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Hydrocodone Bitartrate

Pronunciation

Class: Opiate Agonists
ATC Class: R05DA03
VA Class: RE301
CAS Number: 34195-34-1
Brands: Hydromet, Hysingla ER, Lortab, Norco, Reprexain, Rezira, Tussigon, Tussionex Pennkinetic, Vicodin, Vicoprofen, Vituz, Zohydro ER, Zutripro

Warning(s)

  • Extended-release Hydrocodone Bitartrate
  • Risk of addiction, abuse, and misuse, which can lead to overdose and death, in patients and other users.122 133 Assess each patient’s risk for addiction, abuse, and misuse before prescribing the drug; monitor all patients regularly for development of these behaviors or conditions.122 133 (See Addiction, Abuse, and Misuse under Cautions.)

  • Serious, life-threatening, or fatal respiratory depression may occur.122 133 Monitor for respiratory depression, especially during initiation of therapy and following any dosage increase.122 133 (See Respiratory Depression under Cautions.)

  • Patients must swallow extended-release capsules or tablets whole to avoid exposure to a potentially fatal dose.122 133

  • Accidental ingestion of even 1 dose, especially by a child, can result in a fatal overdose.122 133

  • Prolonged maternal use of opiates during pregnancy can result in neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated.122 133 Advise women who require such therapy during pregnancy of this risk and ensure appropriate treatment will be available.122 133 (See Pregnancy under Cautions.)

  • Use of alcohol with the extended-release capsules may result in increased plasma concentrations of hydrocodone and a potentially fatal overdose; patients must not consume alcoholic beverages or take prescription or nonprescription preparations containing alcohol concomitantly.122

  • Initiation of CYP3A4 inhibitors or discontinuance of CYP3A4 inducers can result in fatal hydrocodone overdosage.122 133

REMS:

FDA approved a REMS for hydrocodone to ensure that the benefits outweigh the risks. The REMS may apply to one or more preparations of hydrocodone and consists of the following: medication guide and elements to assure safe use. See the FDA REMS page () or the ASHP REMS Resource Center (). (Also see Risk Evaluation and Mitigation Strategy under Dosage and Administration.)

Introduction

Opiate agonist; phenanthrene derivative.a b c

Uses for Hydrocodone Bitartrate

Pain

Extended-release hydrocodone: Relief of pain that is severe enough to require long-term, daily, around-the-clock use of an opiate analgesic and for which alternative treatment options (e.g., nonopiate analgesics or immediate-release opiates) are inadequate or not tolerated.122 133 Not indicated for as-needed (“prn”) use.122 133

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Hydrocodone/acetaminophen fixed combinations: Symptomatic relief of moderate to moderately severe pain.123 a

Hydrocodone/ibuprofen fixed combinations: Short-term (generally <10 days) use for the relief of acute pain; not indicated for management of pain associated with such chronic conditions as osteoarthritis or rheumatoid arthritis.124

Combinations of hydrocodone and NSAIAs or acetaminophen may produce additive analgesic effects because of differing mechanisms of action.c

Cough

Symptomatic relief of nonproductive cough, alone or in combination with other antitussives or expectorants.b

Hydrocodone Bitartrate Dosage and Administration

General

Risk Evaluation and Mitigation Strategy

  • FDA has approved a REMS for extended-release and long-acting opiate analgesics, including extended-release hydrocodone.125 (See REMS.)

  • The REMS consists of a medication guide that must be dispensed with every prescription for extended-release hydrocodone, educational programs for prescribers, and information that prescribers can use when counseling patients.125

  • The goals are to reduce the occurrence of addiction, unintentional overdosage, and death resulting from inappropriate prescribing, misuse, and abuse of extended-release and long-acting opiates, while maintaining patient access to these analgesics.125

Administration

Oral Administration

Administer orally.a b 109 122 123 124 133

Hydrocodone Extended-release Capsules (Zohydro ER)

Administer every 12 hours.122

Must be swallowed whole.122 Breaking, cutting, crushing, chewing, or dissolving the capsules will result in uncontrolled delivery of hydrocodone and can result in overdosage and death.122

Patients must not consume alcoholic beverages or take prescription or nonprescription preparations containing alcohol during therapy; concomitant ingestion of alcohol may result in increased plasma concentrations of the drug and a potentially fatal overdose.122

Hydrocodone Extended-release Tablets (Hysingla ER)

Administer every 24 hours without regard to meals.133

Must be swallowed whole.133 Crushing, chewing, or dissolving the tablets will result in uncontrolled delivery of hydrocodone and can result in overdosage and death.133

Administer tablets one at a time with enough water to ensure that each tablet is completely swallowed immediately after it is placed in the mouth.133 Do not wet the tablets (e.g., by soaking or licking) before placing in mouth for swallowing.133 (See GI Complications with Extended-release Tablets under Cautions.)

Multiple tablets of lower-dose strengths that provide the desired total daily dosage can be taken as a once-daily dose.133

Extended-release Suspension containing Hydrocodone Polistirex and Chlorpheniramine Polistirex (e.g., Tussionex Pennkinetic)

Use a calibrated dosing device when measuring doses of the suspension.109 112 Use of a household teaspoon could result in overdosage, especially when pediatric doses (2.5 mL of suspension) are measured.109 112

Do not give more frequently than every 12 hours; if cough is not controlled, contact clinician.112

Do not dilute with fluids or mix with other drugs; shake well prior to administration.109

Dosage

Available as hydrocodone bitartrate and hydrocodone polistirex; dosage expressed in terms of hydrocodone bitartrate.a b c 109

Pediatric Patients

Cough
Hydrocodone Bitartrate
Oral

Children 6–12 years of age: 2.5 mg every 4–6 hours as needed.113

Extended-release Suspension containing Hydrocodone Polistirex and Chlorpheniramine Polistirex (e.g., Tussionex Pennkinetic)
Oral

