Ribavirin oral solution
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral solution containing ribavirin
Chronic hepatitis C - combination therapy
For use as part of combination therapy for the treatment of chronic hepatitis C (CHC) in patients not previously treated and without liver decompensation.
Ribavirin must be used in combination. Refer to individual product details for prescribing information for concurrent medication and to local procedure.
Ribavirin oral solution may be used in combination with peginterferon alfa-2b or interferon alfa-2b. The choice of combination regimen is based on the characteristics of the patient and on the anticipated efficacy and safety of the combination treatment for an individual patient. In patients who weigh more than 47 kg and able to swallow the capsules, see Monograph for ribavirin capsules.
Children 3 to 18 years weighing more than 47 kg
Children able to swallow capsules may take the equivalent dose of ribavirin 200 mg capsules in two divided doses.
Bodyweight over 105 kg
600 mg ribavirin in the morning and 800 mg in the evening.
Bodyweight 81 to 105 kg
600 mg ribavirin in the morning and 600 mg in the evening.
Bodyweight 65 to 81 kg
400 mg ribavirin in the morning and 600 mg in the evening.
Bodyweight 50 to 65 kg
400 mg ribavirin in the morning and 400 mg in the evening.
Bodyweight 47 to 50 kg
200 mg ribavirin in the morning and 400 mg in the evening.
Children 3 to 18 years weighing less than 47 kg
The recommended dose is 15 mg/kg/day in two divided doses.
The manufacturer suggests the following doses:
Children weighing 45 to 47 kg
9 ml of ribavirin oral solution 40 mg/ml in the morning and 8 ml in the evening.
Children weighing 42 to 44 kg
8 ml of ribavirin oral solution 40 mg/ml in the morning and 8 ml in the evening.
Children weighing 40 to 41 kg
8 ml of ribavirin oral solution 40 mg/ml in the morning and 7 ml in the evening.
Children weighing 37 to 39 kg
7 ml of ribavirin oral solution 40 mg/ml in the morning and 7 ml in the evening.
Children weighing 34 to 36 kg
7 ml of ribavirin oral solution 40mg/ml in the morning and 6 ml in the evening.
Children weighing 32 to 33 kg
6 ml of ribavirin oral solution 40 mg/ml in the morning and 6 ml in the evening.
Children weighing 29 to 31 kg
6 ml of ribavirin oral solution 40 mg/ml in the morning and 5 ml in the evening.
Children weighing 26 to 28 kg
5 ml of ribavirin oral solution 40 mg/ml in the morning and 5 ml in the evening.
Children weighing 23 to 25 kg
5 ml of ribavirin oral solution 40 mg/ml in the morning and 4 ml in the evening.
Children weighing 21 to 22 kg
4 ml of ribavirin oral solution 40 mg/ml in the morning and 4 ml in the evening.
Children weighing 18 to 20 kg
4 ml of ribavirin oral solution 40 mg/ml in the morning and 3 ml in the evening.
Children weighing 15 to 17 kg
3 ml of ribavirin oral solution 40 mg/ml in the morning and 3 ml in the evening.
Children weighing 13 to 14 kg
3 ml of ribavirin oral solution 40 mg/ml in the morning and 2 ml in the evening.
Children weighing 10 to 12 kg
2 ml of ribavirin oral solution 40 mg/ml in the morning and 2 ml in the evening.
Children under 3 years
Patients with Renal Impairment
The pharmacokinetics of ribavirin are altered in patients with renal impairment due to reduction of apparent creatinine clearance in these patients. Therefore, it is recommended that renal function be evaluated in all patients prior to initiation of ribavirin. Patients with renal impairment should be more carefully monitored with respect to the development of anaemia.
The manufacturer suggests the below doses for adult patients with renal impairment. At the time of writing, limited data are available for paediatric patients with renal impairment.
Creatinine clearance less than 50 to 30 ml/minute
Alternate doses, 200 mg and 400 mg ribavirin every other day.
