Melatonin Use in School-Aged Children and Adolescents: An Exploration of Caregiver and Pharmacist Perspectives.

OBJECTIVE: This study aims to explore the perspectives and experiences of Australian caregivers and community pharmacists about pediatric melatonin use. METHODS: A convenience sample of caregivers with children (aged 11-16 years) using melatonin as a sleep aid and community pharmacists (including pharmacist interns) were recruited. Participants first completed an online survey followed by an online semi-structured interview. Interviews were guided by a schedule of questions for the respective participant groups, broadly exploring their beliefs about melatonin, experiences in using/supplying melatonin, and perceived facilitators/barriers for melatonin use. Interviews were digitally recorded, transcribed verbatim, and analyzed using the Framework Approach. RESULTS: Fourteen caregivers of predominantly neurodiverse adolescents and 24 community pharmacists were interviewed. While melatonin was perceived by caregivers of both typically developing and neurodiverse dependants as safer than pharmacological sleep aids, treatment was only initiated after trialling non-pharmacological strategies first. Pharmacists expressed concerns around the ambiguities in practice and the limited scope of existing resources for guiding pediatric melatonin use. Caregivers frequently deferred to the information available online to procure products or self-adjust doses and dosing schedules. Both pharmacists and caregivers emphasized the need for more affordable and age-appropriate proprietary formulations that are readily accessible. CONCLUSION: Melatonin is administered predominantly by caregivers of neurodiverse adolescents to address their sleep disturbances. The findings underscore the need for reliable, evidence-based information to guide safe and appropriate use of melatonin in pediatric populations. Patient education is also warranted to address maladaptive medication-administration practices. Lastly, there is a need for stronger regulatory oversight of melatonin products to ensure their quality and safety of use.

Psychotropic and other medicine use at time of death by suicide: a population-level analysis of linked dispensing and forensic toxicology data.

OBJECTIVES: To determine the numbers and types of medicines dispensed around the time of death to people who die by suicide; to compare the medicines recently dispensed and those recorded in post mortem toxicology reports. DESIGN, SETTING, PARTICIPANTS: Analysis of linked National Coronial Information System (NCIS) and Pharmaceutical Benefits Scheme (PBS) data from the Australian Suicide Prevention using Health Linked Data (ASHLi) study, a population-based case series study of closed coronial cases for deaths of people in Australia aged ten years or more during 1 July 2013 - 10 October 2019 deemed by coroners to be the result of intentional self-harm. MAIN OUTCOME MEASURES: Proportions of people to whom medicines were dispensed around the time of death, by medicine group, class, and specific medicine; comparison of medicines recently dispensed and those detected by post mortem toxicology. RESULTS: Toxicology reports were available for 13 541 of 14 206 people who died by suicide (95.3%; 10 246 men, 75.7%); poisoning with medicines contributed to 1163 deaths (8.6%). At least one PBS-subsidised medicine had been dispensed around the time of death to 7998 people (59.1%). For three medicine classes, the proportions of people in whom the medicines were detected post mortem and their death was deemed medicine-related were larger for those without records of recent dispensing than for people for whom they had been dispensed around the time of death: antidepressants (17.7% v 12.0%), anxiolytics (16.3% v 14.8%), and sedatives/hypnotics (24.3% v 16.5%). At least one recently dispensed medicine not detected post mortem was identified for 6208 people (45.8%). CONCLUSIONS: A considerable proportion of people who died by suicide were not taking psychotropic medicines recently dispensed to them, suggesting non-adherence to pharmacotherapy, and a smaller than expected proportion were using antidepressants. Conversely, medicines that had not recently been dispensed were detected post mortem in many people for whom poisoning with medicines was a contributing factor, suggesting medicine stockpiling.

Optimising alkalinisation and its effect on QRS narrowing in tricyclic antidepressant poisoning.

