Delayed-onset neutropenia with divalproex sodium.

OBJECTIVE: To report the development of neutropenia in a patient after almost 8 years of being stabilized on delayed-release divalproex sodium (DVPX).

CASE SUMMARY: A 45-year-old man had been maintained on DVPX for nearly 8 years, with serum valproic acid concentrations of 85-128 mg/L and normal white blood cell (WBC) counts and absolute neutrophil counts (ANCs). Five months prior to the development of neutropenia (defined as ANC <1800 cells/microL), the patient's DVPX dosage was decreased by 250 mg to 1250 mg every morning and 1500 mg every evening. After 2 months of that regimen, the DVPX dosage was increased back to 1500 mg twice daily. Three months after that increase, the patient's WBC count dropped to 3.7 x 10(3)/microL and ANC was 1199 cells/microL. Although the ANC was below 1800 cells/microL, he showed no physical manifestations consistent with neutropenia. DVPX was discontinued, and 2 weeks later the patient's WBC count was 7.2 x 10(3)/microL and ANC was 2290 cells/microL.

DISCUSSION: Although a complete blood cell count with differential is a commonly accepted form of therapeutic drug monitoring with DVPX, the monitoring is considered most necessary to identify dose-related thrombocytopenia. However, neutropenia has been rarely associated with the use of DVPX and could contribute to the development of different types of infection, including those of a bacterial, viral, or fungal origin. Although neutropenia is generally mild in severity, potentially severe DVPX-associated neutropenia can occur any time during the course of therapy, although it is most common within the first few months of treatment. In this case, DVPX was the probable cause of the neutropenia, according to the Naranjo probability scale. However, this case of neutropenia is atypical with respect to the timeframe in which it developed and was identified. Although the documented laboratory findings suggest neutropenia, the patient did not experience any clinical complications as a result. The late onset of the patient's neutropenia is unlike other cases that have been documented in the literature.

CONCLUSIONS: Hematologic therapeutic drug monitoring continues to be clinically important regardless of whether the patient is early in therapy or even years later in the course. In this patient, continued regular therapeutic drug monitoring identified a suspected drug-related complication and the medication was able to be discontinued without the development of clinical complications.