Ribavirin tablets
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulation of ribavirin
Drugs List
Therapeutic Indications
Uses
Chronic hepatitis C - combination therapy
Dosage
Ribavirin must not be used as monotherapy.
Refer to individual product details for prescribing information for concurrent medication.
Adults
The dose of ribavirin is based on the viral genotype and the patients body weight.
Medicinal product used in combination
Direct acting antivirals (DAA)
Daily ribavirin dose
Less than 75kg: 400mg in the morning, 600mg in the evening.
Greater than or equal to 75 kg: 600mg in the morning, 600mg in the evening
Medicinal product used in combination
PegIFN alfa-2a with DAA
Daily ribavirin dose
Less than 75kg: 400mg in the morning, 600mg in the evening.
Greater than or equal to 75kg: 600mg in the morning, 600mg in the evening
Medicinal product used in combination
PegIFN alfa-2a without DAA
Daily ribavirin dose
Genotype 2/3 treatment - naive or genotype 2/3/4 with HIV - coinfection
400mg in the morning, 400mg in the evening
Genotype 1/4 treatment or genotype 2/3 treatment-experienced or genotype 1 HIV-coinfection
Less than 75kg: 400mg in the morning, 600mg in the evening.
Greater than or equal to 75kg: 600mg in the morning, 600mg in the evening
Medicinal product used in combination
IFN alfa-2a without DAA
Daily ribavirin dose
Less than 75kg: 400mg in the morning, 600mg in the evening.
Greater than or equal to 75kg: 600mg in the morning, 600mg in the evening
Medicinal product used in combination
PegIFN alfa-2a with or without DAA
Daily ribavirin dose
Less than 65kg: 400mg in the morning, 400mg in the evening.
65kg to 80kg: 400mg in the morning, 600mg in the evening
81kg to 105kg: 600mg in the morning, 600mg in the evening
Greater than 105kg: 600mg in the morning, 800mg in the evening
Duration of treatment
Duration of treatment depends on medicinal products that it is being combined with and may depend on several patients or virus characteristics including genotype, co-infection status, previous history of treatment, on treatment response.
Dose modifications for all patients If severe adverse reaction potentially related to ribavirin, the ribavirin dose should be modified or discontinued, if appropriate until the adverse reactions abate or decreases in severity. Guidelines for dose modifications and discontinuation based on the patient's haemoglobin concentration and cardiac status are shown below:
Patients without cardiac disease and haemoglobin less than 10g/dl
For patients receiving a 1000mg (less than 75kg) or 1200mg (greater than 75kg) dose, ribavirin dose should be reduced to 600mg per day (administered as one 200mg tablet in the morning and two 200mg tablets or one 400mg tablet in the evening). If the abnormality is reversed, ribavirin may be restarted at 600mg daily, and further increased to 800mg daily at the discretion of the treating physician. However, a return to higher doses is not recommended.
For patients receiving a 800mg (less than 65kg) or 1000mg (65kg to 80kg), 1200mg (81kg to 105kg) or 1400mg (greater than 105kg) dose, first dose reduction of ribavirin is by 200mg per day (except in patients receiving the 1400mg, dose reduction should be by 400mg per day). If needed, second dose reduction of ribavirin is by an additional 200mg/day. Patients whose dose of ribavirin is reduced to 600mg daily receive one 200mg tablet in the morning and two 200mg tablets in the evening.
Patients without cardiac disease and haemoglobin less than 8.5g/dl
Discontinue.
Patients with a history of cardiac disease and haemoglobin greater than or equal to 2g/dl decrease in haemoglobin during any 4 week period during treatment (permanent dose reduction)
For patients receiving a 1000mg (less than 75kg) or 1200mg (greater than 75kg) dose, ribavirin dose should be reduced to 600mg per day (administered as one 200mg tablet in the morning and two 200mg tablets or one 400mg tablet in the evening). If the abnormality is reversed, ribavirin may be restarted at 600mg daily, and further increased to 800mg daily at the discretion of the treating physician. However, a return to higher doses is not recommended.