Children 6–11 years of age: 2.5 mL (5 mg when expressed in terms of hydrocodone bitartrate) every 12 hours.109

Children ≥12 years of age: 5 mL (10 mg when expressed in terms of hydrocodone bitartrate) every 12 hours.109

Adults

Cough
Hydrocodone Bitartrate
Oral

Usual dosage is 5 mg every 4–6 hours as needed.113 114 115 116 Other drugs in combination preparations may limit daily hydrocodone dosage.114 115 116

Extended-release Suspension Containing Hydrocodone Polistirex and Chlorpheniramine Polistirex (e.g., Tussionex Pennkinetic)
Oral

5 mL (10 mg when expressed in terms of hydrocodone bitartrate) every 12 hours.109

Pain (Hydrocodone Bitartrate Extended-release Capsules [Zohydro ER])
Oral

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.122 (See Respiratory Depression under Cautions.) Individualize initial dosage based on patient's prior analgesic use and risk factors for addiction, abuse, and misuse.122

Use single doses >40 mg, the 50-mg extended-release capsules, and total daily dosages >80 mg only in patients in whom tolerance to an opiate of comparable potency has been established.122

Patients are considered opiate tolerant if they have been receiving at least 60 mg of oral morphine sulfate daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone hydrochloride daily, 8 mg of oral hydromorphone hydrochloride daily, 25 mg of oral oxymorphone hydrochloride daily, or an equianalgesic dose of another opiate daily for at least 1 week.122

Initiation of Therapy with Extended-release Hydrocodone Capsules in Opiate-naive or Nontolerant Patients
Oral

Initially, 10 mg every 12 hours.122 Higher initial dosages in patients who are not opiate tolerant may result in fatal respiratory depression.122

Initial Dosage Selection in Patients Being Switched from Other Chronic Oral Opiate Therapy to Extended-release Hydrocodone Capsules
Oral

Discontinue all other around-the-clock opiates when therapy with extended-release hydrocodone capsules is initiated.122

Carefully individualize dosage; overestimation of initial dosage in opiate-tolerant patients can result in fatal overdosage.122

Use conversion factors in Table 1 as a guide for selecting initial dosage of extended-release hydrocodone capsules for patients being transferred from therapy with an oral opiate listed in the table.122 The doses in Table 1 are not equianalgesic, and the table cannot be used to transfer patients from extended-release hydrocodone capsules to another opiate, as this will overestimate the dosage and may result in fatal overdosage.122

For patients receiving a single opiate analgesic, multiply the current total daily dosage of the opiate by the conversion factor to calculate the approximate daily dosage of extended-release hydrocodone capsules; divide the calculated daily dosage in half for administration every 12 hours.122

For patients receiving >1 opiate analgesic, calculate the approximate daily dosage of extended-release hydrocodone for each opiate and then add those totals to obtain the approximate total daily dosage of extended-release hydrocodone capsules; divide the calculated total daily dosage in half for administration every 12 hours.122

For patients receiving analgesics containing opiates and nonopiates in a fixed ratio, consider only the opiate component in the conversion.122

If calculated doses do not correspond to an available capsule strength, always round dosage down to the nearest whole capsule.122

Monitor for opiate withdrawal and for oversedation or toxicity following transfer to extended-release hydrocodone.122

Particularly close monitoring required following switch from methadone, since conversion ratios between methadone and other opiates vary widely depending on extent of prior methadone exposure and because methadone has a long half-life and tends to accumulate in plasma.122

Table 1. Conversion Factors for Transfer from Other Oral Opiates to Extended-release Hydrocodone Bitartrate Capsules (Zohydro ER)122

Prior Oral Opiate

Oral Dose (mg)

Approximate Oral Conversion Factor

Hydrocodone

10

1

Oxycodone

10

1

Methadone

10

1

Oxymorphone

5

2

Hydromorphone

3.75

2.67

Morphine

15

0.67

Codeine

100

0.1

Initial Dosage Selection in Patients Being Switched from Transdermal Fentanyl to Extended-release Hydrocodone Capsules
Oral

Wait 18 hours after removal of the transdermal fentanyl system to initiate therapy with extended-release hydrocodone capsules; use an initial conservative dosage of approximately 10 mg every 12 hours for each 25 mcg/hr of transdermal fentanyl.122

Monitor closely; experience with this dosage conversion is limited.122

Dosage Adjustment to Achieve Adequate Analgesia
Oral

Adjust dosage gradually, every 3–7 days in increments of 10 mg every 12 hours, to provide adequate analgesia and to minimize adverse effects.122

Discontinuance of Therapy
Oral

Gradually taper dosage every 2–4 days to avoid manifestations of abrupt withdrawal.122 Monitor closely for withdrawal manifestations that may indicate need for slower tapering.122

The tapering schedule in Table 2 was used in a phase 3 clinical trial; dosages >100 mg twice daily were not used in this trial.122

Table 2. Dosage Taper Used in Clinical Trial of Extended-release Hydrocodone Bitartrate Capsules (Zohydro ER)122

Stable Dosage at Time of Taper Initiation

Taper Schedule

20–30 mg every 12 hours

10 mg every 12 hours for 2 days, then discontinue on day 3

40–70 mg every 12 hours

40 mg every 12 hours for 2 days, 20 mg every 12 hours for 2 days, 10 mg every 12 hours for 2 days, then discontinue on day 7

80–100 mg every 12 hours

80 mg every 12 hours for 2 days, 60 mg every 12 hours for 2 days, 40 mg every 12 hours for 2 days, 20 mg every 12 hours for 2 days, 10 mg every 12 hours for 2 days, then discontinue on day 11

