Olanzapine (Zyprexa): suspected serious reactions

Five reports of deaths involving suspected cardiac reactions were received. Patient ages ranged from 20 to 89 years. Two patients had underlying heart conditions. In I of the 3 reports of fatal arrhythmia the contribution of olanzapine was unclear. A mixed overdose of other drugs including procyclidine and trimipramine was involved. Two other patients who had fatal cardiac reactions (myocardial infarction and arrhythmia) had received an olanzapine dose of 25-30 mg/d at the time of death. This amount exceeds current dosing recommendations, which range from 5 to 20 mg/d. The safety of dosages above 20 mg/d has not been evaluated.1 Nonfatal possible cardiac reactions included a number of reports of tachycardia or hypotension and one case of possible premature ventricular contractions. In addition, one case of QT prolongation was reported as a result of a possible overdose involving both olanzapine and quetiapine as suspect drugs, with concomitant use of valproic acid. Six reports of hematological reactions were previously reviewed in this newsletter in 1998.2 Since then 5 additional cases have been received. The following is a summary of all 11 cases. The reports described leukopenia, granulocytopenia, neutropenia, pancytopenia or anemia in patients taking olanzapine. The reported onset of neutropenia or granulocytopenis varied from 2 days to 6 months, with a recovery period of 1 day to 3 months. In 5 of the 11 cases the patient had a history of similar problems when taking the chemically related drug clozapine. A history of clozapine-induced leukopenia may be a risk factor for hematological reactions to olanzapine.3 However, some patients have been able to tolerate olanzapine despite a history of clozapine-related neutropenia.4,5 As well, it is not clear whether olanzapine can delay the recovery of clozapine-induced leukopenia, since the recovery time is variable.6