Published: 22 August 2025
Committees
MINUTES OF THE 202nd 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 202nd MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
12 June 2025
The two hundredth and second meeting of the Medicines Adverse Reactions Committee (MARC) was held on 12 June 2025 at the Ministry of Health. The meeting commenced at 9am and closed at 2:20pm.
A/Prof M Doogue (Chair)
Dr A Barrett
Ms A Biggs-Hume
A/Prof A Pomerleau
Dr C Kenedi
Ms L McDermott
Prof L Parkin
Dr M Rademaker
Dr S Leitch
Prof T Lumley
Ms L McCulloch
A Strawbridge (Advisor, Pharmacovigilance)
N Zhong (Senior Advisor, Pharmacovigilance)
T Coventry (Senior Advisor, Pharmacovigilance)
S Kenyon (Manager, Clinical Risk Management)
M Storey (Team Leader, Pharmacovigilance)
L Chan (Principal Technical Specialist, Pharmacovigilance)
V Cheer (Senior Advisor, Pharmacovigilance)
S Tran (Senior Advisor, Pharmacovigilance)
J Prankerd (Senior Advisor, Pharmacovigilance)
J Park (Advisor, Pharmacovigilance)
Dr K Van Bart (Senior Medical Advisor)
N Bere-Adams (Senior Advisor, Regulatory Practice and Analysis)
INVITED GUESTS AND EXPERTS IN ATTENDANCE
Dr A Hynes (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Gordon (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Mehrtens (Registrar, Health New Zealand - Waitaha Canterbury)
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 L Carlyon and Dr H Wilson.
The chair welcomed the newly appointed community pharmacist member of the Committee Ms L McCulloch.
1.2 Minutes of the 201st MARC Meeting
The minutes of the 201st 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
2.1.1 Cases
Members were given a brief description of the reports received in the last quarter.
The Committee discussed a case referred from the coroner regarding a person taking clozapine. The coroner raised concerns over the discrepancies across national guidelines on drug level monitoring. The Committee agreed to write to the coroner with its views on the case.
The Committee discussed a case involving an overdose with paracetamol. The wide public health burden relating to paracetamol overdoses was noted. The Committee considered that the case highlighted the need for prescribers to consider appropriate dispensing frequencies in vulnerable individuals. The Committee agreed their concerns should be conveyed to the National Medicines Steering Group.
The Committee commented on the use of orphenadrine in elderly patients who are more susceptible to the medicine’s anticholinergic properties. The Committee noted that this medicine should be used with caution in the elderly.
The Committee noted a case involving high doses of intranasal budesonide. The Committee commented that patients may experience adverse reactions from the cumulative effect of taking multiple corticosteroids simultaneously, for different indications, via different routes. The Committee did not consider this required further action at this time.
The Committee did not consider any of the reports required further action.
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 Panvax Risk Management Plan
Background
The New Zealand Pandemic Plan details government measures to be taken to prepare for and respond to a pandemic. It was written with influenza and coronaviruses primarily in mind. This plan includes vaccination as part of the ‘Manage It’ phase, which includes pre-pandemic and pandemic vaccines.
The Australian Risk Management Plan (RMP) for the following influenza vaccines manufactured by Seqirus was submitted to Medsafe:
- Panvax H5N8 pre-pandemic vaccine
- Panvax pandemic influenza vaccine
- H5N1 influenza vaccine
Medsafe presented the Australian version of the RMP to the Committee. The Committee was asked to advise on the list of safety concerns, the additional pharmacovigilance activities planned, and if any additional risk minimisation measures are needed.
Discussion
The Committee noted the RMP and discussed the various elements where advice was being sought. The Committee considered the list of safety concerns listed in the RMP to be sufficient in the event of a pandemic.
The Committee discussed the studies planned as additional pharmacovigilance activities. They noted these studies would be conducted in the event of a pandemic being declared by the World Health Organization (WHO). The Committee considered the planned studies appear feasible. However, the Committee considered that a subset of the studies should be conducted in New Zealand to reflect our population, or at least recruit Māori and Pacific Peoples. The studies should also include stratification by age group and other subgroup analyses that are usually conducted in these studies. The Committee also considered the company should have plans to study the effectiveness of the vaccine once it is in use.