Creatinine clearance less than 30 ml/minute
200 mg ribavirin daily.
Patients receiving haemodialysis
200 mg ribavirin daily.
Additional Dosage Information
Duration of treatment
Treatment length is dependant on virus genotype, concurrent illness and chosen therapy type. Refer to individual product details for prescribing information for concurrent medication and to local procedure.
If severe adverse reactions or laboratory abnormalities develop during therapy that relate to ribavirin, modify the dose or discontinue ribavirin, if appropriate, until the adverse reactions abate or decrease in severity. If severe adverse reactions or laboratory abnormalities develop during therapy that relate to products used in combination with ribavirin, consult product information for further information relating to dosage or discontinuation.
As adherence may be an important factor for the outcome of therapy, the dose should be kept as close as possible to the recommended standard dose. The potential negative impact of ribavirin dose reduction on efficacy results could not be ruled out.
Guidance for dose reduction or discontinuation of ribavirin
Indirect bilirubin greater than 5 mg/dl for 4 weeks in patients treated with interferon alfa-2b: Discontinue ribavirin oral solution
Indirect bilirubin greater than 4 mg/dl for 4 weeks in patients treated with peginterferon alfa-2b: Discontinue ribavirin oral solution
Haemoglobin 10 to 8.5 g/dl in patients with no cardiac disease: Reduce ribavirin oral solution dose. For patients who receive ribavirin in combination with interferon alfa-2b, reduce ribavirin dose to 7.5 mg/kg/day. For patients who receive ribavirin in combination with peginterferon alfa-2b, the first ribavirin dose reduction is to 12 mg/kg/day. If a second dose reduction is necessary, the dose can be reduced to 8 mg/kg/day.
Haemoglobin less than 8.5 g/dl in patients with no cardiac disease: Discontinue ribavirin oral solution
Circumstances for reduction of concurrent medication or discontinuation of combination therapy
Refer to individual product details for prescribing information for concurrent medication and to local procedure.
Children under 3 years
Hereditary fructose intolerance
History of severe cardiac disorder
Severe cardiac disorder
Sickle cell disease
Unstable cardiac disorder
Precautions and Warnings
CD4 counts less than 200 cells/microlitre
Children aged 3 to 18 years
Haemoglobin concentration below 10g/dL
Decompensated liver disease
Glucose-galactose malabsorption syndrome
History of cardiac arrhythmias
History of congestive cardiac failure
History of myocardial infarction
HIV patients receiving highly active anti-retroviral therapy
HIV with advanced cirrhosis on highly active anti-retroviral therapy
Positive HIV status
Renal impairment - creatinine clearance below 50ml/minute
Reduce dose in patients with creatinine clearance below 50ml/min
Must be used as part of combination therapy
Treatment to be initiated and supervised by a specialist
Preparation contains sucrose
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Advise patient to take with or after food
Children: Monitor thyroid function before & every 3 months during therapy
Evaluate renal function before and during treatment
Exclude pregnancy prior to initiation of treatment
Monitor cardiac function before and regularly during treatment
Monitor haematological parameters before and during treatment
Monitor hepatic function before treatment and regularly during treatment
Dental check-ups advisable during long-term treatment
Ensure negative monthly pregnancy tests throughout treatment
Monitor and discontinue if appropriate if psychiatric or CNS problems occur
Monitor cardiac function in patients with cardiac disease
Monitor ECG prior to and during treatment in existing cardiac abnormalities
Monitor growth of children on combination therapy
Monitor levels of hepatic enzymes and bilirubin
Monitor patients at risk of gout
Monitor serum creatinine
Monitor serum electrolytes
Monitor uric acid levels
Determine TSH levels if patient develops symptoms of thyroid dysfunction
Discontinue if any deterioration in cardiac status occurs
Modify dose if adverse effects occur
Consider discontinuing treatment if severe hepatic changes occur
Discontinue if hypersensitivity reactions occur
Discontinue in patients developing prolongation of coagulation markers
Female: Contraception required during and for 9 months after treatment
Male & female: Ensure adequate contraception during treatment
Male: Contraception required during and for 6 months after treatment
Male: Use of condoms advised if partner pregnant or may become pregnant
Advise patient on appropriate tooth brushing during treatment
If vomiting occurs, rinse mouth thoroughly afterwards
Refer to individual product details for prescribing information for concurrent medication and to local procedure.
