Issues with the use of medicines in paediatrics: Off-label and unlicensed use, and formulation uncertainty

Prescribing of drugs for children is not always in accordance with their registration specifications or they may even be unlicensed which can give rise to serious adverse events. This study has found that approximately 30% of drugs prescribed in a major teaching hospital for children did not conform to the registration specifications. It has also proposed methods to improve evidenced-based prescribing in children. In addition it has provided enhanced scientific information for the prescribing of lincomycin infusions

Stability studies of lincomycin hydrochloride in aqueous solution and intravenous infusion fluids

Purpose: The purpose of this study was to evaluate the chemical stability of Lincocin® (lincomycin hydrochloride) in commonly used intravenous fluids at room temperature (25°C), at accelerated-degradation temperatures and in selected buffer solutions. Materials and methods: The stability of Lincocin® injection (containing lincomycin 600 mg/2 mL as the hydrochloride) stored at 25°C±0.1°C in sodium lactate (Hartmann’s), 0.9% sodium chloride, 5% glucose, and 10% glucose solutions was investigated over 31 days. Forced degradation of Lincocin® in hydrochloric acid, sodium hydroxide, and hydrogen peroxide was performed at 60°C. The effect of pH on the degradation rate of lincomycin hydrochloride stored at 80°C was determined. Results: Lincomycin hydrochloride was found to maintain its shelf life at 25°C in sodium lactate (Hartmann’s) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution, with less than 5% lincomycin degradation occurring in all intravenous solutions over a 31-day period. Lincomycin hydrochloride showed less rapid degradation at 60°C in acid than in basic solution, but degraded rapidly in hydrogen peroxide. At all pH values tested, lincomycin followed first-order kinetics. It had the greatest stability near pH 4 when stored at 80°C (calculated shelf life of 4.59 days), and was least stable at pH 2 (calculated shelf life of 0.38 days). Conclusion: Lincocin® injection was chemically found to have a shelf life of at least 31 days at 25°C when added to sodium lactate (Hartmann’s) solution, 0.9% sodium chloride solution, 5% glucose solution, and 10% glucose solution. Solutions prepared at approximately pH 4 are likely to have optimum stability

Cross-sectional survey of off-label and unlicensed prescribing for inpatients at a paediatric teaching hospital in Western Australia

Objectives: To evaluate the prevalence of off-label and unlicensed prescribing in inpatients at a major paediatric teaching hospital in Western Australia and to identify which drugs are commonly prescribed off-label or unlicensed, including factors influencing such prescribing. Methods: A retrospective cross-sectional study was conducted in June, 2013. Patient and prescribing data were collected from 190 inpatient medication chart records which had been randomly selected from all admissions during the second week of February 2013. Drugs were catego-rised as licensed, off-label or unlicensed, according to their approved Australian registration product information (PI). All drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code. Results There were 120 male and 70 female inpatients. The average age was 6.0 years (± 4.7). The study included 1160 prescribed drugs suitable for analysis. The number of drugs prescribed per patient ranged from 1 to 25 with an average of 6.1 (± 4.3). More than half (54%) were prescribed off-label. Oxycodone, clonidine, parecoxib and midazolam were always prescribed off-label. The most common off-label drugs were ondansetron (18.5%), fentanyl (12.9%), oxycodone (8.8%) and paracetamol (6.1%). Many ATC classifications included high off-label proportions especially the genitourinary system and sex hormones, respiratory system drugs, systemic hormonal preparations and alimentary tract and metabolism drugs. Conclusions: This study highlights that prescribing of paediatric drugs needs to be better supported by existing and new evidence. Incentives should be established to foster the conduct of evidence-based studies in the paediatric population. The current level of off-label prescribing raises issues of unexpected toxicity and adverse drug effects in children that are in some cases severely ill

The use of initial dosing of gentamicin in the management of pyelonephritis/urosepsis: A retrospective study

