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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Hydrocodone: Drug information

Hydrocodone: Drug information
(For additional information see "Hydrocodone: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
FDA Requiring Updates to Opioid Prescribing Information April 2023

The FDA has issued a drug safety communication to announce safety-related updates to the prescribing information for immediate-release (IR) and extended-release (ER)/long-acting (LA) opioid analgesics, including updates to Boxed Warnings, Indications and Usage, Dosage and Administration, Warnings and Precautions, and the Medication Guide. These safety labeling changes are intended to provide clarity on appropriate patient populations for opioid treatment, appropriate dosage and administration, and updated information on the risks associated with opioid use. The required safety labeling changes include stating:

  • the risk of overdose increases as the dosage increases for all opioid pain medicines;

  • IR opioids should not be used for an extended period of time unless a patient's pain remains severe enough to require them and alternative treatment options continue to be inadequate;

  • many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine;

  • it is recommended to reserve ER/LA opioid pain medicines for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate; and

  • a warning about opioid-induced hyperalgesia (OIH), including information on differentiating OIH symptoms from those of opioid tolerance and withdrawal.

Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-prescribing-information-all-opioid-pain-medicines-provide-additional-guidance-safe-use.

ALERT: US Boxed Warning
Addiction, abuse, and misuse:

Because the use of hydrocodone ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient's risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions.

Opioid analgesic risk evaluation and mitigation strategy (REMS)

Health care providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription.

Life-threatening respiratory depression:

Serious, life-threatening, or fatal respiratory depression may occur with use of hydrocodone ER, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of hydrocodone ER are essential. Instruct patients to swallow hydrocodone ER whole; crushing, chewing, or dissolving hydrocodone can cause rapid release and absorption of a potentially fatal dose of hydrocodone.

Accidental ingestion:

Accidental ingestion of even one dose of hydrocodone ER, especially by children, can result in a fatal overdose of hydrocodone.

Neonatal opioid withdrawal syndrome:

If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome (NOWS), which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery.

Cytochrome P450 3A4 Interaction:

The concomitant use of hydrocodone ER with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. Regularly evaluate patients receiving hydrocodone ER and any CYP3A4 inhibitor or inducer.

Risks from concomitant use with benzodiazepines or other CNS depressants:

Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of hydrocodone ER and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.

Interaction with alcohol (capsule, extended release, 12-hour):

Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking hydrocodone ER. The co-ingestion of alcohol with hydrocodone may result in increased plasma levels and a potentially fatal overdose of hydrocodone.

Brand Names: US
  • Hysingla ER;
  • Zohydro ER [DSC]
Pharmacologic Category
  • Analgesic, Opioid
Dosing: Adult
Cough

Cough ( pdp-Hydrocodone [Canadian product]): Oral: Usual dose: 5 mg every 4 hours. Maximum single dose: 15 mg/dose. Maximum total daily dose: 30 mg in 24 hours.

Pain management

Pain management:

Note: Consider prescribing naloxone for patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, patients with sleep-disordered breathing, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally), and/or concomitant benzodiazepine use (Ref). Dosing provided is based on typical doses; some patients may require higher or lower doses. Individualize dosing based on patient-specific factors (eg, severity of pain, comorbidities, degree of opioid experience/tolerance) and titrate to patient-specific treatment goals (eg, improvement in function and quality of life, decrease in pain using a validated pain rating scale). Use the lowest effective dose for the shortest period of time. Opioids may be part of a comprehensive, multimodal, patient-specific treatment plan for managing moderate to severe pain. Maximize nonopioid analgesia (when appropriate) prior to initiation of opioid analgesia (Ref).

General dosing: Note: For acute non–cancer-related pain severe enough to require an opioid, utilize multimodal pain control, maximize nonopioid analgesics, and limit the quantity prescribed to the expected duration of pain severe enough to require opioids. Do not use long-acting preparations for treatment of acute pain (Ref).

Opioid-naive patients or patients who are not opioid tolerant: Note: Single doses >40 mg (capsule, extended release, 12-hour), or a total daily dose ≥80 mg (tablet, extended release, 24-hour) or >80 mg (capsule, extended release, 12-hour) are only for patients who are opioid tolerant. Opioid tolerance is defined as: patients already taking (for ≥1 week) at least 60 mg of oral morphine daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone daily, 8 mg oral hydromorphone daily, 25 mg oral oxymorphone daily, 60 mg oral hydrocodone or an equivalent dose of another opioid.

Capsule, extended release, 12-hour: Oral: Initial: 10 mg every 12 hours. Dose increases may occur in increments of 10 mg every 12 hours every 3 to 7 days, as needed, to achieve adequate analgesia.

Tablet, extended release, 24-hour: Oral: Initial: 20 mg once daily. Dose increases may occur in increments of 10 to 20 mg every 3 to 5 days as needed to achieve adequate analgesia.

