Abuse-Deterrent Opioids: Where is the Real Value?
December 11th, 2008Ginger S. Johnson, PhD
An Interview with:
Howard A. Heit, MD, FACP, FASAM Board Certified in Internal Medicine and Gastroenterology/Hepatology Certified in Addiction Medicine and a Medical Review Officer Chronic Pain Specialist Assistant Clinical Professor, Georgetown University
Concerning the recent FDA adisory committee recommendations for two new abuse-deterrent opioids –King Pharmaceuticals’ and Pain Therapeutics’ Remoxy (oxycodone hydrochloride controlled-release capsule) and Alpharma’s abuse-deterrent formulation of morphine, Embeda.
On November 13 and 14, the joint meeting of the Anesthetic and Life Support Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee discussed the NDA for King Pharmaceuticals’ and Pain Therapeutics’ Remoxy (oxycodone hydrochloride controlled-release capsule) as well as Alpharma’s abuse-deterrent formulation of morphine, Embeda. King/Pain Therapeutics (Remoxy, oxycodone ER) have been in a race with Purdue (novel formulation of Oxycontin) to have the first abuse-deterrent oxycodone to market. However, the FDA has requested additional clinical data from Purdue for its abuse-deterrent formulation of Oxycontin following a FDA Advisory Committee review in May 2008, and it’s expected that the product may not reach the market for a couple of years. The recent advisory committee asked how much real-world impact on abuse and misuse Remoxy and Embeda might have. The committee also considered how much information regarding the compounds’ abuse-resistant features should be included in the product label, as well as any potential safety issues these products might pose for patients in legitimate search of pain relief.
Via an 11-8 informal vote, the advisory committee concluded that the data for Remoxy demonstrates tamper-resistance advantages over Purdue’s Oxycontin. The committee recommended FDA approval of Remoxy with a suggested recommendation for specific label language for tamper resistance. Negotiations over an acceptable risk management plan are likely to delay Remoxy approval beyond the 12/11 FDA review deadline, perhaps into Q1/09.
The advisory committee also concluded, via a 16-2 informal vote, that Alphama’s Embeda demonstrates tamper/abuse-resistance advantages over traditional extended release morphine. However, the advantages were considered modest. This favorable review came shortly before King and Alpharma finally announced a $1.6 billion merger agreement on November 24 after a protracted period of negotiation. The sale is expected to be completed by the end of the year.
A key issue for the advisory committee is that the tamper-resistant opioid formulations such as Remoxy do not address misuse, such as overdose. The tamper-resistant opioid formulations, however, do address abuse concerns such as opioid extraction for inhalation or injection. While clinicians and regulatory authorities alike realize that it is only a matter of time before hard-core drug abusers / dealers are able to circumvent any abuse deterrent road blocks, these new formulations do have the potential to deter abuse and diversion in some manner. However, we ask, in the presence of generic alternatives, does it make sense to prescribe a high-priced, branded abuse-deterrent opioid for large patient populations that are not considered to be a source of the problem (e.g., cancer patients with disease-related pain)?
