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  • sizopin 25 mg 50mg 100mg side effects Clozapine tablet


    Clozapine Tablets BP 25 mg and Clozapine Tablets 100 mg

    atypical antipsychotic.

    Sizopin 100: Each tablet contains clozapine BP 100 mg Sizopin 25: Each tablet contains clozapine BP 25 mg a tricyclic dibenzodiazepine is an

    Clozapine, a

    Mechanism of Action:

    Clozapine is a novel atypical antipsychotic drug and differs from other antipsychotic medications by its profile of binding to dopamine receptors and its effects on various dopamine mediated behaviours. It does interfere with the binding of dopamine at D1.D2, D3 and D5 but has a high affinity for the D4 receptor. It is also preferentially more active at limbic than at striatal dopaminergic receptors. Thus, clozaine does not produce catalepsy or extrapyramidal side effects. Clozapine produces little or no prolactin elevations. Clozapine also has an antiadrenergic, anticholinergic, antihistaminic and antiserotonergic action.

    The absorption of orally administered clozapine is 90-95%. The 25 mg and the 100 mg tablets are equally bioavailable. Following a dosage of 100 mg b.i.d., the average steady state peak plasma concentration was 319ng/ml occurring at an average of 2.5 hours after dosing. Food does not affect the systemic bioavailability of clozapine.

    Clozapine is subject to a moderate first pass metabolism, resulting in an absolute bioavailability of 50-60%. It is completely metabolised prior to excretion and only trace amounts of unchanged drug are detected in the urine and faeces. Approximately 50% of the administered dose is excreted in the urine ar>d 30% in the faeces. Approximately 97% of it is

    The mean elimination half life after a single 75 mg dose was 8 hours, as against the mean elimination half life of 12 hours after achieving a steady state with 100 mg b.i.d. dosing.

    Clozapine is indicated for the management of severely ill schizophrenic patients who fail to respond adequately to standard psychotic drug treatment.

    Patients with myeloproliferative disorders.

    History of clozapine induced agranulocytosis or granulocytopenia.

    Uncontrolled epilepsy.

    Concomitant use with other myelosuppressant drugs.

    Severe CNS depression or comatose states due to any cause.

    The use of Clozapine should be reserved only for the treatment of severely ill schizophrenic patients because of significant risk of agranulocytosis a potentially life-threatening event.

    It is recommended that each patient should be given at least two trials with different antipsychotics at adequate dose and duration before Clozapine use.

    A baseline WBC count and differential count before treatment and every week thereafter for the first six months is recommended.

    Thereafter if acceptable WBC counts (WBC greater than or equal to 3000/mm3, ANC 3 1500/ mm3.) have been maintained during the first 6 months of continuous therapy, WBC counts can be monitored every other week. WBC counts must be monitored weekly for at least 4 weeks after the discontinuation of clozapine.

    Agranulocytosis is defined as an absolute neutrophil count (ANC) of less than 500/mm3 During clinical testing, a cumulative incidence of 1.3% at one year has been recorded. Tr reaction could prove fatal if it is not detected early and the use of clozapine is not discontinu< immediately although cases of fatalities have occurred even after discontination.

    Treatment with clozapine should not be initiated if the WBC count is less than 3500/mm3 or if the patient has a history of myeloproliferative disorder or granulocytopenia due to previous clozapine use.

    If after the initiation of treatment, the total WBC count has dropped below 3500/mm3 or it has dropped by a substantial amount from baseline even if the count is above 3500/mm3 or if immature forms are present, a repeat WBC count and a differential count should be done.

    e throat or any other sign of

    Patients should be advised to report lethargy, weakness, fever, s infection.

    If the total WBC count falls below 2000/mm3 or ANC count below 1000/mm3 bone marrow aspiration may be considered to determine granulopoietic status. These patients should have daily WBC count and differential and should not be rechallenged with clozapineVeatment.

    Neither the dose nor the duration of treatment is a predictor of the problem of agranulocytosis. Women, elderly age group, cachetic patients and patients with serious underlying medical illness may be at particular risk.

    Seizure has been estimated at incidence of 1 -year use of clozapine in 5% of patients. Higher doses are associated with increased likelihood of seizure.

    Caution is advised while administering clozapine to patients with history of seizures or other predisposing factors. Patients should be advised not to engage in activities where seizure occurrence would cause a serious risk to themselves or others; e.g., operation of complex machinery, swimming, driving an automobile, climbing, etc.

    Orthostatic hypotension can occur with clozapine and represents a risk. Rarely, collapse can be profound accompanied by respiratory and cardiac arrest. It is more likely to occur during initial titration, rapid dose escalation and even at first dose.

