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

Abstract

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. C hronic noncancer pain remains undertreated in the United States despite the availability of effective analgesics, with more than 10% of individuals aged 20 years and older reporting pain lasting more than 1 year. Opioids are standard therapy for postoperative and cancer pain and have gained greater acceptance for moderate to severe chronic noncancer pain in selected patients for whom the benefits of treatment have been determined to outweigh the risks.

Rates of Opioid Dispensing and Overdose After Introduction of Abuse-Deterrent Extended-Release Oxycodone and Withdrawal of Propoxyphene

“…Two different changes in the pharmaceutical market occurred in late 2010: introduction of abuse-deterrent OxyContin and withdrawal of propoxyphene (both the napsylate and hydrochloride formulations). Abuse-deterrent opioid formulations with physical or pharmacologic deterrents to tampering have been proposed 6,7 as part of a comprehensive strategy to combat opioid misuse, abuse, and overdose. OxyContin, an extended-release formulation of oxycodone hydrochloride containing higher doses than immediate-release oxycodone, was introduced in 1995 and soon became a drug of choice among individuals with substance use disorders.…”

The Clinical Applications of Extended-Release Abuse-Deterrent Opioids

“…It is a tamper-resistant formulation that releases naloxone upon cutting, crushing, or chewing and antagonizes the opioid effect. It was withdrawn from the market in 2011 because of drug instability [53] and the possibility of sequelae in addiction-prone patients that could be dangerous [20]. Some examples of such sequelae include abuse-related behavior and overdose fatalities.…”

Ghost pill: knowledge and awareness of this phenomenon among health care professionals

“…the opiate analgesia and some amphetamines carry the potential risk of being abused by drug addicts. However, the incorporation of anti-tamper mechanisms [20][21][22] and the use of SR formulations, which has been shown not to be associated with the anticipated drug euphoric rush, make SR less attractive for illicit use. 23 For drug manufacturers, SR formulations are a source of income and have also been used by drug companies to extend warrant or to provide exclusivity of the product in the market.…”