Zohydro ER (hydrocodone)

Zohydro ER (hydrocodone) is an opioid narcotic pain-reliever similar to oxycodone, morphine, methadone, fentanyl, and other opioids prescribed for long-term treatment of severe pain for which other treatment options are not effective, not tolerated, or would most likely not be strong enough to adequately manage the pain. 

Zohydro ER, like other opioids, stimulates receptors on nerves in the brain to increase the threshold to pain (the amount of stimulation it takes to feel pain) and reduce the perception of pain (the perceived importance of the pain). Unlike other hydrocodone products such as Vicodin which contain acetaminophen, Zohydro ER contains only hydrocodone.

Common side effects of Zohydro ER include

• lightheadedness,
• dizziness,
• sedation,
• nausea,
• vomiting,
• drowsiness,
• constipation, and
• spasm of the ureter, which can lead to difficulty in urinating.

Serious side effects of Zohydro ER include

• impaired thinking and physical abilities required for driving or operating machinery, and
• depressed breathing. Zohydro ER is habit forming.

Mental and physical dependence can occur when used long-term. Withdrawal symptoms may occur if you suddenly stop taking Zohydro ER.

Drug interactions of Zohydro ER include

• alcohol,
• other opioids,
• sedatives,
• hypnotics,
• tranquilizers,
• general anesthetics,
• phenothiazines,
• agonist/antagonist analgesics,
• monoamine oxidase inhibitors (MAOIs), and
• anticholinergics. 

There are no adequate studies of Zohydro ER in pregnant women. Use during pregnancy can cause life-threatening withdrawal symptoms in a newborn baby. 

Zohydro ER is excreted in breast milk, and, therefore should be used cautiously by breastfeeding mothers. Consult your doctor before breastfeeding.

The most frequent adverse reactions include:

• Lightheadedness
• Dizziness
• Sedation
• Nausea
• Vomiting

Other side effects include:

• Drowsiness
• Constipation
• Spasm of the ureter, which can lead to difficulty in urinating.

Other patient warnings include:

• Hydrocodone can impair thinking and the physical abilities required for driving or operating machinery.
• Hydrocodone can depress breathing, and should be used with caution in elderly, debilitated patients, and in patients with serious lung disease.
• Hydrocodone is habit forming. Mental and physical dependence can occur when used long-term.

The following serious adverse reactions are discussed elsewhere in the labeling:

• Addiction, Abuse, and Misuse
• Life-Threatening Respiratory Depression
• Neonatal Opioid Withdrawal Syndrome
• Interactions with Benzodiazepines and Other CNS Depressants
• Adrenal Insufficiency
• Severe Hypotension
• Gastrointestinal Adverse Reactions
• Seizures
• Withdrawal

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

• The safety of Zohydro ER was evaluated in a total of 1,148 subjects in Phase 3 clinical trials.
• Table 3 lists the most frequently occurring adverse reactions occurring at a greater frequency than placebo from the placebo-controlled trial in subjects with moderate-to-severe chronic lower back pain.

Table 3. Treatment-Emergent Adverse Events in ≥2% of Subjects During the Open-Label Titration Period and/or the Double-Blind Treatment Period, by Preferred Term — Number (%) of Treated Subjects (Placebo-Controlled Study in Opioid-Experienced Subjects with Moderate-to-Severe Chronic Lower Back Pain)

The common (≥1% to <10%) adverse drug reactions reported at least once by subjects treated with Zohydro ER in the Phase 3 clinical trials and not represented in Table 3 were:

• Gastrointestinal Disorders: abdominal discomfort, abdominal pain, gastroesophageal reflux disease
• General Disorders and Administration Site Conditions: non-cardiac chest pain, pain, peripheral edema, pyrexia
• Injury, Poisoning and Procedural Complications: contusion, fall, foot fracture, joint injury, joint sprain, muscle strain, skin laceration
• Investigations: increased blood cholesterol, increased gamma-glutamyltransferase
• Metabolism and Nutrition Disorders: dehydration, hypokalemia
• Musculoskeletal and Connective Tissue Disorders: arthralgia, musculoskeletal pain, myalgia, neck pain, osteoarthritis, pain in extremity
• Nervous System Disorders: lethargy, migraine, paresthesia
• Psychiatric Disorders: anxiety, depression, insomnia
• Respiratory, Thoracic, and Mediastinal Disorders: cough, dyspnea
• Skin and Subcutaneous Tissue Disorders: hyperhidrosis, night sweats, rash
• Vascular Disorders: hot flush

Postmarketing Experience

The following adverse reactions have been identified during post approval use of hydrocodone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Serotonin Syndrome

• Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.

Adrenal Insufficiency

• Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.

Anaphylaxis

• Anaphylaxis has been reported with ingredients contained in Zohydro ER.

Androgen Deficiency

• Cases of androgen deficiency have occurred with chronic use of opioids.

Drug Abuse And Dependence

Controlled Substance

• Zohydro ER contains hydrocodone bitartrate, a Schedule II controlled substance.

Abuse

• Zohydro ER contains hydrocodone, a substance with a high potential for abuse similar to other opioids including fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol. Zohydro ER can be abused and is subject to misuse, abuse, addiction, and criminal diversion.
• The high drug content in extended release formulations adds to the risk of adverse outcomes from abuse and misuse.
• All patients treated with opioids require careful monitoring for signs of abuse and addiction as use of opioid analgesic products carries the risk of addiction even under appropriate medical use.
• Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use then to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.
• "Drug-seeking" behavior is very common in persons with substance use disorders. Drug seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers, and people with untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.
• Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.
• Zohydro ER, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.
• Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing, storage, and disposal are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific To Abuse Of Zohydro ER

• Zohydro ER is for oral use only. Abuse of Zohydro ER poses a risk of overdose and death. The risk is increased with concurrent use of Zohydro ER with alcohol and other central nervous system depressants. Taking cut, broken, chewed, crushed, or dissolved Zohydro ER enhances drug release and increases the risk of overdose and death.
• With intravenous abuse, the inactive ingredients in Zohydro ER can result in death, local tissue necrosis, infection, pulmonary granulomas, increased risk of endocarditis and valvular heart injury, embolism, and death. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Dependence

• Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.
• Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.
• Zohydro ER should not be abruptly discontinued. If Zohydro ER is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate.
• Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs.