Published: 20 May 2026
Committees
MINUTES OF THE 205th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
- 1.0 MATTERS OF ADMINISTRATION
- 2.0 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE 3.0 PHARMACOVIGILANCE ISSUES
- 4.0 MEDSAFE PHARMACOVIGILANCE ACTIVTIES
- 5.0 OTHER BUSINESS
MINUTES OF THE 205th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
12 March 2026
The two hundred and fifth meeting of the Medicines Adverse Reactions Committee (MARC) was held on 12 March 2026 at the Ministry of Health. The meeting commenced at 9am and closed at 2.30pm.
Secretariat note for agenda item 3.2.2: Separate to the meeting, Medsafe is consulting on the classification of vitamin B6. The classification document describes the regulation of these products across relevant legislation. The recommendations from this agenda item are on hold pending the outcome of the consultation.
MARC MEMBERS PRESENT
A/Prof M Doogue (Chair)
Prof L Parkin
Dr M Rademaker
Ms L McDermott
A/Prof A Pomerleau
Prof T Lumley
Dr H Wilson
Ms A Biggs-Hume
Ms L Carlyon
Ms L Mcculloch
MARC SECRETARIAT PRESENT
N Zhong (Senior Advisor, Pharmacovigilance)
T Coventry (Senior Advisor, Pharmacovigilance)
L Collings (Senior Advisor, Pharmacovigilance)
MEDSAFE STAFF IN ATTENDANCE
S Kenyon (Manager, Clinical Risk Management)
M Storey (Team Leader, Pharmacovigilance)
L Chan (Principal Technical Specialist, Pharmacovigilance)
V Cheer (Senior Advisor, Pharmacovigilance)
J Park (Advisor, Pharmacovigilance)
J Prankerd (Senior Advisor, Pharmacovigilance)
Dr K Van Bart (Senior Medical Advisor)
H Wilson (Advisor Science)
INVITED GUESTS AND EXPERTS IN ATTENDANCE
Dr J Lee (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr A Hynes (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Gordon (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Baker (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Sanson (Medical Assessor, Centre for Adverse Reaction Monitoring)
Dr M Copland (Clinical Lead - Medicines Management, Pharmac)
1.0 MATTERS OF ADMINISTRATION
1.1 Welcome and Apologies
The Chair welcomed the attendees to the meeting. Apologies were received from Dr C Kenedi, Dr A Barrett and Dr S Leitch.
1.2 Minutes of the 204 th MARC Meeting
The minutes of the 204 th meeting were accepted as a true and accurate record of the meeting.
1.3 Potential Competing Interests
Committee members submitted their Competing Interest Declaration forms to the Secretary. The Chair reminded the MARC members that in addition to competing interests disclosed in the declaration forms, members should declare competing interests at the commencement of discussion of any relevant agenda item.
There were no potential competing interests which were considered likely to influence the discussions or decisions of the MARC at this meeting.
2.0 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE CENTRE
2.1 Centre for Adverse Reactions Monitoring (CARM) Quarterly Reports
Members were provided a summary of serious reports received in the last quarter.
The Committee discussed cases of tioguanine and veno-occlusive disease (sinusoidal obstruction syndrome).
The Committee noted three cases of pure red cell aplasia (PRCA) with Binocrit (epoetin alfa) and a cluster of New Zealand cases recently published in Nephrology . The Committee noted that PRCA is a known adverse effect in the Binocrit data sheet with a frequency of <1/10,000 cases per patient-years. The incidence in New Zealand may be higher, however further analysis of the data is required to confirm this.
The Committee questioned whether the cases of PRCA could be due to the route of administration (eg, subcutaneous injection), changes in formulation, or random noise. They noted that Medsafe has monitored this issue through reviewing the product’s periodic safety update reports (PSURs).
The Committee recommended that CARM undertake a formal epidemiological study to estimate the incidence of PRCA in New Zealand. The Committee also advised engaging with nephrologists to determine whether similar cases are emerging elsewhere and to understand international experience.
3.0 PHARMACOVIGILANCE ISSUES
3.1 Matters Referred to the MARC under Section 36 of the Medicines Act 1981
No items.
3.2 Matters Referred to the MARC by Medsafe
3.2.1 Melatonin safety profile in adults
Background
On 10 October 2025, melatonin was reclassified, meaning that if there are approved medicines meeting the classification specifications, adults aged 18 years and over can purchase melatonin from pharmacies:
- up to 10 days of melatonin in an immediate-release presentation (≤5 mg per dose unit) for the treatment of jet lag
- up to 30 days of melatonin for the treatment of primary insomnia either as:
- o immediate-release (≤3 mg dose unit)
- o modified-release (≤2mg dose unit)
Adults aged 55 years and older can still obtain up to 13 weeks of melatonin following a pharmacist consultation.
Several pharmacy-only 2 mg modified-release melatonin products are approved for the treatment of insomnia in adults aged 55 years and over in New Zealand. Currently, there are no mandatory warning label statements required for melatonin products in New Zealand.
