Published: 13 July 2026
Committees
MINUTES OF THE 206th 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 206th MEDICINES ADVERSE REACTIONS COMMITTEE MEETING
11 June 2026
The two hundred and sixth meeting of the Medicines Adverse Reactions Committee (MARC) was held on 11 June 2026 at the Ministry of Health. The meeting commenced at 9am and closed at 1pm.
MARC MEMBERS PRESENT
Dr C Kenedi (Chair)
Dr A Barrett
Ms A Biggs-Hume
Ms L Carlyon
Dr Sharon Leitch
Prof T Lumley
Ms L McCulloch
Ms L McDermott
Prof L Parkin
A/Prof A Pomerleau
Dr M Rademaker
Dr H Wilson
MARC SECRETARIAT PRESENT
N Zhong (Senior Advisor, Pharmacovigilance)
T Coventry (Senior Advisor, Pharmacovigilance)
L Collings (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)
J Prankerd (Senior Advisor, Pharmacovigilance)
Dr K Van Bart (Senior Medical Advisor)
H Wilson (Advisor Science)
INVITED GUESTS AND EXPERTS IN ATTENDANCE
Dr J Lee (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr A Hynes (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Gordon (Medical Assessor, Centre for Adverse Reactions Monitoring)
Dr J Baker (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 Prof M Doogue.
1.2 Minutes of the 205th MARC Meeting
The minutes of the 205th 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 with a summary of serious reports received in the last quarter.
The Committee was given an update on cases of pure red cell aplasia with epoetin, including that CARM have initiated a study to estimate the incidence of the condition in people with chronic kidney disease initiated on epoetin therapy.
The Committee noted an adverse reaction report associated with a medicine that was prescribed for a patient by a telehealth clinic. The Committee expressed concern around an increasing pattern of patients accessing prescription medicines from telehealth services, sometimes without adequate assessment of appropriateness or safety. There was also concern around the safety risks posed by unlawful internet advertising of services and products based overseas. The Committee emphasised the importance of healthcare professionals asking patients specifically about medicines obtained from online sources including telehealth clinics.
The Committee noted adverse reaction reports in older people taking clozapine. The committee noted that clozapine is being increasingly used off-label to manage psychosis associated with neurological conditions in the elderly.
The Committee was asked for feedback on the format and type of information presented in the quarterly report. The Committee considered that the information currently presented is useful for identifying trends and signals.
Recommendation 1
The Committee recommended that Medsafe remind healthcare professionals to ask patients specifically about use of medicines obtained from online sources including telehealth clinics.
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 Safety of colecalciferol 50,000 IU capsules in pregnancy
Background
In 2024 Medsafe reviewed the Vit.D3 (colecalciferol 50,000 IU capsule) data sheet. During this review the safety sections of the data sheet were compared to equivalent medicines approved by recognised regulatory authorities. As a result, in October 2024 the data sheet was updated to list a contraindication to use in pregnancy and state that a lower strength formulation should be used. Medsafe has since received correspondence from New Zealand Formulary requesting a review of this contraindication, as they had received complaints from physicians.
Vit.D3 (colecalciferol 50,000 IU capsule) is the only approved and available colecalciferol (monotherapy) medicine. Pharmac also funds a liquid drop formulation (colecalciferol 400 IU/drop) which is a dietary supplement rather than an approved medicine.
The Committee was asked to advise whether any changes to the colecalciferol data sheet information on use in pregnancy are recommended based on the available clinical data.
Discussion
The Committee commented that vitamin D deficiency is relatively common in certain regions and populations during winter months, and that vitamin D supplementation is widely prescribed in pregnancy. It was noted that dispensing of funded vitamin D products during pregnancy has increased rapidly in the past five years but information on the formulation dispensed is not available.
The Committee noted that a recent Cochrane review found limited and uncertain evidence on whether vitamin D supplementation improves birth outcomes. It was noted that there is very limited clinical evidence to support the safety and efficacy of a colecalciferol dose of 50,000 IU monthly in pregnancy. The Committee noted the wide range of dosing regimens used in the studies, and that there were no studies that used a dose of 50,000 IU monthly in pregnancy. Many studies had limited reporting of safety data and studies that reported on birth outcomes were not powered to detect differences in rates of infrequent adverse outcomes.
It was noted that pharmacokinetic data demonstrated considerable interindividual variability in response to high-dose vitamin D regimens. It was also highlighted that intermittent high-dose regimens may produce higher short-term peaks in the active vitamin D metabolite compared with daily dosing, although the clinical significance of this remains uncertain.
It was noted that all overseas product information for similar products either contraindicates use in pregnancy, or states that use is not recommended and that a lower-dose formulation should be used. Expert position statements and clinical guidance generally recommend a dose of 400 to 800 IU colecalciferol daily for the prevention of vitamin D deficiency in pregnant women, or 1,000 to 2,000 IU daily for the treatment of identified deficiency. No clinical guidance was identified on the use of high monthly doses in pregnancy.
The Committee considered the benefit-risk balance for use during pregnancy differs between prevention of deficiency in at-risk patients and treatment of confirmed deficiency where rapid repletion of vitamin D is desirable. Due to a lack of data on safety and efficacy, it was considered that use of the high-dose vitamin D capsule for prevention of deficiency is undesirable due to an unclear benefit-risk balance. It was acknowledged that blood tests to identify deficiency are not routinely recommended or funded meaning that supplementation is often used empirically. The issues around practicality of using the funded liquid formulation were also noted. It was suggested that there may be a clinical need for a funded alternative lower-dose capsule or tablet product.
The Committee acknowledged there may be a clinical need for the use of high-doses of vitamin D in pregnancy in specific circumstances but considered that such cases should be managed on an individual basis with specialist advice where appropriate. The Committee considered that there was insufficient evidence to support removing the contraindication to use of colecalciferol 50,000 IU capsules in pregnancy, noting that the threshold for removing a safety warning should be high and based on robust evidence. No changes to the data sheet were recommended.
3.2.2 Paternal exposure to low-dose methotrexate
Background
Methotrexate is used as an antineoplastic agent and in autoimmune conditions. For autoimmune conditions such as psoriasis and rheumatoid arthritis, low doses (typically ≤25 mg/week) are generally prescribed compared to the higher doses used in cancer indications. The methotrexate data sheets currently recommend that males should use effective contraception or avoid conception during treatment and for at least 3 months after stopping treatment. This recommendation does not differentiate between low- vs. high-doses, nor between indications.
A specialist clinician has asked that the Committee review the risks of paternal exposure to low-dose methotrexate because they considered that the data sheet advice is not supported by more recent evidence. International rheumatology and dermatology guidelines no longer recommend methotrexate cessation in men planning conception. In addition, other treatment options may have a less favourable safety profile.
Alongside clinical guidelines, there are also regulatory guidelines on the duration of contraception for genotoxic medicines published by the EMA and US FDA. The EMA recommend male patients should use contraception until the end of systemic exposure to the genotoxic medicine including potential genotoxic metabolites (ie, five half-lives after the last dose) plus 90 days. These recommendations apply to any genotoxic active substance regardless of its therapeutic indication. The US FDA’s guidance on the duration of contraception is the same as the EMA’s, but is specific for genotoxic medicines intended for use in cancer.
The Committee was asked to advise whether the current advice in the methotrexate data sheets for male patients to use effective contraception during treatment and for a minimum of three months after stopping treatment is sufficient.
Discussion
The Committee discussed the pharmacological basis for the current data sheet warnings. It was noted that methotrexate is a genotoxic agent that inhibits dihydrofolate reductase (DHFR) and interferes with DNA synthesis, with theoretical potential to affect spermatogenesis and germ cell DNA. This mechanism underpins regulatory guidance from the EMA and FDA, which recommends contraception for a period corresponding to clearance of the genotoxic medicine and any genotoxic metabolites (generally defined as five half-lives after the last dose) plus 90 days for the duration of spermatogenesis and transport to the epididymis. This equates to approximately three months for methotrexate. It was also discussed that the primary pharmacological mechanism of low methotrexate doses is likely anti‑inflammatory rather than cytotoxic, but some degree of DHFR inhibition cannot be ruled out.
The Committee noted that multiple cohort and registry studies from several countries, including large Scandinavian datasets, did not find a statistically significant increase in major congenital malformations, stillbirth, preterm birth, or other adverse pregnancy outcomes associated with paternal exposure to low‑dose methotrexate. It was observed that these findings are supported by systematic reviews and meta‑analyses, with pooled estimates not indicating an increase in risk. However, the Committee also noted that uncertainty in the risk estimates means that a small increase in risk cannot be definitively excluded.
The Committee also discussed the potential for confounding by indication, as the autoimmune conditions being treated may themselves be associated with an increased risk of congenital malformations.
