Trade Names:Copegus- Tablets 200 mg
Trade Names:Rebetol- Capsules 200 mg- Solution, oral 40 mg/mL
Trade Names:RibaPak- Tablets 400 mg- Tablets 600 mg
Trade Names:Ribasphere- Tablets 200 mg- Tablets 400 mg- Tablets 600 mg- Capsules 200 mg
Trade Names:Ribatab- Tablets 400 mg- Tablets 600 mg
Trade Names:Virazole- Aerosol powder for reconstitution, lyophilized ribavirin 6 g per 100 mL vial.
Has antiviral inhibitory activity against respiratory syncytial virus (RSV) and herpes simplex virus. Exact mechanism is unknown.
Absorbed systemically following nasal and oral inhalation. Bioavailability depends on the method of drug delivery.Tablets
T max following multiple dose is 2 h and C max is 2,478 ng/mL. AUC is 25,361 ng•h/mL.Capsules
T max following multiple-dose administration is 3 h and C max is 3,680 ng/mL. AUC is 228,000 ng•h/mL. Absolute bioavailability is 64%.Oral solution
T max is 1 h, C max is 872 ng/mL, and AUC is 14,098 ng•h/mL.
Highest concentrations found in respiratory tract and erythrocytes.Capsules
Vd is 2,825 L.
Metabolized to deribosylated ribavirin in the liver.
In vitro studies indicate that ribavirin is not a substrate for CYP enzymes.
Mostly excreted in urine as unchanged drug and metabolites. The t ½ is 40 days (t ½ of erythrocytes). Plasma t ½ is 9.5 h (children).Tablets
After a single oral dose, the terminal t ½ and apparent Cl are 120 to 170 h and 26 L/h, respectively.Capsules
The t ½ after single- and multiple-dose administrations are 43.6 and 298 h, respectively. Cl is 38.2 L/h.
Because pharmacokinetics have not been studied in patients with renal function impairment, do not administer to patients with CrCl less than 50 mL/min.Hepatic Function ImpairmentTablets
Pharmacokinetics have not been evaluated.Capsules/Oral solution
C max increases with increasing severity of hepatic function impairment.Elderly
Pharmacokinetic evaluations have not been performed.ChildrenTablets/Oral solution
Pharmacokinetic evaluations have not been performed.Capsules
Pharmacokinetic parameters are similar between adults and children.Gender
Pharmacokinetics similar in men and women.Race
No differences in pharmacokinetics have been demonstrated.
Treatment of hospitalized infants and young children with severe lower respiratory tract infections caused by RSV.Capsules
In combination with recombinant interferon alfa-2b injection for the treatment of chronic hepatitis C in patients 5 yr of age or older with compensated liver disease previously untreated with alpha interferon, or who have relapsed following alpha interferon therapy. The capsules are also indicated in combination with peginterferon alfa-2b for the treatment of chronic hepatitis C in patients 18 yr of age or older with compensated liver disease who have not been previously treated with interferon alfa.Oral solution
In combination with recombinant interferon alfa-2b injection for the treatment of chronic hepatitis C in patients 3 yr of age or older with compensated liver disease previously untreated with alpha interferon, or who have relapsed following alpha interferon therapy.Tablets
In combination with peginterferon alfa-2a for the treatment of adults with chronic hepatitis C virus (HCV) infection who have compensated liver disease and have not been previously treated with interferon alpha.
Treatment of viral hemorrhagic fevers, such as Crimean-Congo hemorrhagic fever. Aerosol ribavirin has shown some success against influenza A and B viruses and herpes simplex virus.
Women who are pregnant or men whose female partners are pregnant; patients with a history of hypersensitivity to ribavirin or any component of the product; patients with hemoglobinopathies (eg, thalassemia major or sickle cell anemia); ribavirin tablet/peginterferon alfa-2a combination is contraindicated in patients with autoimmune hepatitis and hepatic decompensation (Child-Pugh class B and C) before or during treatment; ribavirin capsules or solution/interferon alfa-2b is contraindicated in patients with autoimmune hepatitis.