Conversion from other oral hydrocodone-containing formulations:

Capsule, extended release, 12-hour: Initiate hydrocodone ER with the total daily dose of oral hydrocodone (mg/day) divided in half for administration every 12 hours. Dose increases may occur in increments of 10 mg every 12 hours every 3 to 7 days, as needed, to achieve adequate analgesia.

Tablet, extended release, 24-hour: Initiate hydrocodone ER with the total daily dose of oral hydrocodone (mg/day) administered once daily. Dose increases may occur in increments of 10 to 20 mg every 3 to 5 days as needed to achieve adequate analgesia.

Conversion from other oral opioids (see tables): Discontinue all other around-the-clock opioids when hydrocodone ER is initiated. Substantial interpatient variability exists in relative potency and formulations. Therefore, it is safer to underestimate a patient's daily oral hydrocodone requirement and provide breakthrough pain relief with rescue medication (eg, immediate release opioid) than to overestimate requirements. The following approximate oral conversion factors may be used to convert from oral opioid therapy to hydrocodone ER.

To get the approximate equivalent doses for conversion from current opioid therapy to hydrocodone ER, select the opioid, sum the total daily dose, then multiply by the approximate oral conversion factor to calculate the approximate oral hydrocodone ER daily dose. Initiate with the total daily dose of oral hydrocodone ER (mg/day) once daily (tablet, extended release, 24-hour) or divided in half for administration every 12 hours (capsule, extended release, 12-hour). Titrate until adequate pain relief with tolerable side effects has been achieved.

For patients on >1 opioid, calculate the approximate oral hydrocodone dose for each opioid and sum the totals. Always round the dose down, if necessary, to the appropriate hydrocodone ER strength(s) available. Reduce the calculated total daily dose of oral hydrocodone ER dose by 25%. Initiate with the total daily dose of oral hydrocodone ER (mg/day) once daily (tablet, extended release, 24-hour) or divided in half for administration every 12 hours (capsule, extended release, 12-hour). Titrate until adequate pain relief with tolerable side effects has been achieved.

Conversion Factors to Hydrocodone Tablet, Extended Release, 24-Houra

Previous Oral Opioid

Approximate Oral Conversion Factor

Codeine

0.15

Hydromorphone

4

Methadoneb

1.5

Morphine

0.5

Oxycodone

1

Oxymorphone

2

Tramadol

0.1

a This table cannot be used to convert from hydrocodone ER to another opioid; doing so will result in an overestimation of new opioid dose and may result in fatal overdose.

b Monitor closely; ratio between methadone and other opioid agonists may vary widely as a function of previous drug exposure. Methadone has a long half-life and may accumulate in the plasma.

Conversion Factors to Hydrocodone Capsule, Extended Release, 12-Houra,b

Previous Oral Opioid

Approximate Oral Conversion Factor

a Approximate equivalent doses for conversion from current opioid therapy to hydrocodone capsule, extended release, 12-hour.

b This table cannot be used to convert from hydrocodone ER to another opioid; doing so will result in an over estimation of new opioid dose and may result in fatal overdose.

c Monitor closely; ratio between methadone and other opioid agonists may vary widely as a function of previous drug exposure. Methadone has a long half-life and may accumulate in the plasma.

Codeine

0.1

Hydrocodone

1

Hydromorphone

2.67

Methadonec

1

Morphine

0.67

Oxycodone

1

Oxymorphone

2

Conversion from transdermal fentanyl: Treatment may be started 18 hours after the removal of the fentanyl transdermal patch. For every fentanyl 25 mcg per hour transdermal patch, initially substitute 20 mg every 24 hours (tablet, extended release, 24-hour); or 10 mg every 12 hours (capsule, extended release, 12-hour). Monitor patient closely.

Conversion from transdermal buprenorphine:Tablet, extended release, 24-hour:Initial: 20 mg every 24 hours in patients receiving ≤ 20 mcg/hour buprenorphine transdermal. Monitor patient closely.

Discontinuation of therapy: When reducing the dose, discontinuing, or tapering long-term opioid therapy, the dose should be gradually tapered. An optimal tapering schedule has not been established. Individualize tapering based on discussions with patient to minimize withdrawal, while considering patient-specific goals and concerns and the opioid’s pharmacokinetics. Proposed initial schedules range from slow (eg, 10% reduction per week or 10% reduction per month depending on duration of long-term therapy) to rapid (eg, 25% to 50% reduction every few days) (Ref). Slower tapers may be appropriate after long-term use (eg, >1 year), whereas more rapid tapers may be appropriate in patients experiencing severe adverse effects. During tapering, patients may be at an increased risk of overdose if they return to their original (or higher) opioid dose or use illicit opioids, due to rapid loss of tolerance; consider prescribing naloxone. Monitor carefully for signs/symptoms of withdrawal. If the patient displays withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt autonomic withdrawal symptoms and other adjunctive agents to treat GI symptoms and muscle spasms, as needed. Continue to offer nonopioid analgesics as needed for pain management during the taper (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: ER formulations should preferably be avoided in patients with altered kidney function (Ref).

