Published: 12 January 2025
Committees
MINUTES OF THE 204th 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 204th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
4 December 2025
The two hundred and fourth meeting of the Medicines Adverse Reactions Committee (MARC) was held on 4 December 2025 at the Ministry of Health. The meeting commenced at 9am and closed at 2pm.
MARC MEMBERS PRESENT
A/Prof M Doogue (Chair)
Dr A Barrett
Ms A Biggs-Hume
A/Prof A Pomerleau
Dr C Kenedi
Dr H Wilson
Ms L Carlyon
Ms L McCulloch
Ms L McDermott
Prof L Parkin
Prof T Lumley
MARC SECRETARIAT PRESENT
T Coventry (Senior Advisor, Pharmacovigilance)
N Zhong (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)
S Patel (Advisor, Pharmacovigilance)
Dr K Van Bart (Senior Medical Advisor)
INVITED GUESTS AND EXPERTS IN ATTENDANCE
Dr J Lee (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 S Leitch and M Rademaker.
1.2 Minutes of the 203rd MARC Meeting
The minutes of the 203rd 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 did not consider any of the reports required further action.
The Committee discussed the safety of isotretinoin. It was noted that the Committee previously reviewed the safety of isotretinoin at the September 2023 meeting and the current data sheet is up to date.
The Committee discussed a report describing multiple adverse events, including hepatoxicity and neutropenia, with multiple overlapping antibiotic courses in an eight-year-old patient. The Committee commented that the doses given were the maximum doses for an 18-year-old patient, and that this was a possible contributing factor to the events.
The Committee discussed a case of vomiting, altered state of consciousness and decreased oxygen saturation in a person who had taken ivermectin. The Committee discussed that neurological adverse effects are often seen in ivermectin overdose. However, in this case the dose was appropriate for the patient's weight.
The Committee discussed a case of adrenal crisis in a patient with Addison's disease who was given zoledronic acid. The Committee discussed whether the zoledronic acid data sheet includes information on the risk of adrenal crisis in patients with adrenal insufficiency. However, given that Addison's disease is rare and the adverse effects of a zoledronic acid infusion include influenza-like symptoms, the adjusted steroid dosing for adrenal insufficiency during periods of feeling unwell should be followed.
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 Cystic fibrosis transmembrane conductance regulator (CFTR) modulators and the risk of psychiatric disorders
Background
There have been spontaneous reports of psychiatric disorders with CFTR modulators in New Zealand and internationally. This signal has been reviewed by international medicines regulators, with the EMA requiring warnings on the risk of depression, including suicidal thoughts, unusual changes in behaviour, anxiety, insomnia and behavioural changes in children, in the product information for CFTR modulators. The MHRA has also published a safety communication stating that the product information for Kaftrio (Trikafta) will be updated to include a warning on risk of psychological side effects, including anxiety or low mood, sleep disturbance, poor concentration, forgetfulness and behavioural changes in children.
The Committee was asked to advise on the strength of the available evidence describing a possible relationship between psychiatric disorders and CFTR modulators, and whether the product data sheets should be revised to include warnings on psychiatric disorders.
Discussion
The Committee discussed the international regulatory action and literature concerning psychiatric adverse events reported with CFTR modulator treatment. It was noted that in clinical trials, rates of psychiatric adverse events were similar between the treatment groups and placebo groups, and that post-market reporting rate was within the expected background rate.
It was noted that observational studies have found no overall worsening of depression or anxiety symptom scores during treatment compared to baseline, with the majority of patients having stable or improved scores. There was a small number of people who experienced worsening of depression and anxiety symptom scores during treatment, in general 10-20%. In some cases, these people were noted to have pre-existing mental health problems or concurrent psychosocial stressors.
The Committee discussed anecdotal clinical experience of distinct changes in behaviour in patients, notably in children, temporally associated with initiation or changes in treatment. Concerns were raised about possible underreporting due to concerns around compromising access to highly effective treatment.
The Committee acknowledged that it is difficult to separate possible effects of CFTR modulators from indirect psychological impacts of life changes following treatment, pre-existing mental health problems and other life stressors. The Committee agreed that while a causal relationship between CFTR modulators and psychiatric adverse events has not been established, healthcare professionals and patients should be aware that psychiatric adverse events have been reported. The Committee commented that clinicians treating cystic fibrosis are highly specialised and already accustomed to monitoring mental health, which mitigates the risk of inappropriate discontinuation of treatment.
The Committee concluded that section 4.4 of the data sheets for CFTR modulators should be updated to state that psychiatric effects such as anxiety, low mood, sleep disturbance, poor concentration, and forgetfulness have been reported, and that patients should be monitored for these symptoms.
