Clozaril^®/Clozapine Mylan

The active ingredient and instructions for use are the same for Clozaril^® and Clozapine Mylan. Any mention of Clozaril^® would also apply to Clozapine Mylan.

Clozaril^® is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients with severe, untreatable neurological adverse reactions to other antipsychotic agents, including an atypical antipsychotic agent prescribed for adequate duration. Psychotic disorders occurring during the course of Parkinson's disease, where standard treatment has failed.¹

NICE recommends Clozapine as first-line treatment for Treatment Resistant Schizophrenia (TRS)

NICE guidelines recommend that clozapine should be offered first-line to schizophrenia patients who have not shown satisfactory clinical improvement following sequential treatment with at least two different antipsychotic drugs, including at least one second-generation (atypical) antipsychotic.²

TRS is common among schizophrenia patients

Treatment resistance is a significant barrier to effective treatment. A review of several cohort studies estimates that 20-30% of patients with schizophrenia meet the criteria for TRS.³

Given that an estimated 25‒50% of schizophrenia patients attempt suicide and 10% eventually achieve this⁴, it is essential that patients with TRS are identified in a timely manner so that they can receive appropriate therapy.

Clozapine is under-prescribed in the UK

The national audit of schizophrenia (NAS), which was carried out in 2014 by the Royal College of Psychiatrists and involved all 64 Mental Health Trusts in England and Health Boards in Wales, found that more than 1 in 4 (28%) patients with schizophrenia who failed on at least two antipsychotics, and whose condition may have benefitted from clozapine treatment, were not prescribed it.⁵

This audit identified three main causes for the under-prescription of clozapine:⁵

1. More than two antipsychotics are being tried before prescribing clozapine

• More than half (57%) of schizophrenia patients taking clozapine in 2014 had been prescribed three or more different antipsychotic drugs before initiating treatment with clozapine

2. Polypharmacy is employed to improve response, rather than moving to clozapine

• More than 1 in 10 (11%) people with schizophrenia (who were not taking clozapine) were being prescribed more than one type of antipsychotic at the same time. In some areas, this practice occurred in as many as 24% of schizophrenia patients

3. Patients are treated with higher than recommended doses of antipsychotics

• One in 10 people are being prescribed antipsychotic drugs – other than clozapine – at a higher dose than that recommended by the British National Formulary

Clozaril^®/Clozapine Mylan

The active ingredient and instructions for use are the same for Clozaril^® and Clozapine Mylan. Any mention of Clozaril^® would also apply to Clozapine Mylan.

Clozapine efficacy in treatment resistant schizophrenia (TRS)

Clozapine has demonstrated superior clinical efficacy over typical and atypical antipsychotics in TRS patients.¹

Clinical data shows that clozapine significantly reduces the overall symptom score, and positive and negative symptoms of schizophrenia in TRS patients,^1-10with significant improvement seen as soon as 6 weeks from the start of treatment^1,4(see Figures 1 and 2).

As well as superiority over typical antipsychotics, clozapine has also demonstrated greater clinical efficacy than atypical antipsychotics in TRS patients.^3,6 Trends for greater improvement in positive and negative syndrome scale (PANSS) scores are supported by significant reductions in total PANSS score⁶ (see Figure 3).

Adapted from McEvoy et al,. 2006.⁶

High rates of clinical response to Clozapine

A large proportion of patients on clozapine show a clinical response to treatment, defined as at least 20% improvement in brief psychiatric rating scale (BPRS) score.^1-3 In clinical studies, the proportion of responders ranges from 56.6% (at 29 weeks, mean dose 523 mg/day)² to 86% (at 12 weeks, mean dose 600 mg/day)³, and is higher than that seen in typical antipsychotics (see Table 1).