In June 2025, Prescrire International (Vol. 34, Issue 271) published two articles on the use of melatonin. Both articles noted that melatonin acts as an inducer of Cytochrome P450 (CYP450) enzymes, which may reduce the effectiveness of hormonal contraceptives. Additionally, several other safety concerns were highlighted, pointing out the importance of considering alternative options before initiating melatonin therapy. Advice was sought from the Committee on the safety profile of melatonin when taken by adults.
Discussion
The Committee noted the lack of high quality scientific literature on the safety of melatonin and the that available information on potential interactions suggests that melatonin is not a clinically significant precipitant of pharmacokinetic interactions.
The Committee also noted the safety profile of melatonin and the reports to the New Zealand Pharmacovigilance database involving adults. The Committee did not consider that these reports raised any new safety concerns
The Committee discussed the signals of disproportionate reporting for melatonin containing products in the WHO VigiBase. These safety signals, include serotonin syndrome and suicidality. The Committee considered these signals to be more likely attributable to confounding due to the person’s underlying sleep-related conditions and concomitant medicines rather than melatonin itself.
The Committee noted the extensive long term international use of melatonin, including at higher doses, which provides a reasonable level of confidence in its overall safety profile.
The Committee further noted that most of available safety data relate to adults, despite melatonin also being prescribed for younger age groups.
The Committee discussed the labelling of the pharmacy-only medicine which states “Do not use if you are under 55 years of age” which appeared to the Committee to be a contraindication, although it in fact only describes the limits of the indication. The Committee considered that communicating age limits in this way is not aligned with current uses endorsed in guidelines and this may be confusing for consumers and could reduce public trust in future warnings.
The Committee agreed that the safety information presented was reassuring and concluded that no regulatory action was required at this time.
3.2.2 Pyridoxine (Vitamin B6) safety review
Background
This paper reviewed suspected adverse drug reactions reported in New Zealand for pyridoxine-containing medicines and dietary supplements.
This review was prompted by regulatory action in Australia due to safety concerns, arising from cases of peripheral neuropathy associated with pyridoxine.
Discussion
The Committee noted that when used as a medicine, (ie, for a therapeutic purpose) vitamin B6 (pyridoxine) products are classified as prescription medicines under the Medicines Act 1981 if the maximum recommended daily dose exceeds 200mg. Below this level, vitamin B6 is a general sale medicine. However, vitamin B6 may also be marketed as a dietary supplement when used as a component of food or to supplement a deficient diet, provided it meets the requirements of the Dietary Supplements Regulations, and it is not for a therapeutic purpose (therapeutic claims may not be made, intended or implied). The Dietary Supplements Regulations (DSR) are administered by Medsafe but fall under the Food Act 2014 which is administered by the Ministry for Primary Industries. The Committee noted that there is no maximum daily dose for vitamin B6 specified in the DSR.
The Committee noted that peripheral neuropathy is the main safety concern associated with taking pyridoxine. According to the data sheets, this is seen with long-term administration of high doses (2–6g daily), but doses of 500mg daily have been reported to have toxic effects. The Committee noted that while dose information was not often reported in case reports, some peripheral neuropathy cases in Australia and New Zealand involved daily doses of 50mg of pyridoxine or less.
The Committee discussed the limitations of the current regulatory framework, noting that some products that are legally marketed as dietary supplements fall outside the Medicines Act, yet may contain doses of vitamin B6 that exceed those usually prescribed for therapeutic indications (members noted the parenteral form used for severe depletion contains 50mg). The Committee considered that prescribed vitamin B6 is generally used at lower doses that are unlikely to cause harm. In contrast, some dietary supplements contain substantially higher amounts (for example 100mg), creating a greater risk of harm, such as peripheral neuropathy due to cumulative excessive intake from multiple products (including energy drinks), inconsistent or unclear labelling of vitamin B6 content, and the absence of healthcare professional oversight.
The Committee commented on the limitations of imposing a maximum daily dose for dietary supplements and needing to consider potential cumulative exposure from sources (including products and food). The Committee noted different upper limits for dietary reference values in adults in the EU and NZ/Australia. The upper limit for vitamin B6 in the EU is 12mg/day, while in NZ/Australia it is 50mg/day. They noted that the Australian National Health and Medical Research Council will be reviewing the upper limit for vitamin B6 in 2026.
The Committee noted the rescheduling of vitamin B6 in Australia that will come into effect on 1 June 2027. Products containing a recommended daily dose (RDD) of more than 50mg of vitamin B6 but less than 200mg will be rescheduled as pharmacist-only medicines. Those containing more than 200mg will continue to be prescription medicines and those containing less than 50mg will continue to be available as general sales medicines. The Committee questioned the rationale for allowing high‑dose pyridoxine (up to 200 mg RDD) as pharmacist‑only supply, noting that such doses are generally reserved for acute treatment of diagnosed conditions in New Zealand.
The Committee recommended that the Medicines Classification Committee (MCC) be advised of recent international rescheduling decisions and be asked to consider changing the classification to reduce the amount of pyridoxine permitted in general sales medicines and dietary supplements.
