Appropriateness of timing of drug administration in electronic prescriptions
ABSTRACT For a small number of drugs circadian variability has been shown to modify efficacy, safety, or pharmacokinetics.
We aimed to develop a database containing optimum timing of drug administration and to test how well such information is considered in daily practice.
University hospital providing primary and tertiary care.
We included data of randomised controlled trials collected from Embase and Medline studying the impact of the timing of drug administration on pharmacodynamics, pharmacokinetics, and adverse events. Data were analysed and weighed according to an algorithm considering trial design and assessed endpoints. Each branch of the algorithm led to a specific recommendation as to the time of the day the drug should be administered. A second algorithm was used to establish a recommendation if studies differed in their conclusion. Subsequently we retrospectively analysed the dosing time in consecutive electronic prescriptions issued at our institution in 2007.
For 30 active compounds randomised controlled trials were published assessing optimum timing of their administration. In 33% of them timing had no impact on clinical endpoints while the administration at a certain time of the day significantly improved the outcome of another 64% no clear statement was made for one drug (ketoprofen). We then analysed 478,864 electronic prescriptions. Two percent of them contained drugs with known circadian variability. Only in 14% the suggested time was considered with a range between 0% for telmisartan (bedtime administration) and 85% for perindopril (morning administration).
Thus far, dedicated studies on circadian responsiveness to drugs are sparse and for the few drugs with unequivocal evidence this information is only rarely considered in daily practice. Integration of circadian dosing information into a clinical decision support system linked to electronic prescribing may be one promising way to make this information widely accessible.
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ABSTRACT: Numerous characteristics of a medication regimen can weaken patient adherence to drug therapy and thus impair clinical outcomes of drug therapy. The aim of the study was to investigate the prevalence of medication regimen characteristics that are known to reduce patient adherence to drug therapy. Furthermore, we assessed to what extent complex medication regimens can possibly be simplified through different strategies. We retrospectively evaluated the medication regimens of 500 consecutive patients discharged from the University Hospital of Heidelberg, Germany, in whom the dosages of all drugs were specified. The medication regimens were extracted from the discharge letters issued between 1 January 2007 and 29 December 2007. Each medication regimen was checked for the presence of seven regimen characteristics that are known to reduce patient adherence, and theoretical viable strategies to avoid four of the respective characteristics were identified. The extent of possible simplification through the identified strategies was evaluated for the overall study population and the subgroup of elderly patients (≥65 years) with polypharmacy (≥5 drugs). On average, every medication regimen in the overall study population had 2.9 ± 1.7 (standard deviation) characteristics (range 0-7) known to impair patient adherence. In contrast, the medication regimens of elderly patients with polypharmacy contained 3.7 ± 1.6 characteristics (range 0-7) known to impair patient adherence. The most prevalent complexity characteristics in the overall study population were prescription of ≥1 drug with multiple doses per day (441 patients), ≥3 drugs with different dosing intervals (349 patients), tablet splitting (223 patients), followed by ≥12 daily drug administrations (190 patients). Almost half of the prescribed tablet splitting could be prevented. Moreover, 17.9 % of the multi-dose prescriptions could be switched to once-daily dosing, and thus reduced the number of drugs with different dosing intervals and the number of daily drug administrations. The combined intervention reduced the total number of potentially preventable complexity characteristics by 18.3 % (from 2283 to 1865 characteristics) without reducing prescription quality. Almost one-fifth of all regimen complexity characteristics relevant for patient adherence were avoidable by simple modifications of the medication scheme, stressing the need for targeted interventions.Drug Safety 01/2013; 36(1):31-41. DOI:10.1007/s40264-012-0007-5 · 2.82 Impact Factor
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ABSTRACT: Background Chronotherapy involves altering the timing of medication administration to improve the overall control of a disease and to minimise treatment side-effects, and is an emerging concept in the field of therapeutics. Aim The aim of this review is to conduct an in-depth analysis of the recent literature in order to identify and evaluate the evidence base for drug chronotherapy. Method A literature search was conducted in three databases (Medline, Embase, International Pharmaceutical Abstracts) using the search terms "Chronotherapy", "Chronopharmacology", "Chronopharmacokinetics", "Chronopharmacodynamics", "Chronoefficacy", "Chronoformulation", "Morning and Evening", "Morning and Bedtime" and their combinations. The selection criteria for the inclusion of articles in the review included currency (years 2008-Aug 2011), publication in English language, studies done in Humans and non-review articles that pertained to 'drug' therapy. Results Our search revealed a total of 192 journal articles, of which 41 articles were selected for review. The specific hypothesis for the effectiveness of chronotherapy that was tested in these 41 studies was chronoeffectiveness (n = 34), followed by chronopharmacokinetics (n = 5), chronomodulation (n = 3) and chronopharmacodynamics (n = 2). The findings from two-thirds (n = 27) of the reviewed studies, support the notion of chronotherapy. Conclusion The review presents the scope of chronotherapy in drug utilization. We believe that the knowledge of chronotherapy is growing and the current research for chronotherapy is promisingly in the conceptualization or early experimental phase. Going forward, chronotherapy studies should also explore genetic, gender and age related differences. Preliminary screening of new drugs for chronotherapeutic potential may be a way of enhancing quality use of medicines.01/2013; 35(3). DOI:10.1007/s11096-013-9749-0
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ABSTRACT: A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks enveloped by three drug-free barrier layers was developed for use in chronotherapeutic disorders, employing two model drugs, theophylline and diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC) and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into the diltiazem-containing formulation for delayed drug release. Erosion and swelling studies confirmed the manner in which the drug was released with theophylline formulations exhibiting a maximum swelling of 97% and diltiazem containing formulations with a maximum swelling of 119%. FTIR spectra displayed no interactions between drugs and polymers. Molecular mechanics simulations were undertaken to predict the possible orientation of the polymer morphologies most likely affecting the MLMDT performance. The MLMDT provided two pulses of drug release, separated by a lag phase, and additionally it displayed desirable friability, hardness, and uniformity of mass indicating a stable formulation that may be a desirable candidate for chronotherapeutic drug delivery.BioMed Research International 08/2013; 2013(2013):569470. DOI:10.1155/2013/569470 · 3.17 Impact Factor