Objective: The primary objective was to determine if initial empirical intravenous dosing of gentamicin improved patient’s outcomes in pyelonephritis/urosepsis compared with alternative IV antibiotic management. Design Retrospective cross-sectional descriptive study. Setting: Public TertiaryTeaching Hospital serving adults in an urban centre. Participants: All adult patient records with a recorded diagnosis of any of pyelonephritis/urosepsis, urinary tract infection, UTI, complicated urinary tract infection, bacteriuria, symptomatic bacteriuria and asymptomatic bacteriuria from 2nd February 2012 to 10th May 2014 were reviewed. Only patients treated with an empirical regimen of one or more IV antibiotics were included in the study. Main outcomes The primary outcomes were: duration of IV antibiotic treatment, time to resolution of symptoms and length of hospital stay (LOS). Secondary end points were: compliance with Therapeutic Guidelines: Antibiotic (electronic version) (eTG) for severe pyelonephritis/urosepsis and appropriateness of gentamicin use. Data analysis Univariate and multivariable associations between baseline and demographic variables and the main outcomes were performed using Chi-square tests and a General Linear Model using the SAS version 9.2 software. Results: Of 295 patients reviewed 152 were prescribed one or more IV antibiotics and included in the study. Approximately half of the patients (n = 73, 48%) were prescribed IV piperacillin/tazobactam (Tazocin), while gentamicin was prescribed for 66 patients (43.4%). Of the 152 patients evaluated, 49 (32%) were given gentamicin first. Multivariable regression analysis showed that duration of IV treatment was shorter for those aged over 70 (40.2 hours vs 85.5 hours for those aged up to 70; p = 0.0074), and those who received gentamicin as first line treatment (41.3 hours vs 89.8 hours for those not receiving any gentamicin; p = 0.0312). After adjustment for age and gentamicin administration, there appeared to be no significant difference in duration of IV treatment for any other independent variables. No significant associations between the independent variables (gentamicin, age, gender, comorbidities, and eTG compliance) and either time to resolution of symptoms (median: 68 hours) or hospital LOS (median: 5 days) were observed. Conclusions: Neither time to resolution of abnormal symptoms nor length of stay were significantly influenced by an initial dose of gentamicin when the data were subjected to multivariable analysis. The age of the patient and pattern of gentamicin treatment were the dominant factors associated with duration of IV antibiotics. Piperacillin/tazobactam is not recommended in treatment guidelines for pyelonephritis/urosepsis but was the most commonly prescribed IV antibiotic. This requires review by the appropriate hospital clinicians

Clinical setting influences off-label and unlicensed prescribing in a paediatric teaching hospital

Purpose - To estimate the prevalence of off-label and unlicensed prescribing during 2008 at a major paediatric teaching hospital in Western Australia. Methods - A 12-month retrospective study was conducted at Princess Margaret Hospital using medication chart records randomly selected from 145,550 patient encounters from the Emergency Department, Inpatient Wards and Outpatient Clinics. Patient and prescribing data were collected. Drugs were classified as off-label or unlicensed based on Australian registration data. A hierarchical system of age, indication, route of administration and dosage was used. Drugs were classified according to the Anatomical Therapeutic Chemical Code. Results - A total of 1,037 paediatric patients were selected where 2,654 prescriptions for 330 different drugs were prescribed to 699 patients (67.4%). Most off-label drugs (n = 295; 43.3%) were from the nervous system; a majority of unlicensed drugs were systemic hormonal preparations excluding sex hormones (n = 22, 32.4%). Inpatients were prescribed more off-label drugs than outpatients or Emergency Department patients (p < 0.0001). Most off-label prescribing occurred in infants and children (31.7% and 35.9% respectively) and the highest percentage of unlicensed prescribing (7.2%) occurred in infants (p < 0.0001). There were 25.7% of off-label and 2.6% of unlicensed medications prescribed across all three settings. Common reasons for off-label prescribing were dosage (47.4%) and age (43.2%). Conclusion - This study confirmed off-label and unlicensed use of drugs remains common. Further, that prevalence of both is influenced by the clinical setting, which has implications in regards to medication misadventure, and the need to have systems in place to minimise medication errors. Further, there remains a need for changes in the regulatory system in Australia to ensure that manufacturers incorporate, as it becomes available, evidence regarding efficacy and safety of their drugs in children in the official product information

Incorporating online teaching in an introductory pharmaceutical practice course: a study of student perceptions within an Australian University

