An FDA advisory meeting is scheduled tomorrow (4/22/2010) to review Acura Pharmaceuticals proposed Acurox® (oxycodone + niacin) immediate release tablets. Acura had submitted and NDA in December 2008 and received a Complete Response letter from FDA in June 2009 (a Complete Response letter is a denial of the approval but allowing for additional information). In September 2009, FDA agreed to hold an Advisory Committee meeting to discuss the issues raised in the Complete Response letter.
Acura has incorporated the following features that are intended to reduce abuse:
- Niacin is intended to induce an unpleasant flushing if the dose of drug product administered exceeds the labeled dose.
- Sodium laurel sulfate (SLS) is intended to irritate the nasal mucosa if the drug product is pulverized and snorted.
- The gel-forming polyethylene oxide is a substance that polymerizes upon wetting, forming a gel that is intended to be too viscous to inject through a needle and thus prevent misuse by injection. This excipient also has the potential to make the extraction of oxycodone from the matrix more difficult.
The FDA will present its view that niacin causes an unacceptably high incidence of AEs (flushing) in normal patients and, for abusers, the flushing effects can be easily mitigated by co-administration with NSAIDs or food; the risk/benefit is unacceptable.
Acura Pharmaceutical’s position was summarized in their briefing package as:
- Acurox® Tablets are effective in pain patients supporting the proposed indication for relief of moderate to severe pain;
- Acurox® Tablets are well tolerated when taken at recommended doses for analgesia;
- The disliking effects manifested by niacin when taken orally in excess quantities reduces the potential for abuse of oxycodone hydrochloride, the principal active ingredient in Acurox® Tablets;
- The doses of niacin that may be taken by a prospective abuser when swallowing excess doses of Acurox® Tablets are safe. This is extensively documented by studies of patients being treated chronically for dyslipidemias; and
- The potential benefits versus risks for the inclusion of niacin in Acurox® Tablets to limit or impede abuse are sufficient to warrant approval of Acurox® Tablets.
Thus, the Advisory Committee is being asked to assess the risk/benefit — is the risk of flushing acceptable in normal patients compared to the benefit of reducing the potential of abuse? Moreover, is the reduction of abuse potential overstated?