Let's Get the Facts Straight About Zohydro™ ER--and the Important Patient Need It Fills

 

SAN DIEGO, April 11, 2014 /PRNewswire/ -- Rampant misinformation about Zohydro™ ER continues to be reported by the media and echoed in Washington D.C. and some states' capitals. These inaccurate and misleading statements are often made without proper context, and are intended to be sensational, to create fear, or to generate headlines. In many instances, these statements are not supported by scientific facts or medical evidence.

Let's get the facts straight

Zohydro ER is the first and only extended-release hydrocodone without acetaminophen approved by the U.S. Food and Drug Administration (FDA) 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. The fact is that Zohydro ER is a novel pain medicine that fills an important medical need—a hydrocodone medicine for severe chronic pain that can be taken twice a day, instead of 4-6 times a day, and that does not contain acetaminophen, which carries significant risk of liver toxicity when used for long periods of time.

Acetaminophen overdose is a leading cause of acute liver failure in the U.S., with 63 percent of unintentional acetaminophen overdoses attributed to the use of opioid-acetaminophen combination products. The availability of an acetaminophen-free formulation of extended release hydrocodone, therefore, is an important therapeutic option for certain chronic pain patients.  

FACT: Zohydro ER (extended release hydrocodone capsules without acetaminophen) is no more potent than Vicodin (or other immediate release hydrocodone tablets with acetaminophen) on a per milligram basis.

FACT: Zohydro ER is equally as potent as oxycodone (the active ingredient in OxyContin); and less potent than many other commonly prescribed opioids including oxymorphone, hydromorphone and fentanyl on a per milligram basis.

  • Potency is a measure of a drug's activity in the body. It is related to the molecule itself. Potency of opioids is often measured in "morphine equivalents." (i.e., how many milligrams of a particular opioid are estimated to be equianalgesic to one milligram of morphine)
  • All extended release medicines contain more milligrams of active ingredient per unit dose than comparable immediate release versions because they are dosed less frequently each day.
  • While the highest dosage unit of Zohydro ER (50 mg) contains more hydrocodone than the dosage units of Vicodin (5-10 mg) the products are equally potent since they both contain hydrocodone. Therefore, Zohydro ER is not 10 times more potent than Vicodin.
  • So why different strengths? Zohydro ER is administered every 12 hours rather than every four to six hours like Vicodin. Therefore, to achieve the same total daily dose of hydrocodone, you would expect Zohydro ER to be of a greater dosage per unit than Vicodin and other immediate-release hydrocodone combination products. For example, a patient taking Vicodin 10 mg every four hours will have the same total daily dose of hydrocodone as a person taking Zohydro ER 30 mg every 12 hours.

As shown in the table below, this is true for all extended-release opioids. In fact, doing a similar comparison of the highest dosage strength of commonly prescribed extended release opioids to the lowest dosage strength of their immediate release versions shows that Zohydro ER actually has the lowest difference in single tablet dosage strength as compared to its related immediate release formulation.

FACT: The highest dosage strength of Zohydro ER is lower than the highest dosage strength of OxyContin and other commonly prescribed extended-release opioids on a per milligram basis.

  • FDA Commissioner, Dr. Margaret Hamburg was quoted in a recent article in TIMEi, clarifying this point:

"It's been said that Zohydro is super-potent. That surprises me because the highest dosage unit of Zohydro extended release is lower than the highest dosage unit of all the other available extended release products on a milligram basis."

  • It is important to understand that oxycodone, the active medication in OxyContin, is considered to have the same potency as hydrocodone, the active medication in both Vicodin and Zohydro ER. However, oxymorphone, the active medication in Opana, is regarded as more potent than oxycodone or hydrocodone.
  • Since oxycodone and hydrocodone have the same potency (based on morphine equivalents), they can be compared on a milligram basis. The highest strength of Zohydro ER is 50 mg and the highest strength of OxyContin is 80 mg. OxyContin is therefore available at a 60 percent higher strength than Zohydro ER. This holds true when the same comparison of Zohydro ER is made with all other extended release opioid analgesics. (see graph below)

FACT: In comparison to other opioids, the amount of Zohydro ER that will be available represents less than 0.3 percent of the total quantity available of the majority of opioid pills/capsules in 2014.

  • Many public health experts believe the risk for misuse and abuse of opioids is directly correlated to the amount of opioids sold each year—in other words, the more opioids are prescribed and dispensed, the greater the amount of opioids in the community and the greater the risk of misuse and abuse. The U.S. Drug Enforcement Administration (DEA) allocates quotas for each manufacturer of controlled drugs across the five classes of opioids, based on objective medical and scientific needs, including appropriate maintenance of inventory. For 2014, based on data from DEA, the total quota for these five categories combined is 326,000 kilograms, to be allocated to all manufacturers for extended and immediate release opioids.
  • The amount of the DEA allocation requested and approved to manufacture Zohydro ER in 2014 is less than 1 percent of the total quota just based on hydrocodone and is less than 0.3 percent of the total DEA quota for all five categories of opioids as show in the chart below.

FACT: Only one of more than thirty extended release opioids and none of the immediate release opioids have FDA approved labeling for abuse deterrent properties.

