Published: 5 June, 2020
Updated information about prescribing tramadol
Some important tramadol prescribing changes have recently been announced by
Medsafe, based on information from clinical
trials and data from the Centre for Adverse Reactions Monitoring (CARM):
- Tramadol is now contraindicated in all children aged under 12 years (previously the limit was age two years)
- Tramadol is contraindicated in children aged under 18 years for post-operative pain management
following tonsillectomy and/or adenoidectomy
- Tramadol should be used with care in patients aged 75 years and older due to the prolonged elimination half-life;
a lower maximum daily dose of 300 mg should also be used in this group
- Response to tramadol is variable depending on whether people are fast or slow metabolisers of the CYP2D6 enzyme;
this can explain why some people are more sensitive to the adverse effects of tramadol and why others have reduced
For more information on prescribing tramadol, see: https://bpac.org.nz/2018/tramadol.aspx
A reminder about the safe prescribing of clozapine
Clozapine is an effective treatment for some patients with schizophrenia, however, it is associated with a number
of significant adverse effects that necessitate close monitoring and co-ordinated care between the patient, caregivers,
mental health and primary care teams. A
coroners case has again highlighted the potentially fatal outcomes when
this medicine is not managed optimally.
Key practice points for prescribing clozapine:
- Clozapine-induced constipation is highly prevalent, often difficult to detect and potentially fatal; prophylactic
laxatives are recommended when clozapine is initiated, and constipation should be assessed for at every consultation
- Monitor for symptoms and signs of cardiac toxicity and neutropenia; regular blood tests are mandatory to detect
blood dyscrasias and for continued supply of the medicine (white blood cell count and absolute neutrophil counts weekly
for first 18 weeks, then four-weekly)
- When prescribing other medicines, consider whether they may interact with or exacerbate the adverse effects of clozapine
- Substantial changes in cigarette or caffeine consumption may necessitate a dose adjustment of clozapine
To refresh your knowledge on the safe prescribing of clozapine, see:
Ambulance care summaries to be sent electronically to GPs for patients treated in the community
Approximately one in six people who receive ambulance care are managed in the community without requiring transfer
to a medical facility. In these cases, the patient receives a handwritten Ambulance Care Summary (ACS) Advice Sheet,
with a code which they, or their general practitioner, can use to access their full ACS report online*. However, in
many cases this information "slips through the cracks"
The RNZCGP reports that from 19th June†, 2020 St John and Wellington Free Ambulance services will send an electronic ACS
to a patient's general practitioner, even when the patient is not transported to a medical facility (including patients who
are deceased). The ACS includes the history, details of the clinical problem, treatment and recommendations provided to the
patient. It will be transferred directly into the practice's patient management system via Healthlink.
N.B. An ACS is not intended as a transfer of care document; if urgent action is required ambulance personnel will contact
the GP directly.
* The ACS can be downloaded within 7 days of the event using the patient’s ACS access code and date of birth at
John) or https://acs.wfa.org.nz/ (Wellington Free Ambulance). Reports
can be accessed after this date by requesting directly from the ambulance service.
† A trial will commence from 5th June, 2020 in Bay of Plenty, Wairarapa and Southern DHB areas
For further information about electronic patient records, see
St John or
Wellington Free Ambulance
Reconsider the use of ondansetron in pregnant women during the first trimester
Ondansetron is indicated for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy, and for preventing post-operative nausea and vomiting.
However, it is also prescribed off-label for nausea and vomiting due to other causes, including for women in the early stages of pregnancy.
Two large epidemiological studies* have now been published demonstrating an approximate 25% increase in the relative risk of oral cleft defects,
e.g. cleft lip or cleft palate, when ondansetron is used during the first trimester; amounting to approximately three additional cases per 10,000 exposed pregnancies.
Should these findings influence ondansetron use during pregnancy?
Although the absolute increased risk of oral cleft defects is small, the bottom-line is that
ondansetron should only be prescribed in severe cases (i.e. hyperemesis gravidarum) with informed consent to woman during the first trimester if the benefits of use
clearly outweigh the risks of harm to the woman and foetus, and other non-pharmacological and pharmacological methods have not worked.
In many cases, women with "morning sickness" can be managed with dietary and lifestyle interventions. If pharmacological intervention is
required there are a range of antiemetic medicines that can be considered, however, the adverse effect profile for each option must be taken into account.
For further information on managing nausea and vomiting during pregnancy, see:
* Huybrechts KF, Hernández-Díaz S, Straub L, et al. 2018. Association of maternal first-trimester
ondansetron use with cardiac malformations and oral clefts in offspring. JAMA 320(23): 2429–37. DOI:
Zambelli-Weiner A, Via C, Yuen M, et al. 2019. First trimester ondansetron exposure and risk of
structural birth defects. Reproductive Toxicology 83(Jan): 14–20. DOI:
Paper of the week: Is there a gene for thinness?
A paper published this month in Cell by Orthofer et al, may provide some important clues in unravelling the mystery of how genes influence our weight. But, unlike the
usual studies of obesity, these researchers identified a genetic determination for thinness.
First, a genome-wide association study was performed in cohort of metabolically healthy Estonians in the sixth lowest body mass index (BMI) percentile.
This identified that variations in the gene for anaplastic lymphoma kinase (ALK) were associated with thinness. ALK is an enzyme involved in
neural development and cell growth, it has been studied in detail in the context of cancer, but little is known about its role in other settings.
Next, the researchers demonstrated a potentially evolutionary conserved role for ALK in thinness by performing genetic knockdown of Alk
in the fruit fly Drosophila and found that this was associated with decreased whole-body triglyceride levels. This role was confirmed in
multiple genetic mouse models where deletion of Alk resulted in thin mice that were resistant to diet- and leptin-mutation-induced obesity.
A mechanism for the link between the ALK gene and thinness was also identified by finding that ALK expression in murine hypothalamic
neurons was associated with control of energy expenditure through sympathetic regulation of adipose tissue lipolysis.
This of course does not translate into a "miracle cure" for obesity but it adds to the knowledge in this area and provides a
further avenue of research for therapeutic treatments.
Orthofer M, Valsesia A, Mägi R, et al. Identification of ALK in Thinness. Cell 2020;
[Epub ahead of print]. doi:10.1016/j.cell.2020.04.034
If you have any information you would like us to add to our next bulletin, please email:
ASK A COLLEAGUE: Are they receiving these bulletins?
Sign up to our mailing list here