Hydrocodone

Hydrocodone is a prescription narcotic indicated for the management of pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatment options are inadequate.

• Hydrocodone is available under the following different brand names: Zohydro ER, Hysingla ER, and Vantrela ER.

Common side effects of hydrocodone include:

• constipation
• headache
• fatigue
• back pain
• dry mouth
• tremor
• muscle spasms
• influenza
• ringing in the ears

Serious side effects of hydrocodone include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• breathing that slows with a long pause, 
• blue colored lips, 
• difficult to wake up, 
• skin redness or a rash that spreads and causes blistering and peeling, 
• noisy breathing, 
• sighing, 
• shallow breathing that stops, 
• lightheadedness, 
• nausea, 
• upper stomach pain, 
• tiredness, 
• loss of appetite, 
• dark urine, 
• clay-colored stools, 
• yellowing of the skin or eyes, 
• vomiting, 
• loss of appetite, 
• dizziness, 
• worsening tiredness, 
• weakness, 
• agitation, 
• hallucinations, 
• fever, 
• sweating, 
• shivering, 
• fast heart rate, 
• muscle stiffness, 
• twitching, 
• loss of coordination, and
• diarrhea

Rare side effects of hydrocodone include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage only. Safety and efficacy not established for pediatric use.

Capsule, extended-release (Zohydro ER): Schedule II

Abuse-deterrent product (BeadTek technology)

• 10 mg
• 15 mg
• 20 mg
• 30 mg
• 40 mg
• 50 mg

Tablet, extended-release (Hysingla ER): Schedule II

Abuse-deterrent product (RESISTEC)

• 20 mg
• 30 mg
• 40 mg
• 60 mg
• 80 mg
• 100 mg
• 120 mg

Tablet, extended-release (Vantrela ER): Schedule II

Abuse-deterrent product

• 15 mg
• 30 mg
• 45 mg
• 60 mg
• 90 mg

Dosage Considerations -- Should Be Given As Follows:

Chronic Pain

• Indicated for the management of pain severe enough to require daily, around-the-clock, long-term treatment and for which alternative treatment options are inadequate

Initial dosing

• Should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain
• 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
• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy

Opioid naive or first opioid analgesic

• The use of higher starting doses in patients who are not opioid-tolerant may cause fatal respiratory depression

Zohydro ER

• 10 mg orally every 12 hours initially
• A single dose of Zohydro ER greater than 40 mg, Zohydro ER 50 mg capsules, or a total daily dose greater than 80 mg are only for patients in whom tolerance to an opioid of comparable potency is established

Hysingla ER

• Administer once daily as 20 mg orally every 24 hours initially
• Daily doses of Hysingla ER greater than or equal to 80 mg/day are only for use in opioid-tolerant patients

Opioid tolerant

See prescribing information for conversion table from existing opioid analgesic to hydrocodone extended-release.

Opioid tolerance definition

Defined as patients who are receiving the following opioids (or an equianalgesic dose of another opioid) for 1 week or longer.

• morphine 60 mg/day orally
• transdermal fentanyl 25 mcg/hour
• oxycodone 30 mg/day
• hydromorphone 8 mg/day orally
• oxymorphone 25 mg/day orally

Dose adjustment, maintenance, and discontinuation

• Zohydro ER: Increase by increments of 10 mg every 12 hours every 3-7 days as needed to achieve adequate analgesia
• Hysingla ER: Increase by increments of 10-20 mg/day every 3-5 days as needed to achieve adequate analgesia
• Vantrela ER: May increase to the next higher dose every 3-7 days as needed to achieve adequate analgesia
• Assess pain frequently for toxicity, breakthrough pain, or need for short-acting rescue analgesia
• Discontinue by a gradual downward titration every 2-4 days; do not withdraw abruptly

Dosage Modifications

Liver impairment

Mild-to-moderate (Vantrela ER): Initiate therapy with one-half of the recommended initial dose and adjust the dose carefully; use alternative analgesia for patients requiring less than 15 mg. Severe: Initiate with the lowest dose, 10 mg (Zohydro ER) or 50% of the initial dose (Hysingla ER), and monitor closely for signs of respiratory depression and excessive sedation.

Kidney impairment

Patients with kidney impairment may have higher plasma concentrations than those with normal function. Moderate-to-severe and end-stage renal disease: Initiate therapy with a low initial dose (Zohydro ER) or 50% of the initial dose (Hysingla ER, Vantrela ER) and monitor closely for respiratory depression and sedation.

