Published: 10 October 2025

Committees

MINUTES OF THE 203rd MEDICINES ADVERSE REACTIONS COMMITTEE MEETING

MINUTES OF THE 203rd MEDICINES ADVERSE REACTIONS COMMITTEE MEETING

The two hundred and third meeting of the Medicines Adverse Reactions Committee (MARC) was held on 11 September 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
Mrs A Biggs-Hume
A/Prof A Pomerleau
Dr C Kenedi
Dr H Wilson
Ms L Carlyon
Ms L McDermott
Prof L Parkin
Dr S Leitch
Prof T Lumley

MARC SECRETARIAT PRESENT

A Strawbridge (Advisor, Pharmacovigilance)
N Zhong (Senior Advisor, Pharmacovigilance)
T Coventry (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)
S Patel (Advisor, Pharmacovigilance) 
Dr K van Bart (Senior Medical Advisor)
N Russell (Senior Advisor)
E Hunt (Assistant Advisor)

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 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 Deputy Chair welcomed the attendees to the meeting. Apologies were received from Dr M Rademaker and Ms L McCulloch. Apologies were received from A/Prof M Doogue to chair the meeting. The Deputy Chair, Dr C Kenedi, chaired this meeting.

The Deputy Chair welcomed any comments on the minutes of the 202nd meeting. It was noted that there was a continued increase in orphenadrine prescribing.

1.2 Minutes of the 202nd MARC Meeting

The minutes of the 202nd 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 Secretariat. 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 significant reports received in the last quarter.

The Committee discussed the potential role of posaconazole in a case of veno-occlusive disease with tioguanine. The Committee noted the recent addition of posaconazole as antifungal prophylaxis in the treatment protocol of acute lymphoblastic leukaemia.

The Committee discussed a case of rhabdomyolysis with rosuvastatin. The Committee commented on the role of genetic variants which can result in increased rosuvastatin exposure. The Committee considered Medsafe should review data on genetic polymorphisms relevant to the local population which could impact the safe use of rosuvastatin. The Committee also discussed switching statin medicines.

The Committee discussed a case of patent ductus arteriosus and coarctation of the aorta in a neonate born to a mother taking fluoxetine. It was noted that the effects of taking antidepressants in pregnancy was previously reviewed by the MARC at their 142nd meeting in 2010 which found a small increased risk of congenital cardiac defects associated with these medicines, including fluoxetine. At the time the MARC considered that use of these medicines in pregnancy should be an individual benefit risk decision, and the data sheets should contain information to support this decision making.

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 Possible interaction between GLP-1 receptor agonists and oral contraceptives

Background

In June 2025, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) issued a reminder for women using GLP-1 receptor agonists to use effective contraception.

The currently approved medicines in New Zealand include dulaglutide, liraglutide and semaglutide. Tirzepatide is a dual GLP-1 and GIP receptor agonist, and a new medicine application is currently under Medsafe evaluation. These medicines are indicated for type 2 diabetes mellitus and weight loss.

Oral contraceptives available in New Zealand include combined (estrogen and progestogen) and progestogen-only forms. The mechanism behind drug-drug interactions between GLP-1 receptor agonists and oral contraceptives is thought to be due delayed gastric emptying, which has the potential to impact the absorption of oral contraceptives.

Discussion

The Committee were presented with the data available. On review of the six individual studies included in the Skelley et al (2024) literature review, the Committee noted a number of limitations including the following:

  • The numbers of participants in each study with study confidence intervals that were insufficient to distinguish between GLP-1 agonists.
  • The heterogeneity between study results.
  •  The population of women included in some of the studies (eg, post-menopausal, not overweight) may not be reflective of the real-world population of women using these medicines.
  • The strict dose regimens used in the studies may not be reflective of real-world use.
  • Not all the studies included maximum doses of the GLP-1 medicine.

The Committee discussed the pharmacokinetics and noted that the reduction in area under the curve (AUC) of the oral contraceptive exposure seen in some of the studies was predominantly driven by a reduction in the peak serum concentration (Cmax). The trough concentrations were considered to be more relevant to sustain sufficient estrogen and progestogen levels for contraceptive efficacy. The differences in pharmacokinetics overall were minor, however there were some limitations to those studies. The Committee confirmed that statistically significant difference in AUC may not translate into clinical significance. However, the possible outcome of an unintended pregnancy is a serious consideration.

The Committee noted the increasing use of GLP-1 medicines globally and discussed the limited data and safety information for the use of GLP-1 medicines in pregnancy. Therefore, treatment with a GLP-1 medicine should be discontinued in women planning a pregnancy.

Overall, the Committee determined the available evidence was insufficient to warrant any changes to the data sheets of the GLP-1 medicines currently approved and available for use in New Zealand. The Committee determined no further action was required for these medicines at this time. For other GLP-1 medicines (eg, tirzepatide) that may be approved in future, relevant interaction data should be taken into account as part of Medsafe’s clinical assessment.