Male and female patients must be advised that ribavirin is teratogenic and that effective and continuous contraception is required during treatment and for some months thereafter. They should also be advised that contraceptives may fail and warned of the significant teratogenic risk to the foetus.
Standard haematologic tests and blood chemistries should be performed before treatment, after 2 weeks and 4 of treatment, and periodically thereafter. Tests should include complete blood count (CBC) and differential, platelet count, electrolytes, serum creatinine, liver function tests and uric acid. HCV-RNA should be measured periodically during treatment. Acceptable haemoglobin baseline values that may be considered as a guideline prior to ribavirin therapy are:
Female adults: equal to or greater than 12 g/dl
Male adults: equal to or greater than 13 g/dl
Female children and adolescents: 11 g/dl
Male children and adolescents: 12 g/dl
Although ribavirin has no direct cardiovascular effects, anaemia associated with ribavirin may result in impaired cardiac function or exacerbation of coronary disease. It is recommended that patients with pre-existing cardiac abnormalities should be treated with caution and have their cardiac status assessed prior to treatment and monitored during the course of therapy. Therapy should be discontinued if deterioration in cardiac function occurs.
Patients with a history of congestive heart failure, myocardial infarction and/or previous or current arrhythmic disorders must be closely monitored. Patients with pre-existing cardiac abnormalities should have their electrocardiograms taken prior to and during the course of treatment. Cardiac arrhythmias (primary supraventricular) usually respond to conventional therapy but may require discontinuation of therapy.
At the time of writing, here are no data regarding the use of ribavirin in children or adolescents with cardiac disorders.
Discontinue ribavirin and initiate appropriate treatment if acute hypersensitivity reactions occur. These include urticaria, angioedema, bronchoconstriction and anaphylaxis. Transient rash does not require discontinuation of therapy.
Serious adverse reactions associated with combination therapy have been reported. These include, severe psychiatric and central nervous system effects (such as depression, suicidal ideation, attempted suicide and aggression), growth inhibition in children and adolescents that may be irreversible, increased thyroid stimulating hormone (TSH) in children and adolescents, severe ocular disorders, and dental and periodontal disorders. Before initiating therapy, consult product information for concurrent medication for further details on patient monitoring.
Severe CNS effects have been reported during combination therapy. These effects can also occur during the 6 months after treatment discontinuation. Suicidal ideation and suicide attempts were reported more frequently in children and adolescents than in adults. Patients should be closely monitored for signs of psychiatric disturbances. If patients develop psychiatric or CNS problems, the need for therapeutic management of these conditions should be considered. If symptoms persist or worsen, or suicidal ideation occurs, discontinue both ribavirin and peginterferon alfa-2b or interferon alfa-2b and monitor the patients closely.
During the course of ribavirin and interferon therapy lasting up to 48 weeks, children and adolescents demonstrated a decreased rate of linear growth and a decrease in the rate of weight gain. The long term effects on growth, development and sexual maturity are unknown. The decision to treat should be made on a case by case basis. Whenever possible the child should be treated after the pubertal growth spurt to reduce the risk of growth inhibition.
Studies of ribavirin and interferon alfa-2b or peginterferon alfa-2b therapy in children have demonstrated changes in thyroid stimulating hormone (TSH) levels. Before treatment is initiated in children, TSH levels should be determined and any thyroid abnormality must be treated. If TSH levels can be maintained in the normal range, therapy with ribavirin and interferon alfa-2b or peginterferon alfa-2b may be started. If thyroid changes occur during therapy, the thyroid status of the patient should be evaluated and the condition should be treated appropriately. Thyroid function should be monitored every 3 months in children and adolescents.
