Background: Muscle-related events, or myopathies, are a commonly reported adverse event associated with statin use. In June 2011, the US FDA released a Drug Safety Communication that provided updated product labeling with dosing restrictions for simvastatin to minimize the risk of myopathies. Objective: Our objective was to describe prescribing patterns of simvastatin in combination with medications known to increase the risk of myopathies following updated product labeling dosing restrictions in June 2011. Methods: A retrospective observational analysis was carried out, in which administrative claims data were utilized to identify prescribing patterns of simvastatin in combination with calcium channel blockers (CCBs) and other pre-specified drug therapies. Prescribing patterns were analyzed on a monthly basis 24 months prior to and 9 months following product label changes. Incidence of muscle-related events was also analyzed. Results: In June 2011, a total of 60 % of patients with overlapping simvastatin–CCB claims and 94 % of patients with overlapping simvastatin–non-CCB claims were prescribed an against-label combination. As of March 2012, a total of 41 % and 93 % of patients continued to be prescribed against-label simvastatin–CCB and simvastatin–non-CCB combinations, respectively. The most commonly prescribed dose of simvastatin was 20 mg (39 %). Against-label combinations were most commonly prescribed at a simvastatin dose of 40 mg (56 %). Amlodipine was the most commonly prescribed CCB in combination with simvastatin (70 %) and the most common CCB prescribed against-label (67 %). Conclusions: Despite improvements in prescribing practices, many patients are still exposed to potentially harmful simvastatin combinations. Aggressive changes in simvastatin prescribing systems and processes are needed to improve compliance with FDA labeling to improve medication and patient safety.