ORCID Profile
0000-0001-5121-5827
Current Organisation
University of South Australia
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Publisher: Springer Science and Business Media LLC
Date: 16-04-2016
DOI: 10.1007/S40262-016-0394-3
Abstract: Tyrosine kinase inhibitors have been marketed as a fixed dose, 'one size fits all' treatment strategy. Physicians have also been interested in this method of dosing, knowing the complex planning of other current cancer therapies administered on a mg/m(2) or mg/kg basis and subsequent occurrence of dosing error or concern for underdosing. The 'simple and safe' strategy of a single dose of tyrosine kinase inhibitor for cancer has thus been widely adopted. However, the benefits purported to exist in the clinical trials do not appear to be borne out in clinical practice, particularly in solid tumours. In order to investigate whether pharmacokinetic variability is a contributor to the variable outcomes, pharmacokinetic targets to enable in idualisation of tyrosine kinase inhibitor administration are now emerging. Evidence suggests there is not a clear relationship of a single dose to maximum plasma concentration (C max), steady-state trough concentration (C trough) or area under the curve (AUC). Furthermore, a significant number of questions remain related to the specific timing and frequency of s le collection required to achieve optimal outcomes. This article reviews the wide variability in the literature on this topic, specifically the different pharmacokinetic targets of the same drug for different cancers, for different states of cancer, and changing pharmacokinetic parameters over a treatment interval in cancer. It appears the optimal s ling times to enable appropriate dose recommendations across patients and diseases may vary, and are not always trough concentrations at steady state. Importantly, the need to be pragmatic in a clinical setting is paramount. Lastly, international collaborations to increase s le size are highly recommended to ensure enough patients are s led to be sure of a clinical benefit from this concentration-directed methodology.
Publisher: SAGE Publications
Date: 09-08-2018
Abstract: Dyspnoea, a common and multifactorial symptom in patients with acute coronary syndrome, has been associated with lower quality of life and hospital readmission. Prescriber preference for antiplatelet therapy, the standard of care in this patient group, is shifting to ticagrelor due to mortality benefits demonstrated in trials compared with clopidogrel. In these trials, dyspnoea was more commonly reported in patients prescribed ticagrelor but the aetiology is still debated. An observational cohort study was conducted to quantify the rates and severity of dyspnoea reported in patients with acute coronary syndrome and newly prescribed ticagrelor compared with those prescribed clopidogrel. Dyspnoea was more commonly reported in patients prescribed ticagrelor at each follow up post-discharge ( p = 0.016). Rates were higher than previously reported in clinical trials. In some patients, dyspnoea necessitated drug therapy change and was associated with readmission to hospital ( p = 0.046). As ticagrelor is widely prescribed as a first-line antiplatelet agent for a range of patients with acute coronary syndrome, the incidence of dyspnoea in a generalized patient cohort may result in higher rates of drug discontinuation. This in turn could lead to higher rates of rehospitalisation and potential treatment failure than that reported from the controlled setting of a clinical trial.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.MSARD.2021.103412
Abstract: There is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. To evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). A representative s le of the Australian pharmaceutical benefits scheme data were analysed (2006-2016). Demographics of incident users and trends in incident and prevalent users were determined. In idual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006-2013 and 2014-2019). There were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006-2013 and 28.5% of initiators in 2014-2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006-2013 and 2014-2019, respectively. The availability of new DMTs has influenced both initial treatment choice and prevalence of users. In idualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems.
Publisher: Springer Science and Business Media LLC
Date: 23-03-2023
Publisher: CSIRO Publishing
Date: 25-03-2021
DOI: 10.1071/AH20018
Abstract: Objective The South Australian Medicines Evaluation Panel (SAMEP) was established in 2011 to make evidence-based recommendations on the funding of high-cost medicines in South Australian public hospitals via a high-cost medicines formulary. SAMEP represents one component of South Australia’s process for state-based health technology assessment (HTA). The aim of this study was to describe the experience of SAMEP in the context of Australia’s complex governance model for hospital-based care. Methods A retrospective review was conducted of the SAMEP process and outcomes of medicine evaluations. Decision summaries and meeting minutes were reviewed and reflected upon by the authors to explore the views of the SAMEP membership regarding the function of the committee and state-based HTA more broadly. Results SAMEP has reviewed 29 applications, with 14 (48%) listed on the high-cost medicines formulary. Three applications have been the subject of outcome review and confirm expectations of patient benefit. Conclusion Retrospective review of the committee experience suggests that state-based HTA as operationalised by SAMEP is feasible, provides greater equity of access to high-cost medicines in the South Australian public hospital system and allows for access with evidence development. What is known about the topic? State-based hospital funders often need to make decisions on the provision of high-cost medicines for which there is no national guidance or subsidy. Little published information exists about state-based approaches to medicines evaluation and reimbursement within public hospitals in Australia. What does this paper add? The South Australian experience demonstrates a method for states and territories to tackle the challenges of providing evidence-based access to high-cost medicines in Australian public hospitals. What are the implications for practitioners? This paper provides information for other jurisdictions considering state-based approaches to medicines evaluation and contributes to the broader literature about state-based HTA in Australia.
