Rational and safe dosing of phenprocoumon during loading and maintenance phase

Phenprocoumon is the second most commonly used oral anticoagulant worldwide and the most common agent in many European countries including Switzerland. Given its long half-life of about one week, an initial loading-dose is generally applied. A high loading-dose is helpful to rapidly reach a therapeutic concentration but may be associated with an increased risk of bleeding if the effect overshoots. Phenprocoumon has a narrow therapeutic range, and individual dose requirements are highly variable. In clinical practice the initial dose-finding process for phenprocoumon is largely empiric and often delegated to inexperienced staff members. Thus, both a prolonged loading phase and overshooting of anticoagulation is commonly observed. Question under study The general aim of the thesis was to define one or more algorithms for the loading phase of phenprocoumon-treatment. These algorithms should be easily applicable in a clinical setting and help to improve the drug safety of phenprocoumon especially during the initial dose-finding process. Retrospective study In a retrospective study, predictors of individual dosing needs for a target-INR of 2.0 to 3.0 in medical and orthopaedic inpatients were determined. Several significant predictors of the loading dose could be identified. Using these predictors two simple clinical algorithms for the initial dosing of phenprocoumon in medical and orthopedic inpatients were developed. One algorithm contains clinical data and, additionally, serum albumin; the second algorithm contains clinical data only. Prospective study The aim of the prospective, randomized interventional study was to validate the efficacy and safety of the two previously proposed dosing algorithms for the initiation of oral anticoagulation with phenprocoumon. Additionally, the predictive value of pharmacogenetic markers was to be studied. Both algorithms could be validated and were slightly optimized. They proved to be very safe and effective in hospitalized patients with a high rate of comorbidity. The algorithm using clinical data can be especially recommended due to its simplicity of use

Use of unlicensed drugs in a Swiss Pediatric University Hospital and associated prescribing error rates – a retrospective observational study

AIMS OF THE STUDY: Unlicensed drugs are frequently used in paediatric care. To what extent they are prescribed in hospital care in Switzerland is unclear. Because prescribing errors seem to occur more frequently with unlicensed drugs, we aimed to assess the prevalence of unlicensed drug prescriptions in two study periods (2018 and 2019) at the University Children’s Hospital Zurich, compare these periods and investigate whether unlicensed drugs were more prone to prescribing errors than licensed drugs. METHODS: We conducted a sub-analysis of a retrospective single-centre observational study and analysed 5,022 prescriptions for a total of 1,000 patients from 2018 and 2019 in paediatric general wards. The rate of unlicensed drugs, consisting of imported or formula drugs, was investigated. The prescriptions from 2019 were further analysed on prescribing errors to see whether errors occurred more often in unlicensed or licensed drug use. RESULTS: Of all prescriptions, 10.8% were unlicensed drugs, with around half each being imported and formula drugs. Among all patients, 34% were prescribed at least one unlicensed drug. Younger paediatric patients were prescribed more unlicensed drugs than older paediatric patients (newborns: 15.8% of prescriptions, infants: 13.4%, children: 10.6%, adolescents: 7.1%). Ibuprofen suppositories, midazolam oral solution and gentamicin i.v. solution were the most frequently prescribed imported drugs. Macrogol powder, lisinopril oral suspension and potassium chloride i.v. solution were the most frequently prescribed formula drugs. The most common drug forms in unlicensed use were oral liquid forms and i.v. solutions. Unlicensed drugs had a significantly higher rate of prescribing errors than licensed drugs (31.6 errors per 100 prescriptions [95% CI: 26.1–37.0] versus 24.3 errors per 100 prescriptions [95% CI: 22.3–26.2], p = 0.024). In particular, formula drugs carried a higher risk (36.4 errors per 100 prescriptions, p = 0.012). CONCLUSIONS: Unlicensed drugs are frequently prescribed in this paediatric hospital setting in Switzerland. Around every tenth prescription is an unlicensed drug. Because unlicensed drugs showed a significantly higher rate of prescribing errors, licensed drugs are favourable in terms of medication safety and should be prescribed whenever possible. If no licensed drug is available, imported drugs should be favoured over formula drugs due to lower prescribing error rates. To increase medication safety in paediatrics in Switzerland, efforts are necessary to increase the number of suitable licensed drug formulations for paediatric patients, including developing new innovative drug formulations for children

Randomised trial of a clinical dosing algorithm to start anticoagulation with phenprocoumon

Prospective validation of two algorithms for the initiation of phenprocoumon treatment

Prescribing Patterns in Pediatric General Wards and Their Association with Prescribing Errors: A Retrospective Observational Study

Abstract Purpose There are only limited data on drug utilization patterns in pediatric inpatients, especially on general wards. The aim of the study was to describe prescribing patterns and their associations with prescribing errors in a university children’s hospital in the German-speaking part of Switzerland. Method This was a subanalysis of a retrospective single-center observational study. Patient characteristics and drug use of 489 patients with 2693 drug prescriptions were associated with prescribing errors. Drugs were categorized by the Anatomic Therapeutic Chemical Classification System (ATC), patients were categorized by age group according to European Medicines Agency guidelines, and prescribing errors were analyzed by type [Pharmaceutical Care Network Europe (PCNE) classification] and severity of error [adapted National Coordinating Council for Medication Error Reporting (NCC MERP) index]. Results The most frequently prescribed ATC classes were nervous system (N) (42.6%), alimentary system (A) (15.6%), and anti-infective drugs (J) (10.7%). Eighty-two percent of patients were prescribed an analgesic. Most drugs were prescribed for oral (47%) or intravenous (32%) administration, but the rectal route was also frequent (10%). The most frequently prescribed drugs were paracetamol, metamizole, and ibuprofen. The high number of metamizole prescriptions (37% of patients were prescribed metamizole) is typical for German-speaking countries. Older pediatric patients were prescribed more drugs than younger patients. A statistically significant difference was found in the rate of potentially harmful errors across age groups and for gender; children between 2 and 11 years had a higher rate of potentially harmful errors than infants under 2 years (p = 0.029) and female patients had a higher rate of potentially harmful errors than male patients (p = 0.023). Recurring errors were encountered with certain drugs (nalbuphine, cefazolin). Conclusions Our study provides insight into prescribing patterns on pediatric general wards in a university children’s hospital in Switzerland and highlights some areas for future research. Especially, the higher risk for prescribing errors among female pediatric patients needs further investigation