Dosing Considerations

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 use for patients for whom alternative treatment options (for example non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

Not indicated for acute pain or as an as-needed analgesic.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Severe Interactions of hydrocodone include:
  • alvimopan
  • indinavir
• Hydrocodone has serious interactions with at least 78 different drugs.
• Hydrocodone has moderate interactions with at least 208 different drugs.
• Hydrocodone has minor interactions with at least 23 different drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Addiction, abuse, and misuse

• Long-acting hydrocodone exposes patients and other users to the risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
• Assess each patient's risk before prescribing, and monitor all patients regularly for the development of these behaviors or conditions

Life-threatening respiratory depression

• Serious, life-threatening, or fatal respiratory depression may occur
• Monitor for respiratory depression, especially during initiation or following a dose increase
• Instruct patients to swallow capsules/tablets whole; crushing, chewing, or dissolving the extended-release dosage forms can cause rapid release and absorption of a potentially fatal dose of hydrocodone

Accidental exposure

• Accidental consumption of even 1 dose of hydrocodone, especially by children, can result in a fatal overdose of hydrocodone

Neonatal opioid withdrawal syndrome

• For patients who require opioid therapy while pregnant, be aware that infants may require treatment for neonatal opioid withdrawal syndrome
• Prolonged maternal use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening and requires management according to protocols developed by neonatology experts

Interaction with central nervous system depressants:

• Simultaneous use of opioids with benzodiazepines or other central nervous system depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
• Reserve simultaneous prescribing for use in patients for whom alternative treatment options are inadequate
• Limit dosages and durations to the minimum required, and follow patients for signs and symptoms of respiratory depression and sedation
• Co-ingestion of Zohydro ER with alcohol may increase hydrocodone plasma levels and result in a potentially fatal overdose (alters the release of drug from capsule)

Interaction with CYP3A4 inhibitors

• Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose from hydrocodone ER

This medication contains hydrocodone. Do not take Zohydro ER, Hysingla ER, or Vantrela ER if you are allergic to hydrocodone or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• Hypersensitivity
• Significant respiratory depression
• Acute or severe bronchial asthma or hypercarbia
• Suspected paralytic ileus

Effects of Drug Abuse

• Long-acting hydrocodone exposes patients and other users to the risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
• Hydrocodone is an opioid agonist and a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone

Short-Term Effects

• Caution must be used with potentially hazardous activities
• Hydrocodone is an opioid agonist and a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone

Long-Term Effects

• Hydrocodone is an opioid agonist and a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone
• See also "What Are Side Effects Associated with Using Hydrocodone?”

Cautions

• Do not prescribe for acute pain or as-needed (PRN) pain relief; only for severe chronic pain requiring continuous, around-the-clock opioid analgesia
• Hydrocodone is an opioid agonist and a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone
• Co-administration with other central nervous system depressants may cause profound sedation, respiratory depression, and death; if coadministration is required, consider a dose reduction of 1 or both drugs
• Monitor carefully in elderly, cachectic, debilitated patients, and those with chronic pulmonary disease because of increased risk for life-threatening respiratory depression
• Monitor patients with head injury or increased ICP for sedation and respiratory depression; avoid use in patients with impaired consciousness or coma susceptible to intracranial effects of CO2 retention
• May cause severely low blood pressure, including feeling dizzy or lightheaded when standing and fainting; added risk to individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone
• Prolonged gastric obstruction may occur
• Co-administration with CYP3A4 inhibitors may increase hydrocodone systemic exposure and result in toxicity; if coadministration with CYP3A4 is necessary, monitor patients closely who are currently taking, or discontinuing, CYP3A4 inhibitors or inducers; evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved
• Caution must be used with potentially hazardous activities
• Avoid the use of mixed agonist/antagonist analgesics (such as pentazocine, nalbuphine, or butorphanol) when taking full opioid agonist analgesics
• Hydrocodone ER may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings; monitor patients with a history of seizure disorders for worsened seizure control during hydrocodone ER therapy

Pregnancy and Lactation with Hydrocodone

• Use hydrocodone with caution in pregnancy if the benefits outweigh the risks. Animal studies show risk and human studies are not available or neither animal nor human studies have done
• Fetuses of rabbits administered oral doses of 75 mg/kg/day of hydrocodone bitartrate (15 times an adult human dose of 100 mg/day on an mg/m² basis) during the period of organogenesis exhibited an increased number of malformations consisting of umbilical hernia, and irregularly shaped bones (ulna, femur, tibia and/or fibula)
• Lactation: Low concentrations of hydrocodone and hydromorphone in the breast milk of nursing mothers using hydrocodone for postpartum pain control have been reported in published literature
• Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or  discontinue hydrocodone, taking into account the importance of the drug to the mother