Pain (Hydrocodone Bitartrate Extended-release Tablets [Hysingla ER])
Oral

Appropriate dosage selection and titration are essential to reduce the risk of respiratory depression.133 (See Respiratory Depression under Cautions.) Individualize initial dosage based on patient's prior analgesic use and risk factors for addiction, abuse, and misuse.133

Use dosages ≥80 mg daily only in opiate-tolerant patients.133

Patients are considered opiate tolerant if they have been receiving at least 60 mg of oral morphine sulfate daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone hydrochloride daily, 8 mg of oral hydromorphone hydrochloride daily, 25 mg of oral oxymorphone hydrochloride daily, or an equianalgesic dose of another opiate daily for at least 1 week.133

Initiation of Therapy with Extended-release Hydrocodone Tablets in Opiate-naive or Nontolerant Patients
Oral

Initially, 20 mg every 24 hours.133 Higher initial dosages in patients who are not opiate tolerant may result in fatal respiratory depression.133

Initial Dosage Selection in Patients Being Switched from Other Oral Hydrocodone-containing Formulations
Oral

Administer same total daily dosage once daily.133

Initial Dosage Selection in Patients Being Switched from Other Chronic Oral Opiate Therapy to Extended-release Hydrocodone Tablets
Oral

Discontinue all other around-the-clock opiates when therapy with extended-release hydrocodone tablets is initiated.133

Carefully individualize dosage; overestimation of initial dosage in opiate-tolerant patients can result in fatal overdosage.133

Use conversion factors in Table 3 as a guide for selecting initial dosage of extended-release hydrocodone tablets for patients being transferred from therapy with an oral opiate listed in the table.133 The doses in Table 3 are not equianalgesic, and the table cannot be used to transfer patients from extended-release hydrocodone tablets to another opiate, as this will overestimate the dosage and may result in fatal overdosage.133

For patients receiving a single opiate analgesic, multiply the current total daily dosage of the opiate by the conversion factor to calculate the approximate daily dosage of oral hydrocodone.133 Reduce this calculated dosage by 25% to account for interpatient variability in the relative potency of different opiates.133

For patients receiving >1 opiate analgesic, calculate the approximate daily dosage of oral hydrocodone for each opiate and then add those totals to obtain the approximate total daily dosage of oral hydrocodone.133 Reduce this calculated dosage by 25% to account for interpatient variability in the relative potency of different opiates.133

For patients receiving analgesics containing opiates and nonopiates in a fixed ratio, consider only the opiate component in the conversion.133

If calculated doses do not correspond to an available tablet strength, always round dosage down to the nearest whole tablet.133

If calculated dose is <20 mg, use initial dosage of 20 mg once daily.133

Monitor for opiate withdrawal and for oversedation or toxicity following transfer to extended-release hydrocodone.133

Particularly close monitoring required following switch from methadone, since conversion ratios between methadone and other opiates vary widely depending on extent of prior methadone exposure and because methadone has a long half-life and tends to accumulate in plasma.133

Table 3. Conversion Factors for Transfer from Other Oral Opiates to Extended-release Hydrocodone Bitartrate Tablets (Hysingla ER)133

Prior Oral Opiate

Oral Dose (mg)

Approximate Oral Conversion Factor

Codeine

133

0.15

Hydromorphone

5

4

Methadone

13.3

1.5

Morphine

40

0.5

Oxycodone

20

1

Oxymorphone

10

2

Tramadol

200

0.1

Initial Dosage Selection in Patients Being Switched from Transdermal Fentanyl to Extended-release Hydrocodone Tablets
Oral

Wait 18 hours after removal of the transdermal fentanyl system to initiate therapy with extended-release hydrocodone tablets; use an initial conservative dosage of approximately 20 mg every 24 hours for each 25 mcg/hr of transdermal fentanyl.133

Monitor closely; experience with this dosage conversion is limited.133

Initial Dosage Selection in Patients Being Switched from Transdermal Buprenorphine to Extended-release Hydrocodone Tablets
Oral

Initially, 20 mg every 24 hours in patients who previously received transdermal buprenorphine ≤20 mg/hour.133

Monitor closely; experience with this dosage conversion is limited.133

Dosage Adjustment to Achieve Adequate Analgesia
Oral

Adjust dosage gradually, every 3–5 days in increments of 10–20 mg every 24 hours, to provide adequate analgesia and to minimize adverse effects.133

Discontinuance of Therapy
Oral

Gradually taper dosage every 2–4 days to avoid manifestations of abrupt withdrawal.133

Each new dose in the taper should be ≥50% of the prior dose; decrease dosage to 20 mg daily for 2–4 days, then discontinue therapy.133

Pain (Immediate-release Fixed Combinations)
Oral

5–10 mg (in fixed combination with acetaminophen) every 4–6 hours as needed.123 a

2.5–10 mg (in fixed combination with ibuprofen) every 4–6 hours as needed, generally for <10 days.124 132 Manufacturers state total daily dosage should not exceed 5 tablets (each providing from 2.5–10 mg of hydrocodone bitartrate and 200 mg of ibuprofen).124 132

Adjust dosage according to severity of pain and response and tolerance of the patient.123 124 a

Nonopiate-containing analgesic fixed combinations: Nonopiate component may limit dosage of opiate component.117 119 120 121 Nonopiate analgesics are available in various fixed ratios with hydrocodone and also are available in many other prescription and OTC preparations; ensure that therapy is not duplicated and that nonopiate dosage does not exceed maximum recommended dosages.117 118 119 121

Prescribing Limits

Pediatric Patients

Cough
Hydrocodone Bitartrate
Oral

Children 6–12 years of age: Maximum is 15 mg daily.113

Extended-release Suspension Containing Hydrocodone Polistirex and Chlorpheniramine Polistirex (e.g., Tussionex Pennkinetic)
Oral

