The March 2026 issue of Prescriber Update, published by the New Zealand Medicines and Medical Devices Safety Authority (Medsafe), presents critical safety information for healthcare professionals. This comprehensive review analyzes key articles covering drug-induced gynaecomastia, safety updates on empagliflozin and Fournier’s gangrene, tolerability of zoledronic acid in elderly patients, emerging concerns with GLP-1 receptor agonists, and recent regulatory changes under the Medicines Amendment Act 2025.
The newsletter also provides quarterly summaries of safety communications, new adverse reaction reports, and important updates to product information. This article synthesizes these findings to support healthcare professionals in delivering safer, more effective patient care.
1. Introduction
Prescriber Update is Medsafe’s quarterly publication dedicated to promoting safer, more effective use of medicines and medical devices in New Zealand. The March 2026 issue (Volume 47, Number 1) contains a wealth of clinically relevant information, including:
- In-depth articles on specific safety topics
- Quarterly summaries of recent safety communications
- Updates from the Medicines Adverse Reaction Committee (MARC)
- New adverse reaction case reports
- Recent approvals and data sheet updates
2. Gynaecomastia: Medicine-Induced Hormone Imbalance
2.1 Understanding Gynaecomastia
Gynaecomastia is defined as a benign proliferation of glandular breast tissue in males, accompanied by localized fat deposition . Clinical features include firm or rubbery subareolar tissue, with breast enlargement or tenderness .
The underlying mechanism is a hormonal imbalance characterized by an increased oestrogen-to-androgen ratio . Contributing factors include:
| Category | Examples |
|---|---|
| Physiological changes | Puberty, ageing |
| Medical conditions | Hypogonadism, chronic liver disease, chronic kidney disease, hyperthyroidism, testicular or adrenal disorders |
| Metabolic factors | Obesity |
| Substance use | Cannabis, alcohol, anabolic steroids |
| Medicines | Wide range of medications (10-25% of cases) |
2.2 Mechanisms of Medicine-Induced Gynaecomastia
Medicines can cause hormonal imbalances through several mechanisms:
| Mechanism | Effect |
|---|---|
| Reduced androgen action | Androgen receptor antagonism or inhibition of androgen synthesis |
| Reduced testosterone production | Relative oestrogen excess |
| Increased prolactin concentration | Promotes glandular breast tissue proliferation |
| Increased peripheral conversion | Androgens converted to oestrogens, particularly in adipose tissue |
| Direct oestrogenic effects | Altered oestrogen metabolism increasing oestrogen exposure |
2.3 Medicines Associated with Gynaecomastia
Table 1 in the newsletter provides examples of medicines approved in New Zealand associated with gynaecomastia:
| ATC Group | Examples of Medicines |
|---|---|
| Alimentary tract and metabolism | Omeprazole, domperidone |
| Cardiovascular system | Digoxin, spironolactone, amlodipine, verapamil, diltiazem, simvastatin, atorvastatin, rosuvastatin |
| Dermatologicals | Isotretinoin |
| Genitourinary system and sex hormones | Testosterone, cyproterone, finasteride |
| Anti-infectives for systemic use | Darunavir, zidovudine, efavirenz |
| Anti-neoplastic and immunomodulating agents | Methotrexate, flutamide, bicalutamide |
| Nervous system | Risperidone, paliperidone, olanzapine, sertraline, fluoxetine, amitriptyline, methylphenidate |
2.4 New Zealand Case Reports
From 1 January 2016 to 31 December 2025, there were 24 case reports of gynaecomastia in men reported to the New Zealand Pharmacovigilance Database. Age was reported in 21 cases with a median of 62 years (range 18 to 76 years).
The most frequently reported medicines were:
- Atorvastatin (3 reports)
- Finasteride (3)
- Omeprazole (3)
- Isotretinoin (2)
- Risperidone (2)
- Rosuvastatin (2)
Time to onset ranged from immediate to 10 years after starting treatment.