For patients receiving a 800mg (less than 65kg) or 1000mg (65kg to 80kg), 1200mg (81kg to 105kg) or 1400mg (greater than 105kg) dose, first dose reduction of ribavirin is by 200mg per day (except in patients receiving the 1400mg, dose reduction should be by 400mg per day). If needed, second dose reduction of ribavirin is by an additional 200mg per day. Patients whose dose of ribavirin is reduced to 600mg daily receive one 200mg tablet in the morning and two 200mg tablets in the evening.
Patients with a history of cardiac disease and haemoglobin less than 12g/dl despite 4 weeks at reduced dose
Discontinue.
Elderly
(See Dosage; Adult).
There does not appear to be a significant age-related effect on the pharmacokinetics of ribavirin in patients aged over 65 years. However, as in younger patients, renal function must be determined prior to administration of ribavirin.
Children
The manufacturer does not recommend the use of ribavirin tablets in children under 18 years.
Patients with Renal Impairment
The recommended dose regimes (adjusted by the body weight cut off of 75kg) of ribavirin give rise to substantial increases in plasma concentrations of ribavirin in patients with renal impairment. The total daily dose of ribavirin should be reduced for patients with creatine clearance less than or equal to 50ml/minute as shown below:
Dosage modification for renal impairment
Creatine clearance 30ml/minute to 50ml/minute: Alternating doses, 200mg and 400mg every other day.
Creatine clearance less than 30ml/minute: 200mg daily.
Haemodialysis: 200mg daily.
Therapy should be initiated (or continued if renal impairment develops while on therapy) with extreme caution and intensive monitoring of haemoglobin concentrations, with corrective action as may be necessary, should be employed throughout the treatment period.
If severe adverse reactions or laboratory abnormalities develop, Ribavirin should be discontinued, if appropriate, until the adverse reactions abate or decrease in severity. Intolerance persists after restarting ribavirin, ribavirin therapy should be discontinued.
Contraindications
Autoimmune disease
Children under 18 years
History of autoimmune disorder
Severe debilitation
Autoimmune hepatitis
Breastfeeding
Haemoglobinopathies
History of severe cardiac disorder
History of severe psychiatric disorder in children
Pregnancy
Severe cardiac disorder
Sickle cell disease
Unstable cardiac disorder
Precautions and Warnings
CD4 counts less than 200 cells/microlitre
Cardiac arrhythmias
Cardiac impairment
Decompensated liver disease
Galactosaemia
Glucose-galactose malabsorption syndrome
Gout
Haemodialysis
History of cardiac arrhythmias
History of congestive cardiac failure
History of myocardial infarction
History of severe psychiatric disorder in adults
HIV patients receiving highly active anti-retroviral therapy
Lactose intolerance
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic impairment
Severe psychiatric disorder in adults
Advise ability to drive/operate machinery may be affected by side effects
Must be used as part of combination therapy
Patients at risk of arrhythmias perform ECG prior to initiating therapy
Treatment to be initiated and supervised by a specialist
Some formulations contain lactose
Advise patient to take with or after food
Consider liver biopsy for hepatitis C patients prior to treatment
Exclude pregnancy prior to initiation of treatment
Monitor cardiac function before and regularly during treatment
Monitor haematological parameters before and during treatment
Monitor ophthalmic function before and during long-term use
Monitor renal function prior to initiating 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 hepatic function
Monitor levels of hepatic enzymes and bilirubin
Monitor patients at risk of gout
Monitor renal function regularly
Monitor serum creatinine
Monitor serum electrolytes
Monitor uric acid levels
Perform monthly pregnancy test for several months after stopping therapy
Discontinue if abnormal liver function tests persist or worsen
Modify dose if adverse effects occur
Patient should report worrying psychological changes esp. suicidal thoughts
Discontinue if depression worsens or recurs
Discontinue if hepatic decompensation develops
Discontinue if hypersensitivity reactions occur
Discontinue if jaundice or other evidence of hepatic impairment occurs
Discontinue if worsening symptoms of cardiac failure develop
Female: Contraception required during and for 4 months after treatment
Male: Contraception required during and for 7 months after treatment
Male: Use of condoms advised if partner pregnant or may become pregnant
Refer to individual product details for prescribing information for concurrent medication.