Children 6–11 years of age: Maximum 5 mL (10 mg when expressed in terms of hydrocodone bitartrate) daily.109

Children ≥12 years of age: Maximum 10 mL (20 mg when expressed in terms of hydrocodone bitartrate) daily.109

Adults

Cough
Hydrocodone Bitartrate
Oral

Maximum 30 mg daily.113 However, other drugs in combination preparations may further limit daily hydrocodone dosage.114 115 116

Extended-release Suspension Containing Hydrocodone Polistirex and Chlorpheniramine Polistirex (e.g., Tussionex Pennkinetic)
Oral

Maximum 10 mL (20 mg when expressed in terms of hydrocodone bitartrate) daily.109

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: No initial dosage adjustment required.122 133

Severe hepatic impairment (extended-release capsules [Zohydro ER]): Initially, 10 mg every 12 hours.122

Severe hepatic impairment (extended-release tablets [Hysingla ER]): Reduce initial dosage by 50%.133

Monitor closely for adverse effects.122 133

Renal Impairment

Manufacturer of extended-release capsules recommends use of low initial dosage in patients with renal impairment.122

Manufacturer of extended-release tablets states that no initial dosage adjustment required in mild renal impairment; reduce initial dosage by 50% in patients with moderate or severe renal impairment, including end-stage renal disease.133

Monitor closely for adverse effects.122 133

Geriatric Patients

Use low initial dosage in older patients.a b 109 122 123 133 Monitor closely for adverse effects.122 133

Cautions for Hydrocodone Bitartrate

Contraindications

  • Known hypersensitivity to hydrocodone or any ingredient in the formulation.b 109 122 123 124 133

  • Possible cross-sensitivity to hydrocodone if hypersensitive to other opiates.123 124

  • Extended-release hydrocodone: Substantial respiratory depression, acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment, known or suspected paralytic ileus and GI obstruction.122 133

  • Extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex: Children <6 years of age.109

Warnings/Precautions

Warnings

Respiratory Depression

Possible dose-related respiratory depression.b c e 109 112 123 124 133

Even therapeutic doses of hydrocodone may decrease respiratory drive to the point of apnea in patients with COPD, cor pulmonale, substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression.122 133 Monitor closely, particularly when initiating therapy or titrating dosage.122 133 Use nonopiate analgesics if possible.122 133

Geriatric, cachectic, and debilitated patients are at increased risk of life-threatening respiratory depression.122 133 Close monitoring of therapy with extended-release hydrocodone is required, particularly following initiation of therapy, during dosage titration, and during concomitant therapy with other respiratory depressants.122 133

Carbon dioxide retention from opiate-induced respiratory depression can exacerbate the drug's sedative effects.122 133

Serious, life-threatening, or fatal respiratory depression reported with use of modified-release (e.g., extended-release) opiates, even when used as recommended; can occur at any time during therapy, but risk is greatest during initiation of therapy and following dosage increases.122 133 Monitor for respiratory depression, especially during the first 24–72 hours of therapy and following any dosage increase.122 133

Only clinicians who are knowledgeable in the use of potent opiates for the management of chronic pain should prescribe extended-release hydrocodone.122 133

Appropriate dosage selection and titration of extended-release hydrocodone are essential to reduce the risk of respiratory depression; overestimation of the dosage when transferring patients from another opiate analgesic can result in fatal overdosage with the first dose.122 133

Accidental ingestion of even 1 dose of extended-release hydrocodone capsules or tablets, especially by a child, can result in respiratory depression and a fatal overdose.122 133

Potential for increased viscosity of bronchial secretions and suppression of cough reflex, with subsequent respiratory insufficiency, in patients with asthma or pulmonary emphysema who indiscriminately use antitussives.b

Overdosage and toxicity (including fatal respiratory depression) reported in adults and children receiving the extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex.109 112 Patients should seek immediate medical assistance if they experience respiratory depression.109 112 (See Advice to Patients.)

Addiction, Abuse, and Misuse

Addiction can occur with appropriately prescribed or illicitly obtained opiates, and at recommended dosages or with misuse or abuse.122 133

Assess each patient’s risk for addiction, abuse, and misuse prior to prescribing; monitor all patients for development of these behaviors or conditions.122 133 Personal or family history of substance abuse (drug or alcohol addiction or abuse) or mental illness (e.g., major depression) increases risk.122 133

The potential for addiction, abuse, and misuse should not prevent opiate prescribing for appropriate pain management,122 133 but does necessitate intensive counseling about risks and proper use and intensive monitoring for these behaviors and conditions.122

Modified-release (e.g., extended-release) opiates are associated with a greater risk of overdose and death because of the larger amount of drug contained in each dosage unit.122 133

Abuse or misuse of extended-release hydrocodone formulations by crushing or chewing the capsules or tablets, snorting the contents, or injecting the dissolved contents will result in uncontrolled delivery of hydrocodone and can result in a fatal overdose.122 133

Because of the challenges associated with providing access to an adequate array of options for management of chronic pain while simultaneously preventing prescription opiate abuse and misuse, FDA's decision to approve hydrocodone bitartrate extended-release capsules (Zohydro ER) was controversial, as the formulation lacks tamper-resistant features that might deter abuse and, like other extended-release opiates, some strengths contain substantial amounts of the drug (up to 50 mg122 ).126 127 128 129 130

Physical and chemical properties of Hysingla ER extended-release tablets (containing up to 120 mg of the drug) are intended to hinder manipulation for IV or intranasal abuse and misuse; some extended-release characteristics are retained if the tablet is physically compromised.133 Exposure to water results in formation of a viscous hydrogel that resists passage through a needle; the tablets resist crushing, breaking, and dissolution by various tools and solvents; and clinical studies suggest reduced potential for intranasal abuse or oral abuse by chewing the tablets.133 However, potential for IV, intranasal, and oral abuse still exists.133

Potential for abuse of hydrocodone-containing combinations is similar to that of schedule II (C-II) oxycodone-containing combinations.290 291 Because of increasing concerns about misuse, abuse, and diversion, hydrocodone-containing fixed-combination analgesic and antitussive preparations previously subject to control as C-III drugs were rescheduled as C-II drugs effective October 6, 2014.290 291 (See Preparations.)