2.5 Clinical Implications
| Recommendation | Action |
|---|---|
| Consider medicines | In male patients presenting with breast enlargement or other breast tissue changes |
| Timing matters | Onset can occur weeks to years after starting treatment or dose adjustment |
| Early intervention | Dose reduction or discontinuation may lead to improvement, particularly if identified early |
| Persistence | Gynaecomastia persisting beyond 12 months may be less likely to resolve without intervention |
2.6 Monitoring Communication: Atomoxetine
Medsafe is currently reviewing the risk of gynaecomastia with atomoxetine. A recent report described a 36-year-old male who developed bilateral gynaecomastia following a dose increase. Gynaecomastia is not currently listed in the atomoxetine data sheets, and Medsafe encourages reporting of suspected cases.
3. Update: Fournier’s Gangrene with Empagliflozin
3.1 Key Finding
Fournier’s gangrene (necrotising fasciitis of the perineal, perianal or genital areas) has been known to occur in patients treated with empagliflozin for type 2 diabetes mellitus. New evidence shows it can also occur in patients taking empagliflozin without type 2 diabetes—such as those being treated for heart failure or chronic kidney disease.
3.2 New Zealand Case Reports
As of 31 December 2025, there were 44 case reports of Fournier’s gangrene associated with empagliflozin:
| Characteristic | Data |
|---|---|
| Median age | 57.5 years (range 35-81) |
| Gender | Male: 27; Female: 14; Unknown: 3 |
| Indication | Type 2 diabetes: 30; Heart failure: 2; Unknown: 12 |
| Outcome | All serious; 3 fatal outcomes |
3.3 Clinical Recommendations
| Action | Details |
|---|---|
| Prompt evaluation | Evaluate any patient on empagliflozin presenting with pain, tenderness, erythema, swelling in genital/perineal area, fever, or malaise |
| Immediate discontinuation | Stop empagliflozin if Fournier’s gangrene is suspected |
| Urgent treatment | Broad-spectrum antibiotics and surgical debridement if necessary |
4. Zoledronic Acid: Tolerability in Elderly Patients
4.1 Key Message
Elderly patients receiving zoledronic acid infusions are at higher risk of adverse reactions and may experience more severe reactions or find them more disabling than younger people.
4.2 New Zealand Case Reports (2016-2025)
| Parameter | Data |
|---|---|
| Total reports | 428 cases |
| Median age | 70 years (range 15-94) |
| Elderly cases (≥65 years) | 290 cases (219 serious) |
4.3 Specific Adverse Reactions in Elderly Patients
| Reaction Type | Number of Reports |
|---|---|
| Acute phase reactions | 220 reports (159 serious) |
| Renal adverse events | 22 reports (14 acute renal failure) |
| Hypocalcaemia | 17 reports |
| Hypophosphatemia | 9 reports |
4.4 Clinical Recommendations
| Pre-Infusion Action | Details |
|---|---|
| Patient education | Inform that acute phase reactions are common (especially after first infusion) and usually resolve in a few days |
| Hydration | Ensure adequate hydration before and after infusion |
| Renal function | Measure serum creatinine; calculate creatinine clearance |
| Calcium/Vitamin D | Treat pre-existing hypocalcaemia before administration |
| Ocular symptoms | Promptly refer patients with eye redness, pain, light sensitivity, or blurred vision to an ophthalmologist |
5. GLP-1 Receptor Agonists and Altered Skin Sensations
5.1 Key Finding
GLP-1 receptor agonists, including semaglutide and tirzepatide, can cause altered skin sensations.
5.2 Terminology
| Term | Definition |
|---|---|
| Dysaesthesia | Abnormal and unpleasant skin sensations (burning, tingling, numbness, cold sensation) |
| Allodynia | Painful sensation in response to a stimulus that does not normally cause pain (e.g., light touch from clothes) |
5.3 Clinical Trial Data
| Drug | Incidence of Altered Skin Sensations |
|---|---|
| Semaglutide (Wegovy) | 2.1% (vs. 1.2% placebo) |
| Tirzepatide (Mounjaro) | Dysaesthesia reported |
Most patients recovered while continuing treatment.
5.4 New Zealand Case Reports
As of 31 January 2026, there were 9 cases of altered skin sensations reported with semaglutide:
- Allodynia: 6 reports
- Burning skin sensation: 1
- Hypersensitive skin: 1
- Skin pain: 1
5.5 Clinical Recommendation
Consider GLP-1 receptor agonists as a possible cause in patients presenting with altered skin sensations.
