Clinical Zoom meeting snippets - February 2024

The NZF notes that ACE inhibitors should be avoided at all stages of pregnancy. Fetal skull defects have been reported following first trimester exposure to ACE inhibitors although evidence of teratogenicity is inconclusive. In the second and third trimesters ACE inhibitors can cause abnormalities including fetal growth retardation, oligohydramnios and fetal or neonatal renal failure. Fetal death in utero has also been reported. Pregnant people who are taking an ACE inhibitor should be changed to an alternative antihypertensive as soon as possible. Like ACE inhibitors ARBs should be avoided in pregnancy, particularly in the second and third trimesters, as similar effects to those caused by ACE inhibitors in pregnancy are expected.  

NZF notes also that Statins should be avoided in pregnancy as congenital anomalies have been reported and the decreased synthesis of cholesterol possibly affects fetal development. The individual statin monographs state the drug is contraindicated during the first trimester and adequate contraception is required during treatment and for 1 month afterwards.  However, a 2022 metanalysis and systematic review noted there are some patients for whom there may be a significant benefit of maintaining statin therapy, in particular in the second and third trimesters. The risk and benefit of statins treatment during pregnancy need to be evaluated in an individualized approach and every trimester apart.

A September NZ Doctor article on monitoring drug interactions with lithium is a helpful refresher on monitoring recommendations for patients on lithium therapy:

(i)  Usual monitoring: (current reference range for chronic use is 0.6-0.8 mmoL/L):

• three to six-monthly (depending on stability) – serum lithium level, electrolytes, eGFR
• six-monthly – thyroid function, calcium, weight
• annually (if over age 40 or obese) – HbA1c, lipids, consider ECG.

(ii)  When adding or removing medicines:

• ACE inhibitors – baseline serum lithium level and renal function tests, then weekly for six weeks or until stable. For “at-risk” people (impaired renal function, volume depletion or heart failure) consider further two-weekly checks for six weeks.

20 to 35 % of people will have an increase in lithium levels if an ACE inhibitor is added to their regime, usually by around 33 %. The interaction can be delayed for up to five weeks, so it is important not to be reassured by steady lithium levels initially.  ARB interaction less likely but dose dependent (ARB) increases in lithium levels of up to 20 % after up to five weeks of treatment have been reported. 

• Diuretics – baseline serum lithium level and renal function tests, then weekly for four weeks.

If a thiazide needs to be introduced, there may be a rapid increase in serum lithium levels by 20-25 % in 3-10 days, although this effect may also be delayed.  Loop diuretics have less impact, with potentially only up to a 20% increase in levels, and potassium-sparing diuretics appear to have no effect.

• NSAIDs – baseline serum lithium level and renal function tests, then weekly for two weeks or until stable.

This interaction is well described for decreasing lithium clearance and increasing its toxicity, although it is unpredictable. While the average decrease in lithium clearance is usually 10-25%, there is wide variation, especially in people with impaired renal function. It is unlikely that COX-2 inhibitors would be any different to traditional NSAIDs regarding this interaction.

The risk is cumulative with concomitant use of ACE inhibitors, diuretics and NSAIDs.

The October 2023 NZ Doctor includes a refresher on shared care prescribing of clozapine.  Points include:

(i)  Clozapine can only be initiated by a psychiatrist. In some localities within Te Whatu Ora, GPs and nurse practitioners can be responsible for ongoing prescribing under the supervision of a psychiatrist. GPs can also prescribe for those with stable illness in collaboration with a community mental health team.  Patients are considered stable if they have been taking clozapine continuously for two years, had no mental-health-related hospital admissions in the last 12 months, are not taking other medications requiring close monitoring by a psychiatrist, and have been adherent to treatment and attending appointments.

(ii)  Due to the risk of agranulocytosis, all patients prescribed Clopine in New Zealand must be registered to ClopineCentral™ (the Clopine Monitoring System) or CareLink Plus (the Clozaril Monitoring System) by a registered medical practitioner.  Prescribing physicians must also register themselves onto the relevant monitoring system to access patient information. Brand swapping between clozapine products is discouraged and should occur on the advice of the initiating clinician or team. 

(iii)  The adverse effect and drug interaction profile of clozapine is wide (in particular agranulocytosis, severe constipation and cardiomyopathy/myocarditis) and there are specific requirements for pre-prescribing screening and subsequent monitoring which are critical to reduce the risk of patient harm.  There is comprehensive practical information available on HealthPathways (not yet localised for Midlands) and in publications by BPAC (2017) and SafeRx. 