Combination therapy may lead to dental and periodontal disorders, including the loss of teeth. Dry mouth could also have an adverse effect on teeth and mucous membranes of the mouth during long term treatment. To minimise these risks, patients should be advised to brush their teeth thoroughly twice daily and have regular dental examinations. If vomiting occurs, patient should rinse mouth thoroughly.
Patients co-infected with HIV and receiving nucleoside reverse transcriptase inhibitor (NRTI) therapy may have an increased risk of developing mitochondrial toxicity, lactic acidosis and hepatic decompensation. Markers of mitochondrial toxicity and lactic acidosis should be monitored in these patients.
Patients co-infected with HIV and advanced cirrhosis who are receiving combined anti-retroviral therapy (cART) may be at an increased risk of hepatic decompensation and death. Co-infected patients receiving both antiretroviral (ARV) treatment and ribavirin should be monitored closely with continual assessment of their Child-Pugh score during treatment. Patients who show progression towards hepatic decompensation should have anti-hepatitis treatment discontinued immediately.
Patients receiving treatment with ribavirin, peginterferon alfa-2b and cART are at greater risk of developing haematological abnormalities (neutropenia, thrombocytopenia and anaemia). Close monitoring of haematological parameters and dose reduction, should help manage the problems in this patient population.
Pancytopenia and bone marrow suppression may occur within 3 to 7 weeks after the administration of peginterferon and ribavirin concomitantly with azathioprine. This was reversible upon discontinuation of HCV antiviral therapy and concomitant azathioprine. There was no reoccurrence upon reintroduction of either treatment alone.
Pregnancy and Lactation
Ribavirin is contraindicated in pregnancy.
The manufacturer suggests ribavirin must not be used in pregnancy and extreme care must be taken to avoid pregnancy. Ribavirin must not be administered during pregnancy. Female patients must have had a negative pregnancy test immediately before treatment is started. Routine monthly pregnancy tests should be performed during treatment and for 9 months thereafter. Advise patients of the significant teratogenic risk to the foetus if pregnancy occurs during treatment or within 9 months of finishing therapy. Schaefer suggests there is insufficient information regarding exposure to this drug during pregnancy to make any conclusion about its safety.
Malformations have occurred in animal species given doses well below the recommended human dose. Serious problems with the development of the skeleton, skull, palate, eye, jaw, limbs and the gastrointestinal tract have been shown. On increasing the ribavirin dosage the severity and incidence of the teratogenic effect increases and the survival of foetuses and offspring was reduced.
Male patients and their female partners
Ribavirin accumulates intracellularly and is cleared from the body very slowly. Changes in sperm have been shown in animal studies at doses below the clinical dose. It is unknown whether ribavirin contained within sperm will cause teratogenic or genotoxic effects upon the human embryo or foetus.
Male patients and their female partners should be advised to use effective contraception throughout the treatment period and for 6 months thereafter. Men whose partners are pregnant should be advised to use a condom to prevent exposure to ribavirin in semen. Available data on approximately 300 prospectively followed pregnancies with paternal exposure to ribavirin have not shown an increased risk of malformation compared to the general population.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Ribavirin is contraindicated in breastfeeding.
The manufacturer suggests because of the potential for adverse reactions in nursing infants, breastfeeding must be discontinued prior to initiation of therapy.
It is not known whether ribavirin is excreted in human milk. Due to the molecular weight (about 244) and prolonged plasma elimination half life of ribavirin, it is likely to be secreted in breast milk.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Injection site reactions
Right upper quadrant pain
Suppression of growth in children and adolescents
Urinary tract infections
Virilism in females
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: January 2016
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 19 January 2016.
Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 19 January 2016.
Summary of Product Characteristics: Rebetol 40mg/ml oral solution. Merck Sharp & Dohme (UK) Limited. Revised August 2021.
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