Suspected Hepatotoxicity With a Supercritical Carbon Dioxide Extract of Artemisia annua in Grapeseed Oil Used in New Zealand.

A case series of hepatotoxicity associated with an extract of Artemisia annua L. was identified through the New Zealand spontaneous adverse drug reaction reporting system. A. annua extract, produced using a supercritical carbon dioxide extraction method and formulated with grapeseed oil, has been marketed in New Zealand as a natural product for joint health. As of 31 January 2019, the New Zealand Pharmacovigilance Centre had received 29 reports of hepatic adverse reactions occurring in patients taking A. annua extract in grapeseed oil. The case reports were assessed for patient and adverse reaction characteristics, patterns of A. annua extract use and causality (based on the WHO-UMC system for standardized case causality assessment). Patients were aged 47 to 93 years (median 67). Time to onset of hepatotoxicity from starting A. annua extract was 7 days to approximately 12 months in the 23 reports with this information. Nineteen of these reports indicated onset within 12 weeks. A. annua extract was the sole suspect medicine in 27 reports. A few patients had possible predisposing conditions. Twenty-seven patients were reported to have recovered or improved on stopping A. annua extract. Nine patients required hospital admission. The pattern of hepatic injury varied. Jaundice, often with pruritus and dark urine, was experienced by 16 patients. There was considerable consistency across case reports from various reporters. We assessed the case reports as a series using the Bradford Hill guidelines for causal inference and concluded that there was a safety signal of a causal association between the A. annua extract and hepatotoxicity sufficient to be communicated and investigated further.

Clozapine and myocarditis: a case series from the New Zealand Intensive Medicines Monitoring Programme.

AIM: To examine a New Zealand case series of clozapine-associated myocarditis. METHODS: All cases of myocarditis in the Intensive Medicines Monitoring Programme's (IMMP) clozapine database were identified and reviewed. RESULTS: 25 cases of myocarditis associated with the use of clozapine have been reported to the IMMP. The majority of cases (84%) were male and the mean age was 35.5 years. Myocarditis occurred at daily clozapine doses ranging from 12.5 mg to 500 mg. Eighty percent of the cases developed within 1 month of starting the medicine, although in three cases the onset was more than a year after commencing clozapine. Of the 25 cases, 2 patients died. CONCLUSIONS: This New Zealand case series of clozapine-associated myocarditis is similar to a recent Australian case series. Clozapine-associated myocarditis most often occurs within 1-2 months of starting clozapine, but it may develop at any time while on the medicine, and can occur even at very low doses. A data-linkage study using national morbidity and mortality datasets could estimate the incidence of clozapine-associated myocarditis in New Zealand.

Sibutramine usage in New Zealand: an analysis of prescription data by the Intensive Medicines Monitoring Programme.

PURPOSE: To describe patterns of sibutramine usage in New Zealand during the first 3 years of marketing using data acquired during post-marketing safety surveillance. METHODS: Demographic and prescription data were examined from a nationwide cohort of 17 298 patients prescribed sibutramine between 1 February 2001 and 31 March 2004. Outcome measures were age and sex distribution of the cohort; period prevalence of sibutramine usage for each ethnic group; duration of treatment and reasons for cessation of therapy. Limited BMI data were also examined. RESULTS: About 0.5% of the NZ population were prescribed sibutramine in the period studied. Overwhelmingly, the highest users of sibutramine were NZ European women aged 30-59 years. Maori and Pacific Peoples were under-represented in the cohort, despite the higher prevalence of obesity among these populations. Sibutramine usage was predominantly short-term: 59% of the cohort used sibutramine for 90 days or less, half of whom used it for only 1 month. CONCLUSIONS: There has been extensive use of sibutramine in New Zealand. Sibutramine has been relatively under-utilised by Maori and Pacific ethnic groups, compared to New Zealand Europeans, despite their higher prevalence of obesity. A number of factors may have contributed to the predominantly short-term use of this medicine, including the cost of the medicine to the consumer, weight loss not meeting expectations and adverse effects of the medicine.

QT interval prolongation associated with sibutramine treatment.

AIMS: To investigate a possible association of sibutramine with QT interval prolongation. METHODS: Post-marketing surveillance using prescription event monitoring in the New Zealand Intensive Medicines Monitoring Programme (IMMP) identified a case of QT prolongation and associated cardiac arrest in a patient taking sibutramine for 25 days. This patient was further investigated, including genotyping for long QT syndrome. Other IMMP case reports suggesting arrhythmias associated with sibutramine were assessed and further reports were obtained from the World Health Organisation (WHO) adverse drug reactions database. RESULTS: The index case displayed a novel mutation in a cardiac potassium channel subunit gene, KCNQ1, which is likely to prolong cardiac membrane depolarization and increase susceptibility to long QT intervals. Assessment of further IMMP reports identified five additional patients who experienced palpitations associated with syncope or presyncopal symptoms, one of whom had a QT(c) at the upper limit of normal. Assessment of reports from the WHO database identified three reports of QT prolongation and one fatal case of torsade de pointes in a patient also taking cisapride. CONCLUSIONS: This case series suggests that sibutramine may be associated with QT prolongation and related dysrhythmias. Further studies are required, but in the meantime we would recommend that sibutramine should be avoided in patients with long QT syndrome and in patients taking other medicines that may prolong the QT interval.