Published: 23 July 2024
Committees
MINUTES OF THE 198th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
- 1.0 MATTERS OF ADMINISTRATION
- 2.0 MATTERS ARISING FROM THE NEW ZEALAND PHARMACOVIGILANCE
CENTRE
PHARMACOVIGILANCE ISSUES
- 3.1 Matters Referred to the MARC under Section 36 of the Medicines Act 1981
- 3.2 Matters Referred to the MARC by Medsafe
- 3.2.1 Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) with systemic antibiotics and systemic antifungals
- 3.2.2 Pascomer topical cream Risk Management Plan
- 3.2.3 AREXVY vaccine Risk Management Plan
- 3.2.4 Nuvaxovid and Nuvaxovid XBB.1.5 Risk Management Plan
- 3.2.5 Summary of Bexsero adverse reaction reports
- 4.0 MEDSAFE PHARMACOVIGILANCE ACTIVTIES
- 5.0 OTHER BUSINESS
MINUTES OF THE 198th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
13 June 2024
The one hundred and ninety eighth meeting of the Medicines Adverse Reactions Committee (MARC) was held on 13 June 2024 at the Mercy Conference Centre. The meeting commenced at 9.15am and closed at 1.30pm.
MARC MEMBERS PRESENT
Dr M Rademaker (Acting Chair)
Ms A Biggs-Hume
Ms L Carlyon
Dr S Leitch
Ms L McDermott
Prof L Parkin
A/Prof A Pomerleau
Dr R Savage
Dr L Te Karu
Dr H WilsonMARC SECRETARIAT PRESENT
T Coventry (Senior Advisor, Pharmacovigilance)
L Collings (Senior Advisor, Pharmacovigilance)
N Zhong (Senior Advisor, Pharmacovigilance)MEDSAFE STAFF IN ATTENDANCE
S Kenyon (Manager, Clinical Risk Management
M Storey (Team Leader, Pharmacovigilance)
Dr T Ireland (Senior Medical Advisor)
Dr T O’Flynn (Medical Advisor)
L Chan (Principal Technical Specialist, Pharmacovigilance)
J Prankerd (Senior Advisor, Pharmacovigilance)
V Cheer (Senior Advisor, Pharmacovigilance)
S Tran (Senior Advisor, Pharmacovigilance)
J Park (Advisor, Pharmacovigilance)INVITED GUESTS AND EXPERTS IN ATTENDANCE
Dr A Hynes (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Lee (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr M Wang1.0 MATTERS OF ADMINISTRATION
1.1 Welcome and Apologies
The acting Chair welcomed the attendees to the meeting. Apologies were received from Prof M Doogue and Dr C Kenedi.
Information was provided to the Committee about the recent appointment of Dr A Barrett to the Committee as a specialist clinician member and the reappointment of Ms L Carylon (lay-person) and Ms L McDermott (clinical pharmacist) to the Committee for a further term.
Dr J Lee has also been appointed as an ex officio member of the Committee as a representative of the New Zealand Pharmacovigilance Centre, should the Director be unavailable.
1.2 Minutes of the 197th MARC Meeting
The minutes of the 197th 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 Fatal Cases
Members were given a brief description of the fatal reports received in the last quarter.
The Committee discussed cases of deaths associated with colchicine. The Committee emphasised that there is a need to implement strategies to reduce the number of these deaths.
The Committee considered the following might be helpful:
- limiting the dispensing frequency to monthly
- dispensing colchicine in bottles with a child resistant closure
- changing the packaging to blister packs
- reminding healthcare professionals to counsel patients on safe use and storage of medicines
- asking the New Zealand Formulary to expand the blue box warning within the colchicine monograph.
Recommendation 1
The Committee recommended that Medsafe work with relevant healthcare groups to try to reduce harm from colchicine.
2.1.2 Serious Cases associated with vaccines
Reports of serious cases associated with vaccines were briefly outlined for the Committee.
The Committee did not consider any of the reports required further action.
2.1.3 Serious Cases associated with medicines
Reports of serious cases associated with medicines were briefly outlined for the Committee.
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 Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) with systemic antibiotics and systemic antifungals
Background
The Committee was presented with a review of information on SDRIFE with a particular focus on systemic antibiotics and systemic antifungals.
