Evaluation of Bayesian Forecasting Methods for Prediction of Tacrolimus Exposure Using Samples Taken on Two Occasions in Adult Kidney Transplant Recipients.

Background: Bayesian forecasting-based limited sampling strategies (LSSs) for tacrolimus have not been evaluated for the prediction of subsequent tacrolimus exposure. This study examined the predictive performance of Bayesian forecasting programs/services for the estimation of future tacrolimus area under the curve (AUC) from 0 to 12 hours (AUC0-12) in kidney transplant recipients.

Methods: Tacrolimus concentrations were measured in 20 adult kidney transplant recipients, 1 month post-transplant, on 2 occasions one week apart.

Investigation of the Association Between Total and Free Plasma and Saliva Mycophenolic Acid Concentrations Following Administration of Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients.

Background And Objectives: Mycophenolic acid (MPA) is commonly used following renal transplant. Saliva MPA concentrations may reflect the pharmacologically active form of MPA in plasma. Therapeutic drug monitoring using saliva is convenient and non-invasive.

Prednisolone Concentrations in Plasma (Total and Unbound) and Saliva of Adult Kidney Transplant Recipients.

Background: Prednisolone displays significant pharmacokinetic variability and exposure-outcome relationships in renal transplant recipients, suggesting a role for drug monitoring in some scenarios. It is highly protein-bound, and the free form is pharmacologically active but cumbersome to measure. Saliva concentrations might reflect free plasma prednisolone and present an alternative measurement.

Is Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium Justifiable for Gastrointestinal Quality of Life?

Background: Globally, enteric-coated mycophenolate sodium (EC-MPS) is replacing mycophenolate mofetil (MMF) in maintenance immunosuppressant regimens. The predominant reason for conversion is the purported improvement in gastrointestinal (GI) quality of life. This paper considers the level of bias associated with studies comparing EC-MPS and MMF for GI-related improvement and provides insight into whether conversion is supported by evidence.

Psychiatric adverse events in oseltamivir prophylaxis trials: Novel comparative analysis using data obtained from clinical study reports.

Purpose: Estimating the rate of adverse events (AEs) caused by a treatment in clinical trials typically involves comparing the proportions of patients experiencing AEs in intervention and control groups. However, potentially important information, including duration, recurrence, and intensity of events, is lost. In this study, we illustrate how the additional information can be obtained and incorporated into analyses of AEs.

Evaluation of Multiple Linear Regression-Based Limited Sampling Strategies for Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients.

Background: Although multiple linear regression-based limited sampling strategies (LSSs) have been published for enteric-coated mycophenolate sodium, none have been evaluated for the prediction of subsequent mycophenolic acid (MPA) exposure. This study aimed to examine the predictive performance of the published LSS for the estimation of future MPA area under the concentration-time curve from 0 to 12 hours (AUC0-12) in renal transplant recipients.

Methods: Total MPA plasma concentrations were measured in 20 adult renal transplant patients on 2 occasions a week apart.

Development of Improved Dosing Regimens for Mycophenolate Mofetil Based on Population Pharmacokinetic Analyses in Adults with Lupus Nephritis.

Background And Objective: Mycophenolic acid (MPA) provides effective treatment for lupus nephritis patients. Owing to its large pharmacokinetic variability, it is questionable whether standard fixed dose therapy can achieve optimal MPA exposure. The aim of this study was to develop a population pharmacokinetic model of MPA and its metabolite, 7-O-MPA-β-glucuronide (MPAG), to identify important covariate influences and better predict patient dosing requirements.

New-Onset Diabetes After Statin Exposure in Elderly Women: The Australian Longitudinal Study on Women's Health.

Introduction: Extensive clinical research has consistently shown statins lower the risk of cardiovascular events and mortality. Some studies also suggest statins increase the risk of new-onset diabetes. Research to date has rarely included elderly women, hence little is known about the risk of diabetes after statin exposure in this population.

Ezetimibe: Use, costs, and adverse events in Australia.

Aim: To analyze the subsidized use and reported adverse events of ezetimibe, used to lower cholesterol, in Australia over the 11 years following its inclusion on the Pharmaceutical Benefits Scheme (PBS) in 2004.

Methods: Pharmacoepidemiological analysis of dispensed prescriptions from Medicare Australia. Adverse event data were obtained from the Therapeutic Goods Administration.

Population Pharmacokinetic Modelling and Bayesian Estimation of Tacrolimus Exposure: Is this Clinically Useful for Dosage Prediction Yet?

