Ribavirin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Chronic hepatitis C, in combination with peginterferon alpha-2a or with interferon alfa-2a, in adults positive for serum HCV-RNA,  including those with compensated cirrhosis

Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication. The primary clinical toxicity of ribavirin is haemolytic anaemia. The anaemia associated with ribavirin therapy may result in worsening of cardiac disease that has led to fatal and nonfatal myocardial infarctions. Patients with a history of significant or unstable cardiac disease should not be treated with ribavirin. Ribavirin must not be taken during pregnancy or lactation. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. In addition, ribavirin has a multiple dose half-life of 12 days, and it may persist in non-plasma compartments for as long as 6 months. Ribavirin therapy is contra-indicated in women who are pregnant and in the male partners of women who are pregnant. Extreme care must be taken to avoid pregnancy during therapy and for 6 months after completion of treatment in both female patients and in female partners of male patients who are taking ribavirin therapy. At least two reliable forms of effective contraception must be utilised during treatment and during the 6-month post-treatment follow-up period.

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Women who are pregnant or who intend to become pregnant
• Men whose female partners are pregnant
• Patients with haemoglobinopathies (e.g., thalassemia major or sickle-cell anaemia)
• Patients with autoimmune hepatitis
• Patients with moderate to severe hepatic impairment (Child-Pugh class B and C)
• Patients with moderate to severe renal impairment (CrCl<50ml/min)

Cautions

• Breastfeeding
• Mild renal impairment
• Monotherapy
• Cardiac disease
• Gout
• Autoimmune hepatitis
• Dental and periodontal disorders
• Pancytopenia
• Carcinogenicity
• HIV/HCV co-infection

Forms avail. in SA and covered in this monograph: tab

Infections caused by: Hepatitis C virus

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Chronic Hepatitis C

• Oral (tab): 

Ribavirin dosing recommendation according to the medication used in combination
Medicinal product used in combination	Daily dose	Number of 200/400mg tablets
Direct acting antivirals (DAA)	< 75kg: 1000mg > 75kg: 1200mg	5 x 200mg (2 morning, 3 evening) 6 x 200mg (3 morning, 3 evening)
PegIFN alfa-2a with DAA	< 75kg: 1000mg > 75kg: 1200mg	5 x 200mg (2 morning, 3 evening) 6 x 200mg (3 morning, 3 evening)
PegIFN alfa-2a without DAA	Genotype 2/3 treatment-naive Genotype 2/3/4 with HIV coinfection: 800mg	4 x 200 mg (2 morning, 2 evening) 2 x 400 mg (1 morning, 1 evening)
	Genotype 1/4, Genotype 2/3 treatment-experienced Genotype 1 HIV coinfection: < 75kg: 1000mg > 75kg: 1200mg	5 x 200mg (2 morning, 3 evening) 6 x 200mg (3 morning, 3 evening)
IFN alfa-2a without DAA	< 75kg: 1000mg > 75kg: 1200mg	5 x 200mg (2 morning, 3 evening) 6 x 200mg (3 morning, 3 evening)
PegIFN alfa-2b with or without DDA	< 65kg: 800mg	4 x 200mg (2 morning, 2 evening) 2 x 400mg (1 morning, 1 evening)
	65-80kg: 1000mg	5 (2 morning, 3 evening)
	81-105kg: 1200mg	6 (3 morning, 3 evening)
	> 105kg: 1400mg	7 (3 morning, 4 evening)

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Should not be used as monotherapy

Should not be broken or crushed

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Treatment duration depends on the medicinal product that it is being coadministered with; May also depend on patient and virus characteristics

Not established for use in children below 18 years

Pregnancy

• Contraindicated
• Significant teratogenic and/or embryocidal potential have been demonstrated for ribavirin in all animal species in which adequate studies have been conducted, occurring at doses well below the recommended human dose
• Malformations of the skull, palate, eye, jaw, limbs, skeleton and gastrointestinal tract were noted
• The incidence and severity of teratogenic effects increased with escalation of the ribavirin dose. The survival of foetuses and offspring was reduced
• Men whose partners are pregnant must be instructed to use a condom to minimise delivery of ribavirin to the partner

Breastfeeding

• Caution; not recommended

Renal Impairment

• Mild: Caution; no dose adjustment recommended
• Moderate to severe: Contraindicated

