Co-Prescription of QT-Interval Prolonging Drugs: An Analysis in a Large Cohort of Geriatric Patients.

BACKGROUND: Drug-induced QT-interval prolongation is associated with occurrence of potentially fatal Torsades de Pointes arrhythmias (TdP). So far, data regarding the overall burden of QT-interval prolonging drugs (QT-drugs) in geriatric patients are limited. OBJECTIVE: This study was performed to assess the individual burden of QT-interval prolonging drugs (QT-drugs) in geriatric polymedicated patients and to identify the most frequent and risky combinations of QT-drugs. METHODS: In the discharge medication of geriatric patients between July 2009 and June 2013 from the Geriatrics in Bavaria-Database (GiB-DAT) (co)-prescriptions of QT-drugs were investigated. QT-drugs were classified according to a publicly available reference site (CredibleMeds®) as ALL-QT-drugs (associated with any QT-risk) or High-risk-QT-drugs (corresponding to QT-drugs with known risk of Torsades de Pointes according to CredibleMeds®) and in addition as SmPC-high-risk-QT-drugs (according to the German prescribing information (SmPC) contraindicated co-prescription with other QT-drugs). RESULTS: Of a cohort of 130,434 geriatric patients (mean age 81 years, 67% women), prescribed a median of 8 drugs, 76,594 patients (58.7%) received at least one ALL-QT-drug. Co-prescriptions of two or more ALL-QT-drugs were observed in 28,768 (22.1%) patients. Particularly risky co-prescriptions of High-risk-QT-drugs or SmPC-high-risk-QT-drugs with at least on further QT-drug occurred in 55.9% (N = 12,633) and 54.2% (N = 12,429) of these patients, respectively. Consideration of SmPCs (SmPC-high-risk-QT-drugs) allowed the identification of an additional 15% (N = 3,999) patients taking a risky combination that was not covered by the commonly used CredibleMeds® classification. Only 20 drug-drug combinations accounted for more than 90% of these potentially most dangerous co-prescriptions. CONCLUSION: In a geriatric study population co-prescriptions of two and more QT-drugs were common. A considerable proportion of QT-drugs with higher risk only could be detected by using more than one classification-system. Local adaption of international classifications can improve identification of patients at risk.

Implementation of warnings from Dear Doctor Letters (Rote-Hand-Briefe): an analysis of medication data from a large cohort of elderly patients.

BACKGROUND: Dear Doctor Letters (also known as Direct Healthcare Professional Communications) inform physicians about significant newly discovered drug risks and about measures to take to reduce these risks. How far these warnings actually influence prescribing behavior is unclear. METHOD: The Geriatrics in Bavaria-Database (GiB-DAT, Geriatrie in Bayern Datenbank) collects data from more than 50 centers offering inpatient geriatric health care. Based on GiB-DAT data, the discharge medication of 76 568 patients (81 ± 8 years, 67% women) was recorded in a standardized manner and analyzed for the implementation of information contained in two Dear Doctor Letters about the risks of dose-related or drug interaction-related QT interval prolongation caused by citalopram or escitalopram. RESULTS: Patients were discharged with a median of 8 drugs. In the four quarters of 2012 following release of the Dear Doctor Letters, in comparison to the four quarters before their publication, a marked drop from 9.8% to 4.1% was seen in prescriptions for >20 mg/day citalopram--a dosage no longer recommended in elderly patients--and a similar drop from 23.6% to 12.8% in prescriptions for >10 mg/day escitalopram (p<0.0001). Co-prescription of either of these two drugs with other QT interval-prolonging drugs, which was now contraindicated, remained almost unchanged (citalopram: 19.3% [95% confidence interval (CI): 17.9-20.9%] versus 18.4% [95% CI: 17.0-19.8%]; escitalopram: 17.6% [95% CI: 15.8-19.6%] versus 17.1% [95% CI: 14.5-19.9%]). CONCLUSION: Simple information in Dear Doctor Letters, such as a reduction of the maximum daily dose, was better implemented than complicated information regarding contraindicated co-medication. Quality assurance systems such as the GiB-DAT network make it possible to identify problems of this kind. Licensing authorities and pharmaceutical companies should should improve the clinical usability, e.g., by providing official reference lists of drugs with safety warnings.