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DENZAPINE is a brand name for Clozapine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Treatment-resistant schizophrenia Denzapine is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics. Treatment resistance is defined as a lack of satisfactory…
Verbatim from this product's MHRA label. Tap a section to expand.
Posology The dosage must be adjusted individually. For each patient the lowest effective dose should be used. For doses not realisable/practicable with this strength, other strengths of this medicinal product are available. Cautious titration and a divided dosage schedule are necessary to minimise the risks of hypotension, seizure, and sedation.
0 x 109/L) within standardised normal limits. 5). Switching from a previous antipsychotic therapy to Denzapine It is generally recommended that Denzapine should not be used in combination with other antipsychotics, including depot preparations, which may have a myelosuppressive effect.
When Denzapine therapy is to be initiated in a patient undergoing oral antipsychotic therapy, it is recommended that the other antipsychotic should first be discontinued by tapering the dosage downwards. 5 mg (half a 25 mg tablet) once or twice on the first day, followed by one or two 25 mg tablets on the second day.
If well tolerated, the daily dose may then be increased slowly in increments of 25 to 50 mg in order to achieve a dose level of up to 300 mg/day within 2 to 3 weeks. Thereafter, if required, the daily dose may be further increased in increments of 50 to 100 mg at half- weekly or, preferably, weekly intervals.
Therapeutic dose range In most patients, antipsychotic efficacy can be expected with 200 to 450 mg/day given in divided doses. The total daily dose may be divided unevenly, with the larger portion at bedtime. For maintenance dose, see below.
e. not exceeding 100 mg) are permissible up to 900 mg/day. The possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be borne in mind. Maintenance dose After achieving maximum therapeutic benefit, many patients can be maintained effectively on lower doses.
Careful downward titration is therefore recommended. Treatment should be maintained for at least 6 months. If the daily dose does not exceed 200 mg, once daily administration in the evening may be appropriate. Ending therapy In the event of planned termination of Denzapine therapy, a gradual reduction in dose over a 1- to 2-week period is recommended.
g. 4). 5 mg (half a 25 mg tablet) given once or twice on the first day. If this dose is well tolerated, it may be feasible to titrate the dose to the therapeutic level more quickly than is recommended for initial treatment. 4), but was then able to be successfully titrated to a therapeutic dose, re-titration should be carried out with extreme caution.
Summary of the safety profile For the most part, the adverse event profile of clozapine is predictable from its pharmacological properties. 4). Because of this risk, its use is restricted to treatment-resistant schizophrenia and psychosis occurring during the course of Parkinson's disease in cases where standard treatment has failed.
While blood monitoring is an essential part of the care of patients receiving clozapine, the physician should be aware of other rare but serious adverse events, which may be diagnosed in the early stages only by careful observation and questioning of the patient in order to prevent morbidity and mortality.
4). The most common side effects are drowsiness/sedation, dizziness, tachycardia, constipation, and hypersalivation. 6%) were discontinued due to an adverse event, including only those that could be reasonably attributed to clozapine.
The more common events considered to be causes of discontinuation were leucopenia, somnolence, dizziness (excluding vertigo) and psychotic disorder. Blood and lymphatic system Development of granulocytopenia and agranulocytosis is a risk inherent to Denzapine treatment.
Although generally reversible on withdrawal of treatment, agranulocytosis may result in sepsis and can prove fatal. 4). Table 3 below summarises the estimated incidence of agranulocytosis for each Denzapine treatment period. 8 1 From the UK Patient Monitoring Service lifetime registry experience between 1989 and 2001.
2 Person-time is the sum of individual units of time that the patients in the registry have been exposed to clozapine before experiencing agranulocytosis. For example, 100,000 person-weeks could be observed in 1,000 patients who were in the registry for 100 weeks (100*1000 = 100,000), or in 200 patients who were in the registry for 500 weeks (200*500 = 100,000) before experiencing agranulocytosis.
