Management of adverse effects
This section gives details on the range of known adverse effects arising from treatment, and their management.
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Flu-like symptoms
Virtually all patients taking pegylated IFN and ribavirin will experience flu-like symptoms such as fever, myalgia, rigors, arthralgia and headache. These tend to become less severe after the first month of treatment.150 Simple interventions such as paracetamol use, increased fluid intake and rest can minimise these effects.150, 151 4
Patients experiencing flu-like side effects from pegylated IFN and ribavirin can be advised to use paracetamol within manufacturers’ guidelines.
Patients should be advised to maintain an adequate fluid intake throughout treatment with pegylated IFN and ribavirin.
Patients should be advised to coordinate their injections of pegylated IFN and ribavirin with periods of reduced activity, such as weekends and holidays.
Anaemia and neutropenia
Haemoglobin levels should be maintained at a level that prevents a need for dose reduction or discontinuation of pegylated IFN and ribavirin therapy as this can cause a reduction in SVR.131 Up to a third of patients receiving combination therapy develop anaemia and 13% progress to a haemoglobin of less than 100 g/l. 2+
In clinical trials the use of erythropoietin in patients who developed anaemia (haemoglobin level ≤ 120 g/l) while on pegylated IFN and ribavirin therapy improved the anaemia and lessened the need to reduce the dose of ribavirin. It also improved quality of life.152, 153 There is no direct evidence that this results in an increase in the SVR. None of the erythropoietins are currently licensed for this indication. 1+
Granulocyte-colony stimulating factor (G-CSF) may relieve drug-induced neutropenia in patients receiving pegylated IFN and ribavirin therapy. It is most commonly needed in patients given antiviral therapy post liver transplant.154 3
Erythropoietin should be considered in CHC patients receiving pegylated IFN and ribavirin therapy who develop anaemia, to prevent curtailment or dose reduction of ribavirin.
G-CSF should be considered on a case-by-case basis for patients who develop significant neutropenia while receiving treatment with pegylated IFN and ribavirin for CHC infection, to prevent curtailment or dose reduction of pegylated IFN.
Depression
Depression is a commonly reported side effect of pegylated IFN and ribavirin therapy in both patients who have previously experienced depression and those who have not.155 Antidepressants can be successfully used for treatment related depression and as a preventative measure prior to exposure to antiviral treatment.148, 156 1++ 1- 3
All patients receiving pegylated IFN and ribavirin should be monitored for signs of depression before, during and immediately post-treatment.
Patients treated with pegylated IFN and ribavirin who experience depression should be considered for treatment with antidepressants and for referral to a specialist, if necessary.
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A validated assessment tool (eg Hospital Anxiety and Depression score) should be used for monitoring depression.
Skin reactions
Severe skin reactions are uncommon during pegylated IFN or ribavirin therapy but dry skin, pruritus and diffuse eczematous lesions occur in approximately 20% of patients.150 Psoriasis may also be exacerbated by treatment for CHC. Injection site reactions occur in over 50% of treated patients.151 Skin lesions appear most commonly on the distal limbs and head and neck region, suggesting a predominance in sun-exposed areas.157 Patients respond well to antihistamines, emollients and topical steroids, allowing continuation of treatment.157 Discontinuation rates for dermatological side effects are approximately 3-4%.158 4 3
All patients on pegylated IFN and ribavirin should be advised to ensure appropriate skin hygiene and hydration.
Patients should be advised to avoid overexposure to sun.
Patients should be advised to rotate injection sites.
The use of emollients and topical corticosteroids can be considered for non-specific rashes.
Good practice points
The use of antihistamines can be considered for pruritus.
Severe dermatological reactions or those that do not respond to first line treatment should be referred for dermatological opinion.
Thyroid dysfunction
IFN therapy is associated with the development of thyroid dysfunction (both hypothyroid and hyperthyroid) in up to six per cent of those treated.150 Females are more at risk, especially those with thyroid autoantibodies before treatment.159 IFN is associated with the induction and enhancement of thyroid autoimmunity, which is not always reversible.160, 161 Pre-treatment autoantibodies are not universally predictive of thyroid dysfunction during treatment.150 4 1- 2+
Thyroid function should be monitored at baseline before IFN therapy, at week 12 of treatment and at any time where there is a suspicion of thyroid dysfunction.
Good practice points
Patients developing thyroid dysfunction should be referred to an endocrinologist.
Weight loss
Chronic hepatitis C infection causes increased basal metabolic rate in non-cirrhotic patients.162 Weight loss is commonly reported in patients on antiviral treatment.150, 151, 163 Nutritional therapy of patients with HCV is discussed in Nutritional interventions. 2- 4
Dyspnoea
Dyspnoea is a rarely reported side effect of pegylated interferon and ribavirin therapy. It may occur as a result of treatment related anaemia but may also be caused by more serious cardiovascular or respiratory conditions.150, 151, 164 2- 4
Patients treated with pegylated IFN or ribavirin who report dyspnoea that is not related to anaemia should be urgently assessed medically for cardiopulmonary problems.
Retinopathy
Retinopathy during pegylated IFN therapy is common but generally mild and transient. It resolves spontaneously on discontinuing IFN and treatment is seldom required. The long term consequences are unknown.165 Patients with hypertension or diabetes are at greater risk of developing retinopathy.151 Other ophthalmic side effects are uncommon. 1+ 4
Patients with CHC and hypertension or diabetes should have an ophthalmic examination prior to commencing treatment, paying particular attention to cotton wool spots and retinal haemorrhage.
Any patient reporting visual disturbance during treatment should be examined further by an ophthalmologist.
IFN should be discontinued in any patient with visual disturbance until it has resolved or an ophthalmologist has confirmed there is no retinal injury.
Alopecia
Alopecia is a relatively common reported side effect of IFN and ribavirin therapy. Hair will grow again on cessation of treatment.150, 151 4
Patients should be advised that treatment related hair loss is reversible on cessation of treatment.
Other side effects
Other reported side effects include insomnia, poor concentration, oral disease, nausea, and post-treatment withdrawal symptoms. No evidence on their effective management was identified.
Fatigue is one of the most commonly reported side effects of IFN or ribavirin treatment and may be multifactorial with anaemia, hypothyroidism, sleep disturbance and depression all contributing.150, 151 4
