TABLE 8.4 Dose modiications recommended in the product literature for pegylated interferon
and ribavirin
Liver cirrhosis
The CUPIC study
171,172
found a very high risk of side-effects in treatment- experienced patients with compensated cirrhosis treated with PEG-IFN, RBV
and either boceprevir or telaprevir. Among patients who received at least 16 weeks of treatment, 40 of patients developed a serious adverse event and
11.7 had to cease therapy. Six patients died; ive from severe infection and one from oesophageal variceal haemorrhage. Hepatic decompensation occurred in
2.4 of patients manifesting as ascites, encephalopathy or variceal bleeding.
8.2 Dose modification
Recommendations for dose modiication based on abnormal haematological parameters are summarized below and in Table 8.4, based on the relevant
product literature.
187,188
Reduce IFN dose Discontinue IFN
Neutrophil count At 0.75 cells x10
9
L reduce to 135 μg PEG-IFN
α2a. At 0.75 cells x10
9
L PEG-IFN α2b
should be reduced in increments of 0.5 μgkgweek, e.g. from 1.5 μgkgweek to
1 μgkgweek and then if required to 0.5 μgkgweek.
At 0.5 cells x10
9
L PEG- IFN
α2a treatment should be suspended until neutrophils
reach 1.0 cells x10
9
L Reinstitute at a dose of 90 μg
and monitor. At 0.5 cells x10
9
L PEG- IFN
α2b should be permanently discontinued.
Platelets 25–50 cells x10
9
L reduce dose of IFN to 90 μg or reduce PEG-IFN
α2b as above. 25 cells x10
9
L discontinue PEG-IFN
α2a and PEG-IFNα2b. Haemoglobin
When Hb 10 gdL reduce RBV to 600 mgday when given with PEG-IFN
α2a. When Hb 10 gdL, the starting dose of
RBV should be reduced sequentially by 200 mg when given with PEG-IFN
α2b unless starting dose is 1 400 mg when
reduction should be to 1 000 mg. Discontinue PEG-IFN
permanently if Hb is 8.5 gdL.
Dose adjustment of ribavirin
Anaemia is a common side-effect of RBV therapy and dose adjustment is often required. Patients whose haemoglobin Hb level falls below 10 gdL should have
their RBV dose reduced. A patient whose Hb level falls below 8.5 gdL should discontinue therapy. For patients with a history of stable cardiovascular disease,
RBV dose reduction is required if the Hb decreases by ≥2 gdL during any
4-week period. In addition, for these patients, if the Hb remains 12 gdL after 4 weeks on a reduced dose, the patient should discontinue combination therapy.
The dose of RBV in patients with renal failure must also be adjusted; patients with creatinine clearance 50 mLmin should not be treated with RBV and those
on dialysis must have the dose lowered to 200 mg per day or take it three times per week. Increased monitoring is required in this group.
Dose adjustment of interferon
Discontinuation of PEG-IFN α2b is recommended if the Hb is 8.5 gdL or 12
gdL after 4 weeks of dose reduction in patients with cardiac failure, total white blood cell count 1.0 x 10
9
L, neutrophil count 0.5 x 10
9
L, platelet count 25 x 10
9
L in patients with genotype 1 infection or 50 x 10
9
L in those with non- genotype 1 infection, bilirubin direct 2.5 x upper limit of normal, total bilirubin
4 mgdL for 4 weeks, creatinine 2.0 mgdL or ALTAST 2 x baseline and 10 x upper limit of normal.
Discontinuation of PEG-IFN α2a is recommended if the platelet count is 25 x
10
9
L, Hb 8.5 gL or the Hb is 12 gdL despite 4 weeks of dose adjustment in patients with cardiac failure.
In patients with end-stage renal disease creatinine clearance 20–40 mLmin, a starting dose of PEG-IFN
α2a of 135 μg once a week should be used.
8.3 Monitoring for efficacy