Objectives: To examine student perceptions regarding online lectures and quizzes undertaken during a pharmaceutical practice course for first year undergraduate students enrolled in the Bachelor of Pharmacy course at an Australian University. Methods: The University uses a standard instrument to collect feedback from students regarding unit satisfaction. Data were collected for three different teaching modalities: traditional face-to-face, online and partially online. Results: Descriptive statistics support that, from a student's perspective, partial online delivery is the preferred teaching methodology for an introductory pharmaceutical practice unit. Conclusion: This study has served to highlight that while there are a few points of significant difference between traditional and online teaching and learning, a combination of the two provides a reasonable avenue for teaching exploration. This result has implications for teaching practice generally, and within the pharmacy discipline, specifically.Objetivos. Examinar las percepciones de los estudiantes en relación a las clases y exámenes on-line realizados durante un curso de farmacia práctica para pre-graduados de primer año cursando la licenciatura en farmacia en una Universidad Australiana. Métodos: La Universidad utiliza un instrumento estándar para recoger la retroalimentación de los estudiantes sobre la asignatura. Se recogieron los datos de tres diferentes modalidades de enseñanza: tradicional presencial, on-line, y parcialmente on-line. Resultados: La estadística descriptiva apoyó que, desde el punto de vista del estudiante, em método de enseñanza preferido para un curso introductorio de farmacia práctica es parcialmente on-line. Conclusión: Este estudio sirvió para subrayar que, mientras que existen algunos puntos significativamente diferentes entre la enseñanza y el aprendizaje tradicionales y on-line, una combinación de los dos proporciona una situación razonable para la exploración docente. Este resultado tiene implicaciones para la enseñanza en general y para la disciplina de farmacia específicamente

Evaluation of the stability of linezolid in aqueous solution and commonly used intravenous fluids

Purpose: The aim was to evaluate the stability of linezolid in commonly used intravenous fluids and in aqueous solution to determine the kinetics of degradation and shelf-life values at alkaline pH values. Methods: Forced degradation studies were performed on linezolid in solution to develop a validated high-performance liquid chromatography analysis. Sodium chloride 0.9%, sodium lactate, and glucose 5% and glucose 10% solution containing 2.0 mg/mL linezolid were stored at 25.0°C (±0.1°C) for 34 days. The effect of temperature on the stability of linezolid in 0.1 M sodium hydroxide solution was investigated to determine the activation energy. The degradation rates of linezolid at selected pH values at 70.0°C and the influence of ionic strength were also examined. Activation energy data were applied to determine the shelf-life values at selected pH values, and a pH rate profile was constructed over the pH range of 8.7–11.4. The stability of intravenous linezolid (Zyvox®) solution was evaluated by storing at 70.0°C for 72 hours. Results: Linezolid was found to maintain &gt; 95.0% of its initial concentration after storage at 25.0°C for 34 days in sodium lactate, 0.9% in sodium chloride, and 5% and 10% in glucose solutions. Linezolid was degraded at alkaline pH values by first-order kinetics. Activation energy data showed that temperature, but not ionic strength, influenced the degradation rate significantly. An activation energy of 58.22 kJ/mol was determined for linezolid in 0.1 M sodium hydroxide solution. Linezolid was least stable at high pH values and at elevated temperatures. It was determined that linezolid has adequate stability for the preparation of intravenous fluids for clinical administration. Conclusion: Linezolid was found to have a shelf life of 34 days at 25°C when added to sodium lactate, 0.9% sodium chloride, and 5% and 10% glucose solutions. It was least stable at high pH values and at elevated temperatures

An evaluation of the reclassification of ophthalmic chloramphenicol for the management of acute bacterial conjunctivitis in community pharmacies in Western Australia

© 2014 Royal Pharmaceutical Society. Objective The study aims to evaluate factors influencing pharmacists' management of eye infections following the reclassification of ophthalmic chloramphenicol to pharmacist supply. Methods Data were collected using a self-administered questionnaire posted to a random sample of community pharmacies in urban and rural areas in Western Australia. Data were entered into Excel and analysed using SPSS v17 (SPSS Inc., Chicago, IL, USA) and SAS v9.2 (SAS Institute Inc., Cary, NC, USA). Descriptive statistics were used to summarise the responses and demographics of respondents. Regression analysis was used to identify relationships between variables. Factor analysis was conducted to pool variables and the derived factors were subjected to regression analysis. Key findings Of the 240 community pharmacies surveyed, 119 (49.5%) responded (79% urban and 21% rural pharmacies). Urban and rural pharmacies provided ophthalmic chloramphenicol over-the-counter (OTC) 3-4 and 1-2 times weekly, respectively (P-=-0.021), with some pharmacies providing 12 or more per week. Over 82% of respondents claimed that sales of other OTC products used for acute bacterial conjunctivitis had 'decreased/decreased markedly'. A majority of respondents (59%) claimed that there was no change in the number of prescriptions received for ophthalmic chloramphenicol. Most respondents (76.4%) agreed/strongly agreed that pharmacist's current level of training was adequate to provide ophthalmic chloramphenicol. However, approximately one-fifth (21.8%) responded that pharmacists required some additional training. Conclusions Down-scheduling of ophthalmic chloramphenicol has improved pharmacists' capability to treat acute bacterial conjunctivitis, largely as a replacement for products previously available OTC, rather than fewer general practitioner consultations. Pharmacists showed overall support for the reclassification as it enabled better use of professional skills and patient access to improved treatment options

