Zidovudine (AZT) overdose in a healthy newborn receiving postnatal prophylaxis.

CONTEXT: Pediatric medication dosing and administration, faced with inherent challenges of dose to body weight adjustment and variable delivery vehicles, may lead to inadvertent errors effectively resulting in overdose. Zidovudine (AZT), a nucleoside analog reverse transcriptase inhibitor (NRTI), is a commonly prescribed medication to treat HIV-exposed newborns, with limited overdose data in this patient population. Metabolic acidosis with elevated lactate is the most serious consequence of AZT toxicity in the adult population, associated with mortality. Other significant effects may include neutropenia and hepatic dysfunction. CASE REPORT: A 4-day-old male infant who received two inadvertent 10-fold overdoses of AZT while being treated for HIV postnatal prophylaxis. The newborn developed a transient metabolic acidosis with elevated lactate that resolved within 24 h, a small increase in AST, and persistent neutropenia for 5 weeks. The patient's mother cited several key factors leading to the dosing error. DISCUSSION: The paucity of AZT overdose data in newborns and infants compels this case report, which reviews the published literature and provides insight into prevention and improvement of pediatric patient safety.

[Acute toxicity of zidovudine. Analysis of the literature and number of cases at the Paris Poison Control Center]. / Toxicité aiguë de la zidovudine. Analyse de la littérature et des cas notifiés au centre Anti-Poisons de Paris.

13 cases of zidovudine overdosage have been previously published; 30 have been notified to Paris Control Poison Centre up to January 1991. This analysis shows that acute toxicity appears infrequent and mild when ingested dose is lower than 25 gr. However it appears from this series that an haematologic monitoring is needed because of the risk of myelosuppression.

Role of heme metabolism in AZT-induced bone marrow toxicity.

We studied the effects of azidothymidine (AZT) on rat bone marrow heme metabolism and colony growth as determined by assays of granulocyte-macrophage (CFU-GM), erythroid (CFU-E), burst-forming erythroid (BFU-E), and alpha-aminolevulinic acid synthase (ALAS), the first enzyme in the heme pathway. In all cases, AZT (1-0.01 microM) was found to be toxic to bone marrow colony growth. When AZT was included in colony assays, 1 microM resulted in 98-100% inhibition, whereas lower concentrations (0.01 microM) inhibited growth by 58-76%. In addition, cultures from AZT-treated animals had a marked reduction in colony growth as compared with sham controls. In most cases, hemin (10(-5) M) was found to overcome some of the colony inhibitory effects of AZT. Analysis of heme metabolism indicated that ALAS activity was reduced by 71% in bone marrow cells from treated animals. ALAS activity for control was 204 +/- 33 pM ALA formed/4 X 10(6) cells/hr, whereas ALAS activity from AZT-treated animals was only 60 +/- 3 pM ALA formed/4 x 10(6) cells/hr. It is considered that AZT toxicity may be due to a depression in the pool of available heme, which is required for adequate hematopoiesis.