Publisher: Bentham Science Publishers Ltd.
Date: 24-01-2018
DOI: 10.2174/1568026619666181220105726
Abstract: Poor profiles of potential drug candidates, including pharmacokinetic properties, have been acknowledged as a significant hindrance to the development of modern therapeutics. Contemporary drug discovery and development would be incomplete without the aid of molecular modeling (in-silico) techniques, allowing the prediction of pharmacokinetic properties such as clearance, unbound fraction, volume of distribution and bioavailability. As with all models, in-silico approaches are subject to their interpretability, a trait that must be balanced with accuracy when considering the development of new methods. The best models will always require reliable data to inform them, presenting significant challenges, particularly when appropriate in-vitro or in-vivo data may be difficult or time-consuming to obtain. This article seeks to review some of the key in-silico techniques used to predict key pharmacokinetic properties and give commentary on the current and future directions of the field.
Publisher: Wiley
Date: 30-12-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2023
DOI: 10.1097/FTD.0000000000001047
Abstract: Different software applications have been developed to support health care professionals in in idualized drug dosing. However, their translation into clinical practice is limited, partly because of poor usability and integration into workflow, which can be attributed to the limited involvement of health care professionals in the development and implementation of drug dosing software. This study applied codesign principles to inform the design of a drug dosing software to address barriers in therapeutic drug monitoring using vancomycin as an ex le. Three workshops (face-to-face and online) were conducted by design researchers with pharmacists and prescribers. User journey storyboards, user personas, and prototyping tools were used to explore existing barriers to practice and opportunities for innovation through drug dosing software design. A prototype of the software interface was developed for further evaluation. Health care professionals (11 hospital pharmacists and 6 prescribers) with ≥2 years of clinical experience were recruited. Confidence and software usability emerged as the main themes. Participants identified a lack of confidence in vancomycin dosing and pharmacokinetic understanding and difficulty in accessing practice guidelines as key barriers that could be addressed through software implementation. Accessibility to information (eg, guidelines and pharmacokinetic resources) and information presentation (eg, graphical) within the dosing software were dependent on the needs and experience of the user. A software prototype with a speedometer-dial visual to convey optimal doses was well received by participants. The perspectives of health care professionals highlight the need for drug dosing software to be user centered and adaptable to the needs and workflow of end users. Continuous engagement with stakeholders on tool usability, training, and education is needed to promote the implementation in practice.
Publisher: Wiley
Date: 26-04-2021
DOI: 10.1111/BCP.14856
Abstract: The consumption of caffeine has been linked to osteoporosis, believed to be due to enhanced bone resorption as a result of increased calcium excretion in the urine. However, the amount of calcium in the urine may not necessarily reflect the true effect of caffeine on calcium clearance. This study therefore examined the impact of high‐dose, short‐term caffeine intake on renal clearance of calcium, sodium and creatinine in healthy adults. In a double‐blind clinical study, participants chewed caffeine ( n = 12) or placebo ( n = 12) gum for 5 minutes at 2‐hour intervals over a 6‐hour treatment period (800 mg total caffeine). Caffeine increased renal calcium clearance by 77%. Furthermore, the effect was positively correlated with sodium clearance and urine volume, suggesting that caffeine may act through inhibition of sodium reabsorption in the proximal convoluted tubule. This study confirmed that caffeine does increase renal calcium clearance and fosters further investigation into safe consumption of caffeine.