Interactions with Drugs that Affect CYP3A4

Concomitant use of CYP3A4 inhibitors may increase plasma hydrocodone concentrations, increasing or prolonging opiate effects.122 133

Concomitant use of CYP3A4 inducers may result in decreased plasma hydrocodone concentrations, lack of efficacy, or manifestations of withdrawal.122 133 (See Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

Other Warnings/Precautions

Shares the toxic potentials of the opiate agonists; observe the usual precautions of opiate agonist therapy.a

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.b c e 109 122 123 124 133

Concurrent use of other CNS depressants may potentiate CNS depression.b e 109 123 124 Concurrent use of other CNS depressants with extended-release hydrocodone may result in profound CNS depression.122 133 (See Specific Drugs under Interactions.)

When considering the use of extended-release hydrocodone in a patient receiving a CNS depressant, assess duration of use of the CNS depressant; patient’s response, including degree of tolerance to CNS depression; and patient’s use of alcohol or illicit drugs that cause CNS depression.122 133

Increased Intracranial Pressure or Head Trauma

Respiratory depressant effects and ability of opiates to increase CSF pressure may be markedly exaggerated in patients with head injury, other intracranial lesions, or preexisting elevation in intracranial pressure.b c e 109 122 123 124 133

Hydrocodone produces effects (e.g., pupillary changes, altered consciousness) that may obscure clinical course and neurologic signs of further increase in CSF pressure in patients with head injuries.b c e 109 122 123 124 133

Closely monitor patients with increased intracranial pressure or impaired consciousness.122 133 Avoid use of extended-release hydrocodone in patients with impaired consciousness or coma.122 133

Hypotension

Possible severe hypotension in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant drugs that compromise vascular tone (e.g., phenothiazines, general anesthetics).122 133 (See Specific Drugs under Interactions.)

May cause severe hypotension, including orthostatic hypotension and syncope, in ambulatory patients.122 133

Avoid use of extended-release hydrocodone in patients with circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and BP.122 133

Seizure Disorders

May aggravate preexisting seizure disorder.122 Monitor for worsened seizure control.122

May induce seizures in some clinical settings.122

GI Complications with Extended-release Tablets

Some patients report difficulty in swallowing the extended-release tablets.133 The tablets form a gelatinous mass when wet.133 (See Hydrocodone Extended-release Tablets [Hysingla ER] under Dosage and Administration.)

Choking, dysphagia, and esophageal obstruction (at least 1 case requiring medical intervention to remove the tablet) reported.133 Increased risk in patients with underlying GI disorders (e.g., esophageal or colon cancer) associated with narrow GI lumen.133

Consider using an alternative analgesic in patients who have difficulty swallowing and in those at risk for underlying GI disorders associated with narrow GI lumen.133

Acute Abdominal Conditions

May obscure diagnosis or clinical course of patients with acute abdominal conditions.e 109 122 123 124 133

Obstructive Bowel Disease

May diminish propulsive peristaltic waves in GI tract and decrease bowel motility.122 133 Use may result in obstructive bowel disease, especially in patients with underlying intestinal motility disorder.109

Monitor postoperative patients for decreased bowel motility.122 133

Extended-release hydrocodone is contraindicated in patients with known or suspected GI obstruction, including paralytic ileus.122 133

Postoperative Patients

Suppression of cough reflex following thoracotomy or laparotomy may lead to postoperative retention of secretions; cautious use recommended.b 109

Biliary Disease

Monitor patients with biliary disease, including acute pancreatitis; may cause spasm of the sphincter of Oddi and decrease biliary and pancreatic secretions.122 133

Debilitated and Special Risk Patients

Use with caution in debilitated patients and in those with hypothyroidism, Addison’s disease, prostatic hypertrophy, urethral stricture, or pulmonary disease.b c e 109 123 124

Tolerance and Dependence

Possible tolerance and physical dependence following prolonged administration.b c e 109 122 123 124 133 When discontinuing therapy, gradually taper dosage to avoid symptoms of withdrawal.122 133

QT Interval Prolongation

Prolongation of corrected QT (QTc) interval observed in healthy individuals receiving 160 mg daily (as extended-release tablets).133

Consider this observation when making decisions regarding monitoring (e.g., periodic monitoring of ECGs and electrolyte concentrations) of patients with CHF, bradyarrhythmias, or electrolyte abnormalities and those receiving drugs that prolong the QTc interval.133

Manufacturer recommends avoiding use of extended-release tablets in patients with congenital long QT syndrome.133

If QTc interval prolongation occurs, consider reducing dosage by 33–50% or using an alternative analgesic.133

Fixed-Combination Preparations

When used in fixed combination with other drugs, consider the cautions, precautions, and contraindications associated with the other drug(s).a 123 124

Specific Populations

Pregnancy

Category C.e 109 122 123 124 133

Analysis of data from the National Birth Defects Prevention Study (large population-based, case-control study) suggests therapeutic use of opiates in pregnant women during organogenesis is associated with a low absolute risk of birth defects, including heart defects, spina bifida, and gastroschisis.134 135

