The supply issue affecting podophyllotoxin (Condyline), reported in Bulletin 133, is ongoing as stock of the alternative product (Section 29) that was listed on the Pharmaceutical Schedule from 1^st October, has been delayed until mid-November. Imiquimod cream may be a suitable alternative for some patients, however, a new prescription will be required, and a supply issue is currently affecting this product also.

The brand and packaging for imiquimod is changing this month; the new brand is Padagis and the cream will be in the form of a stick. Stock of the original brand of imiquimod (Perrigo) is now unavailable and the new brand will not be available until late November.

Pharmac is seeking clinical advice on other suitable alternatives to podophyllotoxin and imiquimod.

Supply issues are affecting all strengths of codeine phosphate tablets. The supplier is currently out of stock of the 30 mg strength; stock of 15 mg and 60 mg tablets are low. Re-supply of all strengths is expected from next week (17^th November). A new prescription will be required for an alternative medicine if codeine is out of stock.

It has also been reported that the shelf life of the currently funded brand of codeine phosphate (Noumed) has been extended from 24 months to 36 months; packaging will be updated to reflect the new 36 month shelf life.

There is a supply issue affecting 10 mg, 20 mg and 40 mg rosuvastatin tablets due to manufacturing delays; stock is currently on allocation by Viatris. A new shipment is expected to arrive by the end of November.

An alternative brand of 20 mg rosuvastatin tablets (Rosuvastatin Sandoz) has been funded since 11^th November, 2025, however, it will not be listed on the Pharmaceutical Schedule until December. The new product should have been automatically updated in pharmacy dispensing software. Pharmacists can either hold off submitting claims until December, or reclaim in December when they are rejected in the November claim.

For further information on rosuvastatin, see: https://bpac.org.nz/2022/rosuvastatin.aspx

From 1^st December, 2025, both Estradiol TDP Mylan (Viatris) and Estradot (Sandoz) will be the main funded brands of oestradiol patches (as reported in Bulletin 126). The following brands will also be delisted from this date: Lyllana, Estradiol Sandoz, Estradiol Viatris and Estraderm MX. Clinicians should ensure that any patients still using these brands are switched to Estradiol TDP Mylan or Estradot.

Clinicians are encouraged to prescribe Estradiol TDP Mylan to patients starting treatment or who are already using it without problems, and reserving the Estradot brand for those who need it. The two patch per week limit will continue to apply to each strength, as well as monthly dispensing. These restrictions will be reviewed in 12 months’ time.

Pharmacists are encouraged to dispense Estradiol TDP Mylan when oestradiol patch prescriptions are written generically. A brand switch fee for Estradiol TDP Mylan will be available from 1^st December, 2025, until 28^th February, 2026.

For further information on menopausal hormone therapy, see: bpac.org.nz/2019/mht.aspx

• COPD continues to disproportionately affect Māori and Pacific peoples; the guideline highlights ways to deliver a culturally safe and equitable healthcare service
• All aspects of Hauora (health and wellbeing): taha tinana (physical), taha hinengaro (mental), taha whānau (family and social) and taha wairua (spiritual), should be considered when tailoring education and support to patients with COPD
• Emerging evidence suggests that vaping may be a cause of COPD, even in people who have never smoked
• A new section has been added on the initial assessment of COPD; the role of spirometry in the diagnosis of COPD continues to be emphasised
  • Diagnostic spirometry can be done if the patient has or has not been using a bronchodilator; post-bronchodilator spirometry is not usually required
• Non-pharmacological interventions (e.g. smoking cessation, regular exercise, pulmonary rehabilitation) continue to underpin COPD management, and these can impact outcomes more than pharmacological treatments
• Self-management plans should be offered to all patients with COPD
  • These now include space to record the patient’s normal oxygen saturation, the distance they can walk when well and a QR code to access the breathlessness quick reference guide
• Short-acting bronchodilators should only be used as needed for short-term relief of breathlessness; regular use is not recommended
• A long-acting antimuscarinic (preferred) or long-acting beta-agonist will benefit most patients with ongoing dyspnoea; many patients will need both (funding restrictions apply)
• An inhaled corticosteroid (ideally prescribed as a triple medicine inhaler) should be added to the patient’s treatment regimen if they have two or more COPD exacerbations per year (or one exacerbation needing hospital admission)
• Influenza (funded), pneumococcal (not funded), COVID-19 (funded; new recommendation) and RSV (unfunded; new recommendation) vaccinations are recommended for patients with COPD
• Opioids are no longer recommended for dyspnoea unless in a palliative or end of life care setting due to a lack of evidence. There is also no evidence for the use of benzodiazepines or antidepressants for dyspnoea.
• Co-morbidities such as lung cancer, cardiovascular disease and depression can impair COPD management; optimise assessment and management of any co-morbid conditions