Publisher: Springer Science and Business Media LLC
Date: 02-04-2013
Publisher: Springer Science and Business Media LLC
Date: 29-04-2015
DOI: 10.1007/S11096-015-0115-2
Abstract: Guidelines recommend patients diagnosed with transient ischaemic attack (TIA) or ischaemic stroke receive antihypertensive, antithrombotic and lipid lowering medicines. Reassessment of the need for medicines associated with an increased risk of stroke is also recommended. To determine changes in the use of medicines recommended for secondary stroke prevention, medicines commonly used for treating stroke-related complications and medicines not recommended for use after ischaemic stroke, and to determine patient characteristics associated with use of all three stroke prevention medicines after TIA or ischaemic stroke. Setting Administrative health claims data from the Australian Government Department of Veterans' Affairs. This retrospective study included patients with a first-ever hospitalisation for TIA or ischaemic stroke in 2009 and alive at 4 months after discharge. Changes to medicines dispensed in the 4 months before and after hospitalisation were compared using McNemar's test. Log binomial regression analysis was used to determine patient characteristics associated with use of all three secondary stroke prevention medicines after hospitalisation for TIA or ischaemic stroke. Prevalence of medicine use after hospitalisation. 1541 patients (853 TIA, 688 ischaemic stroke) were included, with a median age of 85 years. High use of antihypertensive (82% TIA, 86 % ischaemic stroke) and antithrombotic (84% TIA, 90% ischaemic stroke) medicines was observed postdischarge, with 58% of TIA and 73% of ischaemic stroke patients receiving lipid lowering therapy. Half of the population (47% TIA, 61% ischaemic stroke) were dispensed all three classes of medicines recommended for secondary stroke prevention after discharge. Ischaemic stroke patients, younger patients, patients with more comorbid conditions and those discharged home were more likely to receive all three recommended medicine classes. Antibiotics (45% TIA, 46% ischaemic stroke), paracetamol (44% TIA, 47% ischaemic stroke), antidepressants (26% TIA, 31% ischaemic stroke) and laxatives (24% TIA, 32% ischaemic stroke) were commonly used after discharge. Increased use of sedatives and reduced use of non-steroidal anti-inflammatories was also observed after discharge. Changes to pharmacotherapy after TIA or ischaemic stroke were consistent with treatment for stroke risk factors and common stroke-related complications. Use of secondary stroke prevention medicines may be further improved among TIA patients.
Publisher: Hindawi Limited
Date: 25-08-2021
DOI: 10.1111/JCPT.13520
Abstract: Proton pump inhibitors (PPIs), used to treat and prevent gastro-oesophageal conditions, are well-tolerated but have been associated with risk including pneumonia. The extent to which initiation of PPIs can contribute to other respiratory conditions such as chronic obstructive pulmonary disease (COPD) is largely unknown. A sequence symmetry analysis (SSA) approach was applied to the Australian Department of Human Services, Pharmaceutical Benefits Scheme 10% extract. Participants were aged 45 years and older and were dispensed PPIs (ATC Codes A02BC01, A02BC02, A02BC03, A02BC04 and A02BC05) and long-acting bronchodilators (LABDs) for COPD (ATC Codes R03BB04 (PBS Item Code 10509D and 08626B), R03BB05, R03BB06, R03BB07 and R03AC18 (PBS Item Code 05137J and 05134F)) between 2013 and 2019. The analysis included patients initiated on an LABD within 12 months before or after their first prescription of a PPI. The crude sequence ratio (cSR) was calculated as the number of patients prescribed their first LABD after starting a PPI ided by the number of patients prescribed their first LABD before starting a PPI. Calculation of the adjusted sequence ratio (aSR) accounted for prescribing trends over time in initiation of each of the medicines. A signal was identified where the aSR lower 95% confidence interval (CI) was greater than one. Initiation of omeprazole was associated with a 29% increased risk of initiating a LABD (ASR = 1.29 95% CI 1.22-1.36). Initiation of esomeprazole, rabeprazole, pantoprazole or lansoprazole was associated with 25%, 15%, 8% and 8% increased risk, respectively. There is an established association between gastro-oesophageal reflux disease and COPD which has been confirmed by implementation of a sequence symmetry-based approach which demonstrated that PPI initiation is potentially associated with progression or exacerbation of COPD. The impact PPI use has directly on this association requires further investigation.
Publisher: Wiley
Date: 05-12-2019
DOI: 10.1002/PSP4.12364
Publisher: Therapeutic Guidelines Limited
Date: 05-12-2016
Publisher: Wiley
Date: 03-2009
DOI: 10.1002/J.2055-2335.2009.TB00705.X
Abstract: The role of in idual hepatic cytochrome P450 (CYP) enzymes in drug metabolism and the factors that modulate CYP activity are becoming increasingly well understood. These advances have resulted in a better understanding of drug‐drug and drug‐ food interactions and an enhanced capacity to predict drug interactions that may occur with new drugs. This final article in the series describes the issues and principles that are important in identifying and assessing drug interactions that involve CYP enzymes.
