A sustainable pharmaceutical care approach to prevention and management of digoxin toxicity

Abstract

Digoxin, as a treatment option in cardiology, is limited by its narrow therapeutic index. The use of digoxin in Malta is not protocol-regulated and this may pose efficacy and safety risks to the patient. Clinical guidelines recommend targeting a serum digoxin concentration (SDC) between 0.5 and 0.9 ng/ml.1,2,3 The Pathology Laboratory and Drug Information Unit (DIU) at Mater Dei Hospital (MDH) apply a SDC reference range of 0.9 to 2.0 ng/ml. The objectives were to determine the number of digoxin-treated patients in Malta, analyse SDCs recorded at MDH, assess adherence to the clinically recommended SDC target and review queries concerning digoxin processed by the DIU. Data for SDCs recorded at the Pathology Laboratory from January 2008 to December 2017 was collected. Patient variables selected for inclusion in the analyses were gender, age, origin of SDC request, referring physician, reason for SDC request, serum potassium (K+) and estimated glomerular filtration rate (eGFR). Enquiries processed at the DIU between April 2002 and September 2014 were analysed. The JASP software package version 0.7.5.6 was used to generate descriptive statistics (p<0.05 was considered to be statistically significant). The number of patients being treated with digoxin in Malta was 2,059 (January 2017). A total of 19,065 valid SDCs from 6,107 patients (63% female, mean age 78±11, range 1117 years) were analysed. The mean number of SDCs per patient was 3.12±3.35 (range 1-45). The mean SDC was 1.31±1.01 ng/ml (range <0.1-20.0 ng/ml). Variations from the clinically recommended target SDC (0.5-0.9 ng/ml) were 32% within, 11% below and 57% (17% >2.0 ng/ml) above. Eighty-four per cent of SDC requests originated from MDH, 36% from the Accident and Emergency Department (mean SDC 1.17±1.01 range <0.1-11 ng/ml), and 16% from other health care facilities. Mean serum K+ levels in patients with SDCs ≥2.0 ng/ml were significantly higher than patients within range (4.66±0.66 / 4.53±0.69 mEq/L, p=0.020). Patients recording SDCs above the recommended 0.9 ng/ml upper limit exhibited significantly lower eGFR compared to those below 0.9 ng/ml (66.76±36.43 / 73.84±35.21 mL/min/1.73m², p<0.001). Out of a total of 14,368 reviews processed by the DIU, 91 (0.6%) enquiries concerned digoxin. The top three enquiries were related to administration (26%), interactions (19%) and dosing (15%). The mean SDC of 1.31±1.01 ng/ml is higher than the current clinically recommended target SDC. Periodic evaluation of serum K+ and renal function with SDC monitoring is necessary to maintain SDCs within the recommended target range. The number of queries regarding digoxin is low (0.6%) compared to the number of out-of-range SDCs (68%), indicating the need for the DIU to disseminate its services. Consensus on a common target SDC range amongst health care providers in Malta, in line with international guidelines, is necessary to ensure a standardised approach to care. Further investigation to establish the clinical significance of these signals and their potential impact on patient health outcomes is warranted.