4. In this situation, careful psychiatric monitoring of the patient is essential since symptoms may recur quickly. 4). Paediatric population No paediatric studies have been performed. The safety and efficacy of Denzapine in children and adolescents under the age of 16 years have not yet been established.
No data are available. It should not be used in this group until further data become available. 5 mg given once on the first day), with subsequent dose increments restricted to 25 mg/day. 1. • This product contains lactose monohydrate.
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. • Patients unable to undergo regular blood tests. • History of toxic or idiosyncratic granulocytopenia/agranulocytosis (with the exception of granulocytopenia/agranulocytosis from previous chemotherapy).
• History of clozapine-induced agranulocytosis. • Denzapine treatment must not be started concurrently with drugs known to have a substantial potential for causing agranulocytosis; concomitant use of depot antipsychotics is to be discouraged.
• Impaired bone marrow function. • Uncontrolled epilepsy. • Alcoholic and other toxic psychoses, drug intoxication, comatose conditions. • Circulatory collapse and/or CNS depression of any cause. g. myocarditis). • Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure.
• Paralytic ileus. 4 Special warnings and precautions for use Agranulocytosis Denzapine can cause agranulocytosis. The incidence of agranulocytosis and the fatality rate in those developing agranulocytosis have decreased markedly since the institution of white blood cell (WBC) counts and absolute neutrophil count (ANC) monitoring.
The following precautionary measures are therefore mandatory and should be carried out in accordance with official recommendations. 0 x 109/L), and • in whom regular WBC counts and ANC can be performed weekly for the first 18 weeks of therapy, at least every 2 weeks between weeks 18 and 52, and at least 4-week intervals thereafter.
1. • This product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine. • Patients unable to undergo regular blood tests.
• History of toxic or idiosyncratic granulocytopenia/agranulocytosis (with the exception of granulocytopenia/agranulocytosis from previous chemotherapy). • History of clozapine-induced agranulocytosis. • Denzapine treatment must not be started concurrently with drugs known to have a substantial potential for causing agranulocytosis; concomitant use of depot antipsychotics is to be discouraged.
• Impaired bone marrow function. • Uncontrolled epilepsy. • Alcoholic and other toxic psychoses, drug intoxication, comatose conditions. • Circulatory collapse and/or CNS depression of any cause. g. myocarditis). • Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure.
• Paralytic ileus.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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5 mg/day (half a 25 mg tablet), taken in the evening. 5 mg increments, with a maximum of two increments a week up to a maximum of 50 mg, a dose that cannot be reached until the end of the second week. The total daily amount should preferably be given as a single dose in the evening.
5 mg/day. 5 mg/week. Maximum dose The dose of 50 mg/day should only be exceeded in exceptional cases, and the maximum dose of 100 mg/day must never be exceeded. Dose increases should be limited or deferred if orthostatic hypotension, excessive sedation or confusion occurs.
Blood pressure should be monitored during the first weeks of treatment. Maintenance dose When there has been complete remission of psychotic symptoms for at least 2 weeks, an increase in anti-parkinsonian medication is possible if indicated on the basis of motor status.
5 mg/week up to a maximum of 100 mg/day, taken in one or two divided doses (see above). 5 mg over a period of at least one week (preferably two) is recommended. Treatment must be discontinued immediately in the event of neutropenia or agranulocytosis as indicated in section
78%. The majority of cases (approximately 70%) occur within the first 18 weeks of treatment. Metabolic and Nutritional Disorders Impaired glucose tolerance and/or development or exacerbation of diabetes mellitus has been reported rarely during treatment with clozapine.
On very rare occasions, severe hyperglycaemia, sometimes leading to ketoacidosis/hyperosmolar coma, has been reported in patients on clozapine treatment with no prior history of hyperglycaemia. Glucose levels normalised in most patients after discontinuation of clozapine and in a few cases hyperglycaemia recurred when treatment was reinitiated.