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 10-02-2017
Abstract: The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/organic anion-transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John's wort (SJW 1000 mg/kg positive control), or Milli-Q water for 14 days. On day 15, rats either were administered fexofenadine (orally or i.v.), had their livers isolated and perfused with fexofenadine, or had their small intestines ided into four segments (SI-SIV) and analyzed for P-gp and Oatp1a5. In vivo, SJW increased the clearance of i.v. administered fexofenadine by 28%. Garlic increased the area under the curve
Publisher: Springer Science and Business Media LLC
Date: 06-08-2022
DOI: 10.1007/S40801-022-00322-6
Abstract: Studies have found an increased risk of pyoderma gangrenosum associated with rituximab. The structural properties and pharmacological action of rituximab may affect the risk of pyoderma gangrenosum. Additionally, pyoderma gangrenosum is associated with autoimmune disorders for which rituximab is indicated. We aimed to determine whether rituximab is disproportionally associated with pyoderma gangrenosum using a systems biology-informed approach. Adverse event reports were extracted from the US Food and Drug Administration Adverse Event Reporting System (FAERS, 2013-20). The Bayesian Confidence Propagation Neural Network Information Component was used to test for disproportionality. Comparators used to determine potential causal pathways included all other medicines, all medicines with a similar structure (monoclonal antibodies), all medicines with the same pharmacological target (CD20 antagonists) and all medicines used for the same indication(s) as rituximab. Thirty-two pyoderma gangrenosum cases were identified, 62.5% were female, with a median age of 48 years. There was an increased association of pyoderma gangrenosum with rituximab compared with all other medicines (exponentiated Information Component 6.75, 95% confidence interval (CI) 4.66-9.23). No association was observed when the comparator was either monoclonal antibodies or CD20 antagonists. Conditions for which an association of pyoderma gangrenosum with rituximab was observed were multiple sclerosis (6.68, 95% CI 1.63-15.15), rheumatoid arthritis (2.67, 95% CI 1.14-4.80) and non-Hodgkin's lymphoma (2.94, 95% CI 1.80-3.73). Pyoderma gangrenosum was reported more frequently with rituximab compared with all other medicines. The varying results when restricting medicines for the same condition suggest the potential for confounding by indication. Post-market surveillance of biologic medicines in FAERS should consider a multi-faceted approach, particularly when the outcome of interest is associated with the underlying immune condition being treated by the medicine of interest.
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1111/J.1538-7836.2010.03923.X
Abstract: Prasugrel is a newly marketed antiplatelet drug with improved cardiac outcomes as compared with clopidogrel for acute coronary syndromes involving percutaneous coronary intervention (PCI). Analysis of a subset of the TRITON-TIMI 38 trial demonstrated that cytochrome P450 2C19 (CYP2C19) reduced-function genotypes are associated with differential clinical responses to clopidogrel, but not prasugrel. Whether the CYP2C19 genotype has the potential to influence clinical choice of these drugs prior to PCI for in iduals with unstable angina or non-ST segment elevation myocardial infarction is currently uncertain. An exploratory, secondary analysis was undertaken to estimate the clinical benefit of prasugrel over clopidogrel in subgroups defined by CYP2C19 genotype, by integrating the published results of the genetic substudy and the overall TRITON-TIMI 38 trial. In iduals with a CYP2C19 reduced-metabolizer genotype were estimated to have a substantial reduction in the risk of the composite primary outcome (cardiovascular death, myocardial infarction, or stroke) with prasugrel as compared with clopidogrel [relative risk (RR) 0.57 95% confidence interval (CI) 0.39-0.83]. For CYP2C19 extensive metabolizers (∼70% of the population), however, the composite outcome risks with prasugrel and clopidogrel were not substantially different (RR 0.98 95% CI 0.80-1.20). Integration of the TRITON-TIMI 38 data suggests that the CYP2C19 genotype can discriminate between in iduals who receive extensive benefit from using prasugrel instead of clopidogrel, and in iduals with comparable clinical outcomes with prasugrel and clopidorel. Thus, CYP2C19 genotyping has the potential to guide the choice of antiplatelet therapy, and further research is warranted to validate this estimate.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.XPHS.2015.12.001
Abstract: The chairs of each of the 8 Special Interest Groups of the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation have compiled opinions with regard to major challenges for the pharmaceutical sciences over the next 5-10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics harmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-05-2021
Publisher: SAGE Publications
Date: 17-07-2014
DOI: 10.1111/IJS.12303
Publisher: Springer Science and Business Media LLC
Date: 05-04-2022
DOI: 10.1186/S12931-022-02010-Z
Abstract: In elderly populations, paracetamol may be used regularly for conditions such as osteoarthritis. Paracetamol has been associated with respiratory disease through a proposed mechanism of glutathione depletion and oxidative stress. Given that chronic obstructive pulmonary disease (COPD) is frequently co-morbid with osteoarthritis, this study investigated whether the dose and timing of paracetamol exposure may induce COPD exacerbations. The study population was 3523 Australian Government Department of Veterans’ Affairs full entitlement holders who had existing COPD on 1 January 2011, who were dispensed at least one prescription of paracetamol between 1 January 2011 and 30 September 2015, and had no paracetamol dispensed in the 6 months prior to 1 January 2011. The outcome was time to first hospitalisation for COPD exacerbation after initiation of paracetamol. A weighted cumulative exposure approach was used. The association between paracetamol exposure and COPD exacerbation was protective or harmful depending on the dose, duration, and recency of exposure. Compared to non-use, current use at the maximum dose of 4 g daily for 7 days was associated with a lower risk (HR = 0.78, 95% CI = 0.67–0.92) and a higher risk after 30 days (HR = 1.27, 95% CI = 1.06–1.52). Risk declined to baseline after 2 months. For past use, there was a short-term increase in risk on discontinuation depending of dose, duration and time since stopping. Patients and doctors should be aware of the possible risk of COPD exacerbation with higher dose paracetamol 1 to 6 weeks after initiation or discontinuation, but no increased risk after 2 months.