Prolonged maternal use of opiates during pregnancy can result in neonatal opiate withdrawal syndrome; in contrast to adults, withdrawal syndrome in neonates may be life-threatening and requires management according to protocols developed by neonatology experts.122 133 Syndrome presents with irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.122 133 Onset, duration, and severity vary depending on the specific opiate used, duration of use, timing and amount of last maternal use, and rate of drug elimination by the neonate.122 133

Use of opiates during late pregnancy can result in neonatal respiratory depression.134

Extended-release opiates not recommended immediately before or during labor; shorter-acting analgesics or other analgesic techniques may be more appropriate.122 133

Lactation

Low concentrations of hydrocodone and metabolite (hydromorphone) reported in breast milk of women receiving hydrocodone for postpartum pain.122 Discontinue nursing or the drug.109 122 123 124 133

Monitor infants exposed to hydrocodone through breast milk for excessive sedation, respiratory depression, GI effects, and altered feeding patterns.122 133 134 Symptoms of withdrawal can occur in opiate-dependent infants when maternal administration of opiates is discontinued or breast-feeding is stopped.122 133

Pediatric Use

Safety and efficacy as an analgesic not established in pediatric patients.122 123 124 133

Pediatric patients may be at increased risk of esophageal obstruction, dysphagia, and choking (because of their smaller GI lumen) if they ingest the extended-release tablets, which form a gelatinous mass when exposed to fluids.133

Safety and efficacy as an antitussive not established in children <6 years of age.105 106 107 108 109 112 113

Extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex: Contraindicated in children <6 years of age; use with caution in children ≥6 years of age due to the risk of respiratory depression.109 112 Risk of potentially fatal respiratory depression is increased with overdosage or concomitant use of other respiratory depressants.109 (See Warnings/Precautions and see Dosage and Administration.)

Benefit-to-risk ratio should be carefully considered, especially in children with respiratory embarrassment (e.g., croup).109

Risk of overdosage and toxicity (including death) in children <2 years of age receiving preparations containing antihistamines, cough suppressants, expectorants, and nasal decongestants alone or in combination for relief of symptoms of upper respiratory tract infection.110 111 Clinicians should ask caregivers about use of OTC cough/cold preparations to avoid overdosage.

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.109 122 123

May cause confusion and oversedation in geriatric patients.122 123 133 Increased risk of life-threatening respiratory depression in geriatric, cachectic, or debilitated patients.122 124 133

Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy in geriatric patients, use with caution and select dosage at the lower end of the dosage range.109 122 123 124 133

Monitor closely for adverse effects, especially during initiation of therapy and dosage titration and when used concomitantly with other respiratory depressants.122 133

Hepatic Impairment

Exposure to the drug and the risk of adverse effects may be increased.122 133 Monitor closely.122 133 (See Hepatic Impairment under Dosage and Administration and see Absorption: Special Populations, under Pharmacokinetics.)

Renal Impairment

Exposure to the drug and the risk of adverse effects may be increased.122 133 Monitor closely.122 133 (See Renal Impairment under Dosage and Administration and see Absorption: Special Populations, under Pharmacokinetics.)

Common Adverse Effects

Lightheadedness, dizziness, sedation, nausea, vomiting, constipation.b 109 123 124 Adverse effects occur infrequently with usual oral antitussive dosages.b

With extended-release capsules for chronic pain: Constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting, pruritus, abdominal pain, peripheral edema, upper respiratory tract infection, muscle spasms, urinary tract infection, back pain, tremor.122

With extended-release tablets for chronic pain: Nausea, constipation, vomiting, dizziness, headache, somnolence, fatigue, pruritus, tinnitus, insomnia, decreased appetite, influenza.133

Interactions for Hydrocodone Bitartrate

Metabolized by CYP3A4 and to a lesser extent by CYP2D6.122 124 Also may be metabolized to a small extent by CYP2B6 and CYP2C19.133

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Possible decreased clearance and increased plasma concentrations of hydrocodone; may result in increased or prolonged opiate effects, including increased risk of fatal respiratory depression.122 133 If concomitant use is necessary, monitor for respiratory depression and sedation at frequent intervals; consider dosage adjustments until stable drug effects are achieved.122 133

CYP3A4 inducers: Possible increased clearance and decreased plasma concentrations of hydrocodone; may result in lack of efficacy or withdrawal manifestations.122 133 If concomitant use is necessary, monitor for opiate withdrawal; consider dosage adjustments until stable drug effects are achieved.122 133 If CYP3A4 inducer is discontinued, plasma hydrocodone concentrations may increase, possibly increasing or prolonging therapeutic and adverse effects of the drug and increasing risk of fatal overdosage.122 133

Specific Drugs

Drug

Interaction

Comments

Anticholinergic agents

Possible increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileuse 109 122 124 133

Monitor for urinary retention, constipation, and CNS/respiratory depression122 133

Antidepressants, tricyclics

Potentiation of antidepressant adverse effecte 109 123

Use with caution; reduce dosage of hydrocodonee

CNS depressants (e.g., alcohol, antihistamines, general anesthetics, opiate agonists, phenothiazines, sedatives/hypnotics, anxiolytics)

Additive CNS effects;109 123 124 increased risk of respiratory depression, hypotension, profound sedation, coma, or death122 133

Hydrocodone extended-release capsules: Alcohol increases peak plasma hydrocodone concentrations, may result in fatal overdose122

Reduce dosage of one or both agents;e 109 122 123 124 133 reduce initial dosage of extended-release hydrocodone by 20–30% and consider using lower dosage of the concomitant agent122 133

Avoid alcohol use122 124 133

Monitor for respiratory depression, sedation, and hypotension122

Ketoconazole

Increased peak concentrations and AUC of hydrocodone133

Monitor frequently for respiratory depression and sedation; consider hydrocodone dosage adjustments until drug effects are stable133

Laxatives (e.g., lactulose)

