Important considerations

Clozapine is a high-risk medicine. The following points should be considered when treating adults who develop swallowing difficulties.

Avoid missing doses

Clozapine doses should not be missed. Clozapine tablets can be crushed (off-label use) if necessary while waiting for advice on alternatives.

Seek advice from the individual’s specialist mental health team if doses are missed. It can be dangerous to miss clozapine doses and restart at the full dose. If more than two days’ treatment is missed, clozapine must be restarted at the original starting dose and retitrated.

Clozapine doses are adjusted individually and titrated cautiously to minimise adverse effects. On missing doses, tolerance to common side effects such as postural hypotension and tachycardia can be lost very quickly. Restarting without titration may put the individual at risk of seizures, tachycardia, hypotension and circulatory collapse.

Seek specialist advice

Contact the individual’s specialist mental health team for advice. They can initiate changes to brand, formulation or dose. If the individual is in an acute hospital, also contact the psychiatric liaison team.

Clozapine monitoring services

Clozapine can rarely cause fatal agranulocytosis (severe neutropenia). White blood cell and absolute neutrophil counts must be monitored regularly and recorded centrally for individuals taking clozapine. Use of clozapine is restricted to patients registered with a monitoring service.

Supply

Clozapine is always prescribed by brand name. It can only be supplied by hospital or retail pharmacies registered with brand-specific clozapine patient monitoring services. Individuals taking clozapine must also be registered with the monitoring service.

Clozapine can only be supplied for individuals whose blood results are within specified limits. The dispensing pharmacy can only supply as many days’ treatment as the blood test result allows. This is usually between one and four weeks.

Monitoring frequency

The frequency of monitoring depends on previous results and the length of time the individual has been taking clozapine. If doses are missed, or if results are outside the required limits, the frequency of monitoring may be increased.

Brand-specific services

There are three brands of clozapine, each with its own monitoring service. The three monitoring services are:

• UK Clozaril Patient Monitoring Service (CPMS)
• Denzapine Monitoring Service (DMS)
• Zaponex Treatment Access System (ZTAS)

Patients can only be registered with one service at any one time. The prescriber, a nominated pharmacist and the hospital or retail pharmacy that supplies clozapine must also be registered with the relevant monitoring service. Trusts are unlikely to be registered with services for all three brands. Clozapine is not usually prescribed or supplied in primary care.

Choosing clozapine preparations

Choosing formulations of medicines for adults with swallowing difficulties has general advice on choosing medicines formulations for adults with swallowing difficulties.

In an acute situation, choice of clozapine formulation is likely to be limited to that which the patient is currently prescribed. In the longer term it may be possible to switch to a different formulation or brand. It is important that clozapine doses are not missed while an alternative formulation is sought.

It can be safe and practical for individuals to take crushed tablets with soft food. For indiviudals who need a texture-modified diet, use the food texture and fluid consistency that is safe for them.

In all cases, seek advice from the individual’s specialist mental health team. They can initiate changes if necessary and liaise with the appropriate clozapine monitoring service(s). The mental health team may recommend clozapine blood level monitoring if tablets are crushed or the brand or formulation is changed.

Clozaril

Available as tablets only.

Clozaril may only be used if the patient, prescriber and dispensing pharmacy are registered with CPMS, the Clozaril Patient Monitoring Service.

Tablets

Clozaril tablets (available as 25mg and 100mg) are scored and licensed to be split in half. They can be crushed and mixed with water or soft food; this is off-label use. The tablets are uncoated but the drug is insoluble; be careful to ensure the whole dose is taken.

Denzapine

Available as tablets and oral suspension.

Denzapine may only be used if the patient, prescriber and dispensing pharmacy are registered with DMS, the Denzapine Monitoring Service.

Tablets

Denzapine tablets (available as 25mg, 50mg, 100mg and 200mg) are scored and licensed to be split in half. They can be crushed and mixed with water or soft food; this is off-label use. The tablets are uncoated but the drug is insoluble; be careful to ensure the whole dose is taken.

Oral suspension

Denzapine oral suspension (50mg/ml) is a licensed preparation and can be mixed with water if necessary. It is not compatible with orange juice and it would be prudent to avoid other acidic liquids. The oral suspension does not require fridge storage and has an expiry of 90 days after opening. Clozapine particles may settle and it is important to shake the bottle vigorously for 10 seconds before each use. If settling is visible, and on dispensing, the manufacturer advises shaking the bottle vigorously for 90 seconds.

Zaponex

Available as tablets and orodispersible tablets.

Zaponex may only be used if the patient, prescriber and dispensing pharmacy are registered with ZTAS, the Zaponex Treatment Access System.

Tablets

Zaponex tablets (available as 25mg and 100mg) are scored and licensed to be split in half. They can be crushed and mixed with water or soft food; this is off-label use. The tablets are uncoated but the drug is insoluble; be careful to ensure the whole dose is taken.

Orodispersible tablets

Zaponex orodispersible tablets (available as 12.5mg, 25mg, 50mg, 100mg and 200mg) are licensed for oral administration. They should be placed on the tongue and will rapidly disintegrate in saliva to be swallowed. Orodispersible tablets may not be suitable for individuals unable to control their swallow.

Switching preparations

In all cases of switching, liaise with the individual’s specialist mental health team. Monitor the individual for response and tolerability if the brand, formulation or method of administration is changed. Counsel the individual or carer about any changes and ensure they can take or administer the preparation safely.

Reduced blood levels of clozapine have been seen in some individuals switched from whole tablets to crushed tablets or suspension, but data are sparse. Be careful to ensure the whole dose of crushed tablet is taken and that suspensions are shaken before use.

There have been reports of relapse when individuals stabilised on one brand of clozapine have switched to another. However, in most cases, switching appears to be safe and uneventful.

Following a switch, it may be useful to monitor clozapine blood levels if a baseline level is available. Seek advice from the individual’s specialist mental health team who will arrange testing if necessary.

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