12th Congress of the European Hematology ... - Haematologica

and treatment, has rarely been systematically assessed or compared with
the HRQoL of those living with other chronic disease. To appreciate the
impact that new treatment options for ITP may have on HRQoL, it is
imperative to understand the relative influence of ITP on patients, even
while managed according to current standards of care. Aims. To characterize
HRQoL in patients with ITP, treated with at least one prior therapy
and enrolled in a double-blind, randomized, placebo-controlled,
dose-ranging, phase III study of eltrombopag, an oral platelet growth factor,
and to compare the impact of ITP on health status and HRQoL with
that of common chronic diseases. Methods. In this global study of adults
with chronic ITP and entry platelet counts 99% protein bound in the circulation,
has a half-life of about 12 hours, and metabolized in the liver.
With daily administration, increased platelet count is apparent after 7'10
days following initiation of treatment with return to baseline 2 weeks
after the discontinuation of treatment. Aims. To report a single case of
an overdose of eltrombopag in a patient receiving carboplatin and paclitaxel
(CTx) for ovarian cancer. Methods. (Case Report) A 49-year-old
woman with ovarian cancer scheduled to start CTx treatment once every
21 days was included in a phase II randomized, double-blind, placebocontrolled
trial of eltrombopag treatment for chemotherapy-induced
thrombocytopenia. In a suspected attempt to commit suicide, she ingested
5000 mg of eltrombopag, 50 times the assigned daily dose of 100 mg
once daily, the day after the first dose of CTx. Serial pharmacokinetics,
blood chemistry and platelet counts were measured. Results. Initial treatment
for the eltrombopag overdose included gastric lavage, intravenous
fluids, omeprazole, furosemide, oral calcium, laxatives, one plasmapheresis
(12 hours post-overdose) and cessation of eltrombopag treatment.
Platelet counts and corresponding plasma concentrations of
eltrombopag following overdose are given in the table. The peak plasma
level of eltrombopag was 286,480 ng/µL on Day 1; the estimated area
under the curve was 1776 µg.hr/mL, ~10-fold that of steady-state values
typically observed with a 100 mg once-daily dose. Platelet count peaked
at 929,000/µL on Day 14. Liver enzymes measured between Days 2 and
31 peaked at a 2.5-fold increase in alanine aminotransferase activity and
a 6-fold increase in aspartate aminotransferase activity, with slight
anaemia and granulocytopenia. With the exception of a short episode of
bradycardia (30 bpm), which was treated with atropine during the initial
treatment for overdose, and mild asthenia, the patient remained
asymptomatic and continued on CTx treatment. Conclusions. The high
exposure to eltrombopag did not produce life-threatening toxicity. Following
the ingestion of one single massive dose, an increase in platelet
count was seen that followed the same temporal pattern when compared
with the standard 50 mg once daily dose.
Table 1.
12 th Congress of the European Hematology Association
haematologica/the hematology journal | 2007; 92(s1) | 283