Indication(s):

Management of pain severe enough to require daily, around-the-clock, long-term opioid tx and for which alternative tx (eg, non-opioid analgesics or immediate-release opioids) are inadequate. Limitations of use: reserve for use in patients for whom alternative tx options are ineffective, not tolerated, or inadequate to manage pain. Not indicated as an as-needed (prn) analgesic.

Pharmacology:

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.

Clinical Trials:

The efficacy and safety of Zohydro ER have been eva luated in a 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 with Zohydro ER. There were 302 subjects randomized at a ratio of 1:1 into a 12-week double-blind treatment phase with their fixed stabilized dose of Zohydro ER (40–200mg daily) 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 up to 2 doses per day.

Zohydro ER provided greater analgesia vs. placebo. There was a significant difference in the mean changes from baseline to Week 12 in average weekly pain intensity 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%).

Legal Classification:

CII

Adults:

See full labeling. Swallow whole. ≥18years: individualize. Opioid-naïve or non-opioid tolerant: initially 10mg every 12hrs. May increase dose in increments of 10mg every 12hrs every 3–7 days as needed. Conversion from other opioids: see full labeling. When discontinuing, use gradual downward titration every 2–4 days. Severe hepatic impairment: initially 10mg. Renal impairment: use low initial dose. 50mg ER caps, a single dose >40mg, or a total daily dose >80mg: for use in opioid-tolerant patients only.

Children:

<18years: not established.

Contraindication(s):

Significant respiratory depression. Acute or severe bronchial asthma or hypercarbia. Known or suspected paralytic ileus.

Warnings/Precautions:

Abuse potential. Life-threatening respiratory depression; monitor first 24–72hrs during initiation of therapy and following dose increases. Accidental ingestion may cause fatal overdose (esp. in children). COPD, cor pulmonale, or decreased respiratory reserve, hypoxia, hypercapnia. Head injury. Increased intracranial pressure. Impaired consciousness or coma. Shock. Post-op patients. Acute abdominal conditions. Biliary tract disease. Acute pancreatitis. Avoid abrupt cessation. Reeva luate periodically. Drug abusers. Acute alcoholism. Elderly. Cachectic. Debilitated. Pregnancy (Category C); potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: not recommended.

Interaction(s)

Not recommended within 14 days of MAOIs. Potentiation with alcohol or alcohol-containing products (avoid), other CNS depressants (eg, sedatives, hypnotics, tranquilizers, general anesthetics, other opioids), phenothiazines. May be potentiated by CYP3A4 inhibitors; if needed, monitor and consider dose adjustments. May be antagonized by CYP3A4 inducers, mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol); avoid. Paralytic ileus may occur with anticholinergics.

Adverse Reaction(s)

Constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting, pruritus, abdominal pain, peripheral edema, upper respiratory tract infection, muscle spasms, UTI, back pain, tremor.

Notes:

The FDA has mandated a REMS for all extended-release and long-acting (ER/LA) opioids. Further information is available at www.ZohydroerREMS.com or call (866) 964-3649.

How Supplied:

ER caps—100

LAST UPDATED:

3/18/2014