AIMS: The objectives were to determine the effect of NaHCO3 and/or mechanical ventilation on the biochemical profile and serum alkalinisation in tricyclic antidepressant (TCA) poisoning and investigate the impact of effective alkalinisation therapy on the QRS interval in TCA poisoning. METHODS: This was a retrospective review of TCA poisonings from three Australian toxicology units and a poisons information centre (Jan 2013 to Jan 2019). We included patients with TCA toxicity who ingested>10 mg/kg or had clinically significant toxicities consistent with TCA poisoning, and analysed patients' clinical, electrocardiogram and biochemical data. RESULTS: Of 210 patients, 84 received NaHCO3 and ventilation (dual therapy), 12 NaHCO3 , 46 ventilation and 68 supportive care treatment. When compared with single/supportive groups, patients who received dual therapy had taken a significantly higher median dose of TCA (1.5 g vs1.3 g, P < .001), a longer median maximum QRS interval (124 ms, interquartile ranges [IQR] 108-138 vs106 ms, IQR 98-115, P < .001) and were more likely to have seizures (14% vs3%, P = .006) and arrhythmias (17% vs1%, P < .001). The dual therapy group demonstrated greater increases in serum pH (median 0.11, IQR 0.04-0.17) compared to the single/supportive therapy group (median 0.03, IQR -0.01-0.09, p < .001). A greater proportion of patients reached the target pH 7.45-7.55 in the dual therapy group (59%) compared to the single/supportive therapy group (10%) (P < .001). For each 100 mmol bolus of NaHCO3 given, the median increase in serum sodium was 2.5 mmol/L (IQR 1.5-4.0). QRS narrowing occurred twice as quickly in the dual therapy vs single/supportive therapy group. CONCLUSIONS: A combination of NaHCO3 and mechanical ventilation was most effective in achieving serum alkalinisation and was associated with a more rapid narrowing of the QRS interval. We advise that the maximal dose of NaHCO3 should be <400 mmol (6 mmol/kg).

Prescribed medicine use and extent of off-label use according to age in a nationwide sample of Australian children.

BACKGROUND: Medicine prescribing for children is impacted by a lack of paediatric-specific dosing, efficacy and safety data for many medicines. OBJECTIVES: To estimate the prevalence of medicine use among children and the rate of 'off-label' prescribing according to age at dispensing. METHODS: We used population-wide primarily outpatient dispensing claims data for 15% of Australian children (0-17 years), 2013-2017 (n = 840,190). We estimated prescribed medicine use and 'off-label' medicine use according to the child's age (<1 year, 1-5 years, 6-11 years, 12-17 years) defined as medicines without age-appropriate dose recommendations in regulator-approved product information. Within off-label medicines, we also identified medicines with and without age-specific dose recommendations in a national prescribing guide, the Australian Medicines Handbook Children's Dosing Companion (AMH CDC). RESULTS: The overall dispensing rate was 2.0 dispensings per child per year. The medicines with the highest average yearly prevalence were systemic antibiotics (435.3 per 1000 children), greatest in children 1-5 years (546.9 per 1000). Other common medicine classes were systemic corticosteroids (92.7 per 1000), respiratory medicines (91.2 per 1000), acid-suppressing medicines in children <1 year (47.2 per 1000), antidepressants in children 12-17 years (40.3 per 1000) and psychostimulants in children 6-11 years (27.0 per 1000). We identified 12.2% of dispensings as off-label based on age, but 66.3% of these had age-specific dosing recommendations in the AMH CDC. Among children <1 year, off-label dispensings were commonly acid-suppressing medicines (35.5%) and topical hydrocortisone (33.1%); in children 6-11 years, off-label prescribing of clonidine (16.0%) and risperidone (13.1%) was common. Off-label dispensings were more likely to be prescribed by a specialist (21.7%) than on-label dispensings (7.5%). CONCLUSIONS: Prescribed medicine use is common in children, with off-label dispensings for medicines without paediatric-specific dosing guidelines concentrated in classes such as acid-suppressing medicines and psychotropics. Our findings highlight a need for better evidence to support best-practice prescribing.

Vitamin and mineral supplement exposures: cases reported to Australia's largest Poisons Information Centre, 2014-2015 to 2018-2019.

Vitamin and mineral supplements (VMS) are widely available and commonly used. Little is known about patterns of poisoning exposures to VMS in the Australian population. We performed a retrospective study of calls to the New South Wales Poisons Information Centre (NSWPIC), July 2014-June 2019. NSWPIC is Australia's largest PIC, taking approximately 100 000 calls/year (50 % of Australian poisoning calls) from healthcare professionals and members of the public. We conducted additional analyses on Fe exposures due to their high risk of acute toxicity. There were 10 944 VMS exposures reported to NSWPIC during the study period, increasing 9·6 % per annum over a 5-year period (95 % CI, 7·2, 12·1 %). Toddlers (1-4 years) accounted for 41·5 % (4546) of cases. Agents most commonly involved were multivitamins (n 3610), vitamin D (n 2080), Fe (n 1533) and Mg (n 804). In 17·7 % (1934) of cases, the call originated from hospital or the patient was referred to hospital by NSWPIC. Fe exposures increased by 14·0 % per year (95 % CI, 9·5, 18·5 %), and most were associated with high-strength products (> 45 mg elemental Fe per unit dose, n 1036). Fe exposures were hospitalised in 38 % of cases (n 583). We conclude that VMS exposures are increasing in Australia. Although most exposures can be managed at home, many required hospitalisation. Fe exposures are increasing and had higher rates of hospitalisation than other agents. VMS are often considered safe and without the potential for adverse effects, highlighting the importance of public education into the potential risks of misuse of these products.

Opioid exposures in children under 5 years of age (2004-2019): A retrospective study of calls to Australia's largest poisons information centre.

