Clozaril and Agranulocytosis

The use of clozapine is contraindicated in patients with myeloproliferative disorders, preexisting bone marrow depression, or a history of clozapine-induced agranulocytosis or severe granulocytopenia. Clozapine therapy is associated with the development of agranulocytosis, defined as an absolute neutrophil count (ANC) below 500/mm3. The cumulative incidence is estimated at 1% to 2% after one year of use. The onset is generally between 4 to 16 weeks following initiation of therapy, and it is usually reversible if detected early and the drug discontinued promptly. All patients should have a white blood cell (WBC) count prior to initiating therapy, and clozapine should not be administered if baseline WBC count is less than 3500/mm3. WBC counts and differential should be monitored closely during therapy and for 4 weeks after end of therapy according to product labeling. Also, patients should be advised to immediately report signs of infection such as fever, sore throat, malaise, lethargy, and flu-like symptoms. Individuals who develop clozapine-induced agranulocytosis or severe granulocytopenia (WBC count < 2000/mm3 or ANC < 1000/mm3) should not be rechallenged following recovery, since the condition may recur, often with a shorter latency on reexposure. If continued neuroleptic therapy is necessary, other agents may be used with little apparent risk of cross-sensitivity.