RESUMO
BACKGROUND: In outpatient populations, hypoglycemia has been associated with tramadol. We sought to determine the magnitude of risk for hypoglycemia associated with tramadol use in hospitalized patients. METHODS: During a 2-year period of observation, adult inpatients who received ≥1 dose of tramadol were identified and their medical records were reviewed. Patients were included if they had blood or plasma glucose (BG) concentrations measured on at least two occasions within five days after the initial administration of tramadol. A contemporary comparator group of hospitalized oxycodone recipients was similarly reviewed. RESULTS: Tramadol was administered to 2927 patients who met inclusion criteria. Among these, hypoglycemia (BG ≤70 mg/dL) was documented in 22 (46.8%) of 47 patients with type 1 diabetes, 113 (16.8%) of 673 patients with type 2 diabetes, and 103 (4.7%) of 2207 patients who did not have a diabetes mellitus diagnosis. In those without a diabetes diagnosis, the causality association between hypoglycemia and tramadol use was probable in 77 patients (3.5%). By comparison, hypoglycemia was documented in 8 (1.1%) of 716 matched oxycodone recipients without diabetes (p = 0.002). As compared with tramadol recipients who did not develop low BG concentrations, those who experienced tramadol-related hypoglycemia were relatively young (mean age 52.0 versus 59.8 years; p = 0.027) and predominantly female (74.0% versus 59.8%; p = 0.012). CONCLUSIONS: Tramadol use was causally associated with hypoglycemia in hospitalized patients. The proportion of patients without diabetes who developed hypoglycemia was higher among those who received tramadol than among those who received oxycodone. TRIAL REGISTRATION: Colorado Multiple Institutional Review Board Protocol â 15-2215. Registered/approved 8 December 2015.
RESUMO
AIM: To evaluate the drug interactions between valproic acid (VPA) and carbapenem antibiotics. METHODS: The effects of concurrent use of VPA and carbapenem antibiotics were evaluated in a retrospective observational study of hospitalized adults. Patients receiving both VPA and a carbapenem with at least two plasma VPA concentrations serially measured prior to, during, and/or after this combined treatment were included. RESULTS: Six critically ill VPA-treated patients were identified who concurrently received meropenem (n=4), imipenem (n=1), or ertapenem (n=1). As compared with values obtained while not receiving treatment with the carbapenem, mean plasma VPA trough concentrations decreased by 58% (from 51.7 [95% confidence interval {CI} 28.0-75.4] to 21.8 [95% CI 11.1-32.5] mg/L; p = 0.025). Estimated mean VPA clearance increased by 191% (from 0.0158 [95% CI 0.0041-0.0275] to 0.0302 [95% CI 0.0169-0.0591] L/h/kg; p = 0.007). All VPA concentrations measured during concurrent VPA-carbapenem treatment were below the lower boundary of the usual therapeutic range. Five patients (83%) experienced generalized seizures during concurrent VPA-carbapenem treatment, including two with no prior history of seizures or epilepsy. CONCLUSIONS: All recipients showed evidence of a complex pharmacokinetic and pharmacodynamic drug interaction between VPA and a carbapenem. Concurrent use of these medications should be avoided.