AIM: To describe time trends in opioid exposures in children under 5 years, and to describe patient demographics, the medicines involved, the reasons for exposure and disposition. METHODS: A retrospective analysis of paediatric (<5 years of age) opioid exposure calls to the New South Wales Poisons Information Centre (NSWPIC, Australia's largest poison centre), 2004-2019. Joinpoint regression analysis was used to examine temporal trends. RESULTS: There were 4807 cases of paediatric opioid exposure during the 16 year study period, with an average of 300 exposures per year. Exposures increased, 2004-2007, with an annual percentage change (APC) of 14.6% (95% CI = 4.3 to 26.0%), then decreased, 2007-2016, APC -3.4% (95% CI = -5.3 to -1.3%). A steeper decrease was observed after 2016, APC -14.1% (95% CI = -21.8 to -5.6%). The overall APC was -2.3% (95% CI = -4.7 to 0.2%), 2004-2019. Accidental exposures accounted for 86% of calls (4137). The majority of calls were from family members regarding exposures that happened at home, highlighting the need for safety initiatives. The preparations most frequently involved were paracetamol/opioid combination products (primarily codeine), 53% (2566) and ibuprofen/opioid combinations 14% (650). Twenty-two percent of cases were referred to a hospital (1062), and a further 15% (719) of calls originated from hospital staff. CONCLUSION: Opioid exposures in young Australian children continue to occur; however, the rate has declined since 2007. Safe storage and parent education initiatives could further reduce the burden of paediatric opioid poisoning in Australia.

Changes in sales of analgesics to pharmacies after codeine was rescheduled as a prescription only medicine.

OBJECTIVE: To investigate changes in sales to pharmacies of over-the-counter (OTC) and prescription analgesics, cold and flu products, and cough suppressants after the rescheduling of codeine as a prescription only medicine in February 2018. DESIGN: Interrupted time series analysis of sales to pharmacies. SETTING: Pharmaceutical sales to community pharmacies in Australia, March 2015 - March 2019. The period January 2017 (month after rescheduling was announced) to January 2018 (month before rescheduling was implemented) was excluded from the time series analysis. MAIN OUTCOME MEASURES: Monthly pack and tablet sales per 10 000 population of OTC and prescription analgesics, cold and flu products, and cough suppressants. RESULTS: During 2016, 7586 packs and 248 127 tablets of OTC codeine per 10 000 population were sold to pharmacies; in the 14 months after rescheduling, a small level increase in monthly prescription codeine sales was evident (2247 tablets/capsules per 10 000 population; 95% CI, 1231-3264 per 10 000 population). Monthly OTC analgesic sales increased by 258 (95% CI, 151-365) packs per 10 000 population and 37 856 (95% CI, 26 143-49 569) tablet/capsules per 10 000 population. Monthly sales of single ingredient paracetamol (41 415 [95% CI, 31 374-51 456] tablets/capsules per 10 000 population), ibuprofen (1392 [95% CI 916-1868] tablets/capsules per 10 000 population), paracetamol/ibuprofen (1618 tablets [95% CI, 1567-1669] tablets/capsules per 10 000 population), and other paracetamol combinations (233 [95% CI, 112-353] tablets/capsules per 10 000 population) all increased, but not those of prescription analgesic products not containing codeine. Rises for OTC cold/flu products containing the opioid derivative dextromethorphan were small; sales of OTC cough suppressants containing opioid derivatives (dextromethorphan, pholcodine, dihydrocodeine) did not change. CONCLUSIONS: The rescheduling of codeine was followed by increased sales to pharmacies of paracetamol, ibuprofen, and paracetamol combination products. While these products carry no risk of dependence, their inappropriate use is also associated with harms that warrant adverse event monitoring.

Paracetamol poisoning-related hospital admissions and deaths in Australia, 2004-2017.