Overall, the Committee expressed concerns that the current availability of vitamin B6 as a dietary supplement does not adequately mitigate the risk of peripheral neuropathy, given the absence of a maximum daily dose and mandatory warning statements. The Committee decided to write to the Ministry for Primary Industries to consider introducing a limit/maximum daily dose for vitamin B6 in the DSR and include mandatory warning statements on product labels about the risk of peripheral neuropathy.
Recommendation 1
The Chair of the Committee to write to the Ministry for Primary Industries to ask them to consider introducing a limit/maximum daily dose for vitamin B6 in the Dietary Supplements Regulations and include warning statements on product labels for peripheral neuropathy.
Recommendation 2
The Chair of the Committee to write to the Medicines Classification Committee to ask them to consider changing the classification to reduce the amount of pyridoxine permitted in general sales medicine and dietary supplements.
3.2.3 Menopausal hormone therapy (MHT): Risks of breast cancer, cardiovascular disease, and cognitive impairment.
Background
Menopausal hormone therapy (MHT), previously known as hormone replacement therapy (HRT), is using medicines to reduce menopausal symptoms. MHT is either regimens containing estrogen alone or estrogen in combination with a progestogen. There are different formulations available such as oral tablets, transdermal patches and gels, and vaginal preparations.
Long-term, large-scale studies on MHT were published as part of the Women’s Health Initiative (WHI) over 20 years ago. The WHI estrogen-progestogen study was prematurely stopped in 2002 because of an increased risk of breast cancer with combined estrogen-progestogen treatment vs. placebo. There was also an increased risk of cardiovascular disease compared with placebo. The WHI study of estrogen alone did not find an increased risk of breast cancer. The WHI study of estrogen alone found an increased risk of cardiovascular disease compared with placebo. Two other WHI studies that evaluated MHT for dementia prevention in women aged 65 to 79 years reported an increased risk of probable dementia compared to placebo for both estrogen alone and combined estrogen-progestogen.
Additional studies have been published on the risks of breast cancer, cardiovascular disease (CVD) and cognitive impairment with the use of MHT since the WHI studies. These have triggered reviews and regulatory actions by the European Medicines Agency (EMA) and Health Canada for breast cancer. Most recently the United States Food and Drug Administration (US FDA) has also conducted a review and requested removal of boxed warnings on CVD, breast cancer and probable dementia.
This paper discusses the recent studies published on the risks of breast cancer, cardiovascular disease, and cognitive impairment with MHT that were included in the US FDA’s review.
Discussion
The Committee noted the new analyses in the scientific literature.
The Committee discussed the risk of breast cancer associated with MHT and agreed that the updated evidence does not change the established understanding.
For cardiovascular disease, the Committee noted that current evidence does not demonstrate any substantial cardiovascular benefit from MHT, while a modest cardiovascular risk remains. They noted that thromboembolic risk is elevated early in treatment with MHT, particularly with oral forms, and that any potential atherosclerotic benefit is small and delayed, making a net benefit unlikely.
The Committee noted that there is no consistent evidence that MHT has a beneficial effect on cognitive decline, contrary to historical claims. They noted that even in very large studies (including studies with around one million participants), the ability to detect effects on dementia is limited because dementia is a relatively uncommon outcome in study populations healthy enough to participate in long‑term trials.
The Committee noted that the WHI study identified a signal of increased dementia risk with combined MHT. However, no similar signal for mild cognitive impairment was observed, which is a more common outcome and would usually provide greater statistical power to detect an effect. The Committee considered this inconsistency unexpected and noted that it may reflect the complexity and variability inherent in diagnosing cognitive impairment.
The Committee considered that MHT provides substantial benefit in reducing vasomotor symptoms for many women and MHT has additional risks and/or benefits that are relevant for some people but contributes small absolute risk differences in most cases.
4.0 MEDSAFE PHARMACOVIGILANCE ACTIVITIES
4.1 Report on Standing Agenda Items from Previous Meetings of the MARC
The Committee reviewed the list of outstanding recommendations made by the MARC at previous meetings. Background information on these issues can be found in the minutes of previous MARC meetings on the Medsafe website:
www.medsafe.govt.nz/profs/MARC/Minutes.asp
4.2 Medsafe Pharmacovigilance Activities
The Committee noted the report detailing Medsafe’s recent pharmacovigilance activities.
The Committee was provided with a safety review of Contrave (bupropion + naltrexone).
4.3 Prescriber Update Volume 47, Number 1, March 2026
The Committee noted the latest edition of Prescriber Update.
4.4 Quarterly Summary of Medsafe Safety Communications
The Committee noted the quarterly summary of Medsafe safety communications.
5.0 OTHER BUSINESS
5.1 Education/CPD session
A member of the Committee delivered a presentation on immunology/pathogenesis of ADRs from the perspective of a dermatologist.
The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 2.30pm.
A/Prof M Doogue
Chair, Medicines Adverse Reactions Committee
Date 17 April 2026