Inhalation 6 g reconstituted with 300 mL sterile water aerosolized and administered over 12 to 18 h/day for 3 to 7 days. Recommended drug concentration is 20 mg/mL.Capsules/Oral SolutionAdults For patients 75 kg or less
PO Two 200 mg capsules in the morning and three 200 mg capsules in the evening.For patients more than 75 kg
PO Three 200 mg capsules in the morning and evening. For patients previously untreated with ribavirin and interferon, duration of treatment is 24 to 48 wk.Children 3 yr of age and older with chronic HCV infection with compensated liver disease previously untreated with alpha interferon
PO 15 mg/kg/day. For children weighing 25 kg or less or who cannot swallow capsules, oral solution is available in a concentration of 40 mg/mL.For children weighing 25 to 36 kg
PO One 200 mg capsule in the morning and evening daily.For children weighing 37 to 49 kg
PO One 200 mg capsule in the morning and two 200 mg capsules in the evening daily.For children weighing 50 to 61 kg
PO Two 200 mg capsules in the morning and two 200 mg capsules in the evening daily.For children weighing more than 61 kg
PO Refer to adult dosing.
For children with genotype 1, treat for 48 wk. For genotype 2/3, treat for 24 wk.Dose Modification
In patients whose hemoglobin levels fall below 10 g/dL, reduce the ribavirin dose to 600 mg/day (one 200 mg capsule in the morning and two 200 mg capsules in the evening), or 7.5 mg/kg/day (divided dose morning and evening) for children. Permanently discontinue ribavirin in patients whose hemoglobin levels fall below 8.5 g/dL. In patients with a history of stable CV disease, a permanent dose reduction of ribavirin to 600 mg/day in adults or 7.5 mg/kg/day in children is required if the hemoglobin decreased by 2 g/dL or more during any 4-wk treatment period. Permanently discontinue ribavirin therapy in patients with cardiac history if the hemoglobin remains less than 12 g/dL after 4 wk on a reduced ribavirin dose.TabletsAdults
PO 800 to 1,200 mg/day in 2 divided doses with food. Individualize dose depending on baseline disease characteristics (eg, genotype), response to therapy, and tolerability of the regimen. Duration of treatment for patients previously untreated with ribavirin and interferon is 24 to 48 wk.Dose Modification
If severe adverse reactions or laboratory abnormalities develop during combined treatment with ribavirin tablets and peginterferon alfa-2a, modify or discontinue the dose, if appropriate, until adverse reactions subside. If intolerance persists after dosage adjustment, discontinue therapy with these agents. Once ribavirin tablets have been withheld because of clinical manifestation or laboratory abnormality, an attempt may be made to restart ribavirin at 600 mg/day with a further increase in the dose to 800 mg/day. Increasing the dose to the original assigned dose of 1,000 to 1,200 mg is not recommended.
Store capsules at controlled room temperature (59° to 86°F). Keep bottle tightly capped. Store oral solution in refrigerator (36° to 46°F) or at controlled room temperature (59° to 86°F). Store tablets at controlled room temperature (59° to 86°F). Keep bottle tightly capped. Store lyophilized powder in a dry place at controlled room temperature (59° to 78°F). Reconstituted aerosol solutions may be stored under sterile conditions at controlled room temperature (68° to 86°F) for 24 h.
Avoid coadministration because of risk of fatal hepatic failure, peripheral neuropathy, pancreatitis, and symptomatic hyperlactatemia/lactic acidosis.Stavudine, zidovudine
Avoid coadministration because antagonistic antiviral activity against HIV has been demonstrated in vitro. Risk of severe anemia and neutropenia may be increased.
None well documented.
The following adverse reactions were reported with combined use of ribavirin and peginterferon alfa-2a or interferon alfa-2b. The incidence is not specified for aerosolized ribavirin.
Aerosolized: Bigeminy, bradycardia, and tachycardia have been reported in patients with underlying congenital heart disease; bradycardia, cardiac arrest, digitalis toxicity, hypotension.
Fatigue (70%); fatigue/asthenia (68%); headache (66%); rigors (48%); anxiety/emotional lability/irritability (47%); insomnia (41%); depression (36%); dizziness (26%); impaired concentration (21%); emotional lability (12%); asthenia (10%); agitation (8%); impaired memory, mood alteration, nervousness (6%). Children: Headache (69%); fatigue (58%); rigors (25%); dizziness (20%); emotional lability (16%); insomnia (14%); depression (13%); asthenia, impaired concentration (5%); nervousness (3%).