3.2.2 Angiotensin Converting Enzyme inhibitors and Angiotensin-II receptor blockers and the risk of intestinal angioedema

Background

In 2024 the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee reviewed the risk of intestinal angioedema with angiotensin receptor blockers (ARB).

The risk of angioedema associated with angiotensin converting enzyme (ACE) inhibitors is well established, due to a known mechanism involving the inhibition of bradykinin degradation, a peptide that promotes vasodilation.

In contrast, ARBs are not believed to influence bradykinin levels and the risk of angioedema with these medicines is lower.

Bradykinin-induced angioedema commonly affects the lips, tongue, face, pharynx and extremities. It also affects the intestine and patients with intestinal angioedema may present with non-specific gastrointestinal symptoms such as abdominal pain, nausea, and diarrhoea, making this much more difficult to diagnose.

The Committee was asked to review the risk of intestinal angioedema with ACE inhibitors and ARBs and whether regulatory action should be taken.

Discussion

The Committee reviewed the strength of the available evidence between ACE inhibitors and ARBs and intestinal angioedema, which was limited to case reports.

The Committee noted that in the cases reported in the literature, patients presented with non-specific symptoms which resulted in a misdiagnosis and exposure to unnecessary procedures. In some cases, the symptoms of intestinal angioedema resolved spontaneously whilst the person continued to take the ACE inhibitor/ARB. These patients may have recurring symptoms for many years before a diagnosis is made.

The Committee considered the frequency of intestinal angioedema and whether it could occur in the absence of other areas of angioedema but considered that the current information was insufficient to answer these questions.

The Committee noted the data sheets for ACE inhibitors and ARB contain existing information on angioedema, however considered it important to emphasise that intestinal angioedema could also occur as healthcare professionals may not be aware of this presentation.

Based on the available evidence, the Committee considered there was sufficient justification to have consistent information on intestinal angioedema in the data sheets for ACE inhibitors.

The Committee also considered there was sufficient evidence for intestinal angioedema to be considered a class effect for ARBs. Although the risk of this is presumed to be lower than ACE inhibitors, given the risk of angioedema in general is lower for ARB compared to ACE inhibitors. The Committee felt it important to reflect this lower risk in the datasheet wording.

The Committee noted Entresto contains valsartan (an ARB) with the neprilysin inhibitor sacubitril. The Committee considered that Entresto treatment also has a risk of intestinal angioedema.

Recommendation 1

The Committee recommended that Medsafe request companies to update the data sheets for both ACE inhibitor and ARB containing medicines (including Entresto) to include information on intestinal angioedema.

Recommendation 2

The Committee recommended Medsafe writes a Prescriber Update article about angioedema including intestinal angioedema with ACE inhibitors and ARBs to raise awareness of this potential side effect.

3.2.3 Risk of seizures after use of beta-2 agonists in patients with convulsive disorders

Background

Selective beta-2 agonists are a class of medicines primarily used in the treatment of respiratory conditions such as asthma and chronic obstructive pulmonary disease.

These medicines work by relaxing bronchial smooth muscles, improving airflow. The primary target of these medicines are the beta-2 receptors of the lungs. However, they also have systemic effects, and salbutamol is also indicated for preventing miscarriage.

Epilepsy affects an estimated 1-2% of the New Zealand population. Both elevated and lowered levels of noradrenaline have been associated with the risk of seizures. Given that beta-2 agonists can mimic catecholamines such as noradrenaline, a theoretical increased risk of seizures has been raised.

Discussion

The Committee discussed the limited strength of the available evidence in the scientific literature supporting a potential effect on risk of seizures in patients with convulsive disorders. The Committee noted that both asthma and epilepsy are common.

The Committee concluded that the available evidence was insufficient to support an association between beta-2 agonists and an increased risk of seizures in those with convulsive disorders. The Committee considered that no further action was required to update data sheets to include information on seizures.

The Committee noted concerns regarding the existing evidence for medicines currently containing seizure-related information. As a result, the Committee recommended that Medsafe review this data to ensure there is consistent information across the class.

Recommendation 3

The Committee recommended that Medsafe undertake a review of the evidence for beta-2 agonists with data sheets currently containing information related to seizures.

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.

4.2.1 Medicine Safety Reviews: Pembrolizumab

The Committee was presented with a summary of pembrolizumab adverse reaction reports to the New Zealand Pharmacovigilance Database.

4.3 Prescriber Update Volume 46 , Number 3 , September 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 Medicines Safety Week

Discussion

The members we given a short presentation by Medsafe on this year’s international #MedSafetyWeek and the importance of reporting.

5.2 Education Session on Functional Disorders

Discussion

A member of the Committee delivered a presentation on functional disorders.

The Deputy Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 2:00pm.

Dr Chris Kenedi
Deputy Chair, Medicines Adverse Reactions Committee
Date: 6 October 2025 

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