    Tachycardia, EGG changes such as flattening or inversion of T waves or ST segment depression may occur. Some cases of ischaemic changes, nonfatal arrhythmia, myocardial infarction, congestive heart failure, myocarditis also have been reported. Clozapine should be used with caution in patients with known cardiovascular and/or pulmonary disease. Gradual increase in dose is generally advised.

    Neuroleptic malignant syndrome (hyperpyrexia, muscle rigidity, irregular pulse or blood pressure fluctuation, tachycardia, sweating and cardiac arrhythmia) has been noted with clozapine. Prompt and intensive supportive therapy and monitoring with withdrawal of clozapine is indicated in such cases.

    Tardive dyskinesia, a potentially irreversible involuntary dyskinetic movement disorder can occur. The risk of its development and the likelihood that it will be irreversible are believed to increase as the duration and the total dose are increased. The incidence is higher in elderly patients. There have been few reports of tardive dyskinesia. attributable to clozapine alone. There is no known treatment for tardive dyskinesia. Clozapine should be used for smallest possible time with minimal dose and patients should be reassessed periodically.

    Due to risk of agranulocytosis and seizures, avoid treatment for prolonged periods in patients who fail to show significant improvement. Severe hyperglycaemia, sometimes leading to ketoacidosis has been reported during clozapine treatment.

    Do not use clozapine with other myelosuppressive drugs. Elevation of temperature of about 38 degrees centjgrade may occur following clozapine use. Usually the incidence is highest at third week of treatment. The fever is usually self-limiting, but may necessitate discontinuation of clozapine.WBC count may be elevated.

    Because of having potent anticholinergic effects, great caution is advised in the presence of prostatic enlargement, narrow angle glaucoma or paralytic ileus.

    Clozapine should be used with caution in patients with hepatic, renal or cardiac disease. Hepatitis has been reported in both patients with normal and preexisting liver function abnormalities. In patients who develop nausea, vomiting and/Of anorexia during treatment, liver function tests should be performed immediately. Caution is advised in patients being administered general anesthesia because of the CNS effects of clozapine.

    The patients should be warned about the risk of developing agranulocytosis and the importance of regular WBC counts. Patients should also be informed of the risk of seizures, orthostatic hypotension and possible interactions with alcohol or other drugs.

    Drug interactions:

    Myelosuppression may be aggravated with concomitant use of myelosuppressants. Clozapine may interact with other CNS active drugs or alcohol. Orthostatic hypotension may occur with benzodiazepine usage or other psychotropics.

    Since clozapine is highly bound to proteins, it may be displaced by other drugs, which are also highly protein bound. Conversely, clozapine may also displace such highly bound drugs (e.g., warfarin, digoxin). Cimetidine and erythromycin may increase plasma clozapine levels and phenytoin may decrease plasma clozapine levels.

    Although concomitant administration of carbamazepine and clozapine is not recommended, it should be noted that discontinuation of concomitant carbamazepine may result in an increase in plasma clozapine levels. A reduced clozapine dosage should be used when it is combined with drugs like fluvoxamine, paroxetine and sertraline.

    The action of hypotensive drugs may be potentiated. Other anticholinergic drug actions may also be increased. Administration of adrenaline should generally be avoided due to the possibility of reversal of adrenaline effect due to alpha-adrenergic blockade by clozapine.

    Concomitant use of clozapine with other drugs metabolised by cytochrome P450 2D6 (such as phenothiazines, antideressants. propafenone, flecainede and encainide) or those that inhibit this enzyme such as quinidine; require lower doses of either clozapine or the other drug.

    Pregnancy & Lactation:

    There are no adequate and well-controlled st it should be used only if clearly needed.

    Animal studies suggest that clozapine may be excreted in breast milk and have an effect 01 the nursing infant. Therefore, women receiving clozapine should not breast feed.

    The most commonly reported side effects with clozapine in clinical trials were: CNS including drowsiness/sedation, seizures, dizziness/syncope, vertigo, headache, tremor; autonomic complaints including salivation sweating, dry mouth and visual disturbances; cardiovascular including tachycardia, hypotension and ECG changes; gastrointestinal including constipation, nausea/vomiting; haematologic including leucopenia, granulocytopenia, agranulocytosis; fever.