4). Nervous System Disorders The very common adverse events observed include drowsiness/sedation, and dizziness. Denzapine can cause EEG changes, including the occurrence of spike and wave complexes. It lowers the seizure threshold in a dose-dependent manner and may induce myoclonic jerks or generalised seizures.
These symptoms are more likely to occur with rapid dose increases and in patients with pre-existing epilepsy. In such cases the dose should be reduced and, if necessary, anticonvulsant treatment initiated. Carbamazepine should be avoided because of its potential to depress bone marrow function, and with other anticonvulsant drugs the possibility of a pharmacokinetic interaction should be considered.
In rare cases, patients treated with Denzapine may experience delirium. Very rarely, tardive dyskinesia has been reported in patients on clozapine who had been treated with other antipsychotic agents. Patients in whom tardive dyskinesia developed with other antipsychotics have improved on clozapine.
Cardiac Disorders Tachycardia and postural hypotension with or without syncope may occur, especially in the initial weeks of treatment. The prevalence and severity of hypotension is influenced by the rate and magnitude of dose titration.
Circulatory collapse as a result of profound hypotension, in particular related to aggressive titration of the drug, with the possible serious consequences of cardiac or pulmonary arrest, has been reported with clozapine. A minority of clozapine-treated patients experience ECG changes similar to those seen with other antipsychotic drugs, including S-T segment depression and flattening or inversion of T waves, which normalise after discontinuation of clozapine.
The clinical significance of these changes is unclear. However, such abnormalities have been observed in patients with myocarditis, which should therefore be considered. Isolated cases of cardiac arrhythmias, pericarditis/pericardial effusion and myocarditis have been reported, some of which have been fatal.
The majority of the cases of myocarditis occurred within the first 2 months of initiation of therapy with clozapine. Cardiomyopathy generally occurred later in the treatment. Eosinophilia has been co-reported with some cases of myocarditis (approximately 14%) and pericarditis/pericardial effusion; it is not known, however, whether eosinophilia is a reliable predictor of carditis.
Signs and symptoms of myocarditis or cardiomyopathy include persistent tachycardia at […]
Monitoring must continue throughout treatment and for 4 weeks after complete discontinuation of Denzapine. Before initiating clozapine therapy patients should have a blood test (see “agranulocytosis”) and a history and physical examination.
3). The treating physician should consider performing a pre-treatment ECG. Prescribing physicians must comply fully with the required safety measures. Prior to treatment initiation, physicians must ensure, to the best of their knowledge, that the patient has not previously experienced an adverse haematological reaction to clozapine that necessitated its discontinuation.
Prescriptions should not be issued for periods longer than the interval between two blood counts. 5 x 109 /L) at any time during Denzapine treatment. Patients in whom Denzapine has been discontinued as a result of either WBC or ANC deficiencies must not be re-exposed to Denzapine.
At each consultation, a patient receiving Denzapine must be reminded to contact the treating physician immediately if any kind of infection begins to develop. Particular attention should be paid to flu-like complaints such as fever or sore throat and to other evidence of infection, which may be indicative of neutropenia.
Patients and their caregivers must be informed that, in the event of any of these symptoms, they must have a blood cell count performed immediately. Prescribers are encouraged to keep a record of all patients' blood results and to take any steps necessary to prevent these patients from accidentally being rechallenged in the future.
Patients with a history of primary bone marrow disorders may be treated only if the benefit outweighs the risk. They should be carefully reviewed by a haematologist prior to starting Denzapine. Patients who have low WBC counts because of benign ethnic neutropenia should be given special consideration and may be started on Denzapine with the agreement of a haematologist.
0 x 109/L)) will receive the drug. After the start of Denzapine treatment the WBC count and ANC must be monitored weekly for the first 18 weeks, at least every 2 weeks between weeks 18 and 52, and at least at four-week intervals thereafter.
Monitoring must continue throughout treatment and for 4 weeks after complete discontinuation of Denzapine or until haematological recovery has occurred (see below Low WBC count/ANC). At each consultation, the patient must be reminded to contact the treating […]