6. Documenting Clinical Trial Participation in Medical Records
6.1 New Guidance
Medsafe’s updated clinical trial guidelines (Edition 3.0) now encourage documenting clinical trial participation in the patient’s medical record.
6.2 Key Messages
| Action | Rationale |
|---|---|
| Record trial participation | Ensure other healthcare providers are aware of the patient’s involvement |
| Include contact details | Investigator/research team contact (including out-of-hours) |
| Inform usual healthcare provider | If appropriate |
| Update when complete | Remove or mark as completed when trial ends |
6.3 Special Considerations
- Information sharing should be part of the informed consent process
- Ideally, record in electronic medical records for accessibility
- Particularly important for emergency admissions when patients cannot self-report
7. MARC Remarks: December 2025 Meeting
The Medicines Adverse Reaction Committee (MARC) convened for its 204th meeting on 4 December 2025.
7.1 Key Discussions and Outcomes
| Topic | Discussion | Outcome |
|---|---|---|
| CFTR modulators (ivacaftor, Trikafta) | Psychiatric disorders reported | Update data sheets to state psychiatric disorders have been reported; monitor patients |
| Antipsychotic-induced hyperprolactinemia and breast cancer | Biological plausibility but epidemiological evidence unconvincing | Current data sheet information appropriate; no regulatory action |
| DRESS with calcium channel blockers | Limited evidence for association | No regulatory action needed |
| Pregabalin adverse reactions | Increasing usage in NZ; misuse/abuse significant internationally | Noted for awareness |
8. Quarterly Summary of Safety Communications
The newsletter summarizes recent safety communications (September 2025 – February 2026):
| Date | Communication | Topic |
|---|---|---|
| 09/02/2026 | DHPL | Alecensa (alectinib): Severe hypertriglyceridaemia |
| 02/02/2026 | DHPL | Zypine ODT (olanzapine): Alternative registered foils |
| 26/01/2026 | Monitoring | GLP-1 agonists (dulaglutide, liraglutide, semaglutide, tirzepatide): Acute persistent visual loss |
| 16/01/2026 | DHPL | Columvi (glofitamab): Haemophagocytic lymphohistiocytosis |
| 15/12/2025 | Monitoring | Atomoxetine: Possible risk of gynaecomastia |
| 28/11/2025 | Alert | FreeStyle Libre 3 Plus CGM sensors recall |
| 20/11/2025 | DHPL | Codeine Phosphate Tablets (Noumed): Overlabelling due to shortages |
9. Medicines Amendment Act 2025: Key Changes
The Medicines Amendment Act 2025 came into force on 19 November 2025. Key changes affecting prescribers include:
9.1 Verification Pathway
- New pathway for medicine approval based on recognition by two overseas regulatory authorities
9.2 Wider Prescribing of Unapproved Medicines
| Prescriber Type | New Authority |
|---|---|
| Nurse practitioners, pharmacist prescribers | Can prescribe unapproved medicines (including cannabidiol) under Section 29 |
| Any authorised prescriber | Can prescribe unapproved medicines funded by Pharmac as alternative to approved medicines in short supply (Section 29A) |
9.3 Advertising at Medical Conferences
- Exemption for advertising unapproved medicines at medical conferences (Section 34AA)
- Conference organiser must notify Director-General of Health at least 30 working days before the conference
9.4 Pharmacy Ownership
- Section 42C (restricting prescribers from holding interest in pharmacies) repealed
- Most pharmacies must still be majority owned by pharmacists able to exert effective control
9.5 Medicines Classification Committee
- Wider representation allowed; Minister must appoint at least 7 suitably qualified members
- GPs and pharmacists remain core expertise, but consumers and nurses may now contribute
10. Recent Approvals: New Active Ingredients
| Medicine | Active Ingredient | Therapeutic Area |
|---|---|---|
| Comirnaty LP.8.1 | SARS-CoV-2 spike protein (mRNA) LP.8.1 | COVID-19 disease |
| Itovebi | Inavolisib | Breast cancer |
