Published: 24 February 2025
Committees
MINUTES OF THE 200th 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 200th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
5 December 2024
The two-hundredth meeting of the Medicines Adverse Reactions Committee (MARC) was held on 5 December 2024 at the Ministry of Health, Wellington. The meeting commenced at 9am and closed at 3pm.
A/Prof M Doogue (Chair)
Dr C Kenedi
Dr M Rademaker
Dr L Te Karu
Prof L Parkin
Dr A Barrett
Ms L Carlyon
Ms A Biggs-Hume
A/Prof A Pomerleau
Dr H Wilson
Prof T Lumley
N Zhong (Senior Advisor, Pharmacovigilance)
T Coventry (Senior Advisor, Pharmacovigilance)
L Collings (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 Park (Advisor, Pharmacovigilance)
Dr K Van Bart (Medical Advisor)
INVITED GUESTS AND EXPERTS IN ATTENDANCE
Dr J Lee (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Gordon (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Sanson (Medical Assessor, Centre for Adverse Reactions Monitoring)
Prof M Tatley (Medical Assessor, Centre for Adverse Reactions Monitoring)
1.0 MATTERS OF ADMINISTRATION
1.1 Welcome and Apologies
The Chair welcomed the attendees to the meeting. Apologies were received from L McDermott and S Leitch.
The Chair welcomed the new epidemiologist member, Professor T Lumley.
The Chair announced that Professor L Parkin had been appointed as the Director of the New Zealand Pharmacovigilance Centre ex officio position on the Committee.
The Chair noted it was the end of Dr L Te Karu’s term on the Committee and thanked her for her significant contributions.
1.2 Minutes of the 199th MARC Meeting
The Committee reviewed the minutes regarding item 3.2.2: Use of benzodiazepines for non-epilepsy indications during pregnancy and the risk of miscarriage.
The Committee discussed whether there was an inconsistency between the discussion and recommendation for this item in relation to zopiclone.
It was highlighted that while zopiclone is structurally different to benzodiazepines, it has similar pharmacological properties and could be considered to have a similar risk. However, no information on the risk of miscarriage with zopiclone was presented at the meeting for the Committee to review and confirm if the risk is similar to benzodiazepines.
The complexity of how medicines are grouped within a medicine class was also discussed.
The Committee decided that the minutes should be updated to remove zopiclone from the recommendation and provide the reason for this, to better reflect the discussion.
The remainder of the minutes of the 199th 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 further discussed two cases related to colchicine. It was commented how colchicine has a narrow therapeutic index, especially in older people.
The Committee noted that the data sheet recommends that patients who experience gastrointestinal side effects should discontinue treatment. The Committee agreed that patients taking colchicine should be aware of the symptoms of colchicine toxicity.
The Committee also highlighted that colchicine could interact with other medicines which may increase colchicine levels.
Recommendation 1
The Committee recommended a Prescriber Update article is published about the safety of colchicine, including symptoms of toxicity and information on interactions.
The Committee noted a report of encephalitis after vaccination and queried whether this condition was common in the age group reported.
The Committee commented on a report relating to a medication error and noted the risks of sound alike medicines.
The Committee noted a report of a catatonic reaction. It was highlighted that the contributions of the medicines involved in this case was unclear.
A case reported a skin reaction with terbinafine and felodipine. The Committee noted how terbinafine can cause acute generalized exanthematous pustulosis, which could have had a contributory role.
The Committee noted a report of intussusception and rotavirus vaccine. It was highlighted that this vaccine is a live vaccine, and this is a known side effect.
The Committee commented on reports of pneumococcal infection following vaccination with pneumococcal vaccines. It was suggested that relevant immunisation external groups be informed about these reports.
The Committee noted several brand switch reports. The Committee discussed when such reports may indicate a signal for a product.
The Committee did not consider any of these reports highlighted a need 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
[A/Prof M Doogue joined the meeting at this time]
3.2.1 Direct-acting oral anticoagulants and the possible risk of cutaneous small vessel vasculitis
Background
In 2019, Medsafe published a Monitoring Communication highlighting a possible risk of vasculitis with the use of dabigatran. During the monitoring period no further reports were received and no further action was taken. Since that time, additional reports of vasculitis have been reported, prompting further review.
The report presented to the Committee reviewed of the risk of cutaneous vasculitis with direct-acting oral anticoagulants (DOACs).
Discussion
The Committee highlighted that cutaneous vasculitis occurs mostly in children and in older people. It was noted that the cause of this condition can be difficult to identify and may be due to medicines or an autoimmune reaction. Medicine-induced vasculitis may be due to a type III or type IV hypersensitivity reaction. When assessing cutaneous vasculitis in clinical practice, recently started medicines may be considered as a possible cause and stopped. Sometimes patients are rechallenged after they have recovered. It was noted that improvement after stopping a medicine does not necessarily indicate that the medicine was the cause, due to the episodic course of cutaneous vasculitis.
