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 hydrocodone ER and monitor all patients regularly for the development of these behaviors and conditions.
To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Health care providers are strongly encouraged to complete a REMS-compliant education program and counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products; emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist; and consider other tools to improve patient, household, and community safety.
Serious, life-threatening, or fatal respiratory depression may occur with use of hydrocodone ER. Monitor for respiratory depression, especially during initiation of hydrocodone or following a dose increase. 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 of even 1 dose of hydrocodone ER, especially by children, can result in a fatal overdose of hydrocodone.
Prolonged use of hydrocodone ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
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. Monitor patients receiving hydrocodone and any CYP3A4 inhibitor or inducer.
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. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
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.
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:
Note : When used for managing moderate to severe pain, opioids may be part of a comprehensive, multimodal, patient-specific treatment plan for pain. Maximize nonopioid analgesia, if appropriate, prior to initiation of opioid analgesia. Individualize dosing regimen based on patient-specific factors (eg, comorbidities, severity of pain, concomitant medications, cachexia, general condition, 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 (CDC [Dowell 2016]).
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.
|
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. | |
|
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 discontinuing chronic opioid therapy, the dose should be gradually tapered down. An optimal universal tapering schedule for all patients has not been established (CDC [Dowell 2016]). Proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days) (CDC 2015). Tapering schedules should be individualized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmacokinetics of the opioid being tapered. An even slower taper may be appropriate in patients who have been receiving opioids for a long duration (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events (CDC [Dowell 2016]). 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 withdrawal symptoms (Berna 2015; CDC [Dowell 2016]). Continue to offer nonopioid analgesics as needed for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI complaints, muscle spasm) as needed (Berna 2015; Sevarino 2018).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: ER formulations should preferably be avoided in patients with altered kidney function (Tawfic 2015).
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.
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 (Darwish 2016).
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.
Refer to adult dosing. Initiate dosing at the lower end of the dosage range. Monitor closely.
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
Yes
C-II
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
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.
Cough ( pdp-Hydrocodone [Canadian product]): Control of exhausting, nonproductive cough.
Pain management: Management of pain severe enough to require daily around-the-clock opioid, long-term treatment and for which alternative treatment options are inadequate.
Limitations of use: Reserve hydrocodone ER for use in patients for whom alternative treatment options (eg, nonopioid analgesics, immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Hydrocodone ER is not indicated as an as-needed analgesic.
HYDROcodone may be confused with HYDROmorphone, oxyCODONE, oxymorphone
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Constipation (3% to 14%), nausea (7% to 12%)
1% to 10%:
Cardiovascular: Hypertension (≥1% to <5%), peripheral edema (3%)
Central nervous system: Headache (6%), chills (≥1% to <5%), sedation (≥1% to <5%), anxiety (4%), insomnia (3%), dizziness (2% to 3%), drowsiness (1% to 3%), fatigue (2%), depression, falling, lethargy, migraine, pain, paresthesia
Dermatologic: Pruritus (1%), hyperhidrosis, night sweats, skin rash
Endocrine & metabolic: Dehydration, hot flash, hypokalemia, increased gamma-glutamyl transferase, increased serum cholesterol
Gastrointestinal: Vomiting (5% to 6%), dyspepsia (≥1% to <5%), gastroenteritis (≥1% to <5%), upper abdominal pain (≥1% to <5%), viral gastroenteritis (≥1% to <5%), diarrhea (4%), abdominal pain (3%), decreased appetite (2%), xerostomia (1%), abdominal distress, gastroesophageal reflux disease
Genitourinary: Urinary tract infection (5%)
Hematologic & oncologic: Bruise
Infection: Influenza (3%)
Neuromuscular & skeletal: Back pain (4%), muscle spasm (3%), tremor (3%), arthralgia, bone fracture (foot), injury to the joint, joint sprain, limb pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, osteoarthritis, strain
Otic: Tinnitus (2%)
Respiratory: Bronchitis (≥1% to <5%), nasal congestion (≥1% to <5%), nasopharyngitis (≥1% to <5%), oropharyngeal pain (≥1% to <5%), sinusitis (≥1% to <5%), upper respiratory tract infection (3%), cough, dyspnea
Miscellaneous: Fever, laceration
<1%, postmarketing and/or case reports: Abdominal distention, abnormality in thinking, agitation, altered mental status, anaphylaxis, choking sensation, confusion, decreased libido, drug-induced hypersensitivity, drug withdrawal, dysphagia, edema, erythema, esophageal obstruction, flushing, hypogonadism (Brennan 2013; Debono, 2011), hypotension, hypoxia, increased thirst, intestinal obstruction, irritability, malaise, mood changes, muscle twitching, opioid dependence, orthostatic hypotension, palpitations, pancreatitis, presyncope, prolonged QT interval on ECG, respiratory depression, retching, syncope, urinary retention, weakness
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.
Documentation of allergenic cross-reactivity for opioids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
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.
• 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 increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (CDC [Dowell 2016]).
• 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: Opioid use increases the risk for sleep-related disorders (eg, central sleep apnea [CSA], hypoxemia) in a dose-dependent fashion. Use with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing (eg, heart failure, obesity). Consider dose reduction in patients presenting with CSA. Avoid opioids in patients with moderate to severe sleep-disordered breathing (CDC [Dowell 2016]).
