Zohydro ER (hydrocodone bitartrate) Extended-Release Capsules

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved October 2013

Specific Treatments:

severe pain

Therapeutic Areas

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General Information

Zohydro (hydrocodone bitartrate) extended-release capsule, an opioid agonist, is an extended-release oral formulation of hydrocodone without acetaminophen.

Zohydro is specifically 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.

Zohydro ER is supplied as a capsule for oral administration. Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse.
Use of Zohydro ER as the First Opioid Analgesic
Initiate treatment with Zohydro ER with the 10 mg capsule every 12 hours.
Use of Zohydro ER in Patients who are not Opioid Tolerant
The starting dose for patients who are not opioid tolerant is Zohydro ER 10 mg orally every 12 hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, or an equianalgesic dose of another opioid.

Clinical Results

FDA Approval
The FDA approval of Zohydo ER was based on a randomized double-blind, placebo-controlled, multi-center clinical trial in opioid-experienced subjects with moderate to severe chronic low back pain. A total of 510 subjects currently on chronic opioid therapy entered an open-label conversion and titration phase (up to 6 weeks) with Zohydro ER dosed every 12 hours at an approximated equianalgesic dose of their pre-study opioid medication. For inadequately controlled pain, Zohydro ER was increased by 10 mg per 12-hour dose, once every 3 to 7 days until a stabilized dose was identified, or a maximum dosage of 100 mg every 12 hours. There were 302 subjects (59%) randomized at a ratio of 1:1 into a 12-week double-blind treatment phase with their fixed stabilized dose of Zohydro ER (40 to 200 mg daily taken as 20 to 100 mg, every 12 hours) or a matching placebo. Subjects randomized to placebo were given a blinded taper of Zohydro ER according to a pre-specified tapering schedule. During the Treatment Phase, subjects were allowed to use rescue medication (hydrocodone 5 mg/500 mg acetaminophen) up to 2 doses (2 tablets) per day. There were 124 treated subjects (82%) that completed the 12­week treatment with Zohydro ER and 59 subjects (39%) with placebo. Zohydro ER provided greater analgesia compared to placebo. There was a significant difference in the mean changes from Baseline to Week 12 in average weekly pain intensity Numeric Rating Scale (NRS) scores between the two groups. Treatment with Zohydro ER produced a greater number of responders, defined as subjects with at least a 30% improvement, as compared to placebo (67.5% vs. 31.1%).

Side Effects

Adverse effects associated with the use of Zohydro ER may include, but are not limited to, the following:

  • constipation
  • nausea
  • somnolence
  • fatigue
  • headache
  • dizziness
  • dry mouth
  • vomiting
  • pruritus
  • abdominal pain
  • edema peripheral
  • upper respiratory tract infection
  • muscle spasms
  • urinary tract infection
  • back pain
  • tremor

Mechanism of Action

Zohydro (hydrocodone bitartrate) extended-release capsule, an opioid agonist, is an extended-release oral formulation of hydrocodone without acetaminophen. Hydrocodone is a semi-synthetic opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. Hydrocodone acts as a full agonist, binding to and activating opioid receptors at sites in the peri-aquaductal and peri-ventricular gray matter, the ventro-medial medulla and the spinal cord to produce analgesia. The analgesia, as well as the euphorant, respiratory depressant and physiologic dependence properties of µ agonist opioids like hydrocodone, result principally from agonist action at the µ receptors.

Additional Information

For additional information regarding Zohydro ER or severe pain, please visit the Zogenix web page.