Alopecia (36%); pruritus (29%); rash (28%); dry skin (24%); dermatitis (16%); increased sweating (11%); eczema (5%); flushing (4%). Aerosolized: Rash. Children: Alopecia (23%); rash (17%); pruritus (12%).
Pharyngitis (13%); taste perversion (9%); rhinitis (8%); blurred vision (6%); conjunctivitis (5%). Aerosolized: Conjunctivitis.
Nausea (47%); anorexia (32%); diarrhea (22%); dyspepsia (16%); dry mouth, vomiting (14%); abdominal pain (13%); constipation (5%). Children: Anorexia (51%); vomiting (42%); nausea (33%).
Menstrual disorder (7%).
Neutropenia (27%); anemia (17%); lymphopenia (14%); leukopenia (6%); thrombocytopenia (5%).
Hyperuricemia (38%); decreased hemoglobin (30%); hyperbilirubinemia (14%).
Injection-site reaction (58%); injection-site inflammation (25%). Children: Injection-site reaction (19%); injection-site inflammation (14%).
Decreased weight (29%).
Myalgia (64%); arthralgia (34%); musculoskeletal pain (28%); back pain (5%). Children: Myalgia (32%); musculoskeletal pain (21%); arthralgia (15%).
Dyspnea (26%); cough (23%); sinusitis (12%). Aerosolized: Apnea, atelectasis, bacterial pneumonia, bronchospasm, cyanosis, dyspnea, hypoventilation, pneumothorax, pulmonary edema, ventilator dependence, worsening of respiratory distress. Children: Dyspnea (5%).
Pyrexia (55%); flu-like symptoms (18%); resistance mechanism disorders, right upper quadrant pain, viral infection (12%); pain (10%); chest pain (9%); fungal infection, malaise (6%). Children: Fever (61%); flu-like symptoms (31%); chest pain (5%).
Ribavirin monotherapy is not effective for the treatment of chronic HCV infection and should not be used alone for this indication. Primary toxicity is hemolytic anemia, which may result in worsening of cardiac disease that has led to fatal and nonfatal MIs. Do not treat patients with a history of significant or unstable cardiac disease with ribavirin. Contraindicated in women who are pregnant and in the male partners of women who are pregnant. Avoid pregnancy during therapy and for 6 mo after completion of treatment.Aerosol
Sudden deterioration of respiratory function has been associated with initiation of aerosolized ribavirin use in infants. Carefully monitor respiratory function. If treatment appears to produce sudden deterioration of respiratory function, stop treatment and reinstitute only with extreme caution, continuous monitoring, and consideration of coadministration of bronchodilators. Not indicated for use in adults. Ribavirin has been shown to produce testicular lesions in rodents.
Prior to starting therapy, screen women of childbearing potential for pregnancy and obtain baseline laboratory and hematologic values. Also, obtain CBC at 2 and 4 wk of therapy or more frequently if indicated. Monitor ECG. Perform additional tests periodically. Carefully monitor respiratory function during treatment with aerosolized ribavirin.
Category X .
Safety and efficacy not established.Capsule/Oral solution
For treatment of chronic HCV in patients with compensated liver disease untreated with alpha interferon, safety and efficacy not established in children younger than 3 yr of age. Safety and efficacy not established in treatment with Ribaspheres .
Administer ribavirin capsules with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and comorbidity.
Do not use in patients with CrCl below 50 mL/min.
Dental and periodontal disorders have been reported.
Death during or shortly after treatment with aerosolized ribavirin has been reported.
Discontinue therapy in patients with confirmed pancreatitis.
Dyspnea, pneumonia, pneumonitis, and pulmonary infiltrates may occur.
Sudden deterioration of respiratory function has been associated with initiation of aerosolized ribavirin use in infants.
Autoimmune and infectious disorders, diabetes, pulmonary dysfunction, pancreatitis, severe hypersensitivity, and suppression of bone marrow function may occur.
Severe depression and suicidal ideation may occur. Suicidal ideation and attempts occurred more frequently among children, primarily adolescents, compared with adults.
Copyright © 2009 Wolters Kluwer Health.