Publisher: BMJ
Date: 20-12-2022
Publisher: Future Medicine Ltd
Date: 08-2008
DOI: 10.2217/14622416.9.8.1027
Abstract: Objective: Chemotherapy-induced nausea and vomiting is a significant clinical problem. The 5HT 3 receptor antagonists are effective anti-emetic medications but approximately 30% of patients do not respond. Method: We examined the HTR3C gene, which is believed to encode a subunit of the 5HT 3 receptor, for genetic variation and association with anti-emetic efficacy in a group of 70 patients receiving cancer chemotherapy. Results: Seven novel mutations were identified three mutations resulted in amino acid substitutions, two were synonymous and two were intronic. No statistically significant associations between either isolated mutations or estimated haplotypes and anti-emetic efficacy were detected. Conclusion: The results of this investigation indicate that the genetic variants that have been identified within HTR3C do not predict response to 5HT 3 antagonists, necessitating further investigation of possible genetic determinants of 5HT 3 antagonist efficacy.
Publisher: AMPCo
Date: 07-2014
DOI: 10.5694/MJA13.00186
Abstract: To examine recent trends in the use of secondary stroke prevention medicines by transient ischaemic attack (TIA) and ischaemic stroke survivors. Retrospective observational study of patients aged ≥ 65 years who were hospitalised with a TIA or ischaemic stroke between January 2000 and December 2009. Use of antihypertensive, antithrombotic and lipid-lowering medicines by patients was determined monthly, using claims data from the Australian Government Department of Veterans' Affairs, commencing in January 2003. Monthly prevalence of use of secondary stroke prevention medicines. Between 2003 and 2009, small increases in use (less than 2% relative increase annually) were observed for antihypertensive and antithrombotic medicines among 19 019 patients. There was a 9% relative increase in use of lipid-lowering therapy each year. The proportion of patients dispensed all three recommended medicine classes nearly doubled over the 7-year period. By December 2009, about 80% of patients were dispensed an antihypertensive, 75% received an antithrombotic and 60% were dispensed lipid-lowering therapy. Almost half of the population were dispensed all three recommended classes by the end of the study period. Increased use of secondary stroke prevention medicines was shown in this study, in accordance with national stroke guideline recommendations and initiatives supporting quality use of medicines in Australia. There may be opportunity to further increase use of these medicines among older Australians who have had a TIA or ischaemic stroke.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.PBB.2015.09.005
Abstract: There is a complex relationship between drug dependence and stress, with alcohol and other drugs of abuse both relieving stress and potentially inducing physiological stress responses in the user. Opioid drugs have been shown to modulate hypothalamic-pituitary-adrenal (HPA) activity in animal models and in idual response to this modulation may play a role in continuation of drug use. Healthy young Caucasian adults were administered a single dose of immediate release oxycodone (20mg, n=30) or assigned to a control group (n=19) that was not administered the drug. At 0, 1, 2, 4 and 6h post-administration, blood and saliva s les were collected along with assessment of pupil diameter. The HPA response was determined by measurement of salivary cortisol through a commercially available enzyme-linked immunosorbent assay (ELISA). The results were compared to genotype at the -511 and -31 positions in the interleukin1B (IL1B) gene. No difference in cortisol production was initially observed between the two groups, however, when participants were separated based on their genotype for two single nucleotide polymorphisms in the promoter of the IL1B gene, which have been shown to occur at a higher frequency in opioid-dependent populations, in iduals carrying the -511T and -31 C alleles (-511 C/T, -31 C/T or -511 T/T, -31 C/C) had a significantly (p<0.05) higher cortisol levels compared to in iduals homozygous for the -511 C and -31T alleles. These results suggest that in iduals carrying the -511T and -31 C alleles experience HPA activation in response to opioid administration and therefore may be less likely to undertake subsequent self-administration.
