 2 spermatogenic cycles.
Female patients of childbearing potential and male patients with female partners of childbearing potential should not receive Ribavirin () unless the patient and his/her partner are using effective contraception (two reliable forms). Based on a multiple dose half-life (t) of Ribavirin () of 12 days, effective contraception must be utilized for 6 months post therapy (i.e., 15 half-lives of clearance for Ribavirin () ).
No reproductive toxicology studies have been performed using peginterferon alfa-2a in combination with Ribavirin () . However, peginterferon alfa-2a and Ribavirin () when administered separately, each has adverse effects on reproduction. It should be assumed that the effects produced by either agent alone would also be caused by the combination of the two agents.
In a study in rats, it was concluded that dominant lethality was not induced by Ribavirin () at doses up to 200 mg/kg for 5 days (up to 1.7 times the maximum recommended human dose of Ribavirin () ).
Long-term studies in the mouse and rat (18 to 24 months; dose 20 to 75, and 10 to 40 mg/kg/day, respectively, approximately 0.1 to 0.4 times the maximum daily human dose of Ribavirin () ) have demonstrated a relationship between chronic Ribavirin () exposure and an increased incidence of vascular lesions (microscopic hemorrhages) in mice. In rats, retinal degeneration occurred in controls, but the incidence was increased in Ribavirin () -treated rats.
Ribavirin () . Clinical Studies
The safety and effectiveness of peginterferon alfa-2a in combination with Ribavirin () for the treatment of hepatitis C virus infection were assessed in two randomized controlled clinical trials. All patients were adults, had compensated liver disease, detectable hepatitis C virus, liver biopsy diagnosis of chronic hepatitis, and were previously untreated with interferon. Approximately 20% of patients in both studies had compensated cirrhosis (Child-Pugh class A). Patients coinfected with HIV were excluded from these studies.
In Study NV15801, patients were randomized to receive either peginterferon alfa-2a 180 mcg subcutaneous once weekly with an oral placebo, peginterferon alfa-2a 180 mcg once weekly with Ribavirin () 1000 mg by mouth (body weight
Difference in overall treatment response (Peginterferon alfa-2a/Ribavirin () – Interferon alfa-2b/Ribavirin () ) was 9% (95% CI 2.3, 15.3).
In Study NV15942, all patients received peginterferon alfa-2a 180 mcg subcutaneous once weekly and were randomized to treatment for either 24 or 48 weeks and to a Ribavirin () dose of either 800 mg or 1000 mg/1200 mg (for body weight 2 x 10HCV RNA copies/mL serum) were preferentially assigned to treatment for 48 weeks.
Sustained Virologic Response (SVR) and HCV Genotype
HCV 1 and 4- Irrespective of baseline viral titer, treatment for 48 weeks with peginterferon alfa-2a and 1000 mg or 1200 mg of Ribavirin () resulted in higher SVR (defined as undetectable HCV RNA at the end of the 24 week treatment-free follow-up period) compared to shorter treatment (24 weeks) and/or 800 mg Ribavirin () .
HCV 2 and 3- Irrespective of baseline viral titer, treatment for 24 weeks with peginterferon alfa-2a and 800 mg of Ribavirin () resulted in a similar SVR compared to longer treatment (48 weeks) and/or 1000 mg or 1200 mg of Ribavirin () (see
The numbers of patients with genotype 5 and 6 were too few to allow for meaningful assessment.
Treatment response rates are lower in patients with poor prognostic factors receiving pegylated interferon alpha therapy. In studies NV15801 and NV15942, treatment response rates were lower in patients older than 40 years (50% vs. 66%), in patients with cirrhosis (47% vs. 59%), in patients weighing over 85 kg (49% vs. 60%), and in patients with genotype 1 with high vs. low viral load (43% vs. 56%). African-American patients had lower response rates compared to Caucasians.
In studies NV15801 and NV15942, lack of early virologic response by 12 weeks (defined as HCV RNA undetectable or > 2 loglower than baseline) was grounds for discontinuation of treatment. Of patients who lacked an early viral response by 12 weeks and completed a recommended course of therapy despite a protocol-defined option to discontinue therapy, 5/39 (13%) achieved an SVR. Of patients who lacked an early viral response by 24 weeks, 19 completed a full course of therapy and none achieved an SVR.
In Study NR15961, patients with CHC/HIV were randomized to receive either peginterferon alfa-2a 180 mcg subcutaneous once weekly plus an oral placebo, peginterferon alfa-2a 180 mcg once weekly plus Ribavirin () 800 mg by mouth daily or interferon alfa-2a, 3 MIU subcutaneous three times a week plus Ribavirin () 800 mg by mouth daily. All patients received 48 weeks of therapy and sustained virologic response (SVR) was assessed at 24 weeks of treatment-free follow-up. Ribavirin () or placebo treatment assignment was blinded in the peginterferon alfa-2a treatment arms. All patients were adults, had compensated liver disease, detectable hepatitis C virus, liver biopsy diagnosis of chronic hepatitis C, and were previously untreated with interferon. Patients also had CD4+ cell count ≥ 200 cells/mcL or CD4+ cell count ≥ 100 cells/mcL but
Treatment response rates were lower in CHC/HIV patients with poor prognostic factors (including HCV genotype 1, HCV RNA > 800,000 IU/mL, and cirrhosis) receiving pegylated interferon alpha therapy.