Strong laxatives that rapidly increase GI motility: Decreased absorption of hydrocodone from extended-release tablets; possible decreased hydrocodone concentrations133

Monitor for adverse events and changing analgesic requirements133

MAO inhibitors

Severe, unpredictable potentiation of opiates reported122 124 133

Potentiation of antidepressant adverse effect123 124

Caution advised; allow at least 14 days to elapse between discontinuance of MAO inhibitor and initiation of hydrocodone122 124 133

Opiate partial agonists (butorphanol, buprenorphine, nalbuphine, pentazocine)

Possible reduced analgesic effect and/or withdrawal symptoms122 124 133

Caution advised;124 some manufacturers recommend avoiding combined use122 133

Paroxetine

No change in hydrocodone exposure133

Skeletal muscle relaxants

May enhance the neuromuscular blocking action of skeletal muscle relaxants and increase respiratory depressant effects124

Hydrocodone Bitartrate Pharmacokinetics

Absorption

Bioavailability

Well absorbed from the GI tract following oral administration.b

Extended-release capsules or tablets: Overall systemic exposure or bioavailability similar to that observed with immediate-release fixed-combination preparations containing the same or similar hydrocodone dose; however, peak plasma concentrations are lower with the extended-release formulations.122 133

Extended-release capsules: Peak serum concentrations occur 5 hours after administration.122 AUC and peak concentration are approximately twofold higher on day 7 than on day 1 of therapy.122 At doses up to 50 mg, pharmacokinetics are independent of dose.122

Extended-release tablets: Peak concentrations occur 6–30 hours (median: 14–16 hours) after administration.133 Peak concentrations and AUC increase linearly and in a slightly more than dose-proportional manner over the dose range of 20–120 mg.133 With once-daily dosing, peak plasma concentrations and AUC are about 1.1- and 1.3-fold higher at steady state.133 Higher doses (80 or 120 mg versus 30 mg) produce larger fluctuations in peak-to-trough concentrations.133

Immediate-release preparations: Peak serum concentrations of hydrocodone occur after 1.3–1.7 hours.123 124 b e

Extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex (Tussionex Pennkinetic): Peak plasma concentrations of hydrocodone occur after 3.4 hours.109

Duration

Immediate-release preparations: Antitussive action is maintained for 4–6 hours.b

Extended-release oral suspension containing hydrocodone polistirex and chlorpheniramine polistirex (Tussionex Pennkinetic): Symptom control maintained for up to 12 hours.109

Food

Extended-release capsules: Food does not substantially affect extent of absorption, although high-fat meal increased peak plasma concentrations by 27%.122

Extended-release tablets: At 120-mg dose, high-fat meal increased peak plasma concentrations by 54% and AUC by 20%.133

Special Populations

Hepatic impairment: Peak plasma concentrations of hydrocodone (administered as extended-release capsules) increased by 8–10% and AUC increased by 10 or 26% in patients with mild or moderate hepatic impairment, respectively; pharmacokinetics not evaluated in patients with severe hepatic impairment.122

Hepatic impairment: Peak plasma concentrations and AUC of hydrocodone (administered as extended-release tablets) decreased by 6 and 14%, respectively, in patients with mild hepatic impairment; increased by 5 and 13%, respectively, in patients with moderate hepatic impairment; and increased by 5 and 4%, respectively, in patients with severe hepatic impairment.133

Renal impairment: Peak plasma concentrations of hydrocodone (administered as extended-release capsules) increased by 15, 48, or 41% and AUC increased by 15, 57, or 44% in patients with mild, moderate, or severe renal impairment, respectively.122

Renal impairment: Peak plasma concentrations of hydrocodone (administered as extended-release tablets) increased by 14, 23, or 11% and AUC increased by 13, 61, or 57% in patients with mild, moderate, or severe renal impairment, respectively; peak plasma concentrations decreased by 13% and AUC increased by 4% in patients with end-stage renal disease requiring dialysis.133

Distribution

Extent

Distributed into skeletal muscle, kidneys, liver, intestinal tract, lungs, spleen, and brain.c

Low concentrations of hydrocodone and metabolite (hydromorphone) reported in breast milk of women receiving hydrocodone for postpartum pain.122

Readily crosses the placenta.c

Plasma Protein Binding

About 36%.133

Special Populations

Hepatic impairment does not substantially alter plasma protein binding.133

Elimination

Metabolism

Metabolized by N-demethylation, O-demethylation, and 6-keto reduction to the corresponding 6-α-and 6-β-hydroxy metabolites.122 123 124 133 Metabolized principally by CYP3A4 to norhydrocodone (N-demethylation) and to lesser extent by CYP2D6 to hydromorphone (O-demethylation).122 124 133 May be metabolized to small extent by CYP2B6 and CYP2C19.133

Hydromorphone is <3% of the circulating parent drug, but may contribute to hydrocodone's analgesic effects.122 124 133

Elimination Route

Excreted mainly in urine as unchanged drug (about 6.5%) and metabolites.122 133 b About 99% of administered dose is eliminated within 72 hours.133

Half-life

Extended-release preparations: Approximately 7–9 hours.122 133

Immediate-release preparations: 3.8–4.5 hours.e 109 123 124

Special Populations

Gender and age ≥65 years do not appear to substantially affect pharmacokinetics.122 124 133

Stability

Storage

Oral

Extended-release Capsules

25ºC (may be exposed to 15–30°C).122

Extended-release Tablets

25ºC (may be exposed to 15–30°C).133

Tablets

20–25ºC (may be exposed to 15–30°C).123 124

Solution

Tight, light resistant containers at 15–30°C.e

Extended-release Suspension

Tight containers at 20–25ºC (may be exposed to 15–30°C).109 Shake well before use.109