US labeling:

Capsule, extended release, 12-hour: There are no specific dosage adjustments provided in the manufacturer's labeling; initiate therapy with a low dose and monitor closely.

Tablet, extended release, 24-hour:

Mild impairment: No dosage adjustment necessary.

Moderate to severe impairment: Initial: Administer 50% of the usual initial dose; titrate carefully; monitor closely.

End-stage renal disease: Initial: Administer 50% of the usual initial dose; titrate carefully; monitor closely.

Canadian labeling:

pdp-Hydrocodone: There are no specific dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Hepatic Impairment: Adult

US labeling:

Mild impairment: Capsule and tablet, extended release: No dosage adjustment necessary.

Moderate impairment:

Capsule, extended release, 12-hour: No dosage adjustment necessary.

Tablet, extended release, 24-hour: No dosage adjustment necessary according to the manufacturer, however, due to primarily hepatic metabolism, accumulation is likely with moderate hepatic impairment; use and titrate with caution (Ref).

Severe impairment:

Capsule, extended release, 12-hour: Initial: 10 mg every 12 hours; titrate carefully and monitor closely.

Tablet, extended release, 24-hour: Initial: Administer 50% of the usual initial dose; titrate carefully and monitor closely.

Canadian labeling:

pdp-Hydrocodone: There are no specific dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Older Adult

Note: Minimize opioid use in older adults unless for the management of severe acute pain. Opioids are associated with an increased risk of falls and inducing or worsening delirium in older adults (Ref).

Refer to adult dosing. Initiate dosing at the lower end of the dosage range. Monitor closely.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Chest pain (1% to 5%), hypertension (1% to 5%), peripheral edema (3%)

Dermatologic: Hyperhidrosis, night sweats, pruritus (1% to 5%), skin rash

Endocrine & metabolic: Dehydration, hot flash, hypercholesterolemia, hypokalemia

Gastrointestinal: Abdominal distress, abdominal pain (3%), constipation (3% to 8%), decreased appetite (2%), diarrhea (1% to 5%), dyspepsia (1% to 5%), gastroenteritis (1% to 5%; including viral gastroenteritis), gastroesophageal reflux disease, nausea (7% to 8%), upper abdominal pain (1% to 5%), vomiting (5% to 6%), xerostomia (1% to 5%)

Genitourinary: Urinary tract infection (5%)

Hematologic & oncologic: Bruise

Hepatic: Increased gamma-glutamyl transferase

Infection: Influenza (3%)

Nervous system: Anxiety, chills (1% to 5%), depression, dizziness (2% to 3%), drowsiness (1%), falling, insomnia (3%), lethargy, migraine, pain, paresthesia, sedated state (1% to 5%), tremor (3%)

Neuromuscular & skeletal: Arthralgia, back pain (4%), bone fracture (foot), joint injury, joint sprain, limb pain, muscle spasm (3%), muscle strain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, osteoarthritis

Otic: Tinnitus (2%)

Respiratory: Bronchitis (1% to 5%), cough, dyspnea, nasal congestion (1% to 5%), nasopharyngitis (1% to 5%), oropharyngeal pain (1% to 5%), sinusitis (1% to 5%), upper respiratory tract infection (3%)

Miscellaneous: Fever

<1%:

Cardiovascular: Edema, flushing, hypotension, orthostatic hypotension, palpitations, presyncope, syncope

Endocrine & metabolic: Decreased libido, increased thirst

Gastrointestinal: Abdominal distention, dysphagia, esophageal obstruction, retching

Genitourinary: Hypogonadism, urinary retention

Hypersensitivity: Hypersensitivity reaction

Nervous system: Agitation, altered mental status, asthenia, changes in thinking, choking sensation, confusion, depressed mood, irritability, malaise, mood changes, withdrawal syndrome

Neuromuscular & skeletal: Muscle twitching

Respiratory: Hypoxia

Frequency not defined:

Cardiovascular: Prolonged QT interval on ECG

Nervous system: Drug abuse, neonatal withdrawal, opioid dependence

Respiratory: Respiratory depression

Postmarketing:

Cardiovascular: Asystole (ventricular; prolonged) (Sudhakaran 2014)

Hypersensitivity: Anaphylaxis

Nervous system: Allodynia (opioid-induced hyperalgesia) (FDA Safety Communication 2023)

Otic: Sensorineural hearing loss (Ho 2007)

Contraindications

Hypersensitivity (eg, anaphylaxis) to hydrocodone or any component of the formulation; GI obstruction, including paralytic ileus (known or suspected); significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment.

Canadian labeling: Additional contraindications (not in US labeling): Suspected surgical abdomen (eg, acute appendicitis or pancreatitis); chronic obstructive airway; acute respiratory depression, elevated carbon dioxide levels in the blood and cor pulmonale; acute alcoholism, delirium tremens, and convulsive disorders; severe CNS depression, increased cerebrospinal or intracranial pressure, and head injury; concurrent use with or within 14 days of monoamine oxidase inhibitor therapy; pediatric patients <6 years of age.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiovascular effects: QTc prolongation has been observed with hydrocodone ER following doses of 160 mg/day. Use with caution in patients with heart failure, bradyarrhythmias, electrolyte abnormalities, or using other drugs known to prolong the QTc interval. Avoid use in patients with congenital long QT syndrome. If patients develop QTc prolongation, consider dose reduction of 33% to 50% or change to an alternate analgesic.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Constipation: May cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction (MI). Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.