The Committee discussed whether additional risk minimisation measures in the form of healthcare professional and patient guides should be prepared by the company. The Committee acknowledged that the detailed information to be included in a guide for vaccinators and healthcare professionals is not known at this time. However, the Committee considered that the company could prepare the structure, layout, and core information that would be included in a guide for vaccinators and healthcare professionals.
Recommendation 1
The Committee recommended that Medsafe requests the sponsor to perform, as part of the planned studies, the additional analyses discussed by the Committee.
Recommendation 2
The Committee recommended that Medsafe asks the sponsor to prepare a guide for vaccinators and healthcare professionals as an additional risk minimisation measure.
3.2.2 Arexvy and Guillain-Barré Syndrome
Background
Arexvy is indicated for active immunisation for the prevention of lower respiratory tract disease caused by respiratory syncytial virus RSV-A and RSV-B subtypes in adults 60 years of age and older, and adults 50-59 years of age who are at increased risk of RSV.
In January 2025, the United States Food and Drug Administration (US FDA) published a safety communication informing that a new warning on Guillain-Barré syndrome (GBS) has been added to the US data sheets for the respiratory syncytial virus (RSV) vaccines Abrysvo and Arexvy. Based on FDA’s evaluation of data from clinical trials, reports to the Vaccine Adverse Event Reporting System (VAERS), and a post-marketing study conducted by them, the FDA has determined that the overall body of evidence suggests increased risks of GBS with Abrysvo and Arexvy, but that available evidence is insufficient to establish a causal relationship.
The Committee was asked to advise on the strength of the evidence for GBS following RSV vaccination and whether the Arexvy New Zealand data sheet should be updated with information on GBS.
Discussion
The Committee discussed the US FDA’s post-market study for observed vs expected rates and the self-controlled case series (SCCS) analysis, and the Centre for Disease Control’s (CDC) rapid cycle analysis (RCA). The following were noted by the Committee:
- The SCCS analysis had limited ability to ascertain whether there was a difference in GBS risk among persons with and without same day concomitant vaccination with RSV vaccines.
- Feasibility of controlling for seasonality in the SCCS given the short risk window of 1-42 days.
- The finding from the RCA that there was no statistical signal found for GBS following RSV vaccination. However, the findings from the RCA were consistent with the SCCS.
Based on these analyses, the Committee could not exclude GBS as an adverse event following immunisation (AEFI) with Arexvy.
The Committee went on to discuss information on GBS that is contained in international product information (data sheets) for Arexvy. The Committee considered the information on GBS contained in the Arexvy Australian product information was balanced and reflected the available evidence. This includes that there is insufficient evidence to establish a causal relationship between GBS and Arexvy. The Committee considered the Arexvy New Zealand data sheet should align with the Australian product information.
The Committee also noted that the risk of GBS appears to be higher following RSV infection compared to vaccination.
Recommendation 3
The Committee recommended Medsafe asks the sponsor to update the Arexvy data sheet with information on Guillain Barré syndrome to align with the Australian product information.
3.2.3 Nintedanib and Renal Adverse Events
Background
Nintedanib is a tyrosine kinase inhibitor which targets vascular endothelial growth factor receptors (VEGFR), platelet-derived growth factor receptors (PDGFR) and fibroblast growth factor receptors (FGFR). It is indicated for the treatment of idiopathic pulmonary fibrosis, certain interstitial lung diseases, and non-small cell lung cancer (in combination with docetaxel).
In 2018, the European Pharmacovigilance Risk Assessment Committee (PRAC) reviewed the risk of renal failure with nintedanib. On the basis of plausible mechanisms, review of reported cases, and the serious nature of these adverse reactions, the PRAC required new warnings in section 4.4 (special warnings and precautions) and 4.8 (undesirable effects) in the product information regarding renal failure. The sponsor declined to make these updates to the New Zealand data sheet. In 2021, the PRAC reviewed the risk of thrombotic microangiopathy and required additional warnings in the product information.
