Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

The introduction of tacrolimus in clinical practice has improved patient survival after organ transplant. However, despite the long use of tacrolimus in clinical practice, the best way to use this agent is still a matter of intense debate. The start of the genomic era has generated new research areas, such as pharmacogenetics, which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the body. This variability seems to be correlated with the presence of genetic polymorphisms. Genotyping is an attractive option especially for the initiation of the dosing of tacrolim…

Incidence of potential drug interactions in a transplant centre setting and relevance of electronic alerts for clinical practice support

Background Adverse drug events may occur as a result of drug–drug interactions (DDIs). Information technology (IT) systems can be an important decision-making tool for healthcare workers to identify DDIs.Objective The aim of the study is to analyse drug prescriptions in our main hospital units, in order to measure the incidence and severity of potential DDIs. The utility of clinical decision-support systems (CDSSs) and computerised physician order entry (CPOE) in term of alerts adherence was also assessed. DDIs were assessed using a Micromedex healthcare series database.Methods The system, adopted by the hospital, generates alerts for prescriptions with negative interactions and thanks to a…

5PSQ-096 Hazard vulnerability analysis to evaluate the risk of drug shortages according to therapeutic class

Background and importance Drug shortages are a critical challenge for the public health system, as highlighted by EAHP’s position paper. They have a negative impact on quality and efficiency of patient care. Aim and objectives The aim of our study was the application of a revised hazard vulnerability analysis (HVA) to assess which therapeutic classes of drugs are at greatest risk of shortages. Material and methods In September 2019, we analysed the drugs present in our hospital therapeutic formulary and checked which ones were included in the Italian Medicines Agency shortages list: 43 drugs were found. For each drug, we assigned a score using a revised HVA which consists of three macro are…

Rash and multiorgan dysfunction following lamotrigine: could genetic be involved?

We report the case of a 38-year-old woman treated with lamotrigine who experienced multi-organ dysfunction. The patient received the drug at the dose of 100 mg per day. One week later, the treatment was suspended because of an extensive body rash. Twenty-four hours later, the patient appeared drowsy and stuporous and was hospitalized. On the fifth day, the patient was admitted with a clinical picture of acute multi-organ failure in our Institute, where, she, despite the support of vital functions with vasoactive drugs, continuous hemofiltration and ventilation with oxygen, died. Serum lamotrigine concentration was measured 110 h after its last dose and the drug resulted to be still present …

Selective decontamination of the digestive tract in adult-to-adult living related liver transplant patients: a single centre experience

Role of the hospital pharmacist in an Italian antimicrobial stewardship programme

The inappropriate use of antimicrobial agents is contributing to an increasing phenomenon of bacterial resistance. For this reason, there is a growing interest in ‘antimicrobial stewardship’, a series of coordinated and multidisciplinary interventions aimed to promote the safe and appropriate use of antimicrobials in which the pharmacist’s contribution is necessary for the optimal choice of drug, dose, duration of therapy and the implementation of cost containment strategies. AIM OF THE STUDY: We wanted to create a reference model and a specific training manual on antibiotic stewardship to introduce the role of the department pharmacist with specific infection disease skills in the Italian …

Unusual high dose of tacrolimus in liver transplant patient, a case report.

Case We describe the case of a liver transplant patient who had great difficulty in reaching the desired trough blood levels despite the use of high dose tacrolimus. The patient was homozygous for the CYP3A5*3 allele. However, the respective donor carried the wild-type CYP3A5*1/*1 genotype. Regarding ABCB1 SNPs at exon 21 and 26, the patient showed the 2677GT and 3435CC genotypes. For the corresponding donor we observed the 2677GG and 3435CC wild-type genotypes. One, two and three weeks after transplantation the patient received daily 0.219, 0.287 and 0.273 mg/kg of tacrolimus, respectively. However, the corresponding tacrolimus trough blood levels were of 4.6, 5.6 and 6.1 ng/mL. The tacrol…

PS-075 Evaluation of fall risks in elderly patients

Background Falls among hospitalised elderly patients are a major public health concern since they can cause loss of independence, injury and sometimes patient death. Purpose To examine risk factors, especially drugs, potentially related to falls in elderly patients and to define possible actions. Materials and methods A retrospective (May 1 2010–March 31 2013) study was performed at ISMETT, a 90-bed hospital. Patient characteristics (age/gender/body mass index, BMI), clinical conditions (diagnosis/comorbidity), ward (Intensive Care Unit, Step-Down Unit, Cardiothoracic Surgery Unit and Abdominal Surgery Unit), length of stay, number of medicines taken within three days before falling and sev…

Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis.

