title: Detecting drug interactions from adverse-event reports: interaction between paroxetine and pravastatin increases blood glucose levels.
abstract: The lipid-lowering agent pravastatin and the antidepressant paroxetine are among the most widely prescribed drugs in the world. Unexpected interactions between them could have important public health implications. We mined the US Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) for side-effect profiles involving glucose homeostasis and found a surprisingly strong signal for comedication with pravastatin and paroxetine. We retrospectively evaluated changes in blood glucose in 104 patients with diabetes and 135 without diabetes who had received comedication with these two drugs, using data in electronic medical record (EMR) systems of three geographically distinct sites. We assessed the mean random blood glucose levels before and after treatment with the drugs. We found that pravastatin and paroxetine, when administered together, had a synergistic effect on blood glucose. The average increase was 19 mg/dl (1.0 mmol/l) overall, and in those with diabetes it was 48 mg/dl (2.7 mmol/l). In contrast, neither drug administered singly was associated with such changes in glucose levels. An increase in glucose levels is not a general effect of combined therapy with selective serotonin reuptake inhibitors (SSRIs) and statins.
authors: Biomedical Informatics Training Program, Stanford University, Stanford, California, USA.
authors: N P
authors: NP
authors: Tatonetti
authors: J C
authors: JC
authors: Denny
authors: S N
authors: SN
authors: Murphy
authors: G H
authors: GH
authors: Fernald
authors: G
authors: G
authors: Krishnan
authors: V
authors: V
authors: Castro
authors: P
authors: P
authors: Yue
authors: P S
authors: PS
authors: Tsao
authors: P S
authors: PS
authors: Tsau
authors: I
authors: I
authors: Kohane
authors: D M
authors: DM
authors: Roden
authors: R B
authors: RB
authors: Altman
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