Angioedema Caused by Drugs That Prevent the Degradation of Vasoactive Peptides: A Pharmacovigilance Database Study.

Angioedema results from the decreased degradation of vasoactive peptides such as substance P and bradykinin. In this study, we sought to clarify whether dipeptidyl peptidase-4 (DPP-4) and angiotensin-converting enzyme (ACE) inhibitors that suppress the degradation of substance P and bradykinin are involved in angioedema onset. We calculated information coefficients (ICs) by performing a disproportionality analysis to evaluate DPP-4/ACE inhibitor-induced angioedema using the Japanese Adverse Drug Event Report (JADER) database. No angioedema signals were detected for DPP-4 inhibitors; however, a signal was detected for ACE inhibitors (IC: 2.42, 95% confidence interval (CI): 2.19 to 2.65). Of the patients treated with DPP-4 inhibitors, four developed drug-induced angioedema in combination with ACE inhibitors, and all were taking vildagliptin. Signals were detected for enalapril (IC: 2.39, 95% CI: 2.06 to 2.71), imidapril (IC: 2.83, 95% CI: 2.38 to 3.27), lisinopril (IC: 2.28, 95% CI: 1.55 to 3.00), temocapril (IC: 1.35, 95% CI: 0.29 to 2.40), and trandolapril (IC: 1.57, 95% CI: 0.19 to 2.95). Both inhibitors inhibited the degradation of substance P and bradykinin and were thus expected to cause angioedema. However, no signal of angioedema was detected with the DPP-4 inhibitors, in contrast to some ACE inhibitors. This study found that ACE inhibitors and DPP-4 inhibitors, which inhibit the degradation of substance P and bradykinin, tended to have different effects on the onset of angioedema in clinical practice.

The association between polypharmacy and the efficiency of the functional independence measure in an acute-stage hospital: a retrospective cohort study.

BACKGROUND: The Functional Independence Measure (FIM) evaluates the activities of daily living (ADL), and FIM efficiency represents daily improvement in FIM. Polypharmacy affects both ADL and FIM; however, few studies have evaluated its relationship with FIM efficiency. AIM: This retrospective study investigated the effect of polypharmacy on FIM efficiency in patients undergoing rehabilitation at our acute care hospital in 2014. METHODS: We collected data on the patients' age, sex, diagnosis, length of hospital stay, type and duration of rehabilitation, indications for rehabilitation, FIM score before and after rehabilitation, and number of pharmaceuticals being used. Polypharmacy was defined as the administration of five or more pharmaceuticals. Using propensity score matching, we compared the FIM efficiency between the polypharmacy and non-polypharmacy groups (sub-scales and totals). RESULTS: A total of 2455 patients were included. The analytical population included 2168 patients. The analytical population used for propensity score matching included 727 patients in each group (total: 1454 patients). The following FIM sub-scale items were found to be associated with significantly low FIM efficiency in the polypharmacy group: self-care (polypharmacy group FIM efficiency: 0.43 points/day, non-polypharmacy group FIM efficiency: 0.54 points/day) and sphincter control (0.11 points/day and 0.18 points/day, respectively). No significant differences in the FIM efficiency were observed either for any other sub-scales or for totals. DISCUSSION: In the polypharmacy group, self-care and sphincter control, in particular, were associated with inhibited improvement in ADL and FIM. CONCLUSIONS: Reducing polypharmacy among acute-phase patients would allow an earlier return to their normal daily lives.

Effects of the number of drugs used on the prevalence of adverse drug reactions in children.

In pediatric individuals, polypharmacy would increase the prevalence of adverse drug reactions (ADRs). However, there is no report on the ADR increase adjusted for the influence of concomitant disease types. We conducted a retrospective study in pediatric patients to determine whether polypharmacy is a risk factor for ADR development, after the adjustment. Patients aged 1-14 years on medication who visited Gifu Municipal Hospital (Gifu, Japan) were included. We evaluated patient characteristics, ADR causality, ADR classification and severity, and ADR-causing drugs. We examined the association between ADR prevalence and number of drugs used. We performed multiple logistic regression analyses to investigate risk factors for ADR development. Of 1330 patients, 3.5% sought medical attention for ADRs. ADR causality was most often assessed as "possible," with gastrointestinal ADRs being the most common. Grade 1 ADRs were the most and antibiotics were the most common suspected ADR-inducing drug. The multiple logistic regression analysis showed that ≥ 2 or ≥ 4 drug use, neoplasms, mental and behavioral disorders, and circulatory system diseases significantly increased ADR prevalence. Polypharmacy increased the prevalence of ADR resulting in hospital visits in children, after adjusting for the influence of disease types. Therefore, proactive polypharmacy control measures are necessary for children.

Association between dipeptidyl peptidase-4 inhibitor and aspiration pneumonia: disproportionality analysis using the spontaneous reporting system in Japan.

PURPOSE: Dipeptidyl peptidase-4 inhibitor (DPP-4-Is), a kind of drug used for the treatment of diabetes, is considered to prevent the degradation of substance P that suppresses the occurrence of dysphagia. On the other hand, DPP-4 inhibitors are also known to act on the immune system. In this study, we used a spontaneous reporting system to evaluate the signals for dysphagia and aspiration pneumonia with DPP-4-Is. METHODS: We calculated reporting odds ratio (ROR) and information coefficients (IC) as disproportionality analysis to evaluate DPP-4-Is induced dysphagia and aspiration pneumonia using the Japanese Adverse Drug Event Report (JADER) database. RESULTS: For DPP-4-Is as a class, no signals were detected for dysphagia, but the signal for aspiration pneumonia was detected at ROR 1.67 (95% confidence interval [95% CI]: 1.20 to 2.34) and IC 0.70 (95% CI: 0.21 to 1.19). For aspiration pneumonia, trelagliptin was the only drug among the DPP-4-Is for which both ROR and IC signals were detected (ROR 9.99, 95% CI: 4.10 to 24.36; IC: 1.98, 95% CI: 0.78 to 3.18). ROR signals, but not IC signals, were detected for linagliptin (ROR 2.66, 95% CI: 1.19 to 5.94; IC: 1.09, 95% CI: - 0.004 to 2.19) and sitagliptin (ROR 1.84, 95% CI: 1.04 to 3.25; IC: 0.78, 95% CI: - 0.03 to 1.58). CONCLUSION: Since DPP-4 inhibitors prevent the degradation of substance P involved in swallowing reflex, DPP-4 inhibitors were expected to prevent dysphagia and aspiration pneumonia. However, this study revealed that DPP-4 inhibitors strongly were associated with onset rather than preventing aspiration pneumonia. This result suggests that DPP-4 inhibitors may affect the immune function associated with the development of aspiration pneumonia. Furthermore, there is a possibility that the amount of DPP-4-Is used clinically cannot increase the amount of substance P in sufficient quantity to prevent aspiration pneumonia.