Sex Differences in Patterns of Adverse Events to Opioid Analgesics
Authors: Lopes Guilherme S. , Bielinski Suzette J. , Moyer Ann M. , Black John Logan , Jacobson Debra J. , Jiang Ruoxiang S. , Larson Nicholas B. , St. Sauver Jennifer S. 
Published: April 2020

BackgroundOpioid analgesics are among the most commonly prescribed medications in the United States. Opioids are useful in the management of pain, but their use can also adversely affect patients. However, studies reporting patterns of adverse events due to use of opioid analgesics in men and women are still scarce. Understanding the individual characteristics affecting response to opioids may allow clinicians to better individualize treatments. In this study, we investigated sex differences in the patterns of adverse events as a result of opioid use.MethodsWe used data from 8,457 patients participating in the Mayo Clinic Biobank “Right Drug, Right Dose, Right Time (RIGHT protocol)” study of pre‐emptive genotyping who were prescribed at least one of four opioid medications (codeine, tramadol, hydrocodone, or oxycodone) between 01/01/2004 and 12/31/2017. Adverse events due to use of these medications were collected from the allergy section in each patient’s electronical medical record, and were organized into four Medical Dictionary for Regulatory Activities (MedDRA) categories: gastrointestinal (e.g. nausea, vomiting), skin and subcutaneous tissue (e.g. rash, itching), psychiatric (e.g. anxiety, hallucinations), and nervous system (e.g. headache, dizziness). We modeled sex differences in the risk of adverse events by each opioid, and sex differences in the risk of each adverse event due to any opioid using logistic regression adjusted for age, race, ethnicity, and body mass index (BMI).ResultsParticipants with at least one opioid prescription were 60.8% female, mostly white (94.2%) and non‐Hispanic (98.9%). Women (relative to men) were younger (median = 61.6 vs. 69.1, respectively), had lower BMI (median = 27.4 vs. 28.9), and were prescribed more codeine (18.8% vs. 15.5%). Overall, 456 (5.4%) persons had a note in the allergy section of their medical record indicating a problem with an opioid medication. Women were more likely than men to have a note in the allergy section referring to at least one opioid (6.6% and 3.5%, respectively; p < 0.001). In addition, among participants who had at least one note related to opioid use in their allergy section, women were more likely to have notes regarding gastrointestinal complications (OR [95% CI] = 2.07 [1.3 – 3.2], p = 0.002), but less likely to have notes regarding psychiatric issues (OR [95% CI] = 0.30 [0.2 – 0.5], p < 0.001).ConclusionWomen were more likely than men to experience adverse events due to use of codeine, tramadol, hydrocodone, and oxycodone. In addition, the types of adverse reactions differed between men and women. These data suggest that further studies are needed to ensure that both men and women have optimal responses to opioid medications.Support or Funding InformationThis work was supported by the Mayo Clinic Specialized Center of Research Excellent on Sex Differences, the Mayo Clinic Center for Individualized Medicine, the Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, and the National Institutes of Health grants [U19 GM61388 (The Pharmacogenomics Research Network), R01 GM28157, U01 HG005137, R01 GM125633, R01 AG034676 (The Rochester Epidemiology Project)], and [U01 HG06379 and U01 HG06379 Supplement (The Electronic Medical Record and Genomics (eMERGE) Network)].