It was noted that several international rheumatology and dermatology guidelines now state that low‑dose methotrexate can be continued in men attempting conception, and that the risk is considered negligible or very low. In contrast, data sheets in New Zealand and other jurisdictions continue to recommend a three‑month contraception period regardless of dose. It was acknowledged that this discrepancy may lead to concern among patients and prescribers, and potentially to avoidance of methotrexate in favour of other medicines that may have less favourable safety profiles.
Because the contraceptive advice for methotrexate is consistent with regulatory guidance on genotoxic medicines the Committee agreed that the current recommendation for contraception during treatment and for three months after cessation should be retained in the data sheet. However, members agreed that additional information in the data sheet would be helpful to better reflect the available evidence and to support informed decision‑making. The Committee recommended updating the data sheet to include that observational human studies have not demonstrated an increased risk of congenital malformations or adverse pregnancy outcomes with paternal exposure to low‑dose methotrexate, but a small risk cannot be excluded. The benefits and risks of continuing low-dose methotrexate in males trying to conceive should be considered and discussed with patients.
Recommendation 2
The Committee recommended that the data sheet information on paternal exposure to methotrexate be modified to reflect current evidence.
3.2.3 Update on sexual dysfunction (post SSRI sexual dysfunction, PSSD) following discontinuation of serotonin reuptake inhibitors
Background
An Expert Working Group of the Commission on Human Medicines (CHM) in the UK recently concluded a review into how potential risks associated with antidepressant medicines are communicated to patients within the Patient Information Leaflets (PILs). This review was launched after concerns were raised by families and patients that current safety warnings in the PILs did not clearly explain certain side effects.
Recommendations to the Medicines and Healthcare Products Regulatory Agency (MHRA) following the review included that the wording of several PILs should be updated to better reflect patient feedback and emerging evidence on the potential for sexual dysfunction that may continue after stopping treatment.
A warning that long-lasting symptoms of sexual dysfunction following discontinuing of treatment with selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) have been reported, is currently listed in section 4.4 of the data sheets for these medicines.
The Committee was asked to advise whether the current information on sexual dysfunction in data sheets for SSRIs/SNRIs is sufficient, including to review the evidence for Post-SSRI Sexual Dysfunction (PSSD)
Discussion
The Committee noted that sexual dysfunction symptoms are described in section 4.8 of data sheets for SSRIs and SNRIs, and that warnings currently include reference to reports of long‑lasting sexual dysfunction where the symptoms have continued after discontinuation. It was noted that the current data sheet warnings do not describe the specific types of sexual dysfunction that may occur, monitoring, patient counselling, or management.
The Committee discussed how sexual dysfunction is very common in the general population and is also one symptom of depression. It was highlighted that this makes it difficult to confirm a causal relationship with SSRIs/SNRIs
The Committee noted that in the literature, long lasting reports of symptoms of sexual dysfunction have been referred to as the syndrome ‘Post-SSRI sexual dysfunction’.
The Committee considered that the available data for PSSD is limited and primarily derived from observational studies, retrospective analyses, surveys, and case reports. The limitations of such data were acknowledged including selection bias and lack of control for confounding factors.
The Committee commented that the term PSSD encompasses many symptoms and lacks an agreed definition. The Committee expressed caution about introducing or emphasising a poorly defined syndrome in data sheets particularly in the absence of clear mechanistic understanding or high‑quality evidence. The potential for unintended negative consequences was noted, such as discouraging patient engagement with treatment.
The Committee was not in favour of including the term PSSD in data sheets at this time. However, the Committee considered that there would be benefit in reviewing the specific symptoms of sexual dysfunction reported with SSRIs/SNRIs, including whether they continue following discontinuation of treatment. The Committee would then consider whether the specific symptoms covered by the term sexual dysfunction can be more clearly defined in the data sheet. The Committee requested that Medsafe present a review of this evidence at a future meeting.
Recommendation 3
The Committee recommended that Medsafe present a review of specific symptoms of sexual dysfunction with SSRIs/SNRIs at a future meeting.
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.
The Committee was provided with a safety review of Janus kinase inhibitors.
4.3 Prescriber Update Volume 47, Number 2, June 2026
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
Medsafe delivered a presentation on the introduction of a Verification Pathway for New Medicine Applications.
The Chair thanked members, the Secretariat and Medsafe staff for their attendance and closed the meeting at 1pm.
Dr Chris Kenedi
Chair, Medicines Adverse Reactions Committee
Date: 1 July 2026