    Other adverse effects reported were: disturbed sleep/nightmares, restlessness, hypokinesia/akinesia. agitation, rigidity, akathisia, confusion, fatigue, insomnia, hyperkinesia, weakness, lethargy, ataxia, slurred speech, depression, epileptiform movements/myoclonic jerks, anxiety, chest pain/angina, hypertension, abdominal discomfort, heart burn, diarrhoea, liver test abnormality, anorexia, urinary abnormalities, incontinence, abnormal ejaculation, urinary urgency/frequency, urinary retention, rash, musculoskeletal weakness, pain, muscle spasm, muscle pain, throat discomfort, dyspnoea, shortness of breath, nasal congestion, weight gain, tongue numb/sore, loss of speech, amentia, tics, poor coordination, involuntary movement, stuttering, dysarthria, amnesia’memory loss, histrionis movements, libido increase or decrease, paranoia, shakiness, parkinsonism, irritability, oedema, palpitations, phlebitis/thrombophlebitis, cyanosis, premature ventricular contraction, bradycardia, nose bleed, abdominal distention, gastroenteritis, rectal bleeding, nervous stomach, abnormal stools, hematemesis, gastric ulcer, bitter taste, eructation, dysmenorrhoea, impotence, breast pain/discomfort, vaginal itch/infection, numbness, polydipsia, hot flashes, mydriasis, pruritus, pallor, eczema, erythema, bruise, dermatitis, petechiae, urticaria, twitching, joint pain, coughing, pneumonia, pneumonia like symptoms, rhinorrhoea, hype Altered states of consciousness including drowsiness, delirium, coma, tachycardia, hypotension, respiratory depression and failure, typersairvation and occasionally seizures can occur. Aspiration pneumonia and cardiac arrhythmia’s have also been reported. Fatalities have occurred at doses above 2500 mg.


    Use activated charcoal and sorbitol to eliminate unabsorbed drug. Establish adequate life support systems. Cardiac and vital signs monitoring is recommended along with general symptomatic support. Avoid adrenaline and derivatives when treating hypotension; quinidine and procainamide when treating arrhythmia. There are no specific antidotes for clozapine. Forced diuresis, dialysis, hemoperfusion and exchange transfusion is unlikely to be of benefit. Observe patients for several days because of risk of delayed effects.

    Dosage and administration :

    The initial recommended dose is one-half of a 25 mg tablet (12.50) once or twice daily and then continue with daily dosage increments of 25-50 mg/day, If well tolerated to achieve a target dose of 300-450 mg/day at the end of 2 weeks. Subsequent dosage increments may be made once or twice weekly in increments not exceeding 100mg.

    To minimize risk of hypotension seizures and sedation, divided dosage schedule is advised. Majority of patients respond well between 300-600 mg/day dose. Do not exceed doses beyond 900 mg/day. The lowest dose required to maintain remission should be employed and patients should be assessed periodically. For planned termination of treatment, dosage should be reduced gradually over a one-two week period. If abrupt discontinuation is required (e.g., leucopenia). patients should be observed for recurrence of psychotic symptoms.

    When clozapine is to be reinitiated in a patient who is on oral neuroleptic therapy, it is recommended that tapering the dosage downwards discontinue the other neuroleptic, before clozapine is initiated.

    Reinitation of treatment :

    When restarting clozapine after a brief interval of say two days, it is recommended that treatment be reinitiated with one half of the 25mg tablet (12.50 mg) once or twice daily. If that dose is well tolerated, faster titration to the therapeutic dose may be done as compared to the dose recommended for the initial treatment. However, any patient who has previously experienced respiratory or cardiac arrest with initial dosing, but was then able to be successfully titrated to therapeutic dose, should be retitrated with extreme caution after even 24 hours of discontinuation.

    Pediatric use : Safety and effectiveness has not been established.

    Elderly : Dose selection for the elderly should be cautious reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. The initial recommended dose should be 12.50 mg on the first day with the subsequent dose increments being restricted to 25mg/day.

    Special patient groups : In patients with a history of seizures, those suffering from cardiovascular, renal or hepatic disorders, the initial dose should be 12.50 mg given on the first day and dosage increase should be slow and in small increments.


    Store in a

    cool and dry place, away from light. Keep out of the reach of children.

    Presentations :

    Sizopin 25 : Each Box containing 5 x 10’s Tablets in Alu-Alu Poly Strip pack. Sizopin 100 : Each Box containing 5 x 10’s Tablets in Alu-Alu Poly Strip pack.

    Published on July 14, 2013 · Filed under: Science and Medicine; Tagged as: , , ,

2 Responses to “sizopin 25 mg 50mg 100mg side effects Clozapine tablet”

  1. Sizopine :The side effects are too many , the demerits totally out weigh the merits . . . how dangerous this drug is in the long run ! We pity those who receive the same without the routine & regular blood tests .

  2. Any new up date like side effect..,etc

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