• Hyperalgesia: Opioid-induced hyperalgesia (OIH) has occurred with short-term and prolonged use of opioid analgesics. Symptoms may include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily nonpainful stimuli; symptoms may be suggestive of OIH if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Consider decreasing the current opioid dose or opioid rotation in patients who experience OIH.

• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Avoid use in patients with circulatory shock.

• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydromorphone, levorphanol, oxycodone, oxymorphone).

• Respiratory depression: Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of known or suspected overdose.

Disease related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to mood disorders and osteoporosis (Brennan 2013).

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction or acute pancreatitis; may cause constriction of sphincter of Oddi.

• CNS depression/coma: Avoid use in patients with impaired consciousness or coma as these patients are susceptible to intracranial effects of CO2 retention.

• Delirium tremens: Use with caution in patients with delirium tremens.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dose adjustment may be needed.

• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to potential increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (CDC [Dowell 2022]).

• Obesity: Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis: Use with caution in patients with toxic psychosis.

• Renal impairment: Use with caution in patients with moderate to severe renal impairment; dose adjustment may be needed.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or preexisting respiratory depression, particularly when initiating therapy and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Seizures: Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.

• Sleep-related disorders: Use with caution in patients with sleep-related disorders, including sleep apnea, due to increased risk for respiratory and central nervous system depression. Monitor carefully and titrate dosage cautiously in patients with mild sleep-disordered breathing. Avoid opioids in patients with moderate to severe sleep-disordered breathing (CDC [Dowell 2022]).

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Older adult: Use opioids with caution in older adults; may be more sensitive to adverse effects. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increased adverse effects. Monitor closely for adverse effects associated with opioid therapy (eg, respiratory and central nervous system depression, falls, cognitive impairment, constipation) (CDC [Dowell 2022]). Consider the use of alternative nonopioid analgesics in these patients when possible.

• Neonates: Neonatal withdrawal syndrome: Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

Dosage form specific issues:

• Dysphagia/choking: Tablet, extended release, 24-hour: Esophageal obstruction, dysphagia, and choking have occurred. Patients with underlying GI disorders (eg, esophageal or colon cancer) with a small GI lumen are at greater risk. Consider the use of alternative analgesics in these patients. Do not presoak, lick, or wet tablets prior to ingestion; take 1 tablet at a time with enough water to ensure complete swallowing immediately after placing in mouth.

Other warnings/precautions:

• Abrupt discontinuation/withdrawal: Abrupt discontinuation in patients who are physically dependent on opioids has been associated with serious withdrawal symptoms, uncontrolled pain, attempts to find other opioids (including illicit), and suicide. Use a collaborative, patient-specific taper schedule that minimizes the risk of withdrawal, considering factors such as current opioid dose, duration of use, type of pain, and physical and psychological factors. Monitor pain control, withdrawal symptoms, mood changes, suicidal ideation, and for use of other substances; provide care as needed. Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may also precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists.

• Abuse/misuse/diversion: Use with caution in patients with a history of substance abuse disorder; potential for drug dependency exists. Other factors associated with increased risk for misuse include concomitant depression or other mental health conditions, higher opioid dosages, or taking other central nervous system depressants. Consider offering naloxone prescriptions in patients with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents [MME]/day orally), concomitant benzodiazepine use, and patients at risk for returning to a high dose after losing tolerance (CDC [Dowell 2022]).

• Appropriate use: Outpatient setting: Opioids should not be used as first-line therapy for acute (<1 month duration), subacute (1 to 3 month duration), or chronic pain (>3 month duration [outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment]). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, certain antiseizure medications, and antidepressants) as appropriate for the specific condition. If opioid therapy is initiated, it should be combined with nonpharmacologic and nonopioid therapy, as appropriate. Prior to initiation, known risks and realistic benefits of opioid therapy should be discussed with the patient. Therapy should be initiated at the lowest effective dosage using IR opioids (instead of ER/long-acting opioids). For the treatment of acute pain, therapy should only be given for the expected duration of pain severe enough to require opioids and prescribed as needed (not scheduled). For the treatment of subacute and chronic pain, realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Risk to patients increases with higher opioid dosages. Dosages ≥50 MME/day are likely to not have increased benefit to pain relief or function relative to overall risk to patients; before increasing dosage to ≥50 MME/day, readdress pain and reassess evidence of individual benefits and risks (CDC [Dowell 2022]).