| Mounjaro | Tirzepatide | Type 2 diabetes; Chronic weight management |
| Welireg | Belzutifan | von Hippel-Lindau disease-associated tumours; Advanced renal cell carcinoma |
10.2 New Indications
| Medicine | New Indication |
|---|---|
| Mekinist (trametinib) + Tafinlar (dabrafenib) | Paediatric glioma |
11. Informative Adverse Reaction Reports
The newsletter presents several notable case reports from the New Zealand Pharmacovigilance Database:
| Case | Reaction | Data Sheet Status |
|---|---|---|
| 39-year-old female | Biliary spasm after codeine | Listed in data sheet |
| 6-year-old male | Agitated, aggression, violent behaviour after midazolam | Paradoxical reactions listed; particularly among children and elderly |
| 21-year-old | Toxic epidermal necrolysis (TEN) after ibuprofen | Listed as very rare ADR |
| 15-year-old female | Raynaud’s phenomenon after atomoxetine | Listed as very rare ADR |
12. Recent Data Sheet Updates: Important New Safety Information
Key updates to New Zealand data sheets include:
| Active Ingredient | New Safety Information |
|---|---|
| Alfentanil | Opioid class effects: sleep-related breathing disorders, adrenal insufficiency, central sleep apnoea syndrome, toxic leukoencephalopathy with overdose |
| Amoxicillin + clavulanic acid | Haemophagocytic lymphohistiocytosis (HLH)/Macrophage activation syndrome (MAS) |
| Dabrafenib + trametinib | Tattoo-associated skin reaction |
| Dulaglutide | Psychiatric disorders: suicidal behaviour and ideation |
| Empagliflozin | Fournier’s gangrene risk updated for non-diabetic indications |
| Gadobutrol | Acute respiratory distress syndrome (ARDS) |
| Hydroxychloroquine | Haemolytic anaemia associated with G6PD deficiency |
| Isotretinoin | Sexual disorders (may persist after discontinuation); psychiatric disorders (persistent symptoms); anhedonia; gynaecomastia |
| Medroxyprogesterone acetate | Meningioma risk (updated); drug-induced liver injury |
| Mesalazine | Idiopathic intracranial hypertension |
| Tamoxifen | Pulmonary oil microembolism; interaction with SGLT-2 inhibitors |
| Zopiclone | Overdose may cause haemolysis/haemolytic anaemia |
13. Practical Implications for Healthcare Professionals
13.1 Key Takeaways
| Topic | Action Point |
|---|---|
| Gynaecomastia | Consider medicine-induced causes in male patients with breast changes; onset can be delayed |
| Fournier’s gangrene | Suspect in any patient on empagliflozin (diabetic or not) with genital/perineal symptoms |
| Zoledronic acid in elderly | Higher risk of severe reactions; ensure hydration, renal assessment, and patient education |
| GLP-1 agonists | Consider as cause of altered skin sensations (allodynia, dysaesthesia) |
| Clinical trial documentation | Record trial participation in medical records for patient safety |
| Medicines Amendment Act | Understand new prescribing authorities for unapproved medicines |
13.2 Reporting Adverse Reactions
Healthcare professionals are encouraged to report suspected adverse reactions to Medsafe via:
- Online: Suspected Medicines Adverse Reaction Search (SMARS)
- Email: medsafeadrquery@health.govt.nz
14. Conclusion
The March 2026 issue of Prescriber Update provides essential safety information for healthcare professionals. Key highlights include:
- Gynaecomastia can be caused by a wide range of medicines, with onset delayed up to years after initiation
- Fournier’s gangrene is a risk with empagliflozin in all patients, regardless of diabetes status
- Elderly patients receiving zoledronic acid require special precautions due to increased risk of severe reactions
- GLP-1 receptor agonists can cause altered skin sensations; consider in differential diagnosis
- Medicines Amendment Act 2025 introduces important changes to prescribing of unapproved medicines
Medsafe continues to emphasize the importance of adverse reaction reporting in identifying and characterizing medicine safety issues. Healthcare professionals play a vital role in this system through vigilant monitoring and timely reporting.
