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.

Case Series Analysis of New Zealand Reports of Rapid Intense Potentiation of Warfarin by Roxithromycin.

INTRODUCTION: We undertook an analysis of all the reports to the New Zealand Centre for Adverse Reactions Monitoring of a roxithromycin/warfarin interaction after two recent reports described intense rapid warfarin potentiation. The interaction was first published in 1995. Cytochrome P450 3A4 inhibition has been the proposed mechanism but has limited biologic plausibility. There are suggestions that the clinical significance of the interaction may be increased by severe illness, polypharmacy, renal dysfunction, older age and increased warfarin sensitivity. METHODS: To investigate the potentiating effect of warfarin on roxithromycin in this New Zealand case series, the reports were reviewed to identify patients at risk, compare the reporting pattern with published Australian data and evaluate the appropriateness of current prescribing advice. RESULTS: Thirty patient reports were identified. The age range was 23-88 years, mean 66.8, median 73.0 (standard deviation 17.7) and the international normalised ratios after roxithromycin commencement ranged from 3.6 to 16.7 (mean 7.6, median 7.6, standard deviation 3.6). For eight patients with measurements on day 3, international normalised ratios were 4.3-16.7 (mean 10.4, median 8.8, standard deviation 4.4). Four patients had serious haemorrhage. Indications for roxithromycin were a range of respiratory tract infections. Anticoagulation was stable for most patients prior to acute infection. Serious infection occurred in 54.5% (12 of 22 patients with information). Polypharmacy (five or more medicines daily) was used by 36.7% of patients long term, increasing acutely to 83.3%, including additional potentially interacting medicines. Warfarin daily dose (1.5-13.0 mg, mean 4.4, median 4.0, standard deviation 2.2) was moderate to low. Pre-roxithromycin international normalised ratio values ranged from 1.4 to 3.7, mean and median 2.5, standard deviation 0.5. A high proportion of interactions were observed between warfarin and roxithromycin compared with other macrolides and compared with cytochrome P450 3A4-related macrolide interactions. The pattern was similar to published Australian data. CONCLUSION: In this case series, the high prevalence of acute polypharmacy, including potentially interacting medicines, and serious infection suggests that they may have contributed to warfarin potentiation and increased the clinical significance of a roxithromycin/warfarin interaction.

A new web-based Medication Error Reporting Programme (MERP) to supplement pharmacovigilance in New Zealand--findings from a pilot study in primary care.

AIMS: To determine if primary care clinicians would report medication errors using a new web-based system, and to obtain data illustrating the potential of the information collected to improve medication safety. METHOD: The New Zealand Pharmacovigilance Centre led the development of the Medication Error Reporting Programme (MERP) which was then piloted over an 8- month period involving 38 general practice and 28 community pharmacy staff. The Pharmacy Defence Association also contributed dispensing error claims. An analysis of the characteristics of errors was undertaken. RESULTS: A total of 376 reports were submitted; 55 (15%) reported patient harm, 1 of which required lifesaving intervention. The therapeutic groups most commonly implicated were medicines for managing 'nervous' and 'cardiovascular' systems. Wrong dose (25%) and wrong medicine (22%) were the most common error types, occurring predominantly with the prescribing and dispensing of medications. The most frequent contributing factors to errors in general practice were problems in the process of prescribing whereas in community pharmacy they related to product name and packaging factors. Time pressures, workload and interruptions were commonly cited for both settings. CONCLUSION: Primary care clinicians who volunteered for the pilot were willing and able to use the MERP system to report medication errors. The standardised data obtained through MERP enables rapid analysis and has the potential to inform initiatives for improving patient safety.

Vaccines against meningococcal serogroup B disease containing outer membrane vesicles (OMV): lessons from past programs and implications for the future.

The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004-2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains.

Detecting medication errors in the New Zealand pharmacovigilance database: a retrospective analysis.

BACKGROUND: Despite the traditional focus being adverse drug reactions (ADRs), pharmacovigilance centres have recently been identified as a potentially rich and important source of medication error data. OBJECTIVE: To identify medication errors in the New Zealand Pharmacovigilance database (Centre for Adverse Reactions Monitoring [CARM]), and to describe the frequency and characteristics of these events. METHODS: A retrospective analysis of the CARM pharmacovigilance database operated by the New Zealand Pharmacovigilance Centre was undertaken for the year 1 January-31 December 2007. All reports, excluding those relating to vaccines, clinical trials and pharmaceutical company reports, underwent a preventability assessment using predetermined criteria. Those events deemed preventable were subsequently classified to identify the degree of patient harm, type of error, stage of medication use process where the error occurred and origin of the error. RESULTS: A total of 1412 reports met the inclusion criteria and were reviewed, of which 4.3% (61/1412) were deemed preventable. Not all errors resulted in patient harm: 29.5% (18/61) were 'no harm' errors but 65.5% (40/61) of errors were deemed to have been associated with some degree of patient harm (preventable adverse drug events [ADEs]). For 5.0% (3/61) of events, the degree of patient harm was unable to be determined as the patient outcome was unknown. The majority of preventable ADEs (62.5% [25/40]) occurred in adults aged 65 years and older. The medication classes most involved in preventable ADEs were antibacterials for systemic use and anti-inflammatory agents, with gastrointestinal and respiratory system disorders the most common adverse events reported. For both preventable ADEs and 'no harm' events, most errors were incorrect dose and drug therapy monitoring problems consisting of failures in detection of significant drug interactions, past allergies or lack of necessary clinical monitoring. Preventable events were mostly related to the prescribing and administration stages of the medication use process, with the majority of errors 82.0% (50/61) deemed to have originated in the community setting. CONCLUSIONS: The CARM pharmacovigilance database includes medication errors, many of which were found to originate in the community setting and reported as ADRs. Error-prone situations were able to be identified, providing greater opportunity to improve patient safety. However, to enhance detection of medication errors by pharmacovigilance centres, reports should be prospectively reviewed for preventability and the reporting form revised to facilitate capture of important information that will provide meaningful insight into the nature of the underlying systems defects that caused the error.

Pharmacovigilance in New Zealand: the role of the New Zealand Pharmacovigilance Centre in facilitating safer medicines use.

The New Zealand Pharmacovigilance Centre (NZPhvC) is the national centre responsible for monitoring adverse reactions to therapeutic products in New Zealand(NZ). The NZPhvC operates three pharmacovigilance programmes and this article explains how each of these programmes operate, focuses on their strengths and limitations, and looks to the future for medicines safety monitoring in NZ.

The Intensive Vaccines Monitoring Programme (IVMP): an electronic system to monitor vaccine safety in New Zealand.

New Zealand introduced a tailor-made vaccine (MeNZB) for epidemic control of Group B meningococcal disease. The Intensives Vaccine Monitoring Programme (IVMP), which prospectively collected data electronically on a cohort of children receiving vaccinations in sentinel practices across NZ, was developed as part of a national multi-faceted safety strategy. The main aim of the IVMP was to identify the presence of unexpected adverse events occurring with MeNZB vaccination. We describe the methodology and success factors plus consider the limitations encountered in this system which shows potential as a means for post-marketing vaccine and medicine surveillance in the future.