[AF] sobre CLOZAPINA (Drug Dex)

[Mag Carrillo]

Hola Graciela:
  si te sirve de algo te copio lo que encontramos en el Drug Dex o MICROMEDEX por ser muy baja la incidencia tal vez no seria tan necesario 
   
  3.3.5   Hematologic Effects 
  Agranulocytosis
Blood coagulation disorder
Disease of hematopoietic system
Drug-induced eosinophilia
Hematology finding
Neutropenia
Thromboembolic disorder

3.3.5.A   Agranulocytosis  
1)  Summary
  
a)  In pre-marketing evaluation, the cumulative incidence of agranulocytosis at 1 year was 1.3% (15 of 1743  patients). Agranulocytosis was defined as a neutrophil count of less than 500 cells/millimeters cubed. In the US there have been 585 cases (n=150,409) of agranulocytosis as of August 21, 1997; 19 of which were fatal. Few deaths have been reported since 1977 due to increased knowledge of clozapine-induced agranulocytosis and the importance of white blood cell monitoring (Prod Info Clozaril(R), 2002). One reference reports that the incidence of agranulocytosis following clozapine treatment is 10 to 20 times higher than that of phenothiazines (Oren et al, 1993).
b)  Asymptomatic agranulocytosis developing in a patient several months after start of treatment with clozapine for treatment- resistant schizophrenia was initially attributed to clozapine treatment but later was found to be a result of a large B-cell lymphoma. Replacement of clozapine with chlorpromazine and quetiapine resulted in  deterioration of the patient's mental state, resulting in hospitalization. During hospitalization, the lymphoma was discovered and was treated with chemotherapy. Clozapine was later reintroduced for better antipsychotic control and was continued with good effect, despite significant neutropenia secondary to the chemotherapy (Hundertmark & Campbell, 2001).
c)  In data evaluating 11,555 patients, the majority of agranulocytosis occurred within the first three months of drug therapy; older patients and women appeared to be at an increased risk. Recent studies suggest people of Jewish and Asian origin may also be at higher risk (Meged et al, 1999; Munro et al, 1999). The hazard can be reduced by weekly monitoring of the white blood cell count (Alvir et al, 1993). Some cases of clozapine-induced agranulocytosis have been successfully treated with filgrastim or sargramostim (Gullion & Yeh, 1994). The mechanisms of clozapine-induced agranulocytosis have been reviewed (Pirmohamed & Park, 1997a)
2)  Incidence: 1.3%
3.3.5.B   Blood coagulation disorder  
1)  Summary
  
a)  An increased aPPT of 34.2 sec (control 27 sec) was reported as a result of a positive lupus anticoagulant in a 39 year-old male after therapy with clozapine (225 milligrams/day), Klonopin, Cogentin, and Lopid. Normal laboratory tests included PT (14 sec), CBC, TT (21 sec), and a negative ANA titer (Kanjolia et al, 1997).

3.3.5.C   Disease of hematopoietic system  
1)  Summary
  
a)  Adverse effects that were temporally associated with clozapine and occurred in less than 1% of patients include ANEMIA and LEUKOCYTOSIS. Other adverse effects voluntarily reported by the manufacturer include ELEVATED HEMOGLOBIN, ELEVATED HEMATOCRIT, INCREASED ERYTHROCYTE SEDIMENTATION RATE, THROMBOCYTOPENIA, and SEPSIS; a causal relationship could not be determined (Prod Info Clozaril(R), 2002).
  
 

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