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Drugs reference index «Ribavirin»

Ribavirin


Ribavirin

Pronunciation: (RYE-ba-VYE-rin)Class: Antiviral agent

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.

Pharmacology

Has antiviral inhibitory activity against respiratory syncytial virus (RSV) and herpes simplex virus. Exact mechanism is unknown.

Pharmacokinetics

Absorption

Aerosol

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.

Distribution

Aerosol

Highest concentrations found in respiratory tract and erythrocytes.

Capsules

Vd is 2,825 L.

Metabolism

Metabolized to deribosylated ribavirin in the liver.

In vitro studies indicate that ribavirin is not a substrate for CYP enzymes.

Elimination

Aerosol

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.

Special Populations

Renal Function Impairment

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.

Indications and Usage

Aerosol

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.

Unlabeled Uses

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.

Contraindications

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.

Dosage and Administration

RSVInfants and Children

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.

Storage/Stability

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.

Drug Interactions

Didanosine

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.

Laboratory Test Interactions

None well documented.

Adverse Reactions

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.

Cardiovascular

Aerosolized: Bigeminy, bradycardia, and tachycardia have been reported in patients with underlying congenital heart disease; bradycardia, cardiac arrest, digitalis toxicity, hypotension.

CNS

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%).

Dermatologic

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%).

EENT

Pharyngitis (13%); taste perversion (9%); rhinitis (8%); blurred vision (6%); conjunctivitis (5%). Aerosolized: Conjunctivitis.

Endocrine

Hypothyroidism (5%).

GI

Nausea (47%); anorexia (32%); diarrhea (22%); dyspepsia (16%); dry mouth, vomiting (14%); abdominal pain (13%); constipation (5%). Children: Anorexia (51%); vomiting (42%); nausea (33%).

Genitourinary

Menstrual disorder (7%).

Hematologic-Lymphatic

Neutropenia (27%); anemia (17%); lymphopenia (14%); leukopenia (6%); thrombocytopenia (5%).

Hepatic

Hepatomegaly (4%).

Lab Tests

Hyperuricemia (38%); decreased hemoglobin (30%); hyperbilirubinemia (14%).

Local

Injection-site reaction (58%); injection-site inflammation (25%). Children: Injection-site reaction (19%); injection-site inflammation (14%).

Metabolic-Nutritional

Decreased weight (29%).

Musculoskeletal

Myalgia (64%); arthralgia (34%); musculoskeletal pain (28%); back pain (5%). Children: Myalgia (32%); musculoskeletal pain (21%); arthralgia (15%).

Respiratory

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%).

Miscellaneous

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%).

Precautions

Warnings

Oral

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.

Monitor

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.

Pregnancy

Category X .

Lactation

Undetermined.

Children

Tablets

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 .

Elderly

Administer ribavirin capsules with caution, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and comorbidity.

Renal Function

Do not use in patients with CrCl below 50 mL/min.

Dental disorders

Dental and periodontal disorders have been reported.

Fatalities

Death during or shortly after treatment with aerosolized ribavirin has been reported.

Pancreatitis

Discontinue therapy in patients with confirmed pancreatitis.

Pulmonary symptoms

Dyspnea, pneumonia, pneumonitis, and pulmonary infiltrates may occur.

Respiratory function

Sudden deterioration of respiratory function has been associated with initiation of aerosolized ribavirin use in infants.

Severe reactions

Autoimmune and infectious disorders, diabetes, pulmonary dysfunction, pancreatitis, severe hypersensitivity, and suppression of bone marrow function may occur.

Suicidal ideation/depression

Severe depression and suicidal ideation may occur. Suicidal ideation and attempts occurred more frequently among children, primarily adolescents, compared with adults.

Overdosage

Symptoms

Hypocalcemia, hypomagnesemia.

Patient Information

  • Advise family or caregiver that solution for aerosol will be prepared and administered by health care providers in a hospital setting.
  • Advise patient to read Medication Guide before beginning therapy and with each refill of medication.
  • Caution patient that ribavirin is not effective by itself and to continue to take other medications for HCV infection as prescribed by health care provider.
  • Advise patient that it is not known if this therapy will prevent transmission of hepatitis C to others, nor is it known if it can prevent cirrhosis, liver failure, or liver cancer that may develop as a result of hepatitis C infection.
  • Caution patient not to change the dose or stop taking unless advised by health care provider.
  • Advise patient that if a dose is missed and remembered on the same day, to take the missed dose as soon as remembered. Advise patient that if a whole day has passed to talk to health care provider about what should be done. Caution patient not to take 2 doses at the same time to catch up.
  • Advise patient using ribavirin tablets to take prescribed number of tablets twice daily (morning and night) with food.
  • Advise patient using capsules or oral solution to take prescribed dose twice daily (morning and evening).
  • Advise patient that capsules or oral solution, used in combination with interferon alfa-2b, can be taken without regard to food, but to be consistent (ie, take with or without food).
  • Advise patient that capsules or oral solution, used in combination with peginterferon alfa-2b, should be taken with food.
  • Warn female patients of childbearing potential and female partners of male patients to take extreme care to avoid pregnancy during therapy and for 6 mo after completion of therapy because of significant risk of birth defects and/or death of fetus. Instruct patient and his/her partner to use 2 reliable forms of effective contraception during treatment and for 6 mo following completion of therapy.
  • Advise women of childbearing potential that pregnancy tests will have to be performed before starting therapy, monthly during therapy, and then monthly for 6 mo following completion of therapy.
  • Instruct female patients or female partners of male patients to report suspected pregnancy immediately to health care provider.
  • Advise patient to immediately report any of the following to health care provider: bloody diarrhea or bloody bowel movements, bruising or unusual bleeding, change in vision, chest pain, depression or suicidal thoughts, high fever, hives or swelling, severe stomach pain or low back pain, trouble breathing.
  • Caution patient that therapy may cause confusion, dizziness, or drowsiness, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Caution patient to avoid alcoholic beverages because alcohol ingestion can make liver disease worse.

Copyright © 2009 Wolters Kluwer Health.

  • Ribavirin Prescribing Information (FDA)
  • Ribavirin Detailed Consumer Information (PDR)
  • Ribavirin MedFacts Consumer Leaflet (Wolters Kluwer)
  • ribavirin Advanced Consumer (Micromedex) - Includes Dosage Information
  • Copegus Prescribing Information (FDA)
  • Rebetol Prescribing Information (FDA)
  • Rebetol Detailed Consumer Information (PDR)
  • Rebetol MedFacts Consumer Leaflet (Wolters Kluwer)
  • Rebetol Consumer Overview
  • Ribasphere Prescribing Information (FDA)
  • Ribasphere Consumer Overview
  • Virazole Prescribing Information (FDA)
  • Virazole Advanced Consumer (Micromedex) - Includes Dosage Information
  • Virazole Solution MedFacts Consumer Leaflet (Wolters Kluwer)

See Also...

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