The Committee was asked to consider whether the nintedanib data sheet should be updated with respect to renal adverse events.
Discussion
The Committee agreed that nintedanib treatment may plausibly lead to renal failure both through dehydration/hypovolaemia and through effects on the kidney due to VEGFR inhibition. The Committee considered that the data sheet should be updated to state that nintedanib can cause renal failure, in some cases with fatal outcome, and that patients should be monitored appropriately during treatment.
The Committee noted that there appears to be an association between medicines that inhibit VEGF and VEGFR and thrombotic microangiopathy. It was considered that the additional warnings in the European product information regarding proteinuria and thrombotic microangiopathy were appropriate.
It was recommended that the nintedanib data sheet should be updated to include the same warnings on renal failure, proteinuria and thrombotic microangiopathy that are included in the European product information.
Recommendation 4
The Committee recommended that Medsafe request the company to update the nintedanib data sheet to align with international product information with respect to the risks of renal failure, proteinuria and thrombotic microangiopathy.
3.2.4 Macrolides and cardiovascular death
Background
Macrolides are a class of antibiotics which includes erythromycin, roxithromycin, azithromycin and clarithromycin. Macrolide antibiotics work by inhibiting the protein synthesis of bacteria. They are indicated for use in a wide range of bacterial infections.
In 2021, the US FDA requested updates to the product information to include warnings on cardiovascular death with macrolide antibiotics. This was prompted following a review of information from epidemiological studies.
Discussion
The Committee reviewed a range of evidence which examined the risk of cardiovascular death with macrolides. The Committee discussed the studies and noted the mixed data on macrolides and the risk of cardiovascular death.
The duration of study length greatly varied across the studies, making comparison challenging. The Committee commented on the potential for a synergistic interaction between macrolides and other QT prolongating medicines leading to cardiovascular events.
The Committee noted that cardiovascular death is a broad outcome and that more specific terms are needed to categorise this risk. The Committee discussed the well-recognised mechanism behind QT prolongation associated with clarithromycin and erythromycin due to the high affinity to inhibit the HERG potassium ion channel.
The Committee considered that the available evidence supports a class effect for macrolides and cardiovascular death. The Committee considered this was most likely due to arrhythmia, with the strongest evidence for clarithromycin and erythromycin. The Committee commented that the likely mechanism for cardiovascular death is from arrhythmia, however they noted that some studies included events such as myocardial infarction and heart failure as a composite of cardiovascular death. The Committee noted there was limited evidence for roxithromycin, however a class effect cannot be excluded. The Committee recommended updating the data sheets to ensure the risk factors for QT prolongation are consistent and include a class warning for macrolides and cardiovascular death. The Committee discussed the existing wording in the data sheets for macrolides and considered that the wording in the current Klacid (clarithromycin) data sheet reflected their assessment and should be added to the other macrolide data sheets:
“Epidemiological studies investigating the risk of adverse cardiovascular outcomes with macrolides have shown variable results. Some observational studies have identified a rare short-term risk of arrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including [macrolide]. Consideration of these findings should be balanced with treatment benefits when prescribing [macrolide].”
The Committee also noted the place of macrolides in current New Zealand practice and that the current prescribing resources contain information about considerations for these medicines and cardiovascular risks. The Committee noted that the risk of cardiovascular risks did not warrant additional communication.
Recommendation 5
The Committee recommended that Medsafe request companies to update macrolide data sheets to be consistent with the information in the clarithromycin data sheet.
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.
4.3 Prescriber Update Volume 36, Number 2, June 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 Drug-Drug and Drug-Food Interactions
Discussion
The chair provided an educational training session on drug-drug and drug-food interactions, highlighting the clinical significance of these interactions.
The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 2:20pm
A/Prof M Doogue
Chair, Medicines Adverse Reactions Committee
Date 15 August 2025
