Clozapine is indicated for the management of treatment-resistant schizophrenia. Its use is subject to strict regulatory and monitoring requirements due to potential toxicity, most notably agranulocytosis and neutropenia.

Each brand has its own protocol monitoring service^1,2:

• Clozaril (Viatris) – the Clozaril Patient Monitoring System (CPMS), and
• Clopine (Pfizer) – ClopineCENTRAL.

Is registration with these services mandatory?

Yes. Prescribers, pharmacies and pharmacists must be registered with the respective service. Individual pharmacists may be registered to multiple pharmacies. They must be used for every dispense event.

A patient has run out of medicines but now new blood tests have been provided. Can I dispense an emergency supply?

No. Dispensing cannot occur beyond the next blood test due date until a doctor and pharmacist have reviewed a new white blood count (WBC) and neutrophil count and deemed them acceptable.

Is it OK to rely on blood tests I access from MHR or that the prescriber sends to the pharmacy?

Yes. However, the pharmacist must be satisfied the pathology results have been reviewed and approved by the patient’s medical practitioner.

Where the prescriber has not entered these blood results into the relevant monitoring system, the pharmacist must enter these details at the time of dispensing or transmit them to the monitoring system via fax for upload.

What happens if someone does not collect their prescription within 48 hours of the pathology blood test?

Interruptions to therapy may require re-titration, so pharmacists should first check to determine if there has been an interruption in therapy of >48 hours. If so, withhold supply and refer for urgent review.

If therapy is uninterrupted, the amount supplied would be the original quantity minus the number of days late presenting to the pharmacy. This is known as the ’48-hour rule’.

For example, if a patient who had a prescription for 28 days’ therapy presented on Saturday for a blood test taken 5 days earlier on Monday, then up to 25 days’ therapy could be supplied. 

Is other monitoring required? 

Yes. In addition to haematological monitoring, people taking clozapine require monitoring for changes in cardiac, metabolic, gastrointestinal and central nervous system functioning. 

In April 2022, the Therapeutic Goods Administration (TGA) mandated a boxed warning in the product information for clozapine in relation to the potentially fatal risk of gastrointestinal hypomotility. The TGA alert noted that approximately 10% (n = 103) of clozapine reports with a fatal outcome were due to gastrointestinal disorders.³

All health professionals should enquire routinely about patient’s bowel habits. Nausea and/or vomiting, abdominal distension and/or pain, lack of urge and/or inability to defecate or constipation should prompt further assessment and urgent referral for immediate review.

References

1. Chao A. Clopine CENTRAL: Your connection to Clopine (clozapine) patient care, Pfizer Australia, WestRyde. 2017. At: www.clopine.com.au/ClopineCentral
2. Clozaril Patient Monitoring System Protocol.September 2019, ver. 5. Mylan. At: www.ecpms.com.au/
3. Therapeutic Goods Administration, Department of Health and Aged Care, Australian Government.Medicines safety update: clozapine and gastrointestinal hypomotility with severe complications. 2022. At: www.tga.gov.au/news/safety-updates/clozapine-and-gastrointestinal-hypomotility-severe-complications