• Naloxone access: Discuss the availability of naloxone with all patients who are prescribed opioid analgesics, as well as their caregivers, and consider prescribing it to patients who are at increased risk of opioid overdose. These include patients who are also taking benzodiazepines or other CNS depressants, have an opioid use disorder (OUD) (current or history of), or have experienced opioid-induced respiratory depression/opioid overdose. Additionally, health care providers should consider prescribing naloxone to patients prescribed medications to treat OUD; patients at risk of opioid overdose even if they are not taking an opioid analgesic or medication to treat OUD; and patients taking opioids, including methadone or buprenorphine for OUD, if they have household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.

• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.

• REMS program: Additional information is available at http://www.opioidanalgesicrems.com or at 1-800-503-0784.

• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postoperative patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule Extended Release 12 Hour, Oral, as bitartrate:

Zohydro ER: 10 mg [DSC], 15 mg [DSC], 20 mg [DSC], 30 mg [DSC], 40 mg [DSC], 50 mg [DSC] [contains fd&c blue #1 (brilliant blue), fd&c red #40 (allura red ac dye)]

Generic: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 50 mg

Tablet ER 24 Hour Abuse-Deterrent, Oral, as bitartrate:

Hysingla ER: 20 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Hysingla ER: 30 mg, 40 mg, 60 mg, 80 mg

Hysingla ER: 100 mg [contains fd&c blue #2 (indigo carm) aluminum lake]

Hysingla ER: 120 mg

Generic: 20 mg, 30 mg, 40 mg, 60 mg, 80 mg, 100 mg, 120 mg

Generic Equivalent Available: US

Yes

Pricing: US

Capsule, 12-hour (HYDROcodone Bitartrate ER Oral)

10 mg (per each): $9.98

15 mg (per each): $10.67

20 mg (per each): $11.01

30 mg (per each): $11.35

40 mg (per each): $11.69

50 mg (per each): $12.20

Tablet ER 24 Hour Abuse-Deterrent (HYDROcodone Bitartrate ER Oral)

20 mg (per each): $10.19

30 mg (per each): $14.87

40 mg (per each): $20.04

60 mg (per each): $27.75

80 mg (per each): $37.41

100 mg (per each): $47.60

120 mg (per each): $52.75

Tablet ER 24 Hour Abuse-Deterrent (Hysingla ER Oral)

20 mg (per each): $14.47

30 mg (per each): $21.12

40 mg (per each): $28.45

60 mg (per each): $39.39

80 mg (per each): $53.11

100 mg (per each): $67.57

120 mg (per each): $74.88

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Controlled Substance

C-II

Administration: Adult

Oral:

Capsule/tablet: Administer whole; do not crush, chew, or dissolve. Crushing, chewing, or dissolving will result in uncontrolled delivery of hydrocodone and can lead to overdose or death. Do not presoak, lick or wet dosage form prior to ingestion. Capsules or tablets should be administered one at a time, with enough water to ensure complete swallowing immediately after placing in the mouth.

Solution: pdp-Hydrocodone 1 mg/mL [Canadian product]: Administer after meals and at bedtime with food or milk.

Bariatric surgery: Capsule and tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Do not cut, crush, or chew. No IR form available as single ingredient. Consider switching to an IR hydrocodone/acetaminophen product if patient can tolerate acetaminophen or an equivalent dose of a different single-ingredient opioid.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Hydrocodone bitartrate extended-release tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206627s009MG.pdf

Hysingla ER: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/206627s012lbl.pdf#page=39

Zohydro ER: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202880s020lbl.pdf#page=30

Use: Labeled Indications

Cough ( pdp-Hydrocodone [Canadian product]): Control of exhausting, nonproductive cough.

Pain management: Management of severe and persistent pain that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.

Limitations of use: Because of the risks of substance use disorder, abuse, and misuse with opioids, which may occur at any dosage or duration, and because the greater risks of overdose and death with ER opioid formulations, reserve hydrocodone ER for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) have not been tolerated, or are not expected to be tolerated; have not provided adequate analgesia, or are not expected to provide adequate analgesia. Hydrocodone ER is not indicated as an as-needed analgesic.

Medication Safety Issues
Sound-alike/look-alike issues:

HYDROcodone may be confused with HYDROmorphone, oxyCODONE, oxymorphone

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): May enhance the CNS depressant effect of HYDROcodone. Alcohol (Ethyl) may increase the serum concentration of HYDROcodone. Management: Patients using hydrocodone extended-release capsules must not consume alcohol or alcohol-containing products due to possibly fatal outcomes. Other hydrocodone products are also expected to interact, but to a less significant degree. Risk X: Avoid combination

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Alvimopan: Opioid Agonists may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation. Management: Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately prior to alvimopan initiation. Risk D: Consider therapy modification

Amphetamines: May enhance the analgesic effect of Opioid Agonists. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CNS Depressants: May enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

CYP2D6 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of HYDROcodone. Specifically, concentrations of hydromorphone may be decreased. Risk C: Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of HYDROcodone. Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of HYDROcodone. Risk C: Monitor therapy