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
• Ethanol use: Capsule, extended release, 12-hour: Alcohol may disrupt ER characteristic of product.
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 with caution in the elderly; may be more sensitive to adverse effects. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (CDC [Dowell 2016]). Decrease initial dose. Consider the use of alternative nonopioid analgesics in these patients.
• 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 drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated 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), and concomitant benzodiazepine use (CDC [Dowell 2016]).
• Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-based opioid use disorder treatment) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg, nonsteroidal anti-inflammatory drugs, acetaminophen, certain antiseizure medications and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and nonopioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and 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. Therapy should be initiated at the lowest effective dosage using IR opioids (instead of ER/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 MME/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (CDC [Dowell 2016]).
• 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 a previous 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.
• Surgery: Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.
Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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 the Zohydro ER brand of extended-release hydrocodone 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
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. Management: Consider alternatives to this combination when possible. Risk D: Consider therapy modification
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
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.
Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction or infertility (Brennan 2013).
Opioids cross the placenta.
According to some studies, maternal use of opioids may be associated with birth defects (including neural tube defects, congenital heart defects, and gastroschisis), poor fetal growth, stillbirth, and preterm delivery (CDC [Dowell 2016]).
[US Boxed Warning]: Prolonged use of hydrocodone during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. If chronic opioid exposure occurs in pregnancy, adverse events in the newborn (including withdrawal) may occur (Chou 2009). Symptoms of neonatal abstinence syndrome (NAS) following opioid exposure may be autonomic (eg, fever, temperature instability), gastrointestinal (eg, diarrhea, vomiting, poor feeding/weight gain), or neurologic (eg, high-pitched crying, hyperactivity, increased muscle tone, increased wakefulness/abnormal sleep pattern, irritability, sneezing, seizure, tremor, yawning) (Dow 2012; Hudak 2012). Mothers who are physically dependent on opioids may give birth to infants who are also physically dependent. Opioids may cause respiratory depression and psycho-physiologic effects in the neonate; newborns of mothers receiving opioids during labor should be monitored.
Hydrocodone is not commonly used to treat pain during labor and immediately postpartum (ACOG 209 2019) or chronic noncancer pain in pregnant patients or those who may become pregnant (CDC [Dowell 2016]; Chou 2009).
Hydrocodone and the active metabolite hydromorphone are present in breast milk.
The relative infant dose (RID) of hydrocodone (immediate release product) was calculated in one study to be 0.2% to 9% when compared to a weight-adjusted maternal dose of 44 to 423.2 mcg/kg/day.
In general, breastfeeding is considered acceptable when the RID is <10 (Anderson 2016; Ito 2000). Cumulative exposure from hydrocodone and hydromorphone should be considered.
The RID of hydrocodone was calculated using milk concentrations of 1.6 to 99.6 mcg/mL, providing an estimated daily infant dose via breast milk of 0.2 to 14.9 mcg/kg/day. These milk concentrations were obtained following maternal administration of oral hydrocodone in combination with acetaminophen. Hydromorphone was also detected in breast milk (range: 0.2 to 86.7 mcg/L), providing a neonatal dose of 2.1 mcg/kg/day (range: 0.03 to 13 mcg/kg/day) (Sauberan 2011). Note: Information related to hydrocodone and breastfeeding is from studies using short-acting products, not the extended-release formulation. In addition, maternal CYP2D6 status was not evaluated (Anderson 2007; Sauberan 2011).
Grogginess and sleepiness were reported in a mother and breastfeeding infant following maternal use of hydrocodone 10 mg in combination with acetaminophen 650 mg (two tablets every 4 hours) (Bodley 1997). Withdrawal symptoms may occur when maternal use is discontinued or breastfeeding is stopped.
Nonopioid analgesics are preferred for breastfeeding patients who require pain control peripartum or for surgery outside of the postpartum period. When maternal treatment with hydrocodone is needed, doses should not exceed 30 mg/day (ABM [Martin 2018]; ABM [Reece-Stremtan 2017]). When opioids are needed in breastfeeding patients, the lowest effective dose for the shortest duration of time should be used to limit adverse events in the mother and breastfeeding infant. In general, a single occasional dose of an opioid analgesic may be compatible with breastfeeding (WHO 2002). Breastfeeding patients using opioids for postpartum pain or for the treatment of chronic maternal pain should monitor their infants for drowsiness, sedation, feeding difficulties, or limpness (ACOG 209 2019). 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.
Pain relief, respiratory and mental status, blood pressure; bowel function; signs/symptoms of misuse, abuse, and addiction; signs or symptoms of hypogonadism or hypoadrenalism (Brennan 2013)
Alternate recommendations: 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. Re-evaluate benefits/risks every 3 months during therapy or more frequently in patients at increased risk of overdose or opioid use disorder. Urine drug testing is recommended prior to initiation and re-checking should be considered at least yearly (includes controlled prescription medications and illicit drugs of abuse). 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 2016]).
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.
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).
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.
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): $13.12
30 mg (per each): $19.15
40 mg (per each): $25.80
60 mg (per each): $35.73
80 mg (per each): $48.17
100 mg (per each): $61.29
120 mg (per each): $67.92
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.