Background: The comparative efficacy of pirfenidone, nintedanib, and pamrevlumab in slowing the rate of forced vital capacity (FVC) decline and mortality in patients with idiopathic pulmonary fibrosis (IPF) is unknown. Objective: To perform a systematic review and meta-analysis (MA) of these drugs for IPF. Methods: We searched CENTRAL, PubMed, EMBASE, ClincalTrials.gov, and the World Health Organization’s registry databases up to March 2020. Phase II/III randomized controlled trials in adults with IPF were eligible. The random-effect model was implemented calculating the effect size and respective 95% CI as Cohen’s d for change from baseline FVC (in percentage predicted and liters) and odds…

The evolution of European Medicines Agency drug approval: the adaptive licensing: Table 1

In March 2014, the European Medicines Agency (EMA) launched a pilot project of ‘adaptive licensing’ to speed up access to drugs in development, in order to respond to unmet medical needs. The project will involve parallel scientific advice from the regulatory agency, pharmaceutical industry, the companies Health Technology Assessment (HTAs) bodies, organisations studying guidelines on clinical treatment and patient associations. The traditional process of drug authorisation is divided into several parts, involving in vitro studies and in vivo studies in animals (preclinical studies), as well as phase 1–3 randomised controlled trials conducted in humans over a predefined period. When authori…

2SPD-025 Application of hazard vulnerability analysis to evaluate the risk level of medicine shortages

Background and importance Drug shortages have become a worldwide phenomenon which has repercussions on patient care and on the hospital’s budget. Aim and objectives The aim of our study was to assess the risk of shortages of drugs included in our hospital therapeutic formulary (HTF), for which there is shortage reporting, using a hazard vulnerability analysis (HVA). Material and methods We performed an HVA on 43 drugs in our HTF, which were also included in the Italian Medicines Agency list of shortages. The HVA used to assign the risk of shortage (ROS) included three macro areas: probability that the shortages will occur based on shortages in the past 2 years; magnitude factors which incre…

The European COVID-19 drugs calculation tool: an aid for the estimation of the drugs needed during the SARS-CoV 2 pandemic

Objective To create an informatics supportive tool, which can assist healthcare professionals in estimating potential requirements for essential drug supplies to respond to the current SARS-CoV-2 pandemic based on epidemiological forecasting. Methods The tool was based on a Susceptible-Infected-Removed (SIR) epidemiological model in which the population is divided into three compartments and transmission parameters are specified to define the rate at which people move between stages. Appropriate data entry was guaranteed by the creation of structured guided paths. The drugs needed for the forecasted patients were estimated according to a list of critical care drugs compiled by consulting pr…

5PSQ-100 Comparative analysis of the safety and tolerability profile of pirfenidone and nintedanib in the treatment of idiopathic pulmonary fibrosis

Background and importance The main treatments for idiopathic pulmonary fibrosis are pirfenidone and nintedanib. Although their efficacy is known, further studies are needed to evaluate the safety and tolerability profiles (STPs) based on real world data. Aim and objectives The aim of this study was to evaluate the STP of nintedanib and pirfenidone according to our hospital data. Material and methods We analysed 148 patients treated with pirfenidone (72% men; 28% women) and 120 treated with nintedanib (77% men; 23% women) from September 2016 to September 2019. The average age of the patients treated with pirfenidone and nintedanib was 72.7 and 74.4 years, respectively. Drug tolerability was …

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5*1 and *3 …