Should You Discontinue PRN Zyprexa in a Patient with Leukopenia?
Yes, you should discontinue PRN Zyprexa (olanzapine) immediately in this patient with leukopenia and potential bone marrow suppression, as the FDA label explicitly states that patients with severe neutropenia (absolute neutrophil count <1000/mm³) should discontinue olanzapine and have their WBC followed until recovery. 1
Immediate Actions Required
Discontinue olanzapine immediately and obtain complete blood count with differential to determine the absolute neutrophil count (ANC) and assess severity of leukopenia. 1
The FDA label warns that leukopenia/neutropenia has been reported temporally related to olanzapine, and patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms of infection and treated promptly if such symptoms occur. 1
Monitor CBC frequently during the first few months after discontinuation, as patients with a history of clinically significant low WBC or drug-induced leukopenia/neutropenia require close hematologic surveillance. 1
Risk Assessment and Evidence
The decision to discontinue is supported by multiple lines of evidence showing olanzapine's hematologic toxicity:
Case reports document olanzapine-induced leukopenia occurring as early as 3 weeks after initiation at 10 mg/day, with fever and significant decrease in leukocyte count requiring immediate discontinuation. 2
Three case reports demonstrate dose-dependent olanzapine-associated leukopenia, where dose reduction allowed normalization of white blood count, suggesting a direct toxic effect rather than purely allergic mechanism. 3
A fatal case of agranulocytosis occurred in a schizophrenia patient receiving olanzapine, though confounded by underlying myelodysplastic syndrome, highlighting the serious potential consequences of continuing therapy in the setting of bone marrow suppression. 4
Clinical Pitfalls to Avoid
Do not attempt dose reduction as a compromise strategy in the setting of active leukopenia and potential bone marrow suppression. While dose reduction successfully managed leukopenia in some case reports, this approach is only appropriate for mild, asymptomatic leukopenia discovered incidentally, not for patients with established bone marrow suppression or clinical symptoms. 3
Do not continue olanzapine while "monitoring closely" - the FDA label is explicit that severe neutropenia mandates discontinuation, not just increased surveillance. 1
Alternative Management Strategies
Consider alternative antipsychotics with lower hematologic toxicity risk if ongoing psychiatric medication is required, though all antipsychotics carry some risk of leukopenia/neutropenia. 5
If the patient previously required clozapine and developed leukopenia, lithium carbonate 300 mg at bedtime can stimulate leukocyte production and has been used successfully to allow continuation of antipsychotic therapy, though this is primarily documented with clozapine rather than olanzapine. 6
Filgrastim or sargramostim may be considered as treatment options for drug-induced bone marrow suppression if psychiatric medication must be continued, though evidence is limited for olanzapine-induced leukopenia specifically. 5
Monitoring After Discontinuation
Obtain CBC with differential immediately, then weekly until WBC normalizes and stabilizes. 1
Assess for fever, sore throat, or other signs of infection at each encounter, as neutropenic patients are at high risk for serious bacterial infections. 1
Document the temporal relationship between olanzapine use and leukopenia development, as this patient should avoid olanzapine in the future if causality is established. 2