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Do Package Inserts Reflect Symptoms Experienced in Practice?

Assessment Using an Automated Phone Pharmacovigilance System with Varenicline and Zolpidem in a Primary Care Setting

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Abstract

Background: while the US FDA maintains a voluntary reporting system, postmarketing adverse drug events (ADEs) are underreported, and this case report-based system does not allow accurate determination of incidence.

Objective: The aim of the study was to assess the usefulness of an automated phone pharmacovigilance system for ambulatory patients by comparing systematically collected, patient-reported symptoms to reflect possible ADEs with those reported on the package inserts of two drugs with postmarketing safety concerns, varenicline and zolpidem.

Methods: English-speaking adults who received a prescription for zolpidem (n=370) or varenicline (n=107) from a primary care physician at one of 11 participating clinics, and who participated in the pharmacovigilance system during 2008–2010, were included in the study. Patients were called approximately 4 weeks following their visit and asked to complete a standard script that asked about adherence and pre-specified symptoms.

Main Outcome Measures: The main outcome measures were elicited rates of pre-specified symptoms or possible ADEs.

Results: Compared with the package insert, patients taking zolpidem were significantly (p<0.001) more likely to report fatigue (9.0% vs 1.0%), itching (4.5% vs 1.0%) and muscle aches (5.6% vs 1.0%). Elicited rates of depression and hallucination were similar to those reported in the package insert. Patients taking varenicline were significantly more likely to report confusion (1.7% vs 0.1%), depression (3.4% vs 0.1%), fatigue (6.0% vs 1.0%), hallucinations (1.7% vs 0.1%), muscle aches (6.0% vs 1.0%) and sexual dysfunction (4.3% vs 0.1%).

Conclusions: Automated phone pharmacovigilance can provide estimates of possible ADEs in clinical practice. In the case of varenicline, these data support some of the safety concerns that have come to light postmarketing, while others such as depression and hallucination related to zolpidem were not detected. These data highlight the potential value of, and innovative ways of collecting, information about possible ADEs directly from patients.

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Acknowledgements

This project was supported by grant number U18HS016970 from the Agency for Healthcare Research and Quality. The funder did not have any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. Dr Bates has consulted for TransCept, which is a manufacturer of a product containing zolpidem. Dr Schiff has received grants from AHRQ CERT and CRICO, the Harvard Risk Management Foundation. None of the other authors report a conflict of interest.

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Authors and Affiliations

  1. Division of General Medicine and Primary Care, Brigham and Women’s Hospital, 1620 Tremont Street, Boston, Massachusetts, MA 02120, USA

    Jennifer S. Haas MD, MSPH, Mary Amato, Lucas Marinacci, E. John Orav, Gordon D. Schiff & David W. Bates

  2. Department of Society, Human Development, and Health, Harvard School of Public Health, Boston, Massachusetts, USA

    Jennifer S. Haas MD, MSPH & David W. Bates

  3. Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Boston, Massachusetts, USA

    Mary Amato

  4. Department of Health Policy and Management, Harvard School of Public Health, Boston, Massachusetts, USA

    David W. Bates

Authors
  1. Jennifer S. Haas MD, MSPH
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  2. Mary Amato
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  3. Lucas Marinacci
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  4. E. John Orav
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  5. Gordon D. Schiff
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  6. David W. Bates
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Correspondence to Jennifer S. Haas MD, MSPH.

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Haas, J.S., Amato, M., Marinacci, L. et al. Do Package Inserts Reflect Symptoms Experienced in Practice?. Drug Saf 35, 623–628 (2012). https://doi.org/10.1007/BF03261959

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  • DOI: https://doi.org/10.1007/BF03261959

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