(iv) Clozapine levels are reduced by cigarette smoking; however, it is the constituents of smoke, not nicotine itself, that is responsible.  Elevated clozapine levels, up to double baseline, may occur when patients stop smoking and this is not affected by NRT.  If patients stop smoking it is advisable to monitor plasma clozapine levels, dose reduction may be required in conjunction with mental health service advice. Conversely, if a patient starts smoking during treatment, the therapeutic effect of clozapine may be reduced. The plasma concentration of clozapine can also be increased by a high caffeine intake (more than 400mg/day - colas, tea and many energy drinks contain significant amounts of caffeine). Clozapine levels can subsequently decrease by nearly 50% after a 5-day caffeine-free period.

(v)  The article concludes:  Every time a patient comes in, there is an opportunity to query about adverse effects (with a focus on smoking status and bowel habits), check they are taking their medication appropriately, and offer lifestyle advice. Blood test results should be checked and compared with baseline. It is also important to ensure patients are aware of the need for blood tests to be done on the day they are due.  The Porirua Protocol is an evidence-based bowel management regime for patients taking clozapine.  

Issue 106 of the Māori Health Review reported a recent retrospective study from the Midland region on prescribing of cardioprotective medications and the impact on survival for patients with peripheral artery disease that undergo intervention. Findings included the following.

• Overall, 80.7% of patients received a prescription for antihypertensive medication, 77.4% for lipid-lowering medication and 89.9% for antithrombotic medication with prescribing of all three noted as ‘best medical therapy’. 
• Patients with concomitant ischaemic heart disease were more likely to be prescribed cardioprotective medication. Women were less likely to be prescribed lipid-lowering medication than men and younger patients were less likely to be prescribed lipid lowering medication than older patients. Māori men were less likely to be prescribed antiplatelet medication compared with non-Māori men although were more often prescribed antihypertensive agents and no significant difference in statin prescribing. 
• Lipid-lowering and antiplatelet medication showed a survival advantage on univariate analysis, while antihypertensive and anticoagulant medication did not. Best medical therapy was associated with better survival after adjustment for age, sex, end stage renal failure and presence of chronic limb-threatening ischaemia. 

On the equity theme, there is a great article from Cook Street Medical Centre in the January edition of GP Voice about their equity journey and outcomes. 

In January Medsafe released a monitoring communication regarding the DPP4 inhibitor vildagliptin (Galvus, Galvumet).  The communication requested reporting to CARM of any patients on the medication being diagnosed with ileus.  While there is insufficient evidence currently to confirm any association between use of DPP4 inhibitors and ileus, the association may have biological plausibility as DPP-4 inhibitors act by inhibiting the breakdown of endogenous glucagon-like peptide-1 (GLP-1), which has a role in inhibition of gastrointestinal motility.

Online mental health provider, Just a Thought, has launched CBT courses titled Pregnancy Wellbeing and Postnatal Wellbeing for people who experience depression and anxiety during their perinatal journey. The courses are evidence-based and free of charge. You can refer your patients and follow their progress via the online dashboard once you are registered as a clinician with Just a Thought, or the patient can self-access.

Educational provider Skin Cancer Symposiums offers a variety of on-line and in-person courses aimed at facilitating accurate and timely diagnosis of skin cancers, particularly melanoma.  They are currently offering a complimentary on-line mini-course on the basics of dermatoscopy and diagnosing melanomas (Register here)  with the goal of the course described as: to facilitate the basic understanding of the visual "red flags" of diagnosing melanoma.  In all of the cases presented, we include clinical and dermatoscopic images. In some, the diagnosis will be evident in the clinical image and reviewing the dermatoscopic image will further reinforce this. In some examples, the diagnosis is only evident in the dermatoscopic image.

Manatu Hauora confirmed at the end of December that a vaccine to combat the newer strains of COVID-19 has been approved by Medsafe and will be available to New Zealanders in time for winter 2024.  The COVID-19 XBB.1.5 (Comirnaty® Omicron XBB.1.5) has been approved for the 12+ age group with no plan reported for any changes in current eligibility criteria.   Eligible people are encouraged not to defer booster shots of the existing vaccine if due in view of prevalence of Covid-19 in the community.  While the most prevalent subvariant currently internationally and in NZ is JN.1, the receipt of updated SARS-CoV-2 vaccines containing the monovalent XBB.1.5 spike protein is anticipated to provide protection against JN.1[1].

[1] https://www.idsociety.org/covid-19-real-time-learning-network/vaccines/will-covid-vaccines-continue-to-work-against-jn.1-and-other-new-variants#/+/0/publishedDate_na_dt/desc/