A meta-analysis has shown that clozapine-treated patients are nearly 2.5 times more likely to experience a 20-30% decrease from baseline in total BPRS score compared with those treated with typical antipsychotics (p=0.001).⁷

Some patients achieve at least 50% improvement in symptoms score.¹ In a 6-week study of 51 patients with TRS, 1 in 10 (10.5%) of the 38 patients who remained on clozapine achieved at least a 50% decrease in BPRS score.¹

Low rates of treatment withdrawal with Clozapine

In clinical studies, fewer patients with TRS on clozapine discontinue treatment due to lack of efficacy compared with those on typical^2,5 and atypical^{3, 6} antipsychotics.²

Examples include:

• A large study of 423 patients: 6.3% of patients on clozapine discontinued due to lack of efficacy, compared with 36.7% on the typical antipsychotic, haloperidol (p<0.001)⁵
• A study of 273 patients: drop-out rates due to poor efficacy were 0.7% for clozapine compared with 6.7% for the atypical antipsychotic, risperidone (p<0.01)³

Treatment withdrawal due to adverse events is similar for patients on clozapine and those on some typical and atypical antipsychotics:

• In a study of 71 patients with TRS randomised to clozapine or haloperidol, 2/37 patients discontinued due to adverse events on clozapine, compared with 3/34 on haloperidol²
• A large study of 423 TRS patients randomised to clozapine or haloperidol found withdrawal rates due to adverse events of 12.7% and 12.4%, respectively⁵
• In a study of 273 patients with TRS randomised to clozapine or risperidone, withdrawal rates due to adverse events were 11.6% for those on clozapine and 8.9% for those on risperidone (this difference was not statistically significant)³

As an indicator of tolerability, the overall dropout rates from long-term antipsychotic treatment are also lower for clozapine compared with typical antipsychotics. Two meta-analyses of clinical studies show discontinuation rates of 33% and 38% for clozapine, and 56% and 67% for conventional agents.^8,9

Fewer hospitalisation days with Clozapine

For outpatients with TRS, treatment with clozapine results in fewer days in hospital for schizophrenia symptoms compared with typical and atypical antipsychotics: 14.4% fewer and 27.3% fewer, respectively.^5,11

Clozapine improves quality of life in patients with TRS

Clinical data in patients with TRS followed-up for 12 months shows that clozapine significantly improves the total score and all 21 item scores of the quality of life scale (QLS).¹ Up to 48% of patients on clozapine show clinically important improvement in quality of life scores during 12 months of treatment.⁵

Significant improvement in can occur from as early as 6 weeks into treatment,⁵ and improvements in social and occupational functioning have been seen during long-term therapy.¹⁰

Clozaril^®/Clozapine Mylan

The active ingredient and instructions for use are the same for Clozaril^® and Clozapine Mylan. Any mention of Clozaril^® would also apply to Clozapine Mylan.

The Summary of Product Characteristics (SmPC) states that blood monitoring should be carried out¹

The Clozaril^® Patient Monitoring Service provides for the centralised monitoring of leucocyte (WBC) and neutrophil (ANC) counts which is a mandatory requirement for all patients in the UK who are treated with Clozaril^®. The use of Clozaril^® is restricted to patients who are registered with the Clozaril^® Patient Monitoring Service.

Pre-treatment blood testing¹

WBC with differential blood counts must be performed within 10 days prior to initiating Clozaril^®treatment to ensure that only patients with a WBC >3500/mm³ (3.5x10⁹/L) and an ANC >2000/mm³ (2.0x10⁹/L) receive Clozaril^®.

Blood monitoring after Clozaril^®initiation¹

After the start of Clozaril^® treatment, regular WBC count and ANC must be performed and monitored weekly for the first 18 weeks, then every two weeks up to week 52, then at least four-weekly thereafter.

Monitoring must continue throughout treatment and for 4 weeks after complete discontinuation of Clozaril^® or until haematological recovery has occurred. WBC and differential blood counts must be performed immediately if any symptoms or signs of an infection occur.

Action if a patient has low WBC count/ANC¹

If a patient develops a low WBC count and /or low ANC while on Clozaril^® treatment, monitoring must be increased to at least twice weekly until counts recover to within an accepted range. If WBC count and ANC fall below a specific threshold, Clozaril^® must be discontinued immediately.

Table 1 summarises the actions required for WBC counts and ANC thresholds.

PRESCRIBING INFORMATION

CLOZARIL^® | CLOZAPINE MYLAN 25 MG AND 100 MG TABLETS (clozapine)

Please refer to the Summary of Product Characteristics (SmPC) before prescribing

The use of Clozaril/Clozapine Mylan is restricted to patients, physicians and nominated pharmacists registered with the Clozaril Patient Monitoring Service (CPMS).