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of HYDROcodone. Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of HYDROcodone. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Desmopressin: Opioid Agonists may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Diuretics: Opioid Agonists may enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Eluxadoline: Opioid Agonists may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gastrointestinal Agents (Prokinetic): Opioid Agonists may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of HYDROcodone. HYDROcodone may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Consider alternatives to this combination when possible. If coadministration is required, use test doses, titrate small doses frequently, and monitor patients closely for evidence of serotonergic and opioid toxicities. Risk D: Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Nalfurafine: Opioid Agonists may enhance the adverse/toxic effect of Nalfurafine. Opioid Agonists may diminish the therapeutic effect of Nalfurafine. Risk C: Monitor therapy

Nalmefene: May diminish the therapeutic effect of Opioid Agonists. Management: Avoid the concomitant use of oral nalmefene and opioid agonists. Discontinue oral nalmefene 1 week prior to any anticipated use of opioid agonists. If combined, larger doses of opioid agonists will likely be required. Risk D: Consider therapy modification

Naltrexone: May diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Risk X: Avoid combination

Nefazodone: Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Nefazodone may increase the serum concentration of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for increased opioid effects, including fatal respiratory depression, when these agents are combined and consider opioid dose reductions until stable drug effects are achieved. Additionally, monitor for serotonin syndrome/serotonin toxicity. Risk C: Monitor therapy

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Ombitasvir, Paritaprevir, and Ritonavir: May increase the serum concentration of HYDROcodone. Management: Reduce the hydrocodone dose by 50% during concurrent use of ombitasvir, paritaprevir, and ritonavir; monitor closely for both analgesic effectiveness and for signs of toxicity or withdrawal. Risk D: Consider therapy modification

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of HYDROcodone. Management: Reduce the hydrocodone dose by 50% during concurrent use of ombitasvir, paritaprevir, ritonavir, and dasabuvir; monitor closely for both analgesic effectiveness and for signs of toxicity or withdrawal. Risk D: Consider therapy modification

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Opioids (Mixed Agonist / Antagonist): May diminish the analgesic effect of Opioid Agonists. Management: Seek alternatives to mixed agonist/antagonist opioids in patients receiving pure opioid agonists, and monitor for symptoms of therapeutic failure/high dose requirements (or withdrawal in opioid-dependent patients) if patients receive these combinations. Risk X: Avoid combination

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Pegvisomant: Opioid Agonists may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy

PHENobarbital: May enhance the CNS depressant effect of HYDROcodone. PHENobarbital may decrease the serum concentration of HYDROcodone. Management: Avoid use of hydrocodone and phenobarbital when possible. Monitor for respiratory depression/sedation. Because phenobarbital is also a strong CYP3A4 inducer, monitor for decreased hydrocodone efficacy and withdrawal if combined. Risk D: Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Primidone: May enhance the CNS depressant effect of HYDROcodone. Primidone may decrease the serum concentration of HYDROcodone. Management: Avoid use of hydrocodone and primidone when possible. Monitor for respiratory depression/sedation. Because primidone is also a strong CYP3A4 inducer, monitor for decreased hydrocodone efficacy and withdrawal if combined. Risk D: Consider therapy modification

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Ramosetron: Opioid Agonists may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Samidorphan: May diminish the therapeutic effect of Opioid Agonists. Risk X: Avoid combination

Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may diminish the therapeutic effect of Opioid Agonists (metabolized by CYP3A4 and CYP2D6). Management: Monitor for decreased therapeutic response (eg, analgesia) and opioid withdrawal when coadministered with SSRIs that strongly inhibit CYP2D6. Additionally, monitor for serotonin syndrome/serotonin toxicity if these drugs are combined. Risk C: Monitor therapy

Serotonergic Agents (High Risk): Opioid Agonists (metabolized by CYP3A4 and CYP2D6) may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy

Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification

Somatostatin Analogs: Opioid Agonists may diminish the analgesic effect of Somatostatin Analogs. Opioid Agonists may enhance the analgesic effect of Somatostatin Analogs. Risk C: Monitor therapy

Succinylcholine: May enhance the bradycardic effect of Opioid Agonists. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Food Interactions

Ethanol may disrupt extended-release characteristics and increase plasma levels of hydrocodone potentially leading to fatal overdose. Management: Do not administer hydrocodone ER with alcoholic beverages or ethanol-containing products.

Reproductive Considerations

Chronic opioid use may cause hypogonadism and hyperprolactinemia which may decrease fertility in patients of reproductive potential. Menstrual cycle disorders (including amenorrhea), erectile dysfunction, and impotence have been reported. The incidence of hypogonadism may be increased with the use of opioids in high doses or long-acting opioid formulations. It is not known if the effects on fertility are reversible. Monitor patients on long-term therapy (de Vries 2020; Gadelha 2022).

Consider family planning, contraception, and the effects on fertility prior to prescribing opioids for chronic pain to patients who could become pregnant (ACOG 2017; CDC [Dowell 2022]).

Pregnancy Considerations

Opioids cross the placenta.