Effective communication and collaboration with health professionals: A qualitative study of primary care pharmacists in Western Australia.

BackgroundThe expanded provision of professional services by community pharmacists in the primary care setting encompasses the necessity to communicate and collaborate with other health professionals. Little is currently known about contemporary processes employed for their achievement.ObjectiveTo explore contemporary processes employed for effective communication and collaboration between primary care pharmacists and health professionals.MethodsIn-depth semi-structured interviews were conducted with pharmacists practising in primary care settings requiring varying expertise, practice experience and speciality backgrounds. Interviews were audio-recorded, transcribed verbatim and coded using NVivo version 11. Data were analysed following an inductive approach to facilitate thematic analysis.ResultsTwenty-six pharmacists were interviewed, which achieved data saturation. Five overarching themes emerged as participants described their experiences and perspectives regarding processes employed for communication and collaboration: i) tailored means of communication, ii) referral processes, iii) facilitators for effective interactions, iv) barriers to effective interactions, and v) implementation of a national digital health record. Participants acknowledged that the changing landscape of the Australian health system affected communication and collaboration with other health professionals. The changes resulted in participants' acceptance of a multidisciplinary approach to healthcare, which was contingent upon effective communication, interactions and relationships with other health professionals. Varying levels of formality and characteristics of referrals were identified, however the nature of the communication was tailored to the individual scenario or circumstance that was considered appropriate.ConclusionsPharmacists exercised judgment on a case-by-case basis when tailoring the means of communication. The establishment of a consistent and structured two-way referral process between health professionals within the primary care setting is important, which includes use of the national digital health record. Increased awareness and appreciation of each health professional's roles and expertise would further enhance inter-professional collaboration

A survey of the views and capabilities of community pharmacists in Western Australia regarding the rescheduling of selected oral antibiotics in a framework of pharmacist prescribing

© 2018 Sinkala et al. Background. Antibiotic misuse in the community contributes to antimicrobial resistance. One way to address this may be by better utilizing community pharmacists' skills in antibiotic prescribing. The aims of this study were to examine the level of support for "down-scheduling" selected antibiotics and to evaluate factors determining the appropriateness of community pharmacist prescribing for a limited range of infections, including their decision to refer to a doctor. Methods. Self-administered questionnaires, including graded case vignette scenarios simulating real practice, were sent to Western Australian community pharmacists. In addition to descriptive statistics and chi-square testing, a General Estimating Equation (GEE) was used to identify factors associated with appropriateness of therapy and the decision to refer, for each of the seven vignettes. Results. Of the 240 pharmacists surveyed, 90 (37.5%) responded, yielding 630 responses to seven different case vignettes. There was more than 60% respondent support for expanded prescribing (rescheduling) of commonly prescribed antibiotics. Overall 426/630 (67.6%) chose to treat the patient while the remaining 204/630 (32.4%) referred the patient to a doctor. Of those electing to treat, 380/426 (89.2%) opted to use oral antibiotics, with 293/380 (77.2%) treating with an appropriate selection and regimen. The GEE model indicated that pharmacists were more likely to prescribe inappropriately for conditions such as otitis media (p = 0.0060) and urinary tract infection in pregnancy (p &lt; 0:0001) compared to more complex conditions. Over 80% of all pharmacists would refer the patient to a doctor following no improvement within 3 days, or within 24 h in the case of community acquired pneumonia. It was more common for younger pharmacists to refer the patient to a doctor (p=0:0165). Discussion. This study adds further insight into community pharmacy/pharmacist characteristics associated with appropriateness of oral antibiotic selection and the decision to refer to doctors. These findings require consideration in designing pharmacist over-the-counter prescribing models for oral antibiotics