In the UK a white cell count with differential count must be monitored:

• At least weekly for the first 18 weeks of treatment
• At least at 2-week intervals between weeks 18 and 52
• After 1 year of treatment with stable neutrophil counts, patients may be monitored at least at 4-week intervals
• Monitoring must continue throughout treatment and for at least 4 weeks after discontinuation

Blood clozapine level monitoring is advised in situations such as a patient ceases smoking or switches to e-cigarettes, when concomitant medicines may interact to increase clozapine blood levels, where poor clozapine metabolism is suspected, when a patient has pneumonia or other serious infection and in the event of onset of symptoms suggestive of toxicity.

Clozaril/Clozapine Mylan is associated with an increased risk of myocarditis and cardiomyopathy. If suspected Clozaril/Clozapine Mylan must be stopped immediately and the patient referred to a cardiologist and not re-exposed to Clozaril/Clozapine Mylan.

Indications:

Treatment-resistant schizophrenic patients and in schizophrenia patients who have severe, untreatable neurological adverse reactions to other antipsychotic agents, including atypical antipsychotics. Psychotic disorders occurring during the course of Parkinson's disease, in cases where standard treatment has failed.

Presentation:

Clozaril/Clozapine Mylan 25 mg Tablets containing 25 mg clozapine. Clozaril/Clozapine Mylan 100mg Tablets containing 100 mg clozapine.

Dosage and administration:

Oral administration

Treatment-resistant schizophrenic patients

12.5 mg once or twice on the first day, followed by 25 mg tablets once or twice on the second day. If well tolerated, the daily dose may 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. If required, the daily dose may be further increased in increments of 50 to 100 mg at half-weekly or, preferably, weekly intervals. In most patients, antipsychotic efficacy can be expected with 200 to 450 mg/day given in divided doses. If the daily dose does not exceed 200 mg, it can be taken as a single dose in the evening. Doses up to 900 mg/day can be used but the possibility of increased adverse reactions (in particular seizures) occurring at doses over 450 mg/day must be considered. Once control is achieved, a lower maintenance dose may be effective. Treatment should be maintained for at least 6 months. See SmPC for details on re-starting therapy, ending therapy or switching from another antipsychotic.

Psychotic disorders occurring during the course of Parkinson's disease in cases where standard treatment has failed

The starting dose must not exceed 12.5 mg/day, taken in the evening. Increase dose by 12.5 mg increments, with a maximum of two increments a week up to a maximum of 50 mg, preferably given as a single dose in the evening. The mean effective dose is usually between 25 and 37.5 mg/day. If satisfactory therapeutic response is not achieved for at least one week with a dose of 50 mg, dosage may be cautiously increased by increments of 12.5 mg/week. 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. When there has been complete remission of psychotic symptoms for at least two weeks, an increase in anti-parkinsonian medication is possible on the basis of motor status. A gradual reduction in dose by steps of 12.5 mg over a period of at least one week (preferably two) is recommended in the event of termination.

Contraindications: Hypersensitivity to the active substance or to any of the excipients. 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. Concurrent treatment with substances known to have a substantial potential for causing agranulocytosis; concomitant use of depot antipsychotics is 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. Severe renal or cardiac disorders (e.g. myocarditis). Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure. Paralytic ileus.

Warning and precautions: Contains lactose monohydrate

Agranulocytosis: Clozapine can cause agranulocytosis, so is restricted to patients who have initially normal leukocyte findings (White Blood Cell (WBC) count > 3.5x 109/l and Absolute Neutrophil Count (ANC) > 2.0x 109l), and in whom regular WBC counts and ANC can be performed within 10 days prior to starting clozapine, weekly for first 18 weeks, and at least at 4-week intervals thereafter throughout treatment and for 4 weeks after complete discontinuation. Before initiating clozapine therapy, patients should have a blood test and a history and physical examination. Patients with history of cardiac illness or abnormal cardiac findings on physical examination prior to treatment should be referred to a specialist for other examinations that might include an ECG, and the patient treated only if the expected benefits clearly outweigh the risks. The treating physician should consider performing a pre-treatment ECG. Prescribing physicians must comply fully with the required safety measures. Physicians must ensure 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. Immediate discontinuation of clozapine treatment is mandatory if either the WBC count is less than 3000/mm3 (3.0x109/l) or the ANC is less than 1500/mm3 (1.5x109/l) during clozapine treatment. If clozapine has been withdrawn and either a further drop in the WBC count below 2000/mm3 (2.0x109/l) occurs or the ANC falls below 1000/mm3 (1.0x109/l), the management of this condition must be guided by an experienced haematologist. Patients in whom clozapine has been discontinued as a result of either WBC or ANC deficiencies must not be re-exposed to clozapine.

