Each film-coated tablet contains: Clozapine (Cloxipene) 100mg.
Pharmacology: Pharmacokinetics: Although clozapine is well absorbed from the gastrointestinal tract, its bioavailability is limited to about 50% by first-pass metabolism. Peak plasma concentrations are achieved, on average, about 2.5 hours after oral doses. Clozapine is about 95% bound to plasma proteins and has a mean terminal elimination half-life of about 12 hours at steady state. It is almost completely metabolised and routes of metabolism include N-demethylation, hydroxylation, and N-oxidation; the desmethyl metabolite (norclozapine) has limited activity. The metabolism of clozapine is mediated mainly by the cytochrome P450 isoenzyme CYP1A2. Metabolites and trace amounts of unchanged drug are excreted mainly in the urine and also in the faeces. There is wide interindividual variation in plasma concentrations of clozapine and no simple correlation has been found between plasma concentrations and therapeutic effect. It is distributed into breast milk.
Used for treatment-resistant schizophrenia, serious psychosis with tardive dyskinesia, negative symptom schizophrenia, schizo-affective disorder, severely manic bipolar I disorder, and borderline personality disorder.
In the treatment of schizophrenia, including reducing the risk of suicidal behaviour, the usual oral dose is 12.5mg once or twice on the first day followed by 25mg once or twice on the second day. Thereafter the daily dosage may be increased gradually in steps of 25 to 50mg to achieve a daily dose of up to 300mg within 14 to 21 days. Subsequent increases in steps of 50 to 100mg may be made once or twice weekly, a daily dosage of 900 mg should not be exceeded. Once a therapeutic response has been obtained, a gradual reduction of dosage to a suitable maintenance dose is recommended, most patients respond to 200 to 450 mg daily. The total daily dose is given in divided doses; a larger portion may be given at night. Daily maintenance doses of 200mg or less may be given as a single dose in the evening. If clozapine is to be withdrawn, this should be done gradually over a 1-to 2 week period. However, immediate withdrawal with careful observation is essential if neutropenia develops or if myocarditis or cardiomyopathy is suspected. Elderly patients may require lower doses of clozapine and it is recommended that treatment should start with a dose of 12.5 mg on the first day and that subsequent dose increments should be restricted to 25 mg.
For patients who are restarting treatment after an interval of more than 2 days, 12.5 mg may be given once or twice on the first day. If this dose is well tolerated it may be possible to increase the dosage more quickly than when first starting. However, patients who have had respiratory or cardiac arrest with initial dosing, but were then successfully titrated to a therapeutic dose, should be re-titrated with extreme caution after a break of even 24 hours. Additional monitoring of blood cell counts may also be required if treatment is interrupted. It is recommended that oral therapy with other antipsychotics should be withdrawn gradually before treatment with clozapine is started.
The most commonly reported signs and symptoms associated with Clozapine overdosage are altered states of consciousness, including drowsiness, delirium and coma; tachycardia; cardiac arrhythmias have also been reported with Clozapine generally at doses above 2500 mg. There have also been of patients recovering from overdoses well in excess of 4 g.
Treatment: Establish and maintain an airway; ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdosage. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Additional surveillance should be continued for several days because of the risk of delayed effects. Avoid epinephrine and derivatives when treating hypotension, and quinidine and procainamide when treating cardiac arrhythmia. There are no specific antidotes for Clozapine. Forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.
Clozapine is contraindicated in patients with a previous hypersensitivity to clozapine or any other component of this drug, in patients with myeloproliferative disorder, uncontrolled epilepsy, or a history of clozapine induced agranulocytosis or severe-granulocytopenia. As with more typical antipsychotic drugs, clozapine is contraindicated in severe central nervous system depression or comatose states from any cause. Clozapine should not be used simultaneously with other agents having a well-known potential to cause agranulocytosis or otherwise suppress bone marrow function. The mechanism of clozapine induced agranulocytosis is unknown; nonetheless, it is possible that causative factors may interact synergistically to increase the risk and / or severity of bone marrow suppression.
General: Because of the significant risk of agranulocytosis, a potential life-threatening adverse event, clozapine should be reserved for use in the treatment of severely ill patients with schizophrenia who fail to show an acceptable response to adequate courses of standard drug treatment for schizophrenia, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs, or for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at risk of re-experiencing suicidal behavior. Patients who are being treated with Clozapine must have a baseline white blood cell (wbc) and differential count before initiation of treatment, and a wbc count every week for the first six months.
Caution should be used in administering Clozapine to patients having a history of seizures or other predisposing factors. Because of the substantial risk of seizure associated with Clozapine use, patients should be advised not to engage in any activity where sudden loss of consciousness could cause serious risk to themselves or others, e.g., the operation of complex machinery, driving an automobile, swimming, climbing, etc.
The use of Clozapine in pregnancy has not been established. Therefore, Clozapine is not recommended for use during pregnancy and should only be used if the benefits clearly outweigh the risks. Women receiving Clozapine should not breast-feed.
The most serious adverse reactions experienced with Clozapine are agranulocytosis, seizure, cardiovascular effects and fever.
The most common side effects are drowsiness, dizziness, hypersalivation, dry mouth, tachycardia and sedation. Other side effects are constipation, headache, nausea, and changes in eyesight.
This includes monoamine oxidase inhibitors (MAOIs), cyproheptadine, selegiline, lithium, fenfluramine, dexfenfluramine, and tramadol.
Clozapine may potentiate the hypotensive effects of antihypertensive drugs and the anticholinergic effects of atropine-type drugs. The administration of epinephrine should be avoided in the treatment of drug induced hypotension because of a possible reverse epinephrine effect.
Store at temperatures not exceeding 30°C. Protect from light.
N05AH02 - clozapine ; Belongs to the class of diazepines, oxazepines and thiazepines antipsychotics.
Clopixene tab 100 mg
100's
Sign Out