This review summarises the available data on the population pharmacokinetics of tacrolimus and use of Maximum A Posteriori (MAP) Bayesian estimation to predict tacrolimus exposure and subsequent drug dosage requirements in solid organ transplant recipients. A literature search was conducted which identified 56 studies that assessed the population pharmacokinetics of tacrolimus based on non-linear mixed effects modelling and 14 studies that assessed the predictive performance of MAP Bayesian estimation of tacrolimus area under the plasma concentration-time curve (AUC) from time zero to the end of the dosing interval. Studies were most commonly undertaken in adult kidney transplant recipients and investigated the immediate-release formulation.

Associations of Guideline Recommended Medications for Acute Coronary Syndromes With Fall-Related Hospitalizations and Cardiovascular Events in Older Women With Ischemic Heart Disease.

Background: Guidelines for acute coronary syndrome recommend statins, β-blockers, angiotensin-converting-enzyme inhibitors or renin-angiotensin system blockers, and antiplatelet agents for the secondary prevention of cardiovascular events. The aim was to examine associations between guideline recommended medications and fall-related hospitalizations and cardiovascular events in robust and frail older women.

Methods: 2002-2011 surveys from the Australian Longitudinal Study on Women's Health linked with administrative hospital, pharmaceutical and death registry data (2003-mid-2011) were used.

Associations Between Statin Use and Physical Function in Older Adults from The Netherlands and Australia: Longitudinal Aging Study Amsterdam and Australian Longitudinal Study on Women's Health.

Background: Statin therapy may cause myopathy, but long-term effects on physical function are unclear.

Objective: We investigated whether statin use is associated with poorer physical function in two population-based cohorts of older adults.

Methods: Data were from 691 men and women (aged 69-102 years in 2005/2006) in the LASA (Longitudinal Aging Study Amsterdam) and 5912 women (aged 79-84 years in 2005) in the ALSWH (Australian Longitudinal Study on Women's Health).

Multinational Evaluation of Mycophenolic Acid, Tacrolimus, Cyclosporin, Sirolimus, and Everolimus Utilization.

Background: Increasing immunosuppressant utilization and expenditure is a worldwide challenge as more people successfully live with transplanted organs. Our aims were to characterize utilization of mycophenolate, tacrolimus, cyclosporin, sirolimus, and everolimus in Australian transplant recipients from 2007 to 2013; to identify specific patterns of usage; and to compare Australian utilization with Norwegian, Danish, Swedish, and the Netherlands use.

Material And Methods: Australian utilization and expenditure data were captured through national Pharmaceutical Benefits Scheme and Highly Specialized Drug administrative databases.

Actions following adverse drug events - how do these influence uptake and utilisation of newer and/or similar medications?

Background: Over the last decade, actions following some adverse drug events received major publicity. This study investigated changes in usage patterns of medications in Australia following two examples - rofecoxib market withdrawal (2004) and warnings about jaw necrosis following bisphosphonates (2007).

Methods: Dispensing data for COX-2 inhibitors (2000-2008) and anti-osteoporosis medications (2003-2012) were obtained from the Australian Pharmaceutical Benefits Scheme database.

The effect of dose and type of proton pump inhibitor use on risk of fractures and osteoporosis treatment in older Australian women: A prospective cohort study.

Objectives: Proton pump inhibitors (PPIs) are among the most prescribed medications worldwide, however, there is growing concern regarding potential negative effects on bone health. The aim was to examine the effect of dose and type of PPI use on subsequent use of osteoporosis medication and fractures in older Australian women.

Methods: Data were included from 4432 participants (born 1921-26) in the 2002 survey of the Australian Longitudinal Study on Women's Health.

Clinical Pharmacokinetics of Once-Daily Tacrolimus in Solid-Organ Transplant Patients.

Tacrolimus is a pivotal immunosuppressant agent used in solid-organ transplantation. It was originally formulated for oral administration as Prograf(®), a twice-daily immediate-release capsule. In an attempt to improve patient adherence, retain manufacturer market share and/or reduce health care costs, newer once-daily prolonged-release formulations of tacrolimus (Advagraf(®) and Envarsus(®) XR) and various generic versions of Prograf(®) are becoming available.

Exposure-effect relationship of mycophenolic acid and prednisolone in adult patients with lupus nephritis.

Aims: The aim was to examine relationships between total and unbound mycophenolic acid (MPA) and prednisolone exposure and clinical outcomes in patients with lupus nephritis.

Methods: Six blood samples were drawn pre- and at 1, 2, 4, 6 and 8 h post-dose and total and unbound MPA and prednisolone pre-dose (C0 ), maximum concentration (Cmax ) and area under the concentration-time curve (AUC) were determined using non-compartmental analysis in 25 patients. The analyses evaluated drug exposures in relation to treatment response since starting MPA and drug-related adverse events.