Low WBC count/ANC: If, during clozapine therapy, either the WBC count falls to between 3500/mm³ (3.5x10⁹/l) and 3000/mm³ (3.0x10⁹/l) or the ANC falls to between 2000/mm³ (2.0x10⁹/l) and 1500/mm³ (1.5x10⁹/l), haematological evaluations must be performed at least twice weekly until the patient’s WBC count and ANC stabilise within the range 3000-3500/mm³ (3.0-3.5x10⁹/l) and 1500-2000/mm³ (1.5-2.0x10⁹/l), respectively, or higher.

Eosinophilia: Discontinue clozapine 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).

Thrombocytopenia: Discontinue clozapine if the platelet count falls below 50 000/mm³ (50x10⁹/l).

Cardiovascular disorders: Orthostatic hypotension, with or without syncope, can occur during clozapine treatment. Rarely, collapse can be profound and may be accompanied by cardiac and/or respiratory arrest. Such events are more likely to occur with concurrent use of a benzodiazepine or any other psychotropic agent (see Section 4.5) and during initial titration in association with rapid dose escalation; on very rare occasions they may occur even after the first dose. Therefore, patients starting clozapine treatment require close medical supervision. Monitoring of standing and supine blood pressure is necessary during the first weeks of treatment in patients with Parkinson’s disease. Clozapine is associated with an increased risk of myocarditis, pericarditis/pericardial effusion and cardiomyopathy. Myocarditis or cardiomyopathy should be suspected in patients who experience persistent tachycardia at rest, especially in the first two months of treatment, and/or palpitations, arrhythmias, chest pain and other signs and symptoms of heart failure (e.g. unexplained fatigue, dyspnoea, tachypnoea), or symptoms that mimic myocardial infarction. Other symptoms which may be present in addition to the above include flu-like symptoms. If myocarditis or cardiomyopathy is suspected, clozapine treatment should be promptly stopped and the patient immediately referred to a cardiologist. In patients who are diagnosed with cardiomyopathy while on clozapine treatment, there is potential to develop either mild or moderate mitral regurgitation. Patients with clozapine-induced myocarditis or cardiomyopathy should not be re-exposed to clozapine.

Myocardial infarction: There have been post-marketing reports of myocardial infarction including fatal cases.

QT interval prolongation: As with other antipsychotics, caution is advised in patients with known cardiovascular disease or family history of QT prolongation. As with other antipsychotics, caution should be exercised when clozapine is prescribed with medicines known to increase QTc interval.

Cerebrovascular adverse events: Clozapine should be used with caution in patients with risk factors for stroke.

Risk of thromboembolism: Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with clozapine and preventive measures undertaken.

Seizures: Patients with a history of epilepsy should be closely observed during clozapine therapy since dose-related convulsions have been reported. In such cases, the dose should be reduced (see Section 4.2 of SmPC) and, if necessary, an anti-convulsant treatment should be initiated.

Anticholinergic effects: Clozapine exerts anticholinergic activity, which may produce undesirable effects throughout the body such as impairment of intestinal peristalsis, ranging from constipation to intestinal obstruction, faecal impaction, paralytic ileus, megacolon and intestinal infarction ischaemia (see Section 4.8 of SmPC). Careful supervision is indicated in the presence of prostatic enlargement and narrow-angle glaucoma and in patients who are receiving concomitant medications known to cause constipation (especially those with anticholinergic properties such as some antipsychotics, antidepressants and antiparkinsonian treatments), have a history of colonic disease or a history of lower abdominal surgery as these may exacerbate the situation.