Publisher: Informa UK Limited
Date: 11-03-2014
Publisher: Springer Science and Business Media LLC
Date: 22-12-2021
DOI: 10.1007/S40264-020-01027-X
Abstract: Antidepressant use during the first trimester is reported in 4-8% of pregnancies. The use of some selective serotonin reuptake inhibitors during the first trimester has been identified as increasing the odds for congenital heart defects however, little is known about the safety of non-selective serotonin reuptake inhibitor antidepressants. The objective of this study was to assess the odds of congenital heart defects associated with the use of antidepressants during the first trimester of pregnancy, and to update the literature as newer studies have been published since the latest systematic literature review and meta-analysis. PubMed and Embase were searched till 3 June, 2020. Study quality was assessed, and study details were extracted. Meta-analyses were performed using RevMan 5.4, which assessed: (1) any antidepressant usage (2) classes of antidepressants and (3) in idual antidepressants. Twenty studies were identified, encompassing 5,337,223 pregnancies. The odds ratio for maternal use of any antidepressant during the first trimester of pregnancy and the presence of congenital heart defects from the random effects meta-analysis was 1.28 (95% confidence interval [CI] 1.17-1.41). Significant odds ratios of 1.69 (95% CI 1.37-2.10) and 1.25 (95% CI 1.15-1.37) were reported for serotonin norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors, respectively. A non-statistically significant odds ratio of 1.02 (95% CI 0.82-1.25) was reported for the tricyclic antidepressants. Analyses of in idual SSRIs produced significant odds ratios of 1.57 (95% CI 1.25-1.97), 1.36 (95% CI 1.08-1.72), and 1.29 (95% CI 1.14-1.45) for paroxetine, fluoxetine, and sertraline, respectively. The norepinephrine-dopamine-reuptake inhibitor bupropion also produced a significant odds ratio of 1.23 (95% CI 1.01-1.49). The selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor classes of antidepressants pose a greater risk for causing congenital heart defects than the tricyclic antidepressants. However, this risk for in idual antidepressants within each class varies, and information regarding some antidepressants is still lacking.
Publisher: Bentham Science Publishers Ltd.
Date: 31-01-2013
Publisher: Bentham Science Publishers Ltd.
Date: 08-2012
Publisher: Wiley
Date: 11-2014
DOI: 10.1111/IMJ.12582
Abstract: Hospital audits may underestimate anticoagulant use among acute ischaemic stroke patients with atrial fibrillation (AF), as treatment may commence after discharge. To account for this, antithrombotic use in the 4 months after hospitalisation for transient ischaemic attack or ischaemic stroke among AF patients was assessed using claims data. Results suggest that treatment may be commenced soon after discharge and should be considered when assessing prevalence of use.
Publisher: Elsevier BV
Date: 09-2022
Publisher: Wiley
Date: 13-06-2023
DOI: 10.1111/JOIM.13681
Abstract: This study aimed to compare the cardiovascular safety of interleukin‐6 inhibitors (IL‐6i) and Janus Kinase inhibitors (JAKi) to tumour necrosis factor inhibitors (TNFi). We conducted a retrospective cohort study using population‐based electronic databases from Hong Kong, Taiwan and Korea. We identified newly diagnosed patients with rheumatoid arthritis (RA) who received b/tsDMARDs first time. We followed patients from b/tsDMARD initiation to the earliest outcome (acute coronary heart disease, stroke, heart failure, venous thromboembolism and systemic embolism) or censoring events (death, transformation of b/tsDMARDs on different targets, discontinuation and study end). Using TNFi as reference, we applied generalized linear regression for the incidence rate ratio estimation adjusted by age, sex, disease duration and comorbidities. Random effects meta‐analysis was used for pooled analysis. We identified 8689 participants for this study. Median (interquartile range) follow‐up years were 1.45 (2.77) in Hong Kong, 1.72 (2.39) in Taiwan and 1.45 (2.46) in Korea. Compared to TNFi, the adjusted incidence rate ratios (aIRRs) (95% confidence interval [CI]) of IL‐6i in Hong Kong, Taiwan and Korea are 0.99 (0.25, 3.95), 1.06 (0.57, 1.98) and 1.05 (0.59, 1.86) and corresponding aIRR of JAKi are 1.50 (0.42, 5.41), 0.60 (0.26, 1.41), and 0.81 (0.38, 1.74), respectively. Pooled aIRRs showed no significant risk of cardiovascular events (CVEs) associated with IL‐6i (1.05 [0.70, 1.57]) nor JAKi (0.80 [0.48, 1.35]) compared to TNFi. There was no difference in the risk of CVE among RA patients initiated with IL‐6i, or JAKi compared to TNFi. The finding is consistent in Hong Kong, Taiwan and Korea.
