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.