The ACC definitions for medical certification have evolved over time with “Fully unfit” undergoing the most significant change. The three categories of medical certification when lodging ACC45 and ACC18 forms are:

• Fully fit– able to functionally perform full pre-injury work duties and hours
• Fit for selected work– able to engage in physical rehabilitation and some level of work with support, e.g. amended duties, workplace adaptations, altered hours or a phased return to work
• Fully unfit– essentially hospitalised or “house-bound”, and should meet one of the following limited criteria:
  1. Total inability to work– the patient is either admitted to hospital or unable to effectively mobilise from their bed
  2. Contagion risk or quarantine need– the patient is at risk of infection due to their injury and the environment they usually work in and is unable to work remotely
  3. Health and safety risk– the patient being in the workplace, even with assistance or modifications, poses a specific health and safety hazard to themselves, their co-workers or the general public, e.g. due to the impact of the injury or the medicines being taken. This criterion does not apply when the patient is functionally able to perform alternative tasks, even if these do not align with their usual role in the workplace.

Understanding the distinctions between these categories is essential to facilitate delivery of the recovery at work model, and to guide provision of additional ACC-mediated supports such as financial/social assistance, treatment and vocational rehabilitation services.

This month, the NZF team highlight contraceptive requirements and considerations when prescribing medicines with known teratogenic potential.

• Females of child-bearing potential should use highly effective contraception when taking a teratogenic medicine; this may also apply to females of child-bearing potential whose male partner is taking a teratogenic medicine
• Assess pregnancy risk prior to prescribing
• No method of contraception is 100% effective
  • Highly effective contraceptive options (failure rate with typical use < 1%):
    • Sterilisation
    • Long-acting reversible contraception: progesterone-only implant (should not be relied upon alone if taken with hepatic-enzyme inducing medicines), copper intra-uterine device and progestogen-releasing intra-uterine system
  • Other contraceptive options: combined oral contraceptives and progestogen-only pills (approximately 9% failure rate) and depot injections (approximately 6% failure rate).
    • Additional contraceptive precautions, e.g. condoms, abstinence, are required with these options, or switch to a highly effective contraceptive method (above)
  • Other contraceptive methods (e.g. barrier methods, withdrawal or fertility awareness) alone are not recommended due to high failure rates

For information on selecting the right contraceptive option for a patient, see the bpac^nz contraception series: https://bpac.org.nz/2021/contraception/options.aspx

“Bronze diabetes”, or Troisier-Hanot-Chauffard syndrome, is a historical term referring to a clinical syndrome consisting of a classic trio of diabetes, abnormal skin hyperpigmentation ("bronze" skin) and hepatic dysfunction, first reported by French physician, Dr Victor Hanot in 1882.^{1, 2} The key underlying cause is hereditary haemochromatosis; history attributes the original description of haemochromatosis in a person with diabetes to Dr Arnand Trousseau in 1865 and discovery of excess iron in the liver to Dr Friedrick Daniel von Recklinghausen, a German pathologist in 1889.¹

Bronze diabetes, which is correctly termed as a form of type 3c or pancreatogenic diabetes, occurs when iron overload caused by haemochromatosis results in hyperpigmentation of the skin and diabetes due to destruction of pancreatic beta-cells and hepatic insulin resistance.³ It is less frequently encountered nowadays due to earlier diagnosis and management of haemochromatosis; genetic testing has been available for the past decade or so in New Zealand, so most people with a family history will have been screened.