Recommendation 1
The Committee recommended that the data sheets for CFTR modulators should be updated with information on reported psychiatric events.
3.2.2 Antipsychotic induced hyperprolactinemia and the risk of breast cancer
Background
In animal studies, administering antipsychotics that elevate prolactin has resulted in an increase in mammary neoplasia. There have been concerns that the effect of antipsychotics that elevate prolactin can theoretically increase the risk of breast cancer in humans.
The Committee was asked to advise on the strength of the evidence for an association between the use of antipsychotics and the risk of breast cancer and whether any regulatory action is required.
Discussion
The Committee noted that some systematic reviews and meta-analyses found modest associations between antipsychotic treatment and breast cancer. The risk was associated with longer duration of antipsychotic use and antipsychotics that have greater effects on prolactin, but the effect is small. Possible confounding by severity of the underlying condition was noted. It was also noted that breast cancer diagnosis is sensitive to screening, which may be reduced in people with psychiatric conditions.
The studies were considered to be of varying quality. A Finnish study by Taipale et al (2021)in women with schizophrenia found a small increase in risk with long-term exposure, but the authors were unable to account for all possible confounding factors. Inconsistent findings, such as the increased risk in people with bipolar disorder but not schizophrenia in a study by Chu et al (2023), raised concerns of bias.
It was noted that most data sheets for antipsychotics already include appropriate information on the relationship between elevated prolactin levels and breast cancer from animal studies. Some inconsistencies between brands were noted. The Committee agreed that adding speculative warnings may detract from important safety information on established safety concerns, and may increase the risk of people not receiving treatment they need.
The Committee agreed that there is biological plausibility for an association between increased prolactin due to antipsychotics and breast cancer. However, the epidemiological evidence was considered unconvincing, with small effect sizes subject to possible bias. The Committee concluded that no regulatory action is needed at this time.
3.2.3 Calcium channel blockers and drug reaction with eosinophilia and systemic symptoms (DRESS)
Background
In August 2024, Medsafe received a report of a 67-year-old patient who experienced drug reaction with eosinophilia and systemic symptoms (DRESS) following treatment with atorvastatin, diltiazem and amlodipine. None of the data sheets for these three medicines list DRESS but all three are included in a literature article by Stirton et al (2022). Although atorvastatin was reported as a suspect medicine, the patient had been taking it for a number of years so the other medicines were considered more likely to have been responsible. This is the only New Zealand report received where DRESS is coded with a calcium channel blocker as the suspect medicine.
The Committee was asked to advise on the strength of the evidence for an association between DRESS and calcium channel blockers, individually or as a class, and whether any regulatory action is required.
Discussion
The Committee noted that literature evidence was limited to case reports, often with concomitant medicines. It was noted that DRESS is a subtype of severe cutaneous adverse reactions (SCARs) and other phenotypes should also be considered. It can be difficult to establish a link between DRESS and a causative medicine in individual cases, as a single dose of medicine can trigger DRESS with a time-to-onset of two to eight weeks. The evidence from disproportionality analysis was also considered weak.
The Committee noted that DRESS is not a listed adverse reaction in international product information for calcium channel blockers, though other SCARs are mentioned in some. International consensus guidance from the Council for International Organizations of Medical Sciences (CIOMS) states that calcium channel blockers are associated with acute generalised exanthematous pustulosis (AGEP) but are not listed as established causative medicines for DRESS. The Committee noted that allergic reactions, including rash, are included in current data sheets.
The Committee considered the evidence for an association between calcium channel blockers and DRESS to be limited, and concluded that no regulatory action is needed.
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
There were no standing agenda items for which the MARC made recommendations.
4.2 Medsafe Pharmacovigilance Activities
The Committee noted the report detailing Medsafe's recent pharmacovigilance activities. The Committee was presented with a summary of New Zealand adverse reaction reports for pregabalin. The Committee noted that usage of pregabalin is increasing in New Zealand, while the usage of gabapentin remains steady. The Committee also noted misuse and abuse of pregabalin is a significant problem internationally, and that Medsafe should be alert to new evidence on this risk in New Zealand.
4.3 Prescriber Update Volume 46, Number 4, December 2025
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 session on study designs for medicine adverse reactions.
A member of the Committee delivered a presentation on study designs for investigating suspected adverse reactions to medicines.
The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 2 pm.
Associate Professor Matthew Doogue
Chair, Medicines Adverse Reactions Committee
Date: 19 December 2025
