Prevalence of Exposure to Potential CYP450 Pharmacokinetic Drug–Drug Interactions among Patients with Chronic Low Back Pain Taking Opioids

Drug–drug interactions (DDIs) have been defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system, including some, but not all, opioids experience a drug–drug exposure (DDE), which may result in a potentially dangerous DDI. Using a retrospective analysis of a large commercial claims database and a Medicare database, we evaluated DDEs that have the potential to cause DDIs among chronic low back pain (cLBP) patients on long‐term opioid analgesia, which metabolizes through the CYP450 enzyme system, concomitant with other CYP450‐metabolized drug(s). The overall prevalence of DDEs among cLBP patients was 27%. Women had a higher prevalence of DDEs (30.6% vs. 22% for men). Patients aged 45 to 55 and 56 to 64 years had the highest prevalence of DDEs (30.4% and 29.8%, respectively), followed by patients 34 to 45 years (27.9%). For patients > 65 years, the prevalence of DDEs was 23.1%. In general, the prevalence of DDEs was fairly consistent across age ranges in this population. This study suggests that DDEs are common in the cLBP population. When selecting an opioid to treat cLBP, physicians should consider the potential for exposure of these patients to drugs that might unfavorably interact and, for that reason, the use of opioids that do not rely on the CYP450 system as their primary means of metabolism might be worthy of consideration.

[1]  S. R. Fine,et al.  ADVERSE DRUG REACTIONS , 2009, BMJ : British Medical Journal.

[2]  J. Saurat,et al.  High Prevalence of Potential Drug-Drug Interactions for Psoriasis Patients Prescribed Methotrexate or Cyclosporine for Psoriasis: Associated Clinical and Economic Outcomes in Real-World Practice , 2010, Dermatology.

[3]  Gregory L. Holmquist Opioid Metabolism and Effects of Cytochrome P450 , 2009 .

[4]  R. Mckinnon,et al.  Cytochrome P450 Part 3: Impact of Drug‐Drug Interactions , 2009 .

[5]  M. Dickson,et al.  Potential drug-drug interactions with antiepileptic drugs in Medicaid recipients. , 2008, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[6]  Reamer L. Bushardt,et al.  Polypharmacy: Misleading, but manageable , 2008, Clinical interventions in aging.

[7]  S. Haider,et al.  Trends in polypharmacy and potential drug-drug interactions across educational groups in elderly patients in Sweden for the period 1992 - 2002. , 2007, International journal of clinical pharmacology and therapeutics.

[8]  T. Lynch,et al.  The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. , 2007, American family physician.

[9]  H. Tobi,et al.  Studying co‐medication patterns: the impact of definitions , 2007, Pharmacoepidemiology and drug safety.

[10]  S. Thirstrup,et al.  Prevalence of inappropriate prescribing in primary care , 2007, Pharmacy World & Science.

[11]  J. Berger,et al.  Administrative Claims Analysis of the Relationship Between Warfarin Use and Risk of Hemorrhage Including Drug-Drug and Drug-Disease Interactions , 2006, Journal of managed care pharmacy : JMCP.

[12]  F. Curtiss False-Positive Versus True-Positive Drug-Drug Interactions With Warfarin , 2006, Journal of managed care pharmacy : JMCP.

[13]  R. Lipton,et al.  Assessment of potential drug-drug interactions with a prescription claims database. , 2005, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[14]  G. Wilkinson,et al.  Drug metabolism and variability among patients in drug response. , 2005, The New England journal of medicine.

[15]  Maryann M Fulton,et al.  Polypharmacy in the elderly: A literature review , 2005, Journal of the American Academy of Nurse Practitioners.

[16]  L. Solberg,et al.  Measuring patient safety in ambulatory care: potential for identifying medical group drug-drug interaction rates using claims data. , 2004, The American journal of managed care.

[17]  F. Gebhart Cover Story: A SNAPSHOT OF 2003 Rx MARKET , 2004 .

[18]  P. Glassman,et al.  Retrospective Drug Utilization Review: Incidence of Clinically Relevant Potential Drug-Drug Interactions in a Large Ambulatory Population , 2003, Journal of managed care pharmacy : JMCP.

[19]  G. Pransky,et al.  Recurrence of Low Back Pain: Definition-Sensitivity Analysis Using Administrative Data , 2003, Spine.

[20]  J. Hernández,et al.  Adverse drug events in ambulatory care. , 2003, The New England journal of medicine.

[21]  D. Bates,et al.  Incidence and preventability of adverse drug events among older persons in the ambulatory setting. , 2003, JAMA.

[22]  G. Pransky,et al.  Methodological Challenges in Studying Recurrence of Low Back Pain , 2003, Journal of Occupational Rehabilitation.

[23]  S. C. Armstrong,et al.  Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II. , 2003, Psychosomatics.

[24]  Mellar P. Davis,et al.  The importance of cytochrome P450 monooxygenase CYP2D6 in palliative medicine , 2001, Supportive Care in Cancer.

[25]  B. Pomeranz,et al.  Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. , 1998, JAMA.

[26]  G. Granneman,et al.  Use of In Vitro and In Vivo Data to Estimate the Likelihood of Metabolic Pharmacokinetic Interactions , 1997, Clinical pharmacokinetics.

[27]  J. Chan,et al.  Medication misadventures resulting in emergency department visits at and HMO medical center. , 1996, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[28]  N. Laird,et al.  Incidence of Adverse Drug Events and Potential Adverse Drug Events: Implications for Prevention , 1995 .

[29]  J. Gold,et al.  Validation of a combined comorbidity index. , 1994, Journal of clinical epidemiology.

[30]  C. A. Jankel,et al.  Epidemiology of Drug-Drug Interactions as a Cause of Hospital Admissions , 1993, Drug safety.

[31]  S. Speedie,et al.  Detecting Drug Interactions: A Review of the Literature , 1990, DICP : the annals of pharmacotherapy.

[32]  Neil B. Sandson Drug-drug interactions: the silent epidemic. , 2005, Psychiatric services.

[33]  S. C. Armstrong,et al.  Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I. , 2003, Psychosomatics.

[34]  Linda C. Li,et al.  The economic burden of low back pain: a review of studies published between 1996 and 2001. , 2002, Best practice & research. Clinical rheumatology.

[35]  William R. Hendee,et al.  To Err is Human: Building a Safer Health System , 2001 .

[36]  E. Clancy,et al.  A descriptive study of recurrent low back pain claims. , 1997, Journal of occupational and environmental medicine.

[37]  J L Bootman,et al.  Drug-related morbidity and mortality. A cost-of-illness model. , 1995, Archives of internal medicine.