Often a diagnosis of bronze diabetes may come about when parts of the puzzle are present, and a clever clinician connects the dots. “My next patient was in the waiting room, I hadn’t seen him before, so I looked at his clinical notes and it said he had type 2 diabetes. I have to admit that when I went to greet him and the markedly slimmer of the two gentlemen in the waiting room stood up, it wasn’t who I was expecting. He didn’t have any obvious metabolic risk factors for type 2 diabetes, but he didn’t really fit the picture for type 1 either. I looked at him again and noticed a distinct bronzed hue to his skin, and that’s when all the pieces started to click together in my head. I looked through his notes and saw that he had a history of raised ferritin levels and abnormal LFTs – I think I had just caught my first case of bronze diabetes.”

The typical presentation of an atypical case of diabetes (i.e. type 3c) is a patient who has a “working” diagnosis of diabetes, but they also have various non-specific clinical concerns, e.g. fatigue, aching joints, or unusually tanned skin in the case of underlying haemochromatosis.⁴ Clinical characteristics normally associated with type 2 diabetes are often absent, such as increased BMI and waist circumference, and there are no obvious features that may suggest type 1 diabetes, e.g. autoimmune markers.³ A range of inherited or acquired conditions underlies the development of type 3c diabetes, including hereditary haemochromatosis, chronic pancreatitis, cystic fibrosis, pancreatic cancer, surgery or trauma to the pancreas.⁵

So, should all patients with diabetes be routinely screened for haemochromatosis? The short answer is “no”. Even in populations with a high proportion of “celtic” genes (Caucasian ethnicity is a known risk factor for haemochromatosis), it is felt that there is limited value due to increasing prevalence of type 2 diabetes, and a small likelihood of revealing a previously unknown family history of haemochromatosis;⁶ the old adage^* runs true here – Hear hoofbeats? Think horses, not zebras.

Management of haemochromatosis with ongoing therapeutic phlebotomy is the basis of treatment for patients with bronze diabetes, along with standard diabetes care. Principles of type 3c diabetes management can be more complicated as patients often require insulin, pancreatic enzyme replacement treatment, nutritional support and frequent blood glucose monitoring (continuous glucose monitoring and an insulin pump may be appropriate) as patients are often more “brittle”.^{3, 5} Complications in the longer term include liver disease, cardiomyopathy, heart failure and in addition to diabetes, other endocrine conditions such as hypothyroidism or hypogonadism; ideally these can be prevented or managed with early diagnosis and appropriate treatment, however, regular phlebotomy does not usually improve the associated diabetes, arthritis, hypogonadism and cirrhosis once established.⁴

* The “hoofbeats” phrase was first coined by Dr Theodore Woodward in the 1940s, while instructing medical students that the most common explanation is usually the correct one (also known as Occam’s razor)

For further information on identifying and managing hereditary haemochromatosis, see: https://bpac.org.nz/bt/2015/april/haemochromatosis.aspx (published in 2015; some information may no longer be current)

Although bronze diabetes is the subject of this Factorium, hyperpigmentation of the skin can also be associated with other conditions, including:⁷

• Primary adrenal insufficiency (Addison’s disease) with an “inappropriate tan” in an unwell patient due to increased ACTH and melanocyte-stimulating hormone levels
• Chronic kidney disease due to uraemic hyperpigmentation (usually more yellowish)
• Chronic liver disease causing accumulation of bilirubin which produces characteristic yellow jaundice of the skin, sclerae and mucous membranes
• Excessive consumption of carotene-rich foods can cause carotenoderma where the skin is yellowy-orange, but the sclerae are spared and the patient is healthy
• Medicine-induced hyperpigmentation (e.g. amiodarone, antimalarials) which can produce localised patches or more widespread changes but often blue-grey or slate-grey in colour
• Acanthosis nigricans which is associated with insulin resistance and type 2 diabetes, but tends to result in localised hyperpigmented, velvety plaques in intertriginous areas (usually a dark brownish colour)

References

1. Opie EL. A case of haemochromatosis - the relation of haemochromatosis to bronzed diabetes. Journal of Experimental Medicine 1899;4:279–306. doi:10.1084/jem.4.3-4.279
2. Adams PC. Hemochromatosis: ancient to the future. Clin Liver Dis (Hoboken) 2020;16:83–90. doi:10.1002/cld.940
3. Rasheed A, Galande S, Farheen S, et al. Type 3c diabetes associated with chronic pancreatitis: A narrative review. Pancreatology 2025;25:1003–12. doi:10.1016/j.pan.2025.08.005
4. Palmer WC, Stancampiano FF. Hemochromatosis. Ann Intern Med 2025;178:ITC17–32. doi:10.7326/ANNALS-24-03710
5. Diabetes Info NZ. Type 3c diabetes. Available from: https://www.diabetesinfo.org.nz/type-1-diabetes/type-3c-diabetes/
6. Lockhart M, Salehmohamed MR, Kumar D, et al. Screening for hereditary hemochromatosis in newly referred diabetes mellitus. Am J Med Open 2023;10:100046. doi:10.1016/j.ajmo.2023.100046
7. DermNet. Available from: https://dermnetnz.org/

• The study authors followed a multi-step process to identify laboratory tests used to monitor patients with type 2 diabetes, and their evidence base. The method involved rapid reviews of international guidelines, systematic reviews and individual studies. The reviews guided a consensus group of clinicians and patient representatives who then voted on whether the tests should be included, excluded or if evidence was insufficient in context of type 2 diabetes monitoring.
• A total of 15 laboratory tests were evaluated: HbA_1c, fructosamine, renal function tests (eGFR), liver function tests, lipid profile, full blood count (haemoglobin), thyroid function tests, vitamin B12, ferritin, folate, clotting tests, bone profile (e.g. calcium, phosphate, parathyroid hormone), CRP, ESR and BNP. The evidence for urine ACR was not assessed.
  • Some of these tests, e.g. fructosamine, ESR, are not routinely requested in New Zealand and are restricted
• Only two laboratory tests were found to have strong evidence for use in monitoring patients with type 2 diabetes. While there was less evidence of the usefulness of routinely monitoring other parameters in patients with type 2 diabetes, it is important to note that there is still value in requesting many of these tests if the patient has a specific indication, i.e. a targeted testing approach.
• Tests supported by strong evidence for type 2 diabetes monitoring:
  • HbA_1c for the monitoring of disease progression and treatment response
  • eGFR to detect chronic kidney disease. N.B. Both eGFR and urine ACR are typically used in the detection of chronic kidney disease; the study did not specifically assess the evidence for urine ACR.
• Tests with unclear or insufficient evidence for type 2 diabetes monitoring:
  • Liver function tests to detect non-alcoholic fatty liver disease
  • Lipid panel for dyslipidaemia or cardiovascular disease risk. Increasing evidence suggests there is limited value in frequent lipid monitoring once initiated on a lipid-lowering medicine.
  • Haemoglobin for anaemia
  • Vitamin B12 for metformin-related adverse effects
• Tests that should not be routinely requested for type 2 diabetes monitoring (read the paper for full details of why):
  • Thyroid function tests
  • Renal and liver function tests for metformin-related adverse effects
  • Bone profile
  • Vitamin B12
  • Ferritin
  • Folate
  • Clotting tests
  • CRP
  • ESR
  • BNP
  • Fructosamine
• The study also assessed whether the results of testing, in particular, lipid and liver function tests, affected a person’s likelihood of making behavioural changes. Evidence was insufficient; therefore, testing is not recommended for the sole purpose of modifying a patient’s behaviour.
• All of the laboratory investigations recommended to be included as part of the annual diabetes review in New Zealand that were assessed in the study were found to have evidence for their use, however, liver function tests and lipid panel lacked strong evidence when requested for ongoing monitoring. N.B. Evidence for urine ACR was not included in the study.
• A limitation of the study was that there was potential for relevant evidence to have been missed given that a full systematic review was not conducted. The study also did not address other aspects of testing that may influence recommendations and decision making, e.g. accuracy, variability of the tests, optimal testing frequency.