The Committee noted that cutaneous vasculitis associated with anticoagulants may present with a prominence of purpura. It was discussed that host factors such as poor circulation and obesity may have a role in the variability in cutaneous vasculitis presentation.
The Committee commented on the study by Ajao et al (2022) which used the United States Food and Drug Administration Sentinel System to compare the risk of cutaneous small vessel vasculitis after exposure to DOACs and warfarin. It was considered that the study had sufficient statistical power to exclude large differences in risk.
The Committee highlighted that since the introduction of DOACs, the use in New Zealand has increased over time.
The Committee noted that cutaneous vasculitis is a listed adverse drug reaction in the European and United Kingdom prescribing information for apixaban.
On review of the data presented to the Committee, the Committee concluded that there is a risk of cutaneous vasculitis with anticoagulants
The Committee agreed that the data sheets for anticoagulants should be updated to list cutaneous vasculitis as a class post-market adverse reaction in section 4.8.
Recommendation 2
The Committee recommended that the data sheets for rivaroxaban, apixaban and dabigatran be updated to include cutaneous vasculitis as an adverse reaction.
3.2.2 JYNNEOS Risk Management Plan
Background
JYNNEOS was provisionally approved by Medsafe on 11 September 2024 for the prevention of mpox in at risk adults. Provisional approval is valid for 6 months (expires 11 March 2025).
The EU risk management plan (RMP) was submitted to Medsafe to support its provisional consent application.
The EU RMP is being presented to the committee to consider if there are any regulatory actions needed in light of the current NZ safety data.
The Committee was asked if the data sheet requires updating to include advice to healthcare professionals on signs and symptoms of myo-/pericarditis and tests/examinations that should be performed.
Discussion
The Jynneos EU RMP was briefly outlined to the Committee. The Committee noted that myo-/pericarditis is an important potential risk in the RMP. However, there is no information on myo-/pericarditis in the data sheet.
The Committee commented on the exposure to vaccination versus the number of cases of myo-/pericarditis that have been reported to the New Zealand Pharmacovigilance Database
The Committee highlighted that there is increased awareness of immunogenic adverse effects of vaccines, particularly cardiac, following population vaccination with vaccines for COVID-19, in particular Comirnaty in New Zealand.
The Committee discussed that it would be helpful for healthcare professionals to know about the potential risk of myo-/pericarditis with Jynneos, and to investigate patients further if they present with possible symptoms. The Committee noted more information for healthcare professionals can be incorporated in an update to the currently published monitoring communication on this topic.
The Committee agreed that the Jynneos data sheet be updated with a warning in section 4.4.
Recommendation 3
The Committee recommended that the JYNNOES data sheet is updated with a warning about the risk of myocarditis and pericarditis.
Recommendation 4
The Committee recommended that Medsafe update the currently published monitoring communication on reports of pericarditis following mpox vaccination, including more information for healthcare professionals.
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.
There were no standing agenda items for which the MARC made further recommendations.
4.2 Medsafe Pharmacovigilance Activities
The Committee noted the report detailing Medsafe’s recent pharmacovigilance activities.
4.2.1 Medicine Safety Reviews: Shingrix
The Committee was presented with a summary of Shingrix adverse reaction reports to the New Zealand Pharmacovigilance Database.
4.3 Prescriber Update Volume 46, Number 4, December 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 commented about the communication pathways used by Medsafe for dissemination of safety communications and possible options, including social media channels.
5.0 OTHER BUSINESS
5.1 Update from policy team
The Committee were provided an update from the policy team at the Ministry of Health relating to legislation.
[Dr L Te Karu left the meeting]
5.2 Celebration of 200th MARC meeting
C James (Group Manager of Medsafe) welcomed current and past members who had joined online for a presentation to celebrate the 200th meeting of the MARC.
A number of past and present MARC members took this time to reflect on their time on the Committee.
[Dr H Wilson and Dr M Rademaker left the meeting]
5.3 Review of clozapine safety and monitoring requirements: clozapine-induced neutropenia and agranulocytosis
The Committee further commented about clozapine blood monitoring following on from the report presented on this topic at the previous meeting.
The Committee felt that clozapine is underused in New Zealand, and that part of this is related to the current blood monitoring requirements which the Committee felt were not optimal for everyone.
The Committee agreed that changes to blood monitoring requirements for clozapine are needed.
The Committee asked Medsafe to further review what possible changes could be implemented and to update the Committee at a future meeting.
The Committee discussed that a guideline-based approach to clozapine monitoring as a whole was important for clinical management of this medicine.
[Dr L Parkin and Dr A Barrett left the meeting during this item]
Recommendation
The Committee recommended changes to the blood monitoring with clozapine is needed. The Committee recommended that Medsafe further review possible options for changes relating to blood monitoring and seek additional expert advice and update the Committee at a future meeting.
5.4 Other discussions
The Committee discussed for future meetings for members to share their expertise with each other with short presentations on relevant topics at the end of meetings.
The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 3pm.
Associate Professor M Doogue
Chair, Medicines Adverse Reactions Committee
Date: 29 January 2025
