The most common adverse effects associated with dulaglutide are gastrointestinal-related, including nausea, diarrhoea and vomiting. Serious adverse effects are rare but can still occur, e.g. acute pancreatitis, cholecystitis, hypoglycaemia, acute kidney injury secondary to dehydration. Hypoglycaemia risk is increased when dulaglutide is used with insulin or sulfonylureas; consider lower doses of these medicines if co-prescribing. Click here to read more. Also a reminder that dulaglutide should not be prescribed concurrently with vildagliptin.

N.B. Dulaglutide is currently subject to supply shortages, and it is strongly recommended that it is conserved for patients already initiated on it, who are receiving benefit; see Bulletin 86.

As reported in Bulletin 58 and 71, abnormal uterine bleeding has been noted in some women taking oral anticoagulants. While this risk is low, patients should be informed that they may experience new or increased abnormal uterine bleeding with oral anticoagulant use, and should discuss this with their primary care clinician if it occurs. The bleeding may be caused by the oral anticoagulant, but it is important to investigate and exclude other possible underlying causes, e.g. fibroids, endometriosis or gynaecological cancer. Click here to read more.

Several medicine data sheets have been recently updated with new safety information; for example: amoxicillin + clavulanic acid (drug-induced enterocolitis syndrome has been reported, mainly in children, interaction with methotrexate), estriol (may induce symptoms of hereditary and acquired angioedema; co-administration with hepatitis C combination regimens can significantly increase ALT levels), methotrexate (males should use contraception during treatment and for three months after) and tramadol (hypoglycaemia). Click here to read more.

In the September, 2023, meeting, the Committee recommended updates to medicine data sheets including: GLP-1 receptor agonists (e.g. dulaglutide) should be updated to include the risk of intestinal obstruction (including ileus); Acetylcholinesterase inhibitors (e.g. donepezil, rivastigmine and galantamine) should be updated to include the risk of QT prolongation and torsade de pointes. Click here to read more.

SDRIFE is a type of medicine-induced erythematous rash involving the skin folds. It was originally referred to as “baboon syndrome” as it presents as a v-shaped rash in the gluteal or groin area, with additional involvement in other skin folds or flexural regions, e.g. armpit, behind the knee. It is most commonly caused by beta-lactam antibiotics (e.g. penicillins, cephalosporins - 50% of cases). This is a self-limiting reaction, without systemic symptoms (which is a key characteristic of SDRIFE, i.e. no systemic symptoms), and is expected to resolve when the medicine is stopped. Topical steroids may assist in clearing the rash more quickly. Re-exposure to a medicine that has caused SDRIFE usually results in recurrence of rash. Click here to read more.

The currently funded brand of ciprofloxacin tablets, Cipflox, is being discontinued by the supplier, Viatris. At this stage, ciprofloxacin (Cipflox) 500 mg and 750 mg tablets are out of stock. The remaining supply of ciprofloxacin 250 mg tablets is limited and expected to run out at the end of December, 2023.

An alternative funded product, 500 mg ciprofloxacin (Ciprofloxacin – Torrent) has been listed on the Pharmaceutical Schedule but is not approved by Medsafe. It will need to be prescribed for supply under Section 29 of the Medicines Act 1981. Currently there are no alternative products available to replace the 250 mg and 750 mg ciprofloxacin tablets.

The funded brand of escitalopram is changing. Escitalopram Ethics will cease being funded from 1^st April, 2024. Its replacement, Ipca-Escitalopram, has been listed and funded on the Pharmaceutical Schedule since 1^st November, 2023. Patients should be advised that while the shape of the tablet and packaging are changing, the active ingredient remains the same.

A patient information leaflet about the escitalopram brand change is available here.

There is an ongoing supply issue affecting stock of the olanzapine depot injection. There is limited stock still available, and, as reported in Bulletin 88, no new patients are to be initiated on olanzapine depot injections from 1^st December, 2023. It is expected that stock availability will continue to be limited for the next six to nine months due to global manufacturing and supply constraints.

In situations where the prescriber believes olanzapine depot injections should be initiated for a patient with exceptional clinical circumstances, they can apply for a Named Patient Pharmaceutical Assessment (NPPA); note the deadlines for applications before the summer break.

Pharmac is also currently consulting on a proposal to fund an aripiprazole depot injection. Submissions on this proposal close today (8^th December, 2023).

There continues to be a supply issue affecting stock of oxycodone controlled-release tablets, as reported in Bulletin 85. Currently, 5 mg oxycodone (Sandoz) controlled-release tablets are out of stock, with resupply not expected until January, 2024. Stock of 10 mg and 20 mg oxycodone tablets has been resupplied.

Reminder: Patients should be instructed to swallow 10 mg oxycodone (Sandoz) controlled-release tablets whole. Cutting, crushing or chewing controlled-release tablets may increase the rate of absorption resulting in potentially harmful blood levels and adverse effects. Suitable alternative medicines include morphine modified-release capsules (m-Eslon SR) or oxycodone 5 mg/5 mL oral liquid.