Maternal use of opioids may be associated with poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2022]). Opioids used as part of obstetric analgesia/anesthesia during labor and delivery may temporarily affect the fetal heart rate (ACOG 2019).

Neonatal abstinence syndrome (NAS)/neonatal opioid withdrawal syndrome (NOWS) may occur following prolonged in utero exposure to opioids (CDC [Dowell 2022]). NAS/NOWS may be life-threatening if not recognized and treated and requires management according to protocols developed by neonatology experts. Presentation of symptoms varies by opioid characteristics (eg, immediate release, sustained release), time of last dose prior to delivery, drug metabolism (maternal, placental, and infant), net placental transfer, as well as other factors (AAP [Hudak 2012; AAP [Patrick 2020]). Clinical signs characteristic of withdrawal following in utero opioid exposure include excessive crying or easily irritable, fragmented sleep (<2 to 3 hours after feeding), tremors, increased muscle tone, or GI dysfunction (hyperphagia, poor feeding, feeding intolerance, watery or loose stools) (Jilani 2022). NAS/NOWS occurs following chronic opioid exposure and would not be expected following the use of opioids at delivery (AAP [Patrick 2020]).

Monitor infants of mothers on long-term/chronic opioid therapy for symptoms of withdrawal. Symptom onset reflects the half-life of the opioid used. Monitor infants for at least 3 days following exposure to immediate-release opioids; monitor for at least 4 to 7 days following exposure to sustained-release opioids (AAP [Patrick 2020]; CDC [Dowell 2022]). Monitor newborns for excess sedation and respiratory depression when opioids are used during labor.

When opioids are needed to treat acute pain in pregnant patients, the lowest effective dose for only the expected duration of pain should be prescribed (CDC [Dowell 2022]).

Opioid use for pain following vaginal or cesarean delivery should be made as part of a shared decision-making process. A stepwise, multimodal approach to managing postpartum pain is recommended. A low-dose, low-potency, short-acting opioid such as hydrocodone can be used to treat acute pain associated with delivery when needed (ACOG 2021).

Opioids are not preferred for the treatment of chronic noncancer pain during pregnancy; consider strategies to minimize or avoid opioid use. Advise pregnant patients requiring long-term opioid use of the risk of NAS/NOWS and provide appropriate treatment for the neonate after delivery. NAS/NOWS is an expected and treatable condition following chronic opioid use during pregnancy and should not be the only reason to avoid treating pain with an opioid in pregnant patients (ACOG 2017; CDC [Dowell 2022]). Do not abruptly discontinue opioids during pregnancy; taper prior to discontinuation when appropriate, considering the risks to the pregnant patient and fetus if maternal withdrawal occurs (CDC [Dowell 2022]).

Breastfeeding Considerations

Hydrocodone and the active metabolite hydromorphone are present in breast milk.

Data related to the presence of hydrocodone in breast milk are available following maternal use of hydrocodone in combination with acetaminophen:

• A paper presents data from 2 case reports. The first patient initiated hydrocodone 5 mg/acetaminophen 500 mg following surgery scheduled on postpartum day 7. The total dose of hydrocodone (as hydrocodone base) received over ~4 days was 998.8 mcg/kg. Hydrocodone breast milk concentrations ranged from 8.6 to 127.3 mcg/L. Using the average breast milk concentration of hydrocodone (57.2 mcg/L), the authors of the study calculated the estimated exposure of hydrocodone to the breastfeeding infant to be 8.58 mcg/kg/day, providing a relative infant dose (RID) of 3.1%, based on the weight adjusted maternal dose. The second patient was 16 days postpartum when hydrocodone 5 mg/acetaminophen 500 mg was initiated. Over a period of 36 hours, the total dose of hydrocodone (as base) was 123.5 mcg/kg. Hydrocodone breast milk concentrations ranged from 9.4 to 47.2 mcg/L. Using the average breast milk concentration of hydrocodone (20.4 mcg/L), the authors of the study calculated the estimated exposure of hydrocodone to the breastfeeding infant to be 3.04 mcg/kg/day, providing a RID of 3.7%, based on the weight adjusted maternal dose (Anderson 2007).

• A study was conducted in 30 lactating patients 3 to 11 days postpartum, administered oral hydrocodone in combination with acetaminophen. A total of 125 samples were obtained prior to pumping or expressing breast milk. Average hydrocodone breast milk concentrations ranged from 1.6 to 99.6 mcg/L. Using the mean average concentration (25.9 mcg/L), the authors of the study calculated the estimated exposure of hydrocodone to the breastfeeding infant to be 3.9 mcg/kg/day (range 0.2 to 14.9 mcg/kg/day), providing a RID of 2.4% (range 0.2% to 9%) based on a mean average weight adjusted maternal dose of 175 mcg/kg/day (range 44.3 to 423.2 mcg/kg/day). Hydromorphone was detectable in the breast milk of 12 patients. The average breast milk concentration of hydromorphone was 0.2 to 86.7 mcg/L (Sauberan 2011).

