The US Food and Drug Administration (FDA) has approved the first single-entity extended-release formulation of hydrocodone bitartrate (Zohydro ER, Zogenix Inc) for the management of pain severe enough to require daily around-the-clock long-term treatment and for which alternative options are inadequate.
“Zohydro ER, a Schedule II controlled substance under the Controlled Substances Act, is the first FDA-approved single-entity (not combined with an analgesic such as acetaminophen) and extended-release hydrocodone product,” a statement from FDA released today notes.
“Zohydro ER will offer prescribers an additional therapeutic option to treat pain, which is important because individual patients may respond differently to different opioids.”
This formulation belongs to the class of extended-release/long-acting (ER/LA) opioids, the statement notes. “Due to the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with ER/LA opioid formulations, Zohydro ER should be reserved for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain,” the FDA release said.
It is not approved for as-needed pain relief.
In addition, the labeling approved for this drug conforms to updated labeling requirements for all ER/LA opioids announced by the FDA on September 10 and reported at that time by Medscape Medical News, the first opioid to be labeled in this way, the statement notes.
“The new class of labeling and stronger warnings will more clearly describe the risks and safety concerns associated with ER/LA opioid analgesics, along with the appropriate use of these medications,” the FDA said. “These warnings are expected to improve the safety of all such medicines by encouraging more appropriate prescribing, patient monitoring, and patient counseling practices.”
Schedule II drugs can be dispensed only by prescription, and no refills are allowed. Stringent record-keeping, reporting, and physical security requirements are also in place for these substances.
The FDA will require postmarketing studies of this agent to assess the “known serious risks of misuse, abuse, increased sensitivity to pain (hyperalgesia), addiction, overdose, and death associated with long-term use beyond 12 weeks,” the FDA release said. “These studies will also be required for other ER/LA opioid analgesics.”
Safety of this new formulation of hydrocodone is based on clinical studies that have included more than 1100 patients with chronic pain. Efficacy is based on a clinical study that enrolled more than 500 patients with chronic low back pain and showed a significant improvement in chronic pain vs placebo.
It will also be part of the ER/LA Opioids Analgesics risk evaluation and mitigation strategy (REMS) approved in 2012. The REMS requires companies to make educational programs on how to safety prescribe these agents to healthcare professionals and provide medication guides and patient counseling documents with information on safe use, storage, and disposal of ER/LA opioids.
The most common adverse effects of this single-entity hydrocodone are constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting, and pruritus.
In December 2012, FDA’s Anesthetic and Analgesic Drug Advisory Committee of independent experts voted 11 to 2, with 1 abstention, to recommended against approval of this agent for the treatment of moderate to severe chronic pain.
Most panel members voted that the drug had met regulatory requirements for safety and efficacy, as indicated by their responses to questions on efficacy and safety. However, for the last question voted on — “Based on the data presented and discussed today, do the efficacy, safety and risk-benefit profile of Zohydro ER support the approval of this application?” — most had negative responses.
The main concern of those voting against approval was that the potential for abuse of these agents; because the product does not include acetaminophen, they feared the potential for abuse might be even greater.