Fever: Patients may experience transient temperature elevations above 38°C and should be carefully evaluated to rule out the possibility of an underlying infection or the development of agranulocytosis. In the presence of high fever, the possibility of neuroleptic malignant syndrome (NMS) must be considered. If the diagnosis of NMS is confirmed, clozapine should be discontinued immediately and appropriate medical measures should be administered.

Falls: Clozapine may cause seizures, somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.

Metabolic changes: Atypical antipsychotic drugs, including clozapine, have been associated with metabolic changes (hyperglycaemia, dyslipidaemia, and body weight gain) that may increase cardiovascular/cerebrovascular risk.

Hyperglycaemia: 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. Patients who develop symptoms of hyperglycaemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing.

Dyslipidaemia: Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using clozapine, is recommended.

Weight gain: Clinical monitoring of weight is recommended.

Rebound, withdrawal effects: 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.

Special populations

Hepatic impairment: Patients with hepatic impairment should receive clozapine with caution along with regular monitoring of liver function tests (see Section 4.4 of SmPC).

Paediatric population: No paediatric studies have been performed. The safety and efficacy of clozapine in children and adolescents under the age of 16 years have not yet been established. Clozapine should not be used in this group until further data becomes available.

Patients 60 years of age and older: Initiation of treatment is recommended at a particularly low dose (12.5 mg given once on the first day), with subsequent dose increments restricted to 25 mg/day.

Interaction with other medicinal products: Clozapine must not be used concomitantly with substances having a well-known potential to suppress bone marrow function (see Section 4.3 of SmPC). Long-acting depot antipsychotics (with myelosuppressive potential) must not be used because these cannot be removed from the body in situations where they may be required e.g. neutropenia. Alcohol should not be used with clozapine due to possible potentiation of sedation. Caution is advised if clozapine is used concomitantly with other CNS active agents such as MAOIs, CNS depressants (such as benzodiazepines, narcotics, antihistamines), substances possessing anticholinergic, hypotensive, or respiratory depressant effects, highly protein bound substances (e.g. warfarin and digoxin), phenytoin, lithium, CYP1A2 inducing substances (e.g. omeprazole), and CYP1A2 inhibiting substances (e.g. fluvoxamine, caffeine, ciprofloxacin, perazine) or hormonal contraceptives as they are CYP1A2, CYP3A4, CYP2C19 inhibitors. See SmPC for more details.

Pregnancy and lactation: Caution should be exercised when prescribing to pregnant women. Neonates exposed to antipsychotics (including clozapine) during the third trimester are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, new-borns should be monitored carefully. Animal studies suggest that clozapine is excreted in breast milk and has an effect in the nursing infant; therefore, mothers receiving clozapine should not breast-feed.

Effects on ability to drive and use machines: Owing to the ability of clozapine to cause sedation and lower the seizure threshold, activities such as driving or operating machinery should be avoided, especially during the initial weeks of treatment.

Undesirable effects: Adverse reactions are ranked under headings of frequency, using the following convention: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

Very common: Drowsiness/sedation, dizziness, tachycardia, constipation, hypersalivation.

Common: Leukopenia/decreased WBC/neutropenia, eosinophilia, leukocytosis, weight gain, dysarthria, seizures/convulsions/myoclonic jerks, extrapyramidal symptoms, akathisia, tremor, rigidity, headache, blurred vision, ECG changes, syncope, postural hypotension, hypertension, nausea, vomiting, anorexia, dry mouth, elevated liver enzymes, urinary retention, urinary incontinence, benign hyperthermia, disturbances in sweating/temperature regulation, fever, fatigue.

Uncommon: Agranulocytosis, dysphemia, neuroleptic malignant syndrome, falls. 

For details of rare, very rare and not known undesirable effects please refer to SmPC.