Standard haematologic tests and blood chemistries should be performed before treatment, after 2 weeks of treatment, after 4 weeks 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. Current treatment guidelines should be consulted as to whether a liver biopsy is required prior to commencing treatment.
The tablets should not be broken or crushed. Ribavirin is considered a potential teratogen, therefore caution should be exercised if handling broken tablets.
Serious adverse effects are more likely in patients co-infected with HIV receiving highly active anti-retroviral therapy (HAART). These effects include lactic acidosis, peripheral neuropathy, pancreatitis, and hepatic decompensation. Patients co-infected with HIV should therefore be treated with caution and close monitoring is recommended, including regular Child-Pugh score determinations. Treatment should be discontinued if the Child-Pugh score exceeds 7.
Pregnancy and Lactation
Pregnancy
Ribavirin is contraindicated in pregnancy.
Ribavirin should only be used in pregnancy for life-threatening infections.
Genotoxicity
Ribavirin induces genotoxicity.
Teratogenicity
Ribavirin presents a significant teratogenic and embryocidal risk. Malformations have occurred in all 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.
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 ).
Lactation
Ribavirin is contraindicated in breastfeeding.
It is not known whether ribavirin is excreted in human milk. Limited data are available on the use of ribavirin during breastfeeding, however the molecular weight and prolonged plasma elimination half-life suggest that the drug will be excreted into the breast milk. Long-term use of ribavirin during breastfeeding may be problematic as high concentrations of ribavirin could accumulate in the breastfed infant. Because of the potential for adverse reactions in nursing infants, nursing must be discontinued prior to initiation of therapy.
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
Side Effects
Anaphylaxis
Anorexia
Arthralgia
Blood dyscrasias
Blood pressure changes
Bronchitis
Cardiac disorders
Cerebral haemorrhage
Cholangitis
Coma
Convulsions
Corneal ulcer
Dehydration
Depression
Diabetes
Dizziness
Dry mouth
Dysphagia
Emotional lability
Endocarditis
Epistaxis
Eye pain
Facial palsy
Fatigue
Flushing
Gastro-intestinal disturbances
Gastro-intestinal ulceration and bleeding
Gingival disorder
Glossitis
Gout
Hair disorder
Hallucinations
Headache
Hearing disturbances
Hepatic impairment
Hyperaesthesia
Hyperuricaemia
Hypoaesthesia
Idiopathic thrombocytopenic purpura (ITP)
Impaired concentration
Impaired memory
Impotence
Increase in ALT level
Increased sweating
Infections
Influenza-like symptoms
Interstitial pneumonitis
Lymphadenopathy
Malaise
Migraine
Mouth ulcers
Muscular cramps
Musculoskeletal disturbances
Myalgia
Myocardial infarction
Myositis
Naso-sinus congestion
Neoplasms
Nephrotic syndrome
Oedema
Otitis externa
Otitis media
Pain
Pancreatic disturbances
Paraesthesia
Pericarditis
Peripheral neuropathy
Pharyngitis
Photosensitivity
Pruritus
Psychiatric disorders
Pulmonary embolism
Pyrexia
Rash
Reduced libido
Renal failure
Respiratory disorders
Respiratory tract infection
Retinal haemorrhage
Rhabdomyolysis
Rhinitis
Sarcoidosis
Skin reactions
Sleep disturbances
Stevens-Johnson syndrome
Stomatitis
Suicidal tendencies
Syncope
Systemic lupus erythematosus
Taste disturbances
Thyroid abnormalities
Toxic epidermal necrolysis
Tremor
Urinary tract infections
Vertigo
Visual disturbances
Vogt-Koyanagi- Harada (VKH) syndrome
Weight loss
Xerophthalmia
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: March 2015
Reference Sources
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.
Martindale: The Complete Drug Reference. 39th Edition. London: Brayfield A (ed). Pharmaceutical Press; 2017.
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Copegus 200mg film-coated tablets. Roche Products Ltd. Revised January 2015.
Summary of Product Characteristics: Copegus 400mg film-coated tablets. Roche Products Ltd. Revised January 2015.
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 26 September 2017
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