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Ribavirin capsules

Updated 2 Feb 2023 | Hepatitis C

Presentation

Capsules containing ribavirin.

Drugs List

  • ribavirin 200mg capsules
  • Therapeutic Indications

    Uses

    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.

    Dosage

    Ribavirin must be used in combination. Refer to individual product details for prescribing information for concurrent medication.

    Dose and duration is dependant on the combination therapy used and the patient's weight. In patients who weigh less than 47kg or those unable to swallow the capsules, see Monograph for Ribavirin oral solution.

    Treatment length is also 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.

    Adults

    Where no specific dose suggestion is made, the following should be used:
    Patient weight above 75kg
    1,200mg a day in two divided doses.

    Patient weight below 75kg
    1,000mg a day in two divided doses.

    The following alternative dosing schedule may be suitable:
    Patients weighing more than 105kg: 600mg in the morning and 800mg in the evening.
    Patients weighing between 81kg and 105kg: 600mg twice daily.
    Patients weighing between 65kg and 81kg: 400mg in the morning and 600mg in the evening.
    Patients weighing under 65kg: 400mg twice daily.

    Children

    Children aged 3 to 18 years
    Bodyweight greater than 65kg
    See Dosage; Adult.

    Bodyweight 50kg to 65kg
    Two 200mg capsules of ribavirin in the morning and two capsules in the evening.

    Bodyweight 47kg to 49kg
    One 200mg capsule of ribavirin in the morning and two capsules in the evening.

    Bodyweight under 47kg
    The recommended dose is 15mg/kg/day in two divided doses. Ribavirin oral solution is available for use in these patients.

    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.

    At the time of writing, limited data are available for paediatric patients with renal impairment.

    Creatinine clearance less than 50 to 30ml/minute
    Alternate doses, 200mg and 400mg ribavirin every other day.

    Creatinine clearance less than 30ml/minute
    200mg ribavirin daily.

    Patients receiving haemodialysis
    200mg ribavirin daily.

    Additional Dosage Information

    Dose modifications
    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
    Adults
    Indirect bilirubin greater than 5mg/dl: Reduce ribavirin dose as below.
    Indirect bilirubin greater than 4mg/dl: Discontinue ribavirin.

    Haemoglobin 10g/dl to 8.5g/dl in patients with no cardiac disease: Reduce ribavirin dose as below.
    Haemoglobin less than 8.5g/dl in patients with no cardiac disease: Discontinue ribavirin.

    Patients with history of stable cardiac disease and a decrease in haemoglobin during any 4 week period during treatment of equal to or greater than 2g/dl: Reduce ribavirin dose as below.
    Patients with history of stable cardiac disease and haemoglobin less than 12g/dl despite 4 weeks at reduced dose: Discontinue ribavirin.

    Dose reduction:
    For patients receiving 1,000mg or 1,200mg ribavirin, dose should be reduced to 600mg a day administered as one 200mg capsules in the morning and two in the evening. If the abnormality is reversed, restart ribavirin at 600mg daily. Dose can be increased to 800mg daily. A return to higher doses is not recommended.

    For patients receiving 800mg to 1,000mg or 1,400mg ribavirin, the first dose reduction of ribavirin is by 200mg a day (except in patients receiving 1,400mg ribavirin per day, dose should be reduced by 400mg a day). If a second dose reduction is necessary an additional 200mg should be removed from the daily regimen. Patients whose dose has been reduced to 600mg daily should receive 200mg in the morning and 400mg in the evening.

    Children
    Indirect bilirubin greater than 5mg/dl for greater than 4 weeks in children treated with interferon alfa-2b: Discontinue ribavirin.
    Indirect bilirubin greater than 4mg/dl for greater than 4 weeks in children treated with peginterferon alfa-2b: Discontinue ribavirin.

    Haemoglobin 10g/dl to 8.5g/dl in patients with no cardiac disease: See suggestions for adults.
    Haemoglobin less than 8.5g/dl in patients with no cardiac disease: See suggestions for adults.

    At the time of writing there are no data in paediatric patients with cardiac disease.

    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.

    Contraindications

    Children under 3 years
    Breastfeeding
    Galactosaemia
    Haemoglobinopathies
    History of severe cardiac disorder
    Pregnancy
    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
    Alcoholism
    Cardiac arrhythmias
    Cardiac impairment
    Decompensated liver disease
    Drug addiction
    Glucose-galactose malabsorption syndrome
    Gout
    Haemodialysis
    Hepatic impairment
    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
    Lactose intolerance
    Positive HIV status
    Psychiatric disorder
    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
    Some formulations contain lactose
    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
    Female: Contraception required during and for 4 months after treatment
    Male & female: Ensure adequate contraception during treatment
    Male: Contraception required during and for 7 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 12g/dl
    Male adults: equal to or greater than 13g/dl
    Female children and adolescents: 11g/dl
    Male children and adolescents: 12g/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.

    Combination 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

    Pregnancy

    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 4 months thereafter. Advise patients of the significant teratogenic risk to the foetus if pregnancy occurs during treatment or within 4 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 7 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.

    Lactation

    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.

    Side Effects

    Aches
    Aggression
    Agitation
    Alopecia
    Amnesia
    Anaemia
    Anxiety
    Arthralgia
    Asthenia
    Ataxia
    Bacterial infection
    Blood disorders
    Chest pain
    Confusion
    Cough
    Dehydration
    Depression
    Dizziness
    Dry skin
    Dyspnoea
    Emotional lability
    Enuresis
    Epistaxis
    Eye disorder
    Fatigue
    Fever
    Fungal infection
    Gastrointestinal disorder
    Haemolytic anaemia
    Headache
    Hepatic impairment
    Hepatomegaly
    Herpes simplex
    Hypersensitivity reactions
    Hypertonia
    Hypertriglyceridaemia
    Hyperuricaemia
    Hypocalcaemia
    Impaired concentration
    Increased appetite
    Influenza-like symptoms
    Injection site reactions
    Insomnia
    Irritability
    Jaundice
    Leukopenia
    Malaise
    Mania
    Menstrual disturbances
    Migraine
    Musculoskeletal pain
    Myalgia
    Myelosuppression
    Nasal congestion
    Neoplasms
    Nephrotoxicity
    Nervousness
    Neuralgia
    Neuropathy
    Neutropenia
    Oedema
    Otitis media
    Pallor
    Panic attack
    Paraesthesia
    Pruritus
    Pyrexia
    Rash
    Reduced libido
    Renal failure
    Renal impairment
    Respiratory insufficiency
    Rheumatoid arthritis
    Rhinitis
    Right upper quadrant pain
    Rigors
    Seizures
    Sinusitis
    Skin disorder
    Sleep disturbances
    Somnolence
    Stomatitis
    Suicidal tendencies
    Suppression of growth in children and adolescents
    Syncope
    Tachypnoea
    Testicular pain
    Thyroid abnormalities
    Tooth ache
    Tooth infection
    Tremor
    Urinary incontinence
    Urinary tract infections
    Vascular disorders
    Vasculitis
    Vertigo
    Viral infection
    Virilism in females
    Weight changes

    Overdosage

    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 ).

    Further Information

    Last Full Review Date: February 2021

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Summary of Product Characteristics: Ribavirin 200 mg capsules. Aurobindo Pharma - Milpharm Ltd. Revised April 2016.

    NICE Evidence Services Available at: www.nice.org.uk Last accessed: 05 February 2021

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