Abuse-Deterrent Oxycodone/Naloxone Combination Approved by FDA

The FDA has approved a second extended-release/long-acting (ER/LA) opioid analgesic with FDA-approved labeling describing the product’s abuse-deterrent properties as recommended by the FDA’s 2013 draft guidance for industry, Abuse-Deterrent Opioids – Evaluation and Labeling. The FDA believes that information about a product’s demonstrated abuse-deterrent properties is important to health care providers, patients, and the public. Accordingly, the draft guidance recommends that new drug sponsors appropriately characterize the abuse-deterrent properties of their product in their proposed product labeling.

Abuse-Deterrent Properties

Since the early 1990s, the use of opioid analgesics for chronic pain has resulted in addiction, over-dose and death. In fact, by 2009, 100,000 deaths were attributed to opioid analgesics, with 15,500 reported in 2009 alone (see The risk of opioid abuse, addiction, and overdose in treatment of chronic pain). Targiniq ER® is expected to deter, but not totally prevent, abuse by snorting and injection. When crushed and snorted, or crushed, dissolved and injected, the naloxone blocks the euphoric effects of oxycodone, making it less liked by abusers than oxycodone alone. The drug, however, can still be abused by taking it orally.

Clinical Evaluation

Targiniq ER was evaluated in a clinical trial of 601 human subjects with chronic low back pain, with the safety data supporting approval including treatment of more than 3,000 people. Abuse liability studies from laboratory and human subjects demonstrated the abuse deterrent features of Targiniq ER as they relate to snorting and injecting. The most common side effects noted by clinical study participants were nausea and vomiting.

Approval

Targiniq ER (oxycodone hydrochloride and naloxone hydrochloride extended-release tablets), manufactured by Stamford-based Purdue Pharma LP, has been approved to treat pain severe enough to require daily, 24-hour, long-term treatment, and for which alternative treatment options have proved inadequate. Targiniq ER is not approved for as-needed pain relief. Targiniq ER will be available in 10/5 mg, 20/10 mg and 40/20 mg dosage strengths for dosing every 12 hours.

Postmarket Studies Required

The FDA’s approval is contingent on postmarketing studies to assess the risks of misuse, abuse, increased sensitivity to pain, addiction, overdose, and death associated with use beyond 12 weeks. The studies will also further assess the abuse-deterrent features of the drug. Details of the FDA’s approval and postmarketing requirements are contained in the FDA’s approval letter to Purdue Pharma.

REMS

The FDA has announced that Targiniq ER is part of the Risk Evaluation and Mitigation Strategy (REMS) for ER/LA opioids, a multi-agency federal effort to address the growing problem of prescription drug abuse and misuse. The REMS introduces new safety measures to reduce risks and improve safe use of ER/LA opioids while continuing to provide access to these medications for patients in pain. REMS specifically requires drug manufacturers to make available to health care professionals educational programs on how to safely prescribe ER/LA opioid analgesics and to provide Medication Guides and patient counseling documents on the safe use, storage, and disposal of these opioids.

For further discussion of the REMS program and the uproar over the FDA’s approval of Zohydro®, another ER/LA opioid analgesic with approved deterrent labeling, despite a 12-2 vote for disapproval by the agency’s advisory committee, see Should States Limit Access to FDA-Approved Opioids?