Preventing Prescription Opioid Abuse: New Formulations-But Who Will Benefit?

Mankind has recognized the analgesic effects of opioids for at least 5000 years, and for almost as long, there have been concerns about their potential addictive nature and their destructive impact on lives.¹ Although our knowledge about these drugs far exceeds that of our ancestors, we still debate how to balance the positive and negative aspects of opioids.

The number of persons in the United States who take prescription opioids for pain is growing. Sullivan and colleagues² found that from 2000 to 2005 there was a 19% increase in the number of patients who received prescriptions for opioids to manage chronic noncancer pain conditions. Based on a survey conducted from 1998 to 2006 with more than 19,000 subjects, Parsells Kelly and associates³ reported that 2% of the US population 18 years and older legally used opioids as analgesics at least 5 days per week for 4 or more weeks-and that another 2.9% used these drugs less frequently.

Every patient for whom an opioid is prescribed is at risk for misusing or abusing the agent. However, the percentage of patients who take opioids for pain and who will abuse or become addicted to these drugs remains unclear. A review of the literature on opioid addiction rates among patients who take these medications for chronic pain found results ranging from 0% to 50%.⁴

Steps to reducing abuse
In an attempt to reduce the abuse potential of prescription analgesics, several pharmaceutical companies have developed tamper- or abuse-resistant or deterrent (TARD) opioid formulations. These usually consist of long-acting opioids in combination with an opioid antagonist. There are also new formulations that make it difficult to change an oral preparation, so that the drug cannot be injected or inhaled.

Although these formulations have been presented as something revolutionary, a similar product has been on the market for many years-Talwin Nx (a combination of pentazocine, which is a short-acting opioid, and naloxone). Talwin Nx is an oral prep­aration that provides the analgesic effects of pentazocine when ingested; however, if the drug is crushed or melted, the naloxone is released, which counteracts the effects of the pentazocine.

None of the newer TARD preparations are FDA-approved, but several have been subject to phase 3 trials. Examples include extended-release opioid formulations combined with naltrexone that becomes active if the drugs are crushed. The opioid in Embeda, which is being developed by Alpharma, is extended-release morphine sulfate, and the opioid in a product currently labeled ELI-216 (from Elite Pharmaceuticals) is extended-release oxycodone. Pain Thera­peutics and Purdue Pharma also have developed TARD forms of extended-release oxycodone that make it difficult to melt or crush the medication.

In concept, these TARD drugs appear to have a role in preventing prescription opioid abuse. However, there are many issues that will need to be settled regarding optimal prescribing practices if these formulations are finally FDA-approved.

Spotting abuse potential
For which patients are these new TARD formulations appropriate? Certainly, patients with chronic pain who need the opioids that are contained in these formulations but who have a history of opioid abuse or dependence might appear to benefit. However, these patients would first have to be identified as having such a history of abuse or be at risk for these disorders.

Furthermore, the physician who treats such patients could choose the immediate-release forms of morphine and oxycodone, thus eliminating the risk that patients or others might crush the extended-release formulations to obtain their effects all at once. Another choice is methadone, the long-acting nature of which depends on the drug’s inherent pharmacology rather than its formulation, as in the case of extended-release morphine (eg, Oramorph SR, Avinza, Kadian) and oxycodone (OxyContin).

It may be that the population that would benefit the most from the TARD formulations are not those receiving the prescriptions. The Substance Abuse and Mental Health Services Administration (SAMHSA) found that in 2006, 5.2 million US citizens 12 years and older reported use of prescription opioids for nonmedical reasons during the previous month.⁵ SAMHSA also found that 64% of individuals aged 18 to 25 who were using prescription opioids for nonmedical reasons reported that they were given or bought these medications from a friend or relative. Another 3.8% said they took the medications without permission from someone who had received a prescription.⁶

Thus, physicians may be asked to prescribe a TARD formulation for the benefit of persons who are not only their patients but for whom they have never met or of whom they are not even aware. Extended-release morphine and oxycodone are available in inexpensive generic forms. Who should pay for these more expensive abuse-resistant formulations? Unless every patient who receives a prescription for these opioids is given one for a TARD formulation, we will need guidelines to help us choose which patients should be given these prescriptions.

Obviously, many patients receive medical interventions that serve the public good-most notably vaccinations. However, vaccinations directly benefit the individual by preventing a specific illness. If TARD opioids are approved, they may represent a rare if not unique situation in which patients or their insurance carriers will be asked to cover the cost of medications that provide no direct benefit for many of the patients for whom they will be prescribed, although it may help society in general.

References:

1. Booth M. Opium: A History. New York: St Martin’s Griffin Press; 1999.
2. Sullivan MD, Edlund MJ, Fan MY, et al. Trends in use of opioids for non-cancer pain conditions 2000-2005 in Commercial and Medicaid insurance plans: the TROUP study. Pain. 2008;138:440-449.
3. Parsells Kelly J, Cook SF, Kaufman DW, et al. Prevalence and characteristics of opioid use in the US adult population. Pain. 2008;138:507-513.
4. Højsted J, Sjøgren P. Addiction to opioids in chronic pain patients: a literature review. Eur J Pain. 2007; 11:490-518.
5. Office of Applied Studies, Substance Abuse and Mental Health Services Administration. Results from the 2006 national survey on drug use and health. September 2007. http://oas.samhsa.gov/nsduh/ 2k6nsduh/2k6results.cfm. Accessed December 9, 2008.
6. Office of Applied Studies, Substance Abuse and Mental Health Services Administration. How young adults obtain prescription pain relievers for nonmedical use. The NSDUH Report. Issue 39; 2006. http://oas.samhsa.gov/2k6/getPain/getPain.htm.Accessed December 9, 2008.