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									This document must be filed prominently in the patient’s primary care notes

Clozapine (Clozaril®) for GPs and care co-ordinators
A medicine for schizophrenia, and psychosis in Parkinson’s disease ______________________________________________________________________ Ensure that clozapine is added to the electronic patient’s medication list (GP) Add patient to the mental health register Perform annual physical health check Urgent full blood count if signs of infection inc. sore throat & flu symptoms Do not restart if there has been a break of >48h between doses Check drug interactions Stopping smoking can increase clozapine levels, be alert to smoking status Be alert to constipation, it can lead to clozapine toxicity This document provides important information with respect to the prescribing of clozapine. Clozapine is prescribed, monitored and supplied by the hospital and CMHT, not the GP. However, familiarity with the contents of this document will serve to protect patients treated with clozapine from adverse events associated with its use. Clozapine has been shown to be the drug treatment of choice in treatment resistant schizophrenia. It may also be prescribed for patients with schizophrenia who are nonresponsive to or intolerant of other antipsychotic drug treatment or for patients with psychosis in Parkinson’s disease when other treatment strategies have failed.1 The Clozaril® brand of clozapine is prescribed in Derbyshire Mental Health Trust. Response rates to Clozaril® in patients with refractory schizophrenia are reported to be 30% at 6 weeks and 60% at one year. The average maintenance dose is around 400mg/day, though it is licensed up to 900mg/day. Some patients will complain of adverse effects at doses much less than 400mg/day.2 Dose initiation and breaks in treatment Since many of the adverse effects of clozapine are dose-dependent and associated with speed of titration, therapy is started at a low dose (12.5mg once a day) and increased slowly. If the patient has not taken clozapine for greater than 48 hours advise that the usual dose must not be resumed. The psychiatrist must be contacted urgently as the dose must be re-titrated from 12.5mg/day. Please report any concerns regarding nonadherence with treatment to the psychiatrist. Monitoring All patients receiving clozapine in Derbyshire must be monitored physically by the CMHT as per the Trust’s monitoring guidelines for antipsychotics. In addition, white cells and neutrophils are checked each week, fortnight or month depending on the specification of the Clozaril Patient Monitoring Service (CPMS). Clozapine increases the incidences of diabetes and cardiac events in a group already at increased risk. GPs should perform an annual physical health check for those on clozapine as per the Department of Health Quality and Outcomes Framework (see BMA QOF Page 1 of 3

This document must be filed prominently in the patient’s primary care notes
guidance). Include weight, cardiac checks (inc BP, lipids), assessment of diabetes risk, and smoking. Please review and copy the results of these checks to the psychiatrist. Adverse effects Very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), very rare (<1/10,000), including isolated reports.
Adverse effect Anticholinergic effectsdry mouth



Action Advise symptomatic relief. May be a sign of too high dose, consider informing psychiatrist

blurred vision


May be a sign of too high dose, consider informing psychiatrist. Careful supervision is indicated in the presence of narrow-angle glaucoma. Advise on diet, fluid, exercise and offer laxatives if necessary. Constipation can lead to clozapine toxicity so must be addressed. Manage in consultation with psychiatrist and urologist. Acute retention may need emergency catheterisation and hospital admission May be treated with hyoscine hydrobromide (Kwells), suck and swallow up to three times a day. Unlicensed. Manipulation of dosage times may alleviate daytime sedation. Dose may be too high. Inform psychiatrist. Dose may have been increased too quickly or dose is too high. Inform psychiatrist. Dose may have been increased too quickly or dose is too high. Inform psychiatrist. Lifestyle advice. Referral to dietician may be appropriate. More common with higher doses of clozapine. Inform psychiatrist immediately Urgent full blood count indicated. Inform psychiatrist immediately. Clozapine to be 9 discontinued if WCC<3.5x10 /L or 9 ANC<2.0x10 /L If myocarditis or cardiomyopathy suspected clozapine should be stopped and patient referred to cardiologist. Suspect in patients who have persistent tachycardia at rest, palpitations, arrhythmias, chest pain, and other signs/symptoms of heart failure or symptoms that mimic MI. Flu-like symptoms may also be present. Inform psychiatrist.


Very common

urinary retention (incontinence can also occur ) Hypersalivation


Very common Very common Common Very common Common Common Uncommon/ common


Hypertension, postural hypotension, syncope Tachycardia (see myocarditis/cardiomyopathy) Weight gain Seizures/convulsions/myoclonic jerks Agranulocytosis/neutropenia (patient may report symptoms of infection e.g, flu-like symptoms, sore throat, high temperature) Myocarditis/Cardiomyopathy

Rare/Very rare

Smoking and caffeine Smoking cessation has been reported to increase clozapine plasma levels by up to 72%3 (since cigarette smoke is an inducer of the Cytochrome P450 system). If your patient wants to quit/cut down smoking inform the psychiatric team. A dose reduction

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This document must be filed prominently in the patient’s primary care notes
may be appropriate when stopping smoking. Side effects of clozapine should be reviewed regularly during the period of cutting down. Plasma clozapine concentration is increased by caffeine intake and decreased by 50% following a 5 day caffeine free period1. Advise patient on a stable caffeine intake and inform psychiatric team of any changes. Interactions Clozapine is contraindicated with  other medicines with a substantial potential to depress bone marrow function. Clozapine is cautioned with  other medicines with anticholinergic effects (additive effect) e.g. some drugs for urinary incontinence.  other medicines with hypotensive effects (additive effect)  erythromycin and ciprofloxacin, may increase clozapine levels4  alcohol, due to potential for sedation  benzodiazepines, due to increased risk of circulatory collapse. Try to avoid antibiotics with more potential to cause leucopenia and/or neutropenia e.g. cephalosporins, quinolones, trimethoprim, metronidazole and nitrofurantoin. 5 This is not an exhaustive list. Please see BNF and summaries of product characteristics for further information. Contacts Please see coordination form (to have been sent to GP after clozapine initiation).
Consultant Psychiatrist Community Team & Care Coordinator Pharmacy Kingsway Hospital 01332 371037 Clozaril Patient Monitoring Service 0845 7698269 24h emergency01276 692504

References 1. Summary of Product Characteristics. Novartis. https://www.clozaril.co.uk. Accessed 30th July 2007 (user id and password required). 2. Clozaril assay guidelines. https://www.clozaril.co.uk. Accessed 30th July 2007 (user id and password required). 3. Guidance on the impact of tobacco smoking cessation on prescribed medication. Beverley Thompson, Jan 2007. 4. British National Formulary, number 53, March 2007. 5. Psychotropic Drug Directory, Stephen Bazire, 2005.

Written by: Rebecca Potter, Clinical Pharmacist, DMHST. Approved by Mental Health Trust Drugs Therapeutics Committee 23.8.07 Ratified by the Joint Area Prescribing Committee 13.11.07 Review date: August 2009

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