FACT: In 2013, 98 percent of total opioid prescriptions were written for opioids that do not have FDA approved abuse deterrent properties.

  • Only one extended-release opioid product has a new label claim that the formulation is "expected to make abuse via injection difficult and to reduce abuse via the intranasal route (snorting)" compared to a legacy non-abuse deterrent formulation of the same drug. However, that medication does not address the most acute form of abuse – which is oral.
  • The FDA has publicly stated that current abuse deterrent technologies (ADT) are not adequate, and in fact current abuse deterrent technologies available today do not address the most common route of opioid abuse – which is orally.
  • Abuse deterrent technology is in the early stages of development, as evidenced by only having one product which has received FDA labeling claims. As FDA Commissioner Margaret A. Hamburg, M.D., recently statedii:

"I would love if we had abuse-deterrent formulations that were actually meaningful and effective at deterring abuse in all instances. We are moving in that direction," Hamburg told lawmakers. "Right now, unfortunately, the technology is poor."

  • Zogenix is investing heavily and actively developing two technologies in parallel with the intent of introducing a next-generation abuse-deterrent formulation of Zohydro ER according to the recently published FDA Guidance for Industry, as soon as possible.

FACT: Zogenix has implemented voluntary initiatives, educational tools and safeguards, which began prior to making Zohydro ER available, unlike the introduction of opioids in the past.

  • Zohydro ER is the first and only hydrocodone product that is currently prescribed and dispensed under Schedule II rules, the most restrictive schedule available under the U.S. Drug Enforcement Agency's (DEA) Controlled Substances Act.
  • Zogenix believes that the combination of scheduling, revised class-wide product labeling, the Extended-Release/Long Acting (ER/LA) Opioids Risk Evaluation and Mitigation Strategy (REMS), and our comprehensive suite of voluntary initiatives that include distribution controls, prescriber, pharmacist, and patient educational programs and resources may be more effective to prevent misuse than existing abuse deterrent technologies.  
  • An External Safe Use Board of experts, including pain management, addiction and law-enforcement specialists, independently evaluate data, which will be shared with the FDA if patterns of abuse by prescribers, pharmacists or patients are detected.
  • Sales representatives are compensated not on the number of prescriptions written, but instead for our representatives' efforts to ensure doctors, pharmacists and patients are educated on the risks and benefits of using extended-release opioids.
  • Patients receive access to free locking pill bottle caps and discounted safe-storage units to help prevent others from obtaining unauthorized access to Zohydro ER.

The Bottom Line

Zohydro ER deserves to be judged on its medical merits and the benefits it provides to patients suffering from chronic pain, not on the basis of media reports. Over the coming weeks, we will continue to report and distribute accurate information to address common misperceptions about Zohydro ER.

On behalf of patients and the doctors who serve them, Zogenix will continue to demand due process and fair treatment for our medications and our company. We are dedicated to responsibly serving people suffering with severe chronic pain and the health care professionals who treat them, while doing our very best to set a new standard of transparency and commitment in delivering on our promise to patients.

i Park, Alice. FDA expands access to overdose antidote to stem opiate addiction epidemic. TIME. Apr 3, 2014. time.com/48841/fda-loosens-access-to-overdose-antidote-to-stem-opiate-addiction-epidemic.

ii Federal Register, DEA Aggregate Production Quota History for Selected Substances. Updated October 2013.

iii Heavey, Susan. FDA chief defends new pain drug despite worries about abuse. Reuters. Mar 13, 2014. http://news.yahoo.com/fda-chief-defends-pain-drug-despite-worries-abuse-202159193--finance.html.

About Zohydro ER

INDICATION

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

Zohydro ER exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before prescribing, and monitor regularly for development of these behaviors or conditions.

Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow Zohydro ER whole to avoid exposure to a potentially fatal dose of hydrocodone.

Accidental consumption of Zohydro ER, especially in children, can result in fatal overdose of hydrocodone.

For patients who require opioid therapy while pregnant, be aware that infants may require treatment for neonatal opioid withdrawal syndrome. Prolonged use during pregnancy can result in life-threatening neonatal opioid withdrawal syndrome.

Instruct patients not to consume alcohol or any products containing alcohol while taking Zohydro ER because co-ingestion can result in fatal plasma hydrocodone levels.

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.

Zohydro ER uses Alkermes Pharma Ireland Limited's patented Spheroidal Oral Drug Absorption System (SODAS®) drug delivery technology, which serves to enhance the release profile of hydrocodone to provide extended-release pain relief relative to existing immediate-release combination products.

For more information about Zohydro ER, please visit: www.ZohydroEr.com or the Zohydro ER REMS website at www.ZohydroERREMS.com.

About Zogenix

Zogenix, Inc. (Nasdaq: ZGNX), with offices in San Diego and Emeryville, California, is a pharmaceutical company committed to developing and commercializing therapies that address specific clinical needs for people living with pain-related conditions and central nervous system disorders who need innovative treatment alternatives to help them return to normal daily functioning. More information about Zogenix is available at www.zogenix.com

ZohydroER is a trademark of Zogenix, Inc.

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SOURCE Zogenix, Inc.



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