Hepatic Impairment

• Moderate to severe: Contraindicated

Elderly

• No dose adjustment recommended 

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Insomnia
• Mood alteration
• Anxiety
• Aggression
• Nervousness
• Decreased libido 
• Suicidal ideation
• Hallucinations
• Psychotic disorder
• Mania
• Homicidal ideation
• Headache
• Dizziness
• Impaired concentration
• Memory impairment
• Syncope
• Weakness
• Migraine
• Hypoaesthesia
• Hyperaesthesia
• Paraesthesia
• Tremor
• Nightmares
• Somnolence
• Peripheral neuropathy
• Coma
• Convulsions 
• Facial palsy
• Cerebral ischaemia
• Fatigue

Cardiovascular Disorders

• Tachycardia
• Palpitations
• Oedema peripheral
• Myocardial infarction
• Congestive cardiac failure
• Angina
• Supraventricular tachycardia arrhythmia
• Atrial fibrillation
• Pericarditis
• Flushing
• Hypotension
• Hypertension
• Cerebral haemorrhage
• Vasculitis
• Endocarditis

Respiratory Disorders

• Lower respiratory tract infection
• Pneumonia
• Upper respiratory infection
• Bronchitis
• Dyspnoea
• Cough
• Epistaxis
• Nasopharyngitis
• Nasal congestion
• Rhinitis
• Sore throat
• Wheezing
• Interstitial pneumonitis with fatal outcome
• Pulmonary embolism

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Dyspepsia
• Dysphagia
• Mouth ulceration
• Gingival bleeding
• Glossitis
• Stomatitis
• Flatulence
• Constipation
• Dry mouth
• Gastrointestinal bleeding
• Cheilitis
• Gingivitis
• Peptic ulcer
• Pancreatitis
• Ischaemic colitis
• Ulcerative colitis
• Tongue pigmentation

Hepatobiliary Disorders

• Hepatic dysfunction
• Hepatic failure
• Cholangitis
• Fatty liver

Genitourinary Disorders

• Renal failure
• Nephrotic syndrome
• Impotence
• Urinary tract infection

Endocrine and Metabolic Disorders

• Hypothyroidism
• Hyperthyroidism
• Diabetes
• Anorexia
• Dehydration
• Hot flushes
• Thirst

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Back pain
• Arthritis 
• Muscle weakness
• Bone pain
• Neck pain
• Muscle cramps
• Myositis
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Dermatitis
• Pruritus
• Dry skin
• Increased sweating 
• Psoriasis
• Urticaria
• Eczema
• Photosensitivity reaction
• Night sweats
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Angioedema
• Erythema multiforme

Immune, Blood and Lymphatic System Disorders

• Oral candidiasis
• Herpes simplex
• Anaemia
• Neutropenia
• Thrombocytopenia
• Lymphadenopathy
• Pancytopenia
• Aplastic anaemia
• Pure red cell aplasia
• Sarcoidosis
• Thyroiditis
• Anaphylaxis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Idiopathic or thrombotic thrombocyto-penic purpura
• Hepatic graft rejection
• Renal graft rejection
• Vogt-Koyanagi-Harada disease
• Pyrexia
• Influenza like illness

Sensory Disorders

• Blurred vision 
• Eye pain
• Eye inflammation
• Xerophthalmia
• Retinal haemorrhage
• Optic neuropathy
• Papilloedema
• Retinal vascular disorder
• Retinopathy
• Corneal ulcer
• Loss of vision
• Retinal detachment
• Vertigo
• Earache
• Tinnitus
• Hearing loss
• Taste disturbance
• Otitis externa

• Antacid
• Nucleoside analogues  
• Didanosine
• Azathioprine
• Zidovudine  

• Full blood count
• Cardiac function
• ECG
• Hepatic function
• Renal function
• Uric acid
• Pregnancy test

Ribavirin is a synthetic nucleoside analogue, which inhibits replication of some RNA and DNA viruses. It also inhibits influenza virus RNA polymerase activity and the initiation and elongation of RNA fragments. This results in inhibition of viral protein synthesis.

Spectrum of activity: Hepatitis C virus

Tablet 200mg

• Copegus (Roche) originator