Of the patients who did not demonstrate either undetectable HCV RNA or at least a 2 log reduction from baseline in HCV RNA titer by 12 weeks of peginterferon alfa-2a and Ribavirin () combination therapy, 2% (2/85) achieved an SVR.
In CHC patients with HIV coinfection who received 48 weeks of peginterferon alfa-2a alone or in combination with Ribavirin () treatment, mean and median HIV RNA titers did not increase above baseline during treatment or 24 weeks post treatment.
Ribavirin () . How Supplied/storage And Handling
Ribavirin () Tablets, 200 mg are light pink to pink, round, biconvex, beveled, film-coated tablets debossed with the logo of ‘ZC19’ on one side, other side plain and supplied as follows:
NDC 68382-046-03 in bottle of 168 tablets
NDC 68382-046-28 in bottle of 180 tablets
NDC 68382-046-10 in bottle of 1000 tablets
NDC 68382-046-30 in blister pack of 100 unit dose tablets
Ribavirin () Tablets, 400 mg are light pink to pink, capsule shaped, biconvex, film-coated tablets debossed with ‘ZD’ and ‘07’ on one side and plain on other side and supplied as follows:
NDC 68382-127-17 in bottle of 28 tablets
NDC 68382-127-07 in bottle of 56 tablets
NDC 68382-127-14 in bottle of 60 tablets
Ribavirin () Tablets, 500 mg are light pink to pink, modified capsule shaped, biconvex, film-coated tablets debossed with ‘ZC56’ on one side and plain on the other side and supplied as follows:
NDC 68382-128-17 in bottle of 28 tablets
NDC 68382-128-07 in bottle of 56 tablets
NDC 68382-128-14 in bottle of 60 tablets
Ribavirin () Tablets, 600 mg are light pink to pink, modified capsule shaped, biconvex, film-coated tablets debossed with ‘ZD’ and ‘08’ on one side and plain on other side and supplied as follows:
NDC 68382-129-17 in bottle of 28 tablets
NDC 68382-129-07 in bottle of 56 tablets
NDC 68382-129-14 in bottle of 60 tablets
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Keep bottle tightly closed.
Ribavirin () . Patient Counseling Information
See Medication Guide
Patients must be informed that Ribavirin () may cause birth defects and/or death of the exposed fetus. Ribavirin () therapy must not be used by women who are pregnant or by men whose female partners are pregnant. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients taking Ribavirin () therapy and for 6 months post therapy. Ribavirin () therapy should not be initiated until a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Patients must perform a pregnancy test monthly during therapy and for 6 months post therapy.
Female patients of childbearing potential and male patients with female partners of childbearing potential must be advised of the teratogenic/embryocidal risks and must be instructed to practice effective contraception during Ribavirin () therapy and for 6 months post therapy. Patients should be advised to notify the healthcare provider immediately in the event of a pregnancy [see and
The most common adverse event associated with Ribavirin () is anemia, which may be severe [see and Patients should be advised that laboratory evaluations are required prior to starting Ribavirin () therapy and periodically thereafter [see It is advised that patients be well hydrated, especially during the initial stages of treatment.
Patients who develop dizziness, confusion, somnolence, and fatigue should be cautioned to avoid driving or operating machinery.
Patients should be advised to take Ribavirin () with food.
Patients should be questioned about prior history of drug abuse before initiating Ribavirin () /peginterferon alfa-2a, as relapse of drug addiction and drug overdoses have been reported in patients treated with interferons.
Patients should be advised not to drink alcohol, as alcohol may exacerbate chronic hepatitis C infection.
Patient should be informed about what to do in the event they miss a dose of Ribavirin () . The missed doses should be taken as soon as possible during the same day. Patients should not double the next dose. Patients should be advised to call their healthcare provider if they have questions.
Patients should be informed that the effect of peginterferon alfa-2a/Ribavirin () treatment of hepatitis C infection on transmission is not known, and that appropriate precautions to prevent transmission of hepatitis C virus should be taken.
Patients should be informed regarding the potential benefits and risks attendant to the use of Ribavirin () . Instructions on appropriate use should be given, including review of the contents of the enclosed MEDICATION GUIDE, which is not a disclosure of all or possible adverse effects.
Ribavirin ()
Ribavirin ()
Ribavirin ()
Ribavirin () Package Label.principal Display Panel
NDC 68382-046-03 in bottle of 168 tablets
Ribavirin () Tablets , 200 mg
Ronly
168 tablets
ZYDUS
NDC 68382-127-07 in bottle of 56 tablets
Ribavirin () Tablets , 400 mg
Ronly
56 tablets
ZYDUS
NDC 68382-128-07 in bottle of 56 tablets
Ribavirin () Tablets , 500 mg
Ronly
56 tablets
ZYDUS
NDC 68382-129-17 in bottle of 56 tablets
Ribavirin () Tablets , 600 mg
Ronly
56 tablets
ZYDUS
