Márcia Lombardo

Actual Versus Expected Doses of Half Tablets Containing Prescribed Psychoactive Substances: A Systematic Review

Objective To assess through a systematic review of the literature if the practice of splitting tablets containing psychoactive/psychotropic medications for medical or economic reasons would result in the expected doses. Data Sources A MEDLINE and PsycInfo comprehensive search of English-language publications from January 1999 to December 2015 was conducted using the terms describing tablet splitting (tablet splitting, split tablets, tablet subdivision, divided tablets, and half tablets) and psychoactive substances (psychoactive medicines, psychotropic medicines, antidepressants, anxiolytics, anticonvulsants, antipsychotics, and antiparkinsonian agents). An additional supplementary search included the references from the articles found. Study Selection/Data Extraction Studies were included if splitting content was directly related to psychoactive medications and examined the effect of tablet splitting on drug uniformity, weight uniformity, and adherence of psychoactive drugs. Articles were systematically reviewed and examined regarding the study design, methodology, and results of the study. A total of 125 articles were screened, and 13 were selected. Results Tablet splitting implications are extensive, yet substantial deviations from the ideal weight, potency, and dose uniformity are more prone to be important to patient safety. The uneven division of tablets might result in the administration of different doses than what was prescribed, causing under- or overdosing, which might be relevant depending on the drug. In 55% of the cases, splitting psychoactive drugs was satisfactory. Conclusions It cannot be generalized that splitting psychoactive drugs compromises dose accuracy, thus tablet splitting might still be employed in cases in which the advantages outweigh the disadvantages. It is recommended that alternatives be adopted to prevent the disadvantages related to tablet splitting.

DETERMINATION OF FENTANYL IN INJECTION SOLUTION EXPOSED TO IMPROPER STORAGE CONDITIONS

A estabilidade de medicamentos consiste no potencial do produto em preservar as especificacoes de qualidade em toda a cadeia de suprimento. Embora esforcos devam ser realizados para aprimorar a estabilidade da formulacao, algumas precaucoes podem ser requeridas para minimizar fatores externos que afetem caracteristicas fisico-quimicas determinantes da eficacia e seguranca do produto. Neste trabalho, uma solucao injetavel de citrato de fentanila foi submetida a diferentes esquemas de fotoexposicao a curto prazo, a fim de simular possiveis desvios no manuseio e armazenamento do produto durante a rotina hospitalar. O teor do farmaco foi avaliado por cromatografia liquida de alta eficiencia em fase reversa (CLAE-FR), utilizando um detector de fotodiodos. Os resultados indicaram que o teor de fentanila foi satisfatorio, mesmo apos a exposicao das ampolas a luz solar ou a luz artificial por 18 horas. Estudos futuros se fazem necessarios para avaliar o efeito de condicoes ambientais adversas sobre a solucao injetavel de fentanila.

Tablet splitting: implications in clonazepam dose adjustment?

Tablet splitting is particularly interesting for dose tapering and slow dose titration, especially in psychiatric and geriatric communities. The objective of this study was to investigate the accuracy and precision of splitting clonazepam tablets using a kitchen knife and a commercially available tablet splitter. Whole tablets and split portions were individually weighed to determine weight variation and weight loss. Despite an accurate splitting (mean percentage close to 100%), precision analysis indicated a high variability in half-tablets weight (RSD>6%), ranging around ± 25% for tablet splitter and ± 18% for kitchen knife. There was no significant difference between the splitting techniques used to divide the tablets for both accuracy and weight loss. These preliminary findings indicate that splitting clonazepam tablets either by tablet splitter or kitchen knife might result in an apparent accurate splitting, in spite of the lack of precision between split portions. Future research is needed to investigate if such variations in clonazepam daily drug doses would result in clinical outcomes compromising dose adjustment schedules.