Strategies to reduce the tampering and subsequent abuse of long-acting opioids: potential risks and benefits of formulations with physical or pharmacologic deterrents to tampering

Mayo Clin Proc. 2012 Jul;87(7):683-94. doi: 10.1016/j.mayocp.2012.02.022.


Increased prescribing of opioid analgesics for chronic noncancer pain may reflect acceptance that opioid benefits outweigh risks of adverse events for a broadening array of indications and patient populations; however, a parallel increase in the abuse, misuse, and diversion of prescription opioids has resulted. There is an urgent need to reduce opioid tampering and subsequent abuse without creating barriers to safe, effective analgesia. Similar to the "magic bullet" concept of antibiotic development (kill the bacteria without harming the patient), the idea behind reformulating opioid analgesics is to make them more difficult to tamper with and abuse by drug abusers but innocuous to the compliant patient. As antibiotics exploit differences in bacterial and human physiology, tamper-resistant formulations depend on differences in the way drug abusers and compliant patients consume opioids. Most opioid abusers tamper with tablets to facilitate oral, intranasal, or intravenous administration, whereas compliant patients usually take intact tablets. Pharmaceutical strategies to deter opioid abuse predominantly focus on tablet tampering, incorporating physical barriers (eg, crush resistance) or embedded chemicals that render tampered tablets inert, unusable, or noxious. Deterring tampering and abuse of intact tablets is more challenging. At present, only a few formulations with characteristics designed to oppose tampering for abuse have received approval by the US Food and Drug Administration, and none has been permitted to include claims of abuse deterrence or tamper resistance in their labeling. This review discusses the potential benefits, risks, and limitations associated with available tamper-resistant opioids and those in development.

Publication types

  • Review

MeSH terms

  • Administration, Intranasal
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Chemistry, Pharmaceutical* / methods
  • Chemistry, Pharmaceutical* / standards
  • Chemistry, Pharmaceutical* / trends
  • Delayed-Action Preparations
  • Dosage Forms
  • Drug Combinations
  • Drug Compounding
  • Drug Industry
  • Humans
  • Injections, Intravenous
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / chemical synthesis
  • Opioid-Related Disorders*
  • Risk Assessment
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / prevention & control
  • Tablets / administration & dosage
  • Tablets / chemical synthesis*
  • United States / epidemiology
  • United States Food and Drug Administration


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Dosage Forms
  • Drug Combinations
  • Narcotic Antagonists
  • Tablets