Legal Category: POM

Marketing Authorisation Numbers: 25 mg tablets: PL 46302/0054; 100 mg tablets: PL 46302/0057

MAH: Mylan Products Limited, 20 Station Close, Potters Bar, Herts, EN6 1TL, UK

NHS Price: 28 x 25 mg tablets: £3.02; 84 x 25 mg tablets: £8.40; 100 x 25 mg tablets: £10.00 28 x 100 mg tablets: £12.07; 84 x 100 mg tablets: £33.60; 100 x 100 mg tablets: £39.00

Date of Revision of Prescribing Information: September 2024

CLZ-2024-0034

The SmPC for this product, including adverse reactions, precautions, contra-indications, and method of use can be found at:

http://www.mhra.gov.uk/Safetyinformation/Medicinesinformation/SPCandPILs/index.htm and from Viatris Medical Information, Building 4, Trident Place, Hatfield Business Park, Mosquito Way, Hatfield, Hertfordshire, AL10 9UL, phone no. 01707 853000, Email: info.uk@viatris.com.

Please continue to report suspected adverse drug reactions with any medicine or vaccine to the MHRA through the Yellow Card Scheme. It is easiest and quickest to report adverse drug reactions online via the Yellow Card website: http://www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Alternatively, you can report via some clinical IT systems (EMIS/SystmOne/Vision/MiDatabank) or by calling the Commission on Human Medicines (CHM) free phone line: 0800-731-6789. Adverse reactions/events should also be reported to MAH at e-mail address: cpms@viatris.com.

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Clozaril^®/Clozapine Mylan

The active ingredient and instructions for use are the same for Clozaril^® and Clozapine Mylan. Any mention of Clozaril^® would also apply to Clozapine Mylan.

Contraindications¹

• Hypersensitivity to the active substance or to any of the excipients
• 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 Clozaril^®-induced agranulocytosis 
• Clozaril^® treatment must not be started concurrently with substances 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
• Severe renal or cardiac disorders (e.g. myocarditis)
• Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure
• Paralytic ileus

Adverse reactions¹

The SmPC for Clozaril^® and Clozapine Mylan lists drowsiness/sedation, dizziness, tachycardia, constipation, hypersalivation, leukopenia/decreased WBC/neutropenia, eosinophilia, leukocytosis, weight gain, dysarthria, seizures/convulsions/myoclonic jerks, extrapyramidal symptoms, akathisia, tremor, rigidity, headache, blurred vision, ECG changes, syncope, postural hypotension, hypertension, nausea, vomiting, anorexia, dry mouth, elevated liver enzymes, urinary retention, urinary incontinence, benign hyperthermia, disturbances in sweating/temperature regulation, fever and fatigue as very common or common adverse reactions.  

For a full list of adverse reactions, precautions, contraindications, and method of use please consult the SmPC.¹

https://www.medicines.org.uk/emc/product/10290/smpc

https://www.medicines.org.uk/emc/product/15497/smpc

Side effects of antipsychotics in general²

Every antipsychotic is likely to have side effects, and these may affect the choice of drug prescribed to the patient. The patient should be given information on the antipsychotics and the potential benefits and side effects of each drug should be discussed with them. Side effects may include:

• Metabolic (including weight gain and diabetes)
• Extrapyramidal (including akathisia, dyskinesia and dystonia)
• Cardiovascular (including prolonging the QT interval)
• Hormonal (including increasing plasma prolactin)
• Other (including unpleasant subjective experiences)

Therefore, before starting a patient on antipsychotic medication, the following health check should be made, with regular monitoring thereafter:

• Weight
• Waist circumference
• Pulse and blood pressure
• Fasting blood glucose, glycosylated haemoglobin (HbA1c), blood lipid profile and prolactin levels
• Assessment of any movement disorders
• Assessment of nutritional status, diet and level of physical activity
• ECG – if the patient has a history of cardiovascular disease or is being admitted as an inpatient

Agranulocytosis

Although it has been noted, agranulocytosis is uncommon in patients on clozapine treatment, and it should not be a barrier to prescribing it for patients with TRS who may benefit significantly from it.

In two clinical studies with a total of 250 patients treated with clozapine, four patients developed agranulocytosis (1.6%), all of whom recovered after withdrawal from treatment.^3,4

Clozaril^®/Clozapine Mylan

The active ingredient and instructions for use are the same for Clozaril^® and Clozapine Mylan. Any mention of Clozaril^® would also apply to Clozapine Mylan.

Viatris have created support materials to help your patients who have been prescribed Clozaril^®.

What to expect from the Clozaril^® patient booklet

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