Publisher: Cold Spring Harbor Laboratory
Date: 27-02-2020
DOI: 10.1101/2020.02.24.20027532
Abstract: Antidepressant use during the first trimester is reported in 4% to 8% of pregnancies. The use of some selective serotonin reuptake inhibitors (SSRI) during this stage of gestation has been identified as increasing the odds for congenital heart defects, however little is known about the safety of non-SSRI antidepressants. To assess the odds of congenital heart defects associated with the use of any antidepressant during the first trimester of pregnancy. To investigate in idual classes of antidepressants: SSRIs, serotonin norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and in idual antidepressants. PubMed and Embase were searched without restrictions from inception till 2 January 2020. Prospective and retrospective cohort and case-control studies were included if they documented the maternal usage of antidepressants during the first trimester of pregnancy and assessed the presence of congenital heart defects. Data were extracted by two independent reviewers and the endpoint assessed was congenital heart defects. Where studies reported multiple results for different types of heart defects or in idual antidepressants, results were combined when possible. Analyses assessing in idual antidepressants and classes of antidepressants (SSRIs, SNRIs and TCAs) were undertaken. A total of 16 studies were identified, encompassing 4,564,798 pregnancy outcomes. The odds ratio for maternal use of any antidepressant and the presence of congenital heart defects from the mixed-methods meta-analysis was 1.22 (95% confidence interval (CI): 1.11 to 1.33). Analyses of antidepressants by class produced an odds ratio of 1.50 (95% CI: 1.19 to 1.89) for maternal SNRI use during the first trimester of pregnancy and the formation of congenital heart defects. A significant odds ratio of 1.22 (95% CI: 1.12 to 1.33) was reported for SSRIs. For the TCA class, no increased odds ratio was found. Analyses of in idual antidepressants produced significant odds ratios of 1.53 (95% CI: 1.25 to 1.88), 1.28 (95% CI: 1.01 to 1.62), 1.28 (95% CI: 1.14 to 1.45) and 1.23 (95% CI: 1.01 to 1.50) for paroxetine, fluoxetine, sertraline and bupropion respectively. While some insight has been gained into which classes of antidepressant and in idual antidepressants pose more risk than others for causing congenital heart defects, information regarding some antidepressants is still lacking.
Publisher: SAGE Publications
Date: 05-09-2021
Abstract: Immune checkpoint inhibitors (ICIs) are an emerging treatment in cancer therapy for prolonging life, minimizing symptoms, and selectively targeting cancer. Program death 1 (PD-1) inhibitors, such as nivolumab, fall within this class, enabling the patient’s immune system to detect and destroy cancer. The introduction of ICIs is changing cancer therapy, with new drugs and new toxicities—an evolving area encountered by pharmacists. This study aims to compare the pattern of nivolumab-induced adverse events observed in practice, when compared with clinical trial and literature data. The secondary aim of the study is to identify the presentation and treatment modalities initiated in practice. We performed a retrospective case note review across 2 South Australian hospitals to identify the common toxicities and symptomatic treatments experienced by patients receiving nivolumab. Results were compared with clinical trial data from product innovator Bristol-Myer Squib and other published literature. Seventy patients were included in the study of these, 60 (86%) experienced any grade adverse event(s). A total of 59 (84%) of 70 experienced mild to moderate grade 1 to grade 2 adverse events and 10 (14%) of 70 patients experienced severe grade 3 to grade 4 adverse events, displaying some consistencies with clinical trial and published literature data. Together, the prevalence of adverse events with details on presentation and treatments illustrates possible pharmacy practice strategies and areas for intervention. The listed prevalence of adverse events and practice strategies identified throughout this study highlights how pharmacists may assist in the identification of predictable ICI toxicities associated with gastrointestinal, endocrine, dermatological toxicities, and fatigue.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2011
DOI: 10.1007/S00228-010-0928-9
