Introduction: Hydroxyurea (HU) is used in the treatment of sickle cell disease to increase fetal hemoglobin. This mechanism of action is unknown, however the drug is a known mitotic inhibitor and has been used as an antineoplastic. Pediatric overdoses are extremely rare. We present a case of a child with a massive HU ingestion treated with aggressive GI decontamination.
Case report: The mother of a 3-year-old boy with Hemoglobin S disease called her clinic requesting a refill of HU. She wanted the refill because the child had just ingested the entire bottle of the suspension, containing 9 g, though a small amount was spilled. Poison control was contacted and the child was taken to the ED. Gastric lavage was performed and 25 g of activated charcoal was administered. Lavage was completed within 1 h of ingestion. Baseline labs were drawn, including a white blood-cell count (WBC) of 27,000 cells/mL3. Of note, this child had a baseline leukocytosis between 15,000 and 27,000 cells/mL3. The child was discharged after 6 h with no symptoms. Labs were drawn twice weekly for a period of 4 weeks. In 2 weeks the WBC fell to 10,100 cells/mL3, but returned to baseline 14 days later. At no time did the child develop symptoms.
Discussion: HU is a mitotic inhibitor, inhibiting the enzyme ribonucleoside diphosphate reductase. This enzyme is a crucial rate-limiting step in the synthesis of DNA, and thus HU causes cell-cycle arrest at the G1-S interface. Myelosuppression occurs in adults ingesting 0.8 g/m2. This child had a BSA of 0.61 m2 and ingested 9 g for a maximum ingestion of 14.8 g/m2 of HU. HU is rapidly absorbed within 90 min. If GI decontamination is to be successful, it must be performed early, as in this case. The spilled drug and the preparation of HU may have resulted in a smaller ingestion. HU is compounded because it is not available as a liquid, and patients are instructed to shake the bottle before using. It is likely some drug was out of suspension and thus not ingested. The fall in WBC could represent a mild myelosuppression, so it is possible the GI decontamination prevented absorption of a toxic amount of drug.
Conclusion: GI decontamination should be considered in early presenting overdoses of hydroxyurea.