FDA Committees to Discuss Potential Dosing Error for New Oxycodone IR Formulation
On September 10th, 2015, a joint meeting of the Anesthetic and Life Support Drugs Advisory Committee and Drug Safety & Risk Management Advisory Committee will take place to discuss a new immediate-release (IR) formulation of oxycodone (Avridi; Purdue Pharma). This formulation has been designed with properties intended to deter abuse of the product via IV or intranasal routes.
The reason for this meeting is to discuss the results of pharmacokinetic studies evaluating the effect of food on the absorption of oxycodone from Avridi and the results of studies describing the abuse-deterrent properties, and to consider these data when determining the overall risk and benefit of this product. Pharmacokinetic studies have shown that the absorption of oxycodone from Avridi can be substantially delayed in the presence of food, and this food effect may impact both efficacy and safety. In response to this, the company proposes include in the labeling that the drug should be taken on an empty stomach. However, because this immediate-release product is intended to be dosed every 4–6 hours, the advisory committees are concerned that patients may have difficulty finding a time window during which to take their medication, and may be unable to comply with the instructions.
Opioid analgesics are generally taken without regard to food, and it is not clear whether labeling would be sufficient to change long-standing behaviors of both prescribers and patients. All of these issues may result in patients taking Avridi without regard to food, leading to variability in systemic exposure to oxycodone, variable or delayed efficacy, and the possibility of taking extra doses that could lead to serious adverse events. The potential safety risks and effects associated with delayed absorption when taken with food and the feasibility of labeling as an effective means to mitigate potential risks will be discussed at the meeting. Also, the committee will discuss whether the public health benefit of the product's abuse-deterrent properties outweigh the risk to patients prescribed the drug. These risks include the potential for an increased incidence of overdose due to the delayed onset of analgesic effect leading to patients taking repeated doses that could result in respiratory depression.
Until recently, most manufacturers have focused on the development of abuse-deterrent opioid formulations for extended-release/long-acting (ERLA) opioid analgesics. In general the amount of opioid in an ERLA product is greater than the amount found in IR formulations, and the extraction of the opioid or the defeat of the extended-release mechanism for the ERLA opioids results in greater amounts of drug available for abuse by various routes of administration. However, IR opioids are abused as well, and the development of abuse-deterrent formulations for these products is also an important public health goal.
While the FDA is not bound to the recommendations, the agency typically follows the advice of the advisory committees. If approved, Avridi will be indicated for the management of pain severe enough to require an opioid analgesic and for which alternative options are inadequate.
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