Abstract: It has been demonstrated that genetic variation in CYP2C19 has a significant influence upon H. pylori eradication rates. We have determined a dosage regimen of lansoprazole that will provide EMs with exposure approximately equivalent to that obtained by PMs treated with standard doses and determined the exposure that a PM would experience if they were to be treated with this 'EM optimised' lansoprazole dose. Non-compartmental pharmacokinetic parameters (AUC, C(max), t(max)) for CYP2C19 genotypes were obtained from the literature. Primary pharmacokinetic parameters (CL, Vd, ka) for 200 virtual patients were calculated from the weighted non-compartmental variables and used to simulate a 7 day treatment course of twice daily lansoprazole, at standard and optimised doses for 1,000 patients. The administration of 180 mg twice daily to CYP2C19 EMs results in approximately equivalent exposure to lansoprazole as the administration of standard 30 mg twice daily doses to PMs. Administration of this six-fold dose increase to EMs is predicted to result in only a 2.5-fold increase in C(max) when compared with PMs receiving the standard 30 mg dose. We present a potential lansoprazole dosing regimen that should result in improved H. pylori eradication within CYP2C19 EMs and may not require in idualization. Whilst the optimised dose represents a significant increase, it is below that reported in the chronic management of Zollinger-Ellison syndrome. On the basis that treatment is of limited duration and lansoprazole is generally well tolerated, such an approach warrants further in vivo evaluation to confirm drug exposure, efficacy and tolerability.
Publisher: Springer Science and Business Media LLC
Date: 12-05-2023
DOI: 10.1007/S11095-023-03516-X
Abstract: Chronic Obstructive Pulmonary Disease is characterised by declining lung function and a greater oxidative stress burden due to reduced activity of antioxidant enzymes such as Glutathione Peroxidase 1. The extent to which drugs may contribute to this compromised activity is largely unknown. An integrative drug safety model explores inhibition of Glutathione Peroxidase 1 by drugs and their association with chronic obstructive pulmonary disease adverse drug events. In silico molecular modelling approaches were utilised to predict the interactions that drugs have within the active site of Glutathione Peroxidase 1 in both human and bovine models. Similarities of chemical features between approved drugs and the known inhibitor tiopronin were also investigated. Subsequently the Food and Drug Administration Adverse Event System was searched to uncover adverse drug event signals associated with chronic obstructive pulmonary disease. Statistical and molecular modelling analyses confirmed that the use of several registered drugs, including acetylsalicylic acid and atenolol may be associated with inhibition of Glutathione Peroxidase 1 and chronic obstructive pulmonary disease. The integration of molecular modelling and pharmacoepidemological data has the potential to advance drug safety science. Ongoing review of medication use and further pharmacoepidemiological and biological analyses are warranted to ensure appropriate use is recommended.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2022
Publisher: Elsevier BV
Date: 11-2015
Publisher: SAGE Publications
Date: 11-10-2023
Publisher: Cambridge University Press (CUP)
Date: 18-01-2016
DOI: 10.1017/S1041610215002434
Abstract: Antipsychotic agents have limited efficacy for Behavioral and Psychological Symptoms of Dementia (BPSD) and there are concerns about their safety. Despite this, they are frequently used for the management of BPSD. This study aimed to assess the use of antipsychotics among people on anti-dementia medicines in Australian residential aged care facilities. Data were obtained from an in idual patient unit dose packaging database covering 40 residential aged care facilities in New South Wales, Australia. Residents supplied an anti-dementia medicine between July 2008 and June 2013 were included. Prevalence of concurrent antipsychotic use was established. Incident antipsychotic users between January 2009 and December 2011 were identified. We examined initial antipsychotic dose, maximum titrated doses, type and duration of antipsychotic use, and compared use with Australian guidelines. There were 291 residents treated with anti-dementia medicines, 129 (44%) of whom received antipsychotics concomitantly with an anti-dementia medicine. Among the 59 incident antipsychotic users, risperidone (73%) was the most commonly used antipsychotic agent. Amongst the risperidone initiators, 43% of patients had initial doses greater than 0.5 mg/day and 6% of patients exceeded 2.0 mg/day for their maximum dose. 53% of concomitant users received daily treatment for greater than six months. Our study using records of in idual patient unit dose supply, which represents the intended medication consumption schedule, shows high rates of concurrent use of antipsychotics and anti-dementia medicines and long durations of use. The use of antipsychotics in patients with dementia needs to be carefully monitored to improve patient outcomes.
No related grants have been discovered for Michael Ward.