Cloril Special Precautions

Clozapine can cause agranulocytosis, it should be reserved for use in schizophrenic patients; Who are non-responsive or intolerance to classical neuroleptics.
Who have WBC count ≥3500/mm³ and normal differential blood count.
Who can have WBC counts performed weekly during the first 18 weeks, at least monthly thereafter throughout treatment, and for 1 month after complete discontinuation of Clozapine.
Who are informed about the significant risk of developing agranulocytosis.
Patient should be advised to report the physician immediately the appearance of lethargy, weakness, sore throat, fever or possible signs of infection, which may be indication of neutropenia.
The following patients required at least twice weekly haematological evaluations: During the first 18 weeks of Clozapine therapy, the WBC count falls to between 3000-3500/mm³ and/ or the ANC falls to between 1500-2000/mm³.
After 18 weeks of Clozapine therapy, the WBC count falls to between 2500-3000/mm³ and / or the ANC falls to between 1000-1500/mm³ .
During the therapy, if the WBC count has dropped by a substantial amount from baseline (as single drop of 3000/mm³ or more or a cumulative drop of 3000/mm³ or more within 3 weeks), a repeat WBC count and a differential blood count should be done.
Discontinuation of Clozapine is mandatory if; WBC count of patients <3000/mm³ or ANC <1500/mm³ during the first 18weeks of therapy and WBC, count of patients <2500/mm³ or ANC <1000/mm³ after the first 18 weeks of therapy. Then, WBC counts and differential blood counts should be performed daily and patients should be carefully monitored for flu - like symptom s or other symptoms suggestive of infection.
After discontinuing the Clozapine therapy and a further drop in the WBC count <2000/mm³ and/ or neutrophil granulocytes fall below <1000/mm³, it is recommended that in - patients are placed in protective isolation with observation by haematologist and the administration of GM-CSF (granulocyte­ macrophage colony stimulating factor) or G-CSF (granulocyte colony stimulating factor) may be indicated. It is recommended that the colony stimulating factor therapy be discontinued when the neutrophil count has returned to a level above 1000/mm³.
Interruption of Clozapine therapy due to non-haematological reasons: If patients have been on Clozapine for more than 18 weeks and the treatment was interrupted for more than 3 days but less than 4 weeks, it is recommended to perform WBC count weekly for 6 weeks. If no haematological abnormality occurs, monitoring at intervals not exceeding 4 weeks may be resumed.
If the treatment was interrupted for 4 weeks or longer, weekly monitoring is required for the next 18 weeks of treatment.
Hyperglycemia and Diabetes Mellitus: Hyperglycemia in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given this confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available.
Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g. obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment.
Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotics was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect drug.
Other Precautions: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. In the event of eosinophilia, discontinuation of CLORIL is recommended if the eosinophil count rises above 3000/mm³ (3.0x109/L); therapy should be restarted only after the eosinophil count has fallen below 1000 /mm³ (1.0x10⁹/L). In the event of thrombocytopenia, discontinuation of CLORIL therapy is recommended if the platelet count falls below 50,000/mm³ (50x109/L). Orthostatic hypotension, with or without syncope, can occur during CLORIL treatment. Rarely, collapse can be profound and may be accompanied by cardiac and/or respiratory arrest. The use of CLORIL is associated with an increased risk of myocarditis especially during, but not limited to, the first two months of treatment. Some cases of myocarditis have been fatal. Pericarditis/pericardial effusion and cardiomyopathy have also been reported in associated with CLORIL use; these reports also include fatalities. Patients with a history of epilepsy should be closely observed during CLORIL therapy since dose-related convulsions have been reported. In such cases, the dose should be reduced and, if necessary, an anti-convulsant treatment should be initiated. Patients with stable preexisting liver disorders may receive CLORIL, but need regular liver function tests. Liver function tests should be performed in patients in whom symptoms of possible liver dysfunction, such as nausea, vomiting and/or anorexia, develop during CLORIL therapy. CLORIL exerts anticholinergic activity, which may produce undesirable effects throughout the body. Careful supervision is indicated in the presence of prosatic enlargement and narrow-angle glaucoma. Probably on account of its anticholinergic properties, CLORIL has been associated with varying degrees of impairment of intestinal peristalsis, ranging form constipation to intestinal obstruction, faecal impaction and paralytic ileus. During CLORIL therapy, patients may experience transient temperature elevations above 38°C, with the peak incidence within the first 3 weeks of treatment. This fever is generally benign. Occasionally, it may be associated with an increase or decrease in the WBC count. Since CLORIL may be associated with thromboembolism, immobilisation of patients should be avoided. Acute withdrawal reactions have been reported following abrupt cessation of clozapine therefore gradual withdrawal is recommended. If abrupt discontinuation is necessary (e.g. because of leucopenia), the patient should be carefully observed for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound such as profuse sweating, headache, nausea, vomiting and diarrhoea.