Over the last 18 months, Medsafe and the Centre for Adverse Reactions Monitoring (CARM) have received four case reports of symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). Following signal detection activities of cases reported to the New Zealand pharmacovigilance database, Medsafe reviewed a case of SDRIFE reported with the use of metoprolol and noted another case reporting terbinafine as the suspect medicine. Subsequently, an article on SDRIFE was published in the December 2023 edition of Prescriber Update.
In the published scientific literature, the most common medicines associated with SDRIFE are beta-lactam antibiotics. Based on this and the terbinafine case report, we have expanded this review to include systemic antibiotics and systemic antifungals.
The Committee was asked to advise whether there is an association between systemic antibacterials or systemic antifungals with SDRIFE. This can be considered on an individual medicine level or in medicine groups (eg, beta-lactams, non-beta-lactams, penicillins, tetracyclines, triazoles etc.)
Discussion
The Committee noted that Medsafe published an article in the December 2023 edition of Prescriber Update to raise awareness of SDRIFE among healthcare professionals. It was also noted that SDRIFE is already listed as an adverse reaction in the data sheet for amoxicillin + clavulanic acid, a common suspect medicine in reports of SDRIFE.
The Committee noted that the time to onset for SDRIFE is short, and usually occurs hours to one or two days after medicine exposure. Cases reporting a longer time to onset may suggest an alternative aetiology for the reaction.
The Committee noted that SDRIFE has been associated with many different medicines, with the highest number of reports in association with beta lactams (including amoxicillin + clavulanic acid) and antifungals (including itraconazole). However, given the large variety of reported suspect medicines, it was considered that there was no merit in signalling out associations with specific classes of systemic antibiotics or systemic antifungals.
The Committee noted that while SDRIFE has a striking visual presentation and can be uncomfortable, the condition is usually self-limiting and sequelae are rare. SDRIFE is not known to potentiate to more severe hypersensitivity reactions. It was considered that while the pathophysiology of SDRIFE is likely to differ from classical T-cell mediated allergic responses, the relatively benign clinical manifestations mean that a specific warning in medicine data sheets is not warranted.
The Committee considered that the current warnings in systemic antibiotic and systemic antifungal data sheets regarding skin reactions are adequate and no further actions are needed.
3.2.2 Pascomer topical cream Risk Management Plan
The Committee reviewed the Pascomer (rapamycin/sirolimus) Risk Management Plan (RMP) as part of a new medicine application.
The Committee was satisfied with the RMP.
3.2.3 AREXVY vaccine Risk Management Plan
The Committee reviewed the AREXVY vaccine Risk Management Plan (RMP).
The Committee also confirmed that should this vaccine become part of the immunisation program that additional safety monitoring would occur.
The Committee was satisfied with the RMP.
3.2.4 Nuvaxovid and Nuvaxovid XBB.1.5 Risk Management Plan
The Committee reviewed the updated Nuvaxovid and Nuvaxovid XBB.1.5 vaccine Risk Management Plan (RMP) version 4.2.
The Committee was satisfied with the RMP.
A publicly available RMP is available via this link.
3.2.5 Summary of Bexsero adverse reaction reports
The Committee noted the review of Bexsero (a recombinant meningococcal group B vaccine) adverse reaction reports and agreed with Medsafe’s conclusion that reports do not raise any new safety concerns.
The Committee noted Medsafe have published a Prescriber Update article with this information.
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 45, Number 2, June 2024
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.
The Committee noted the sponsor-initiated change to the contraindications for Phenergan oral formulations, to contraindicate use in children under 6 years of age due to the risk of neuropsychiatric effects. Previously, Phenergan was contraindicated in children under 2 years. The Committee was informed that the Pharmacist and Therapeutics Special Interest Group (SIG) of the Paediatric Society considered there is a continued need for appropriate use in children under 6 years based on clinical guidelines.
5.0 OTHER BUSINESS
5.1 Clozapine Consultation 2023
The Committee was given an update on the progress of the Clozapine Consultation 2023. Medsafe has incorporated feedback from the Committee and stakeholders into the report, which will be published on the Medsafe website shortly.
5.2 CARM quarterly report
The Committee briefly discussed the new Excel format of the CARM quarterly report. Members were asked to consider what content and layout would promote insights and utility for the MARC.
The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 1.30pm.
Dr M Rademaker
Acting Chair, Medicines Adverse Reactions Committee -
