A systematically collated library of prescribing safety indicators for people with chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) have high levels of co-morbidity and polypharmacy placing them at increased risk of prescribing-related harm. Tools for assessing prescribing safety in the general population using prescribing safety indicators (PSIs) have been established. However, people with CKD pose different prescribing challenges to people without kidney disease. Therefore, PSIs designed for use in the general population may not include all PSIs relevant to a CKD population. The aim of this study was to systematically collate a library of PSIs relevant to people with CKD. METHODS: A systematic literature search identified papers reporting PSIs. CKD-specific PSIs were extracted and categorised by Anatomical Therapeutic Chemical (ATC) classification codes. Duplicate PSIs were removed to create a final list of CKD-specific PSIs. RESULTS: Nine thousand, eight hundred fifty-two papers were identified by the systematic literature search, of which 511 proceeded to full text screening and 196 papers were identified as reporting PSIs. Following categorisation by ATC code and duplicate removal, 841 unique PSIs formed the final set of CKD-specific PSIs. The five ATC drug classes containing the largest proportion of CKD-specific PSIs were: Cardiovascular system (26%); Nervous system (13.4%); Blood and blood forming organs (12.4%); Alimentary and metabolism (12%); and Anti-infectives for systemic use (11.3%). CONCLUSION: CKD-specific PSIs could be used alone or alongside general PSIs to assess the safety and quality of prescribing within a CKD population.

Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events? A systematic review.

OBJECTIVES: The objectives of this study were to identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. METHODS: A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles reporting randomized controlled trials, controlled clinical trials, interrupted time series trials, and controlled before and after studies involving amikacin therapeutic drug monitoring (TDM) and dose adjustment were considered for inclusion. RESULTS: Seventeen studies for inclusion were identified, comprising 1677 participants. Amikacin doses ranged from 11 to 15 mg/kg/day with 13 studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only 11 papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 to 40 mg/L and target troughs were typically <10 or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice-daily dosing and 40-45 mg/L for once-daily dosing; troughs averaged 5 and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in 12 and 8 studies. CONCLUSIONS: This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximize therapeutic outcomes and minimize toxicity with amikacin.