• Power differences exist between healthcare providers and service users, i.e. patients. Cultural safety considers how these power differences, along with healthcare providers previous experiences and biases, may negatively influence health interactions and outcomes. Addressing these factors may help to develop health services Māori can relate to and feel comfortable using. “The word safety is deliberately chosen to give power to the consumer.”
• Anti-racism strategies (educating health professionals about how racism may be perpetuated in everyday interactions) aid cultural safety by giving health practitioners the knowledge and tools to identify and address situations or systems in healthcare that enable racism, e.g. invalidation or minimisation of concerns or offensive behaviours
• Reported barriers to effective healthcare for Māori include the availability of health services (e.g. location, timing), health service costs and cultural barriers that result in health services where Māori may feel uncomfortable or unsafe
• Collecting accurate ethnicity data should become an organisational priority. Access to high quality ethnicity data enables healthcare organisations to identify and address disparities between non-Māori and Māori.
• Tikanga Māori, or customs and protocols, may become more important to Māori during times of illness or injury and an understanding of this by the healthcare providers may aid communication, facilitating positive interactions and result in better health outcomes. Examples include:
  • Whakawhanaungatanga – allow space and time during the initial consultation to build rapport between the primary care clinician and the patient and whānau. Rushing or ignoring this step may affect communication at a later stage.
  • Healthcare professionals should make a point of introducing themselves and describe their role. Also, ask the patient or whānau if they have any cultural, spiritual or language needs and record these appropriately.
  • Understand and respect the importance of names and correct pronunciation. If you are unsure, ask and make a record of the preferred name in the patient notes.
  • Respect cultural beliefs (e.g. for Māori, the head is tapu, or sacred, so provide an explanation and seek permission before an examination of the head), allowing time for whānau to perform karakia or blessings (e.g. before a procedure or administration of a blood product)

• A randomised, double-blind, placebo-controlled study was conducted between October, 2019, and April, 2022, including 463 participants from 55 general practices in England
• Eligible participants were aged over 18 years with a primary diagnosis of IBS and had not responded to first-line treatments
  • Females made up a larger portion of the participants (68%)
  • The mean age of participants was 48.5 years
  • Most participants had either diarrhoea predominant IBS (IBS-D) or mixed diarrhoea and constipation IBS (IBS-M) (> 80%), and a moderate to severe IBS-SSS score (> 85%)
• Participants were randomly assigned to receive either low-dose oral amitriptyline or placebo tablets for six months. Patients were initiated on one tablet (10 mg amitriptyline in the intervention group), once daily, at night. This dose was titrated up to a maximum of three tablets (30 mg amitriptyline in the intervention group), once daily, at night, over three weeks.
  • Tolerability was assessed during weeks one and three and participants were permitted to modify their dose during the study period depending on treatment efficacy and adverse effects (as would be the case in primary care). A dose titration document was provided to allow patient self-management and there was access to on-call support nurses, if required. N.B. This resource could be adapted for people who take TCAs for other conditions.
• Treatment efficacy was measured using the IBS Severity Scoring System questionnaire after six months (the primary outcome). IBS-SSS score was also measured at 3 and 12 months.
• A subjective global assessment (SGA) was used to assess relief of IBS symptoms after six months (secondary outcome)
  • Other secondary outcomes measured in this study include IBS-associated somatic symptoms, anxiety and depression scores and the participants ability to work and undertake daily activities
• A significant mean difference in IBS-SSS score was observed in the intervention group after three and six months versus placebo (–23; p=0·014 and –27; p=0·008)
• Participants who took amitriptyline were 70% more likely to report relief of IBS symptoms (based on SGA) after three months and 80% more likely after six months, compared to placebo
• Treatment adherence was similar for both groups after three months, but higher in the amitriptyline group after six months
• Discontinuation rates were 20% in the intervention group and 26% in the placebo group. Reasons for discontinuation included adverse effects (most common), perceived lack of benefit and loss to follow-up.
• There was a significantly higher rate of adverse effects after three months in the intervention group compared to the control group. However, this difference was not apparent after six months. Adverse effects in the intervention group were mainly related to amitriptyline’s anticholinergic activity, e.g. dry mouth (54%), drowsiness (53%), blurred vision (17%), constipation (56%) and difficulty with urination (22%). Very few adverse effects were considered severe (< 5%).
• No improvement in anxiety or depression scores was observed in the intervention group. This supports the hypothesis that the beneficial effects of TCAs for IBS symptoms do not involve the psychological mechanisms.
• Only a small number of people with constipation dominant IBS (IBS-C) were included in this study. Constipation is a recognised adverse effect associated with amitriptyline and this was stated on the information leaflet, therefore, people with IBS-C may have been hesitant to take part. Although the study was not powered to analyse the effect of amitriptyline on the individual IBS subtypes, there was no reported increase in serious adverse effects or study dropout in the IBS-C participant group, therefore, a trial of low-dose amitriptyline could be considered with caution in this group.
• In a recent podcast, the senior/corresponding author, who is a general practitioner, acknowledges concerns regarding anticholinergic burden with TCAs. She argues that the lower doses required for TCAs in the management of IBS (i.e. 10 – 30 mg) are much less likely to induce undesirable anticholinergic effects than the higher TCA doses used for other indications (e.g. up to 150 mg in depression).

In practice, nortriptyline may be better tolerated than amitriptyline, i.e. fewer anticholinergic effects, and may be an appropriate alternative treatment for patients with IBS.