Osteoporosis medication dispensing for older Australian women from 2002 to 2010: influences of publications, guidelines, marketing activities and policy.

Purpose: Developments in anti-osteoporosis medications (AOMs) have led to changes in guidelines and policy, which, along with media and marketing strategies, have had an impact upon the prescribing of AOM. The aim was to examine patterns of AOM dispensing in older women (aged 76-81 years at baseline) from 2002 to 2010.

Methods: Administrative claims data were used to describe AOM dispensing in 4649 participants (born in 1921-1926 and still alive in 2011) in the Australian Longitudinal Study on Women's Health.

Is statin use associated with new joint-related symptoms, physical function, and quality of life? Results from two population-based cohorts of women.

Objective: Previous studies have suggested that statins may prevent development of osteoarthritis and have antiinflammatory effects. Our aim was to examine the associations between statin use and patient-reported joint symptoms in 2 large cohorts of middle-aged and older women.

Methods: Data were from 6,966 middle-aged (born 1946-1951) and 4,806 older (born 1921-1926) participants in the Australian Longitudinal Study on Women's Health who completed surveys from 2001 to 2011, including questions about joint pain/stiffness, physical functioning, and self-rated health (SRH).

Pharmacology and toxicology of mycophenolate in organ transplant recipients: an update.

This review aims to provide an update of the literature on the pharmacology and toxicology of mycophenolate in solid organ transplant recipients. Mycophenolate is now the antimetabolite of choice in immunosuppressant regimens in transplant recipients. The active drug moiety mycophenolic acid (MPA) is available as an ester pro-drug and an enteric-coated sodium salt.

How accurate and precise are limited sampling strategies in estimating exposure to mycophenolic acid in people with autoimmune disease?

Mycophenolic acid (MPA) is a potent immunosuppressant agent, which is increasingly being used in the treatment of patients with various autoimmune diseases. Dosing to achieve a specific target MPA area under the concentration-time curve from 0 to 12 h post-dose (AUC12) is likely to lead to better treatment outcomes in patients with autoimmune disease than a standard fixed-dose strategy. This review summarizes the available published data around concentration monitoring strategies for MPA in patients with autoimmune disease and examines the accuracy and precision of methods reported to date using limited concentration-time points to estimate MPA AUC12.

Safety evaluation of leflunomide in rheumatoid arthritis.

Introduction: Leflunomide is a prodrug which is rapidly converted following oral administration and absorption to an active metabolite with anti-proliferative effects (A77 1726/teriflunomide). Leflunomide was developed as an immunomodulatory agent and subsequently developed as a disease-modifying anti-rheumatic drug (DMARD) for the management of rheumatoid arthritis (RA).

Areas Covered: This review article covers the mechanism of action of the drug, clinical indications, including efficacy data from clinical trials, safety data from clinical trials, post marketing studies and surveillance databases and safety in special populations.

Differences in utilisation of gastroprotective drugs between 2001 and 2005 in Australia and Nova Scotia, Canada.

Purpose: This study aimed to compare use of histamine H2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), 2001-2005, in the elderly and social security beneficiaries in Australia (AUS) and Nova Scotia, Canada (NS).

Methods: Prescription dispensing data were collected for all subsidised H2RAs and PPIs. In AUS, dispensing data for concession beneficiaries were obtained from the Pharmaceutical Benefits Scheme database.

Clinical pharmacokinetics and pharmacodynamics of mycophenolate in patients with autoimmune disease.

Mycophenolic acid (MPA), the active drug moiety of mycophenolate, is a potent immunosuppressant agent, which is increasingly being used in the treatment of patients with various autoimmune diseases. An understanding of the pharmacokinetics and pharmacodynamics of mycophenolate in this population should assist the clinician with rational dosage decisions. This review aims to provide an overview of the published literature on the clinical pharmacokinetics of mycophenolate in autoimmune disease and a briefer summary of current pharmacodynamic knowledge, and to identify areas of potential future research in this field.

Quality Use of Medicines--medication safety issues in naming; look-alike, sound-alike medicine names.

Objective: To review current literature with the objective of developing strategies and recommendations to enhance patient safety and minimise clinical issues with look-alike, sound-alike medication names.

Methods: A comprehensive search of the PubMed database and an Australian online repository of Quality Use of Medicines projects was conducted to identify publications addressing look-alike, sound-alike medication problems. Author networks, grey literature and the reference lists of published articles were also used to identify additional material.