Samantha A Hollingworth1, Karl Winckel2,3, Nargess Saiepour4, Amanda J Wheeler5,6, Nicholas Myles7, Dan Siskind8,9. 1. School of Pharmacy, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Australia. s.hollingworth@uq.edu.au. 2. School of Pharmacy, The University of Queensland, 20 Cornwall St, Woolloongabba, QLD, 4102, Australia. 3. Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba, QLD, 4102, Australia. 4. School of Public Health, The University of Queensland, Herston Rd, Herston, QLD, 4006, Australia. 5. Menzies Health Institute Queensland, Meadowbrook, QLD, 4103, Australia. 6. Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, New Zealand. 7. SA Pathology, PO Box 14 Rundle Mall, Adelaide, SA, 5000, Australia. 8. Metro South Addiction and Mental Health Service, 228 Logan Road, Woolloongabba, QLD, 4102, Australia. 9. School of Medicine, The University of Queensland, Herston Rd, Herston, QLD, 4006, Australia.
Abstract
RATIONALE: Clozapine is the gold-standard medicine for treating refractory schizophrenia but there are some notable serious adverse events (AE). We aimed to analyse reported rates of clozapine cardiac and haematological AEs in Australia. METHODS: Using data from the Therapeutic Goods Administration, we examined all reported clozapine AEs (1993-2014) with a specific focus on neutropenia, myocarditis and cardiomyopathy. We related AEs to clozapine-dispensing data in Queensland, scaled up to Australia. RESULTS: There were 8561 AEs reported: neutropenia (13.7%), myocarditis (9.3%) and cardiomyopathy (3.8%). Reported rates of myocarditis and cardiomyopathy increased after 1999 following a myocarditis case series from Sydney. Cardiomyopathy AE rates have remained stable since then but myocarditis AEs have increased steadily. Neutropenia was more common in women, while cardiomyopathy and myocarditis were more common in men. There were five, 13, and two reported deaths from neutropenia, myocarditis, and cardiomyopathy, respectively. CONCLUSIONS: The rates of serious AEs (including deaths) are low and likely an underestimate of true rates and need to be considered by clinicians in balancing the risks and benefits. Continued education on the monitoring and treatment of these AEs for consumers, carers and health professionals is essential and reporting these to the relevant national reporting agency is crucial.
RATIONALE: Clozapine is the gold-standard medicine for treating refractory schizophrenia but there are some notable serious adverse events (AE). We aimed to analyse reported rates of clozapine cardiac and haematological AEs in Australia. METHODS: Using data from the Therapeutic Goods Administration, we examined all reported clozapine AEs (1993-2014) with a specific focus on neutropenia, myocarditis and cardiomyopathy. We related AEs to clozapine-dispensing data in Queensland, scaled up to Australia. RESULTS: There were 8561 AEs reported: neutropenia (13.7%), myocarditis (9.3%) and cardiomyopathy (3.8%). Reported rates of myocarditis and cardiomyopathy increased after 1999 following a myocarditis case series from Sydney. Cardiomyopathy AE rates have remained stable since then but myocarditis AEs have increased steadily. Neutropenia was more common in women, while cardiomyopathy and myocarditis were more common in men. There were five, 13, and two reported deaths from neutropenia, myocarditis, and cardiomyopathy, respectively. CONCLUSIONS: The rates of serious AEs (including deaths) are low and likely an underestimate of true rates and need to be considered by clinicians in balancing the risks and benefits. Continued education on the monitoring and treatment of these AEs for consumers, carers and health professionals is essential and reporting these to the relevant national reporting agency is crucial.
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