Jana Lass

Drug utilisation pattern and off-label use of medicines in Estonian neonatal units

ObjectivesTo characterise neonatal hospital drug use and to compare the availability of drug information between Estonian Summaries of Product Characteristics (SPCs) and other sources.Study designThis was a prospective cohort study in which pharmacotherapy information on neonates admitted to Tartu University Clinics between 1 February and 1 August 2008 and to Tallinn Children’s Hospital between 1 February and 1 August 2009 was collected. Drug labelling status was determined according to Estonian SPCs, and neonatal information was compared with the British National Formulary for Children (BNFC) and the Thomson Micromedex database.ResultsOf 490 hospitalised neonates, 71% received pharmacotherapy. Within the entire study period, there were 1981 prescriptions for 115 products, with a median of four (interquartile range 2–7) products per child. Antibacterial, cardiovascular and central nervous system drugs were the most commonly prescribed. All treated preterm neonates received at least one unlicensed or age-related off-label prescription. All prescriptions for alimentary, genitourinary, musculoskeletal and sensory system drugs were off-label. There were large differences in the neonatal information provided by the different sources, with the largest differences found for term neonates, for whom the information was available for 67, 38 and 24% of prescriptions according to the BNFC, Micromedex and Estonian SPC, respectively.ConclusionsThe high rate of age-related off-label prescribing for neonates calls for urgent action from medical professionals and others to reinforce effective and safe pharmacotherapy for this age group. The existing SPCs should be regularly updated and more closely harmonised to each other.

Hospitalised neonates in Estonia commonly receive potentially harmful excipients

BackgroundInformation on the neonatal exposure to excipients is limited. Our aim was to describe the extent of excipient intake by Estonian neonates; to classify the excipients according to potential neonatal toxicity and thereby to measure the extent of exposure of neonates to potentially harmful excipients.MethodsA prospective cohort study that recorded all medicines prescribed to patients aged below 28 days admitted to Tartu University Hospital from 01.02-01.08 2008 and to Tallinn Children’s Hospital from 01.02- 01.08 2009 was conducted. Excipients were identified from Summaries of Product Characteristics and classified according to toxicity following a literature review.Results1961 prescriptions comprising 107 medicines were written for 348/490 neonates admitted. A total of 123 excipients were found in 1620 (83%) prescriptions and 93 (87%) medicines. 47 (38%) of these excipients were classified as potentially or known to be harmful to neonates. Most neonates (97%) received at least one medicine (median number 2) with potentially or known to be harmful excipient. Parabens were the most commonly used known to be harmful excipients and sodium metabisulphite the most commonly used potentially harmful excipient, received by 343 (99%) and 297 (85%) of treated neonates, respectively.ConclusionsHospitalised neonates in Estonia are commonly receiving a wide range of excipients with their medication. Quantitative information about excipients should be made available to pharmacists and neonatologists helping them to take into account excipient issues when selecting medicines and to monitor for adverse effects if administration of medicines containing excipients is unavoidable.

Off label use of prescription medicines in children in outpatient setting in Estonia is common.

We aimed to analyse the availability of paediatric information in Summaries of Product Characteristics (SPC) of ambulatory prescription medicines used in children and to compare the SPC information with other information sources.

Potentially harmful excipients in neonatal medicines: a pan-European observational study

Objectives We aimed to describe administration of eight potentially harmful excipients of interest (EOI)—parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride—to hospitalised neonates in Europe and to identify risk factors for exposure. Methods All medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis. Results Overall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates were recorded. EOI were found in 638 (31%) prescriptions and were administered to 456 (63%) neonates through a relatively small number of products (n=142; 27%). Parabens, found in 71 (13%) products administered to 313 (43%) neonates, were used most frequently. EOI administration varied by geographical region, GA and route of administration. Geographical region remained a significant determinant of the use of parabens, polysorbate 80, propylene glycol and saccharin sodium after adjustment for the potential covariates including anatomical therapeutic chemical class of the active ingredient. Conclusions European neonates receive a number of potentially harmful pharmaceutical excipients. Regional differences in EOI administration suggest that EOI-free products are available and provide the potential for substitution to avoid side effects of some excipients.

Antibiotic prescription preferences in paediatric outpatient setting in Estonia and Sweden

Aims of the study were to compare the paediatric outpatient antibiotic use in two countries with low overall antibiotic consumption and antibacterial resistance levels - Sweden and Estonia - and to describe the adherence to Estonian treatment guideline.All prescriptions for systemic antibiotics for children less than 18 years during 2007 from the Swedish Prescribed Drug Register and Estonian Health Insurance Fund database were identified to conduct a descriptive drug utilisation study.The total paediatric antibiotic use was 616 and 353 per 1000 in Estonia and Sweden, respectively. The greatest between country differences occurred in the age group 2 to 6 years –Estonian children received 1184 and Swedish children 528 prescriptions per 1000. Extended spectrum penicillin amoxicillin (189 per 1000) or its combination with beta-lactamase inhibitor (81 per 1000) and a newer macrolide clarithromycin (127 per 1000) were prescribed most often in Estonia whereas narrow spectrum penicillin phenoxymethylpenicillin (169 per 1000) and older generation macrolide erythromycin (21 per 1000) predominated in Sweden. For acute bronchitis, 17 different antibiotics (most commonly clarithromycin) were prescribed in Estonia despite the guideline recommendation not to use antibiotics.The higher rate of antibiotic use especially of extended spectrum antibiotics in Estonia compared to Sweden emphasizes the need for national activities to promote appropriate use of antibiotics while treating children, even when the overall antibiotic consumption is low.

