Drug Interaction Report

MONITOR: Coadministration of paroxetine and pravastatin has been reported to increase blood glucose in some studies. The mechanism of interaction is unclear. In one study using data from three electronic medical record (EMR) systems, a group of investigators retrospectively evaluated 104 patients with diabetes and 135 without diabetes who had received the combination and found that mean random blood glucose levels increased significantly from baseline after initiating the combination. The average increase was 19 mg/dL overall and 48 mg/dL in patients with diabetes. Similar increases were not observed in patients receiving either drug alone or other combinations of statin and selective serotonin reuptake inhibitor (SSRI). Likewise, another group of investigators using data from a different EMR system reported an increase of 19 mg/dL in mean glucose level from baseline in patients receiving the combination. In a third retrospective database study, investigators found no difference in random glucose, fasting glucose, and glycosylated hemoglobin mean values between 65 patients who were prescribed paroxetine and pravastatin and 2084 patients who were prescribed other statin and SSRI combinations after adjusting for the covariates of age, gender, body mass index, and body weight. However, no comparisons with baseline values were performed.

MANAGEMENT: Caution is advisable during concomitant use of paroxetine and pravastatin, particularly in patients with diabetes. More frequent monitoring of blood glucose should be considered.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.