Benzodiazepine and Z-drug use and risk of pneumonia in patients with chronic kidney disease: A population-based nested case-control study

Abstract

Background Concerns were raised about pneumonia development from benzodiazepines (BZDs) and Z-drugs, but direct evidence is limited, conflicting and without examining the highly susceptible patients with chronic kidney disease (CKD) nor specifying the risk for different drug utiliza-tions. This study aimed to investigate whether use of BZDs and Z-drugs was each associated with an increased risk of pneumonia in a CKD population. Methods We performed a nested case-control study of 36,880 CKD patients analyzing the Taiwan National Health Insurance Database between 01/1/2000 and 12/31/2011. Among the study cohort, we identified 4,533 cases of pneumonia based on validated disease codes, chest x-ray examination, and prescriptions of respiratory antibiotics, and randomly selected 16,388 controls from risk sets, matched by sex, age, and number of CKD-related hospitalizations. All prescription filling records of BZDs and Z-drugs in the year before the event/index date were analyzed for cases and controls. Conditional logistic regressions were performed to estimate the odds ratios (ORs). Results Current use of BZDs was associated with a 1.31-fold (95% CI, 1.18–1.26) increased risk of pneumonia compared to nonuse, but not for recent and past use. The risk from current BZD use was confined to new initiation (adjusted OR, 2.47; 95% CI, 2.02–3.03) or use for 30 days, and elevated to 2.88-fold (95% CI, 1.87–4.42) with parenteral administration. New initiation and current short-term use of Z-drugs was associated with a 2.94-fold (95% CI, 1.65–5.26) and 1.75-fold (95% CI, 1.13–2.72) increased risk of pneumonia, respectively. The findings were robust to adoption of a case-crossover study that analyzed cases only. Conclusions Use of BZRAs is associated with an increased risk of pneumonia in CKD patients, especially for patients newly initiating BZDs or Z-drugs or those injected with BZDs. Physicians should exercise cautions for signs of pneumonia when prescribing BZDs or Z-drugs to CKD patients.