Age-Appropriate Formulations Including Pharmaceutical Excipients in Neonatal Medicines

BACKGROUND The development of appropriate pharmaceutical formulations for routine neonatal practice is challenging because of the developmental characteristics and the need for it to be specifically ageappropriate. This has led to wide use of extemporaneous formulations, which lack standardized procedures that can result in medication errors in clinical practice resulting in suboptimal efficacy and safety concerns. METHODS We have reviewed the most recent literature on formulations and pharmaceutical excipients. RESULTS We present the issues related with the lack of age-appropriate formulations, discuss the importance and extent of exposure to pharmaceutical excipients known to be harmful to neonates, indicate ways that can reduce exposure to excipients of concern, and review challenges of the design of age-appropriate drug formulations and dosage forms/drug delivery systems for neonates. Finally, we summarize novel approaches regarding drug delivery for neonates. CONCLUSION Novel approaches in age-appropriate drug delivery should overcome the present obstacles and improve the quality of medicines, thus avoiding errors in treatment and improving the management of neonates. Further basic researches on discovering new technologies and modern formulations, using in vitro testing systems as well as preclinical and clinical trials, are needed to improve the feasibility, practicality and safety of new formulations, including research on pharmaceutical excipients.

Dosing of Ertapenem in an Extreme Obesity: A Case Report of 250 kg Patient

Limited available data for dosing in obesity of the medicines used in this case are discussed, with the emphasis on ertapenem. The case illustrates the difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing but data on adequate doses of medicines are scarce. We demonstrate that ertapenem 1,5 g i.v. once daily provided adequate drug exposure for susceptible bacteria in a 250 kg patient with normal renal function. The case suggests the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients.

MEDICATION USE IN NEONATAL INTENSIVE CARE UNITS ACROSS EUROPE

Objectives This is the first Europe-wide study aiming to describe the medication use in Neonatal Intensive Care Units and to analyse the factors that might influence the prescription pattern. Methods A pan-European one day point-prevalence study was conducted in 2012 where all of the prescriptions for hospitalised neonates were recorded. A trade name, manufacturer, active pharmaceutical ingredients (API), strength, galenic form and route of administration were registered. Results Altogether 2173 prescriptions were administered to 726 neonates from 21 countries, of whom 66% (477/726) were preterm, 12% (84/726) extremely preterm. There was inverse correlation between gestational age (GA) and median number of prescriptions per neonate (group median 2/IQR 1–4, extremely preterm 4/3–6, very preterm 3/2–5, late preterm 2/1–3, full-term 2/1–3). Median number of prescriptions per neonate was highest in the eastern region, among extremely preterm neonates (median=6.5/IQR 6–8.5). Highest prescription rate was for alimentary medicines (93/per 100 admissions), systemic antiinfectives (79/100) and medicines for blood (71/100). Antiinfectives were most frequently prescribed in the southern region (103/100). Multivitamins were most frequently used medications in most regions (western 74, southern 31, northern 31/100), except in eastern region (5/100). Most commonly prescribed API-s were multivitamins (32/100), caffeine (19/100), gentamicin (18/100), amino acids (18/100) and colecalciferol (15/100). Most frequently prescribed medications among extremely preterm neonates were caffeine (60/100), among very preterms multivitamins and caffeine (45 and 43/100), among late preterms multivitamins (44/100) and among full-terms phytomenadione (26/100) and gentamicin (24/100). Conclusions Our study revealed the most commonly used medications in neonates. Higher prescription rate among preterm neonates calls for further analysis of the suitability and safety of medications for infants with lower GA.

O-098 Potentially Harmful Excipients In Medicines Prescribed In Neonatal Intensive Care Units (nicu) – Product Substitution As A Way Forward

Background Excipients are essential for many medicines. Some have been associated with significant consequences in neonates. We aimed to identify substitution possibilities among medicines used in European neonates in order to minimise the administration of potentially harmful excipients of interest (EOI). Methods A 3-day survey recording all medicines prescribed to neonates was performed in European NICUs. Based on existing toxicity data in neonates the EOI included parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride. Opportunities for product substitution were defined as EOI-containing formulations for which an EOI-free product was reported in the survey with identical active pharmaceutical ingredient (API), galenic form and strength. Results Of 31 invited European countries 20 with 115 NICUs responded. A total of 564 trade names (TN) with 53 APIs were used in more than 10% of units. EOI containing formulations (n = 151) were used for 31 APIs, found overall in 363 TNs. Compared to parenteral forms (50/199; 25%), enteral (83/130; 64%) and topical TNs (18/34; 53%) contained EOI more frequently (OR; 95% CI 5.3; 3.3–8.5 and 3.4; 1.6–7.1, respectively). An EOI free substitution was available for 31/50 parenteral (63%), 17/83 enteral (21%) and 3/18 topical (17%) TNs. Overall, 51/151 (34%) TNs with EOI could be replaced; substitution was possible in 92/151 (61%) of cases if the requirement for identical API strength was ignored. Conclusions EOI-free formulations available on the European market could be used to reduce the number of TNs with EOI by at least a third.