• Data related to hydrocodone and breastfeeding are from studies using short-acting products, not the extended-release formulation. In addition, maternal CYP2D6 status was not evaluated (Anderson 2007; Sauberan 2011).

• In general, breastfeeding is considered acceptable when the RID is <10 (Anderson 2016; Ito 2000). Cumulative exposure from hydrocodone and hydromorphone should be considered.

Grogginess and sleepiness were reported in a mother and breastfeeding infant following maternal use of hydrocodone 10 mg in combination with acetaminophen 650 mg (2 tablets every 4 hours) (Bodley 1997).

Due to the potential for serious adverse events in the breastfed infant (including excess sedation and respiratory depression), breastfeeding is not recommended by the manufacturer. Nonopioid analgesics are preferred for lactating patients who require pain control peripartum or for surgery outside of the postpartum period. When opioids are needed for lactating patients, use the lowest effective dose for the shortest duration of time to limit adverse events in the mother and breastfeeding infant. When maternal treatment with hydrocodone is needed, doses should not exceed 30 mg/day (AAP [Sachs 2013]; ABM [Martin 2018]; ABM [Reece-Stremtan 2017]; WHO 2002).

When chronic opioids are prescribed prenatally and continued postpartum, breastfeeding may be initiated to help mitigate potential newborn withdrawal; monitor both the mother and the infant (AAP [Meek 2022]; AAP [Patrick 2020]).

Monitor infants exposed to opioids via breast milk for drowsiness, sedation, feeding difficulties, or limpness (ACOG 2019). Withdrawal symptoms may occur when maternal use is discontinued, or breastfeeding is stopped.

Monitoring Parameters

Pain relief, respiratory and mental status, blood pressure; bowel function; signs/symptoms of misuse, abuse, and substance use disorder; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)

Alternate recommendations: Subacute or chronic pain (long-term therapy outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment): Evaluate benefits/risks of opioid therapy within 1 to 4 weeks of treatment initiation and with dose increases. In patients with subacute pain initially treated for acute pain, reassess pain and function after 30 days to address potentially reversible causes of pain and prevent unintentional long-term opioid therapy. In patients on long-term therapy, re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Toxicology testing is recommended prior to initiation and at least yearly (includes controlled prescription medications, illicit drugs of abuse, and benzodiazepines). State prescription drug monitoring program (PDMP) data should be reviewed by clinicians prior to initiation and periodically during therapy (frequency ranging from every prescription to every 3 months) (CDC [Dowell 2022]).

Mechanism of Action

Binds to opioid receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: ~1,300 to 1,400 L.

Protein binding: 36%.

Metabolism: Hepatic: O-demethylation via primarily CYP2D6 to hydromorphone (major, active metabolite with ~10- to 33-fold higher or as much as a >100-fold higher binding affinity for the mu-opioid receptor than hydrocodone); N-demethylation via CYP3A4 to norhydrocodone (major metabolite); and ~40% of metabolism/clearance occurs via other non-CYP pathways, including 6-ketosteroid reduction to 6-alpha-hydrocol and 6-beta-hydrocol, and other elimination pathways (eg, fecal, biliary, intestinal, renal) (Hutchinson 2004; Volpe 2011; Zhou 2009).

Half-life elimination: Capsule, extended release, 12-hour: ~8 hours (plasma); Tablet, extended release, 24-hour: ~7 to 9 hours.

Time to peak, plasma: Capsule, extended release, 12-hour: ~5 hours; Tablet, extended release, 24-hour: 6 to 30 hours.

Excretion: Urine (26% of single dose in 72 hours, with ~12% as unchanged drug, 5% as norhydrocodone, 4% as conjugated hydrocodone, 3% as 6-hydrocodol, and 0.21% as conjugated 6-hydromorphol (Zhou 2009).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function:

Capsule, extended release, 12-hour: Cmax values were 15%, 48%, and 41% higher and AUC values were 15%, 57%, and 44% higher in patients with mild, moderate, and severe renal impairment, respectively.

Tablet, extended release, 24-hour: Cmax values were 14%, 23%, 11%, and -13% and AUC values were 13%, 61%, 57%, and 4% higher in patients with mild, moderate, or severe renal impairment or end stage renal disease, respectively.

Hepatic function impairment:

Capsule, extended release, 12-hour: Cmax values were 8% to 10% higher in patients with hepatic impairment while AUC values were 10% and 26% higher in patients with mild and moderate hepatic impairment, respectively.

Tablet, extended release, 24-hour: Cmax values were -6%, 5%, and 5% higher and AUC values were -14%, 13%, and 4% higher in patients with mild, moderate, or severe hepatic impairment, respectively.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BE) Belgium: Biocodone;
  • (CH) Switzerland: Dicodid | Dihydrocodeinon Streuli | Hydrocodon Streuli;
  • (DE) Germany: Dicodid;
  • (LU) Luxembourg: Biocodone;
  • (NO) Norway: Hydrokon naf;
  • (PR) Puerto Rico: Hysingla
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