OBJECTIVES: To assess the numbers of paracetamol overdose-related hospital admissions and deaths in Australia since 2007-08, and the overdose size of intentional paracetamol overdoses since 2004. DESIGN, SETTING: Retrospective analysis of data on paracetamol-related exposures, hospital admissions, and deaths from the Australian Institute of Health and Welfare National Hospital Morbidity Database (NHMD; 2007-08 to 2016-17), the New South Wales Poisons Information Centre (NSWPIC; 2004-2017), and the National Coronial Information System (NCIS; 2007-08 to 2016-17). PARTICIPANTS: People who took overdoses of paracetamol in single ingredient preparations. MAIN OUTCOME MEASURES: Annual numbers of reported paracetamol-related poisonings, hospital admissions, and deaths; number of tablets taken in overdoses. RESULTS: The NHMD included 95 668 admissions with paracetamol poisoning diagnoses (2007-08 to 2016-17); the annual number of cases increased by 44.3% during the study period (3.8% per year; 95% CI, 3.2-4.6%). Toxic liver disease was documented for 1816 of these patients; the annual number increased by 108% during the study period (7.7% per year; 95% CI, 6.0-9.5%). The NSWPIC database included 22 997 reports of intentional overdose with paracetamol (2004-2017); the annual number increased by 77.0% during the study period (3.3% per year; 95% CI, 2.5-4.2%). The median number of tablets taken increased from 15 (IQR, 10-24) in 2004 to 20 (IQR, 10-35) in 2017. Modified release paracetamol ingestion report numbers increased 38% between 2004 and 2017 (95% CI, 30-47%). 126 in-hospital deaths were recorded in the NHMD, and 205 deaths (in-hospital and out of hospital) in the NCIS, with no temporal trends. CONCLUSIONS: The frequency of paracetamol overdose-related hospital admissions has increased in Australia since 2004, and the rise is associated with greater numbers of liver injury diagnoses. Overdose size and the proportion of overdoses involving modified release paracetamol have each also increased.

A Review of Baclofen Overdoses in Australia: Calls to a Poisons Information Centre and a Case Series.

AIM: to describe trends in baclofen reports to Australia's largest Poisons Information Centre (PIC) and present a case series detailing severity of overdoses. SHORT SUMMARY: PBS data demonstrates baclofen use is increasing in Australia, while calls to NSWPIC illustrate an increase in number of exposures associated with toxicity. Baclofen toxicity may require prolonged intensive care admission. To minimize harms associated, especially with off-label baclofen prescribing for AUD, prescribers should pay careful attention to psychiatric comorbidities, and closely monitor treatment and dispensing. METHODS: this is a retrospective observational study of baclofen overdoses reported to New South Wales PIC (NSWPIC) from January 1 2004 to 31 December 2016. In addition, referrals to a metropolitan toxicology service relating to baclofen toxicity from 2014 to 2017 were analysed. The number of Pharmaceutical Benefit Scheme (PBS) claims for baclofen were also reviewed. RESULTS: during the 13-year study period, 403 cases of baclofen toxicity were reported to NSWPIC. There was a 230% increase in annual exposures over this period, 71% of patients were symptomatic, with 77% requiring hospitalization. Coingestants were reported in 53%, with 57% being psychoactive medications (including alcohol). An increase in number of baclofen dispensing episodes was also noted. From the five cases of deliberate self-harm reported to the metropolitan toxicology service, three obtained baclofen for management of alcohol use disorder (AUD) and required prolonged treatment in the intensive care unit (ICU). CONCLUSIONS: NSWPIC data shows an increase in number of calls regarding intentional baclofen exposures in parallel with increase the number of baclofen PBS claims. These closely parallel the increase in dispensing of baclofen since 2008. Case studies presented reinforce the severity of baclofen toxicity. Together, they demonstrate the potential risk of harm of baclofen prescribing, and the greater need for caution. Baclofen should be considered carefully in patients high risk of overdose or be used only in specialist services with close monitoring.

Person-level changes in oxycodone use after the introduction of a tamper-resistant formulation in Australia.

BACKGROUND: Australia introduced tamper-resistant controlled-release (CR) oxycodone in April 2014. We quantified the impact of the reformulation on dispensing, switching and poisonings. METHODS: We performed interrupted time-series analyses using population-representative national dispensing data from 2012 to 2016. We measured dispensing of oxycodone CR (≥ 10 mg), discontinuation of use of strong opioids and switching to other strong opioids after the reformulation compared with a historical control period. Similarly, we compared calls about intentional opioid poisoning using data from a regional poisons information centre. RESULTS: After the reformulation, dispensing decreased for 10-30 mg (total level shift -11.1%, 95% confidence interval [CI], -17.2% to -4.6%) and 40-80 mg oxycodone CR (total level shift -31.5%, 95% CI -37.5% to -24.9%) in participants less than 65 years of age but was unchanged in people 65 years of age or older. Compared with the previous year, discontinuation of use of strong opioids did not increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00), but switching to oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32 to 1.79). Switching to morphine varied by age (p < 0.001), and the greatest increase was in participants less than 45 years of age (adjusted HR 4.33, 95% CI 2.13 to 8.80). Participants switching after the reformulation were more likely to be dispensed a tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40, 95% CI 1.09 to 1.79). Calls for intentional poisoning that involved oxycodone taken orally increased immediately after the reformulation (incidence rate ratio (IRR) 1.31, 95% CI 1.05-1.64), but there was no change for injected oxycodone. INTERPRETATION: The reformulation had a greater impact on opioid access patterns of people less than 65 years of age who were using higher strengths of oxycodone CR. This group has been identified as having an increased risk of problematic opioid use and warrants closer monitoring in clinical practice.