DISCUSSION
We are not aware of any previous report of accidental HU overdose of
several times the regular dose in a child with sickle cell anaemia from
Africa. Contrary to the common perception of toxicity associated with
HU, our patient did not show significant myelosuppression or renal and
hepatic dysfunction and was able to resume HU after a short time of
suspension of therapy. HU is a myelosuppressive compound and is
generally expected that all patients taking it will have at least one
episode of myelosuppression with white cell and/or platelet counts
falling into a low range requiring dose adjustment or outright
discontinuation of therapy 13,14. Our patient had a
good response to HU with anticipated degree of myelosuppression within
the first 12 months until this was worsened by accidental overdosage.
HU is very well absorbed orally with a half-life that varies with age
and renal function but on the average is about 2-4 hours after ingestion
of a dose of 20mg/kg 15,16. Our patient was on 20
mg/kg before the accidental overdosage occurred. We had no means of
measuring her serum levels of HU but the mild myelosuppression observed
may be explained by rapid renal clearance such that the deranged
laboratory indices had peaked by 24 hours post ingestion. Children with
diminished glomerular filtration rates might be expected to show more
severe toxicity 17.
So far, only three cases of hydroxyurea overdose have been reported in
the literature. One massive accidental overdose of a two-year-old girl
enrolled in BABY HUG at age 11 months who ingested 35 times her intended
daily dose of 17.5 mg/kg but had just mild and transient
myelosuppression. She had full bone marrow recovery in two weeks18. Our patient also had full recovery of bone marrow
function in less than three weeks. The other two were modest, 15 and 2.5
times the prescribed dosage, reported in the HUSOFT trial18,19. These also resulted in only mild and transient
neutropenia.
Although there are limited readily-available modalities of management of
HU toxicity, a few recommendations have been suggested. One of such
recommendations by manufacturers is gastric lavage if patient presents
within 90 minutes of ingestion, followed by supportive care and close
monitoring of hemopoietic system. Ipecac and activated charcoal are
handy remedies but are unsuitable for home use especially for very young
patients 20. Our patient had none of these
interventions because of late presentation and still did well on active
observation and temporary suspension of therapy.