Ziproc-25/Ziproc-100 Special Precautions

Clozapine can cause agranulocytosis.
Monitoring of white blood cell and absolute neutrophil count is mandatory during treatment. A white blood cell count and a differential blood count must be performed before starting clozapine therapy and regularly throughout the treatment. Treatment should not be started if the white blood cell count is less than 3500 cells/nm³ and the absolute neutrophil count (ANC) is less than 2000 cells/nm³, or there is an abnormal differential count. Monitoring should continue throughout therapy and 4 weeks after discontinuation.
If during therapy the white blood cell count falls to 3000 and 3500 cells/nm³ or the ANC falls between 1500 and 2000 cells/nm³ the monitoring should be performed twice weekly until the value stabilizes or increases.
Clozapine should be withdrawn immediately if the white blood cell count falls below 3000 cells/nm³ or the ANC drops below 1500 cells/nm³, counts should be monitored daily until they return to normal. Clozapine should not be restarted with these patients.
Patients or their carers should report the development of any infection or signs such as fever, sore throat, or flu-like symptoms which suggest infection.
If treatment with clozapine is interrupted for reasons other than abnormal hematological values then more frequent monitoring may be required. Patients who have taken clozapine for at least 18 weeks and stop therapy for more than 3 days but not less than 4 weeks should resume weekly monitoring for the next 6 weeks before reducing to at least every 4 weeks if the counts are stable; a break of 4 weeks or more would require weekly monitoring for the next 18 weeks.
Clozapine should be withdrawn if the eosinophil count is greater than 3000 cells/nm³; it should only be restarted once the count has fallen to below 1000 cells/nm³.
Discontinuation of clozapine is recommended if the platelet count falls below 50000/nm³.
Because of an increased risk of collapse due to orthostatic hypotension associated with initial titration of dosage of clozapine it is recommended that treatment should be initiated under close medical supervision. In addition, patients with Parkinson's disease should have their blood pressure monitored for the first two weeks of treatment.
Patients who develop tachycardia at rest, dyspnea, or signs and symptoms of heart failure should be investigated immediately and clozapine treatment should be discontinued if a diagnosis of myocarditis is suspected.
Clinical monitoring for hyperglycemia has been recommended, especially in patients with or at risk of developing diabetes.
On planned withdrawal the dose of clozapine should be reduced gradually over at least 1 to 2 week period in order to avoid the risk of rebound psychosis. If abrupt withdrawal is necessary then patients should be observed carefully. Clozapine may affect the performance of skilled tasks such as driving.