Zohydro™ ER (hydrocodone bitartrate) Extended Release Capsules, CII, were approved by the Food and Drug Administration (FDA) on October 25, 2013, for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Zogenix is committed to ensuring the appropriate use of Zohydro ER, the first and only extended release hydrocodone product without acetaminophen approved in the US. Because Zohydro ER is the first hydrocodone without acetaminophen, it is subject to schedule II controls under the Controlled Substances Act, the most restrictive schedule available for an FDA approved product, and it is the first hydrocodone product to be subject to the FDA’s class-wide Risk Evaluation and Mitigation Strategy (REMS) for extended release/long-acting (ER/LA) opioid drug products. Moreover, Zohydro ER does not contain acetaminophen, avoiding potential for acetaminophen toxicity in patients for whom Zohydro ER is indicated.
The FDA approval decision came after an extended, 18-month, comprehensive and thorough review process. A summary of FDA’s approval decision can be found in Section 13 of the FDA’s Summary Basis of Approval (attached). The approved label for Zohydro ER includes the new revised label statements required for the class of ER/LA opioid drug products, which includes additional safety information and a revised indication. Zohydro ER should be reserved for use in patients for whom alternative treatment options (e.g. non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Zohydro ER is not indicated for use as an as-needed (prn) analgesic.
The active ingredient in Zohydro ER, hydrocodone, has been available in FDA-approved products since 1943 and is the same active ingredient found in immediate-release hydrocodone combination analgesic products currently on the market. Zohydro ER is approved for twice daily dosage and is available in six dosage strengths ranging from 10 mg to 50 mg. The highest dosage unit of Zohydro ER is lower than the highest dosage unit of all other available extended release opioid products on a milligram basis. For example, the highest dosage unit of Oxycontin is 80 mg, which is approximately 40% higher than the highest dosage unit of Zohydro ER (50 mg).
The safety of Zohydro ER is based on clinical studies of more than 1,100 people living with chronic pain. The safety of Zohydro ER was found to be generally well tolerated. Adverse reactions in ≥ 2% of patients in placebo-controlled trials included constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting, pruritus, abdominal pain, peripheral edema, upper respiratory tract infection, muscle spasms, urinary tract infection, back pain and tremor.
The availability of an acetaminophen-free formulation of extended release hydrocodone is an important therapeutic option for certain chronic pain patients. The use of products containing acetaminophen in high doses over long periods of time has the potential to cause liver injury. Acetaminophen overdose is a leading cause of acute liver failure in the United States, with 63 percent of unintentional acetaminophen overdoses attributed to the use of hydrocodone-acetaminophen combination products.1 Secondly, patients who are responding well to an immediate-release hydrocodone could benefit from being able to switch to an extended-release hydrocodone without acetaminophen and reduce the number of doses needed per day.
In addition, some patients are unable to achieve adequate pain relief from, or unable to tolerate, other FDA-approved opioid products. In short, Zohydro ER will provide an important option for patients while also being the most comprehensively regulated hydrocodone product on the market.
To support the appropriate use of Zohydro ER, Zogenix is committed to responsible management of product distribution and commercialization with the following comprehensive suite of voluntary initiatives, in additional to participation in the ER/LA opioid class REMS:
Furthermore, Zogenix is fully engaged in developing an abuse deterrent formulation of Zohydro ER to minimize the risk of abuse and misuse associated with the class of ER/LA opioids.
Zohydro™ ER is an opioid agonist, extended-release, oral formulation of hydrocodone bitartrate indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
LIMITATIONS OF USE
Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve Zohydro ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
Zohydro ER is not indicated for use as an as-needed (prn) analgesic.
Please see the Zohydro ER full prescribing information for the complete boxed warning and safety information.
WARNING: ADDICTION, ABUSE AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOID WITHDRAWAL SYNDROME and INTERACTION WITH ALCOHOL
IMPORTANT SAFETY INFORMATION
Zohydro ER is contraindicated in patients with: significant respiratory depression; acute or severe bronchial asthma or hypercarbia; known or suspected paralytic ileus; and hypersensitivity to hydrocodone bitartrate or any other ingredients in Zohydro ER.
Zohydro ER contains hydrocodone, a Schedule II controlled substance. As an opioid, Zohydro ER exposes users to the risks of addiction, abuse, and misuse. As modified-release products, such as Zohydro ER, deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of hydrocodone present.
Potential serious adverse events caused by opioids include respiratory depression, potential for misuse and abuse, CNS depressant effects, prolonged gastric obstruction, and severe hypotension. The most common adverse reactions associated with Zohydro ER (≥2%) include constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting, pruritus, abdominal pain, peripheral edema, upper respiratory tract infection, muscle spasms, urinary tract infection, back pain and tremor.
Zogenix, Inc. (Nasdaq: ZGNX), is a pharmaceutical company committed to developing and commercializing therapies that address specific clinical needs for people living with pain-related conditions and CNS disorders who need innovative treatment alternatives to help them return to normal daily functioning.