Actions

  • Shares the actions of the opiate agonists.122 123 124 133 c

  • Opiate agonists alter perception of and emotional response to pain.c

  • Precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia.c

  • Pain perception is altered in the spinal cord and higher CNS levels (e.g., substantia gelatinosa, spinal trigeminal nucleus, periaqueductal gray, periventricular gray, medullary raphe nuclei, hypothalamus).c

  • Opiate agonists do not alter the threshold or responsiveness of afferent nerve endings to noxious stimuli, nor peripheral nerve impulse conduction.c

  • Opiate agonists act at specific receptor binding sites in the CNS and other tissues; opiate receptors are concentrated in the limbic system, thalamus, striatum, hypothalamus, midbrain, and spinal cord.c

  • Agonist activity at the opiate μ- or κ-receptor can result in analgesia, miosis, and/or decreased body temperature.c

  • Agonist activity at the μ-receptor can also result in suppression of opiate withdrawal (and antagonist activity can result in precipitation of withdrawal).c

  • Respiratory depression may be mediated by μ-receptors, possibly μ2-receptors (which may be distinct from μ1-receptors involved in analgesia); κ- and δ-receptors may also be involved in respiratory depression.c

  • Suppresses cough reflex by direct effect on cough center in medulla of brain.b 109 122 133

  • Exerts drying effect on respiratory tract mucosa and increases viscosity of bronchial secretions.b

  • Antitussive activity is slightly greater than that of codeine (on a weight basis).b

  • Hydrocodone may release histamine with or without associated peripheral vasodilation.122 133

Advice to Patients

  • Importance of not exceeding the recommended dosage.109 122 123 124 133

  • Consequences of overdosage may include potentially fatal respiratory depression.109 122 133

  • Importance of seeking medical attention if signs or symptoms of overdosage (trouble breathing, slow heartbeat, severe sleepiness, muscle flaccidity, dizziness, confusion, or cold, clammy skin) develop.109 112 122 123 124 133

  • Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.b c e 109 122 123 124 133

  • Importance of informing clinician if pain control is inadequate or adverse effects (e.g., constipation) occur, so that therapy may be adjusted based on individual requirements.122 133

  • Importance of informing patients that hydrocodone is a drug of potential abuse and should be protected from theft or misuse.122 124 133 Importance of properly disposing of the drug when no longer needed.122 133

  • Importance of not abruptly discontinuing hydrocodone following prolonged opiate therapy.122 133

  • Potential for severe constipation to occur.122 133

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and alcohol consumption.122 123 124 133 e Importance of avoiding alcohol-containing beverages or products.122 123 124 133

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.e 109 122 123 124 133 Importance of informing women that chronic use during pregnancy may result in neonatal opiate withdrawal syndrome, which can be life-threatening if not recognized and treated.122 133

  • Importance of advising patients of other important precautionary information.e 109 122 123 124 133 (See Cautions.)

  • Extended-release Oral Suspension Containing Hydrocodone Polistirex and Chlorpheniramine Polistirex
  • Importance of ensuring that the correct amount of medication required for the intended dose is administered (e.g., importance of using a calibrated dosing device).109

  • Hydrocodone Bitartrate Extended-release Capsules and Tablets
  • Medication guide must be dispensed with each prescription.125 Importance of patients reading the medication guide before initiating therapy and each time the extended-release capsules or tablets are dispensed.125

  • Respiratory depression is most likely to occur following initiation of therapy or an increase in dosage; may occur at recommended dosages.122 133

  • Extended-release hydrocodone, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdosage or death.122 133

  • Accidental ingestion of extended-release hydrocodone, especially by a child, may result in respiratory depression or death.122 133 Keep out of reach of children and do not share the drug with others.122 133

  • Importance of swallowing capsules whole.122 Crushing, chewing, or dissolving the capsules can result in overdosage and death.122

  • Importance of swallowing tablets whole, one at a time, with enough water to ensure complete swallowing of the tablet immediately after it is placed in the mouth.133 Do not wet the tablet (e.g., by soaking, licking) before placing it in the mouth; wetting can lead to difficulty in swallowing the tablet.133 Crushing, chewing, or dissolving the tablets can result in overdosage and death.133

  • Importance of not consuming alcoholic beverages or taking prescription or nonprescription preparations that contain alcohol.122 133 Respiratory and CNS depressant effects of alcohol and hydrocodone are additive;122 133 ingestion of alcohol with extended-release capsules may increase hydrocodone absorption and result in fatal overdosage.122 Do not use other CNS depressants concomitantly unless use is supervised by clinician.122 133

  • Risk of orthostatic hypotension and syncope.122 133 Importance of rising slowly from a seated or supine position and of sitting or lying down if symptoms occur.122 133

  • Prolongation of QT interval observed with use of extended-release tablets; depending on coexisting medical conditions and concurrent drug therapy, periodic ECGs and electrolyte monitoring may be needed.133

  • Importance of seeking medical attention if symptoms of severe hypersensitivity (e.g., anaphylaxis) occur.122 133

  • When assessing own ability to perform hazardous tasks, consider that hydrocodone concentrations may still be high 24 hours after taking the extended-release tablets.133

  • Importance of monitoring analgesic response to hydrocodone extended-release tablets following the use of strong laxatives; inform clinician of any changes in response.133

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Single-entity hydrocodone preparations: Subject to control under the Federal Controlled Substances Act of 1970 as schedule II (C-II) drug.

Fixed-combination preparations containing hydrocodone in a concentration of ≤15 mg per dosage unit or 5 mL combined with a therapeutic amount of one or more non-opiate drugs or with a fourfold or greater quantity of isoquinolone opium alkaloid: Previously subject to control as schedule III (C-III) drug; however, rescheduled as C-II drug effective October 6, 2014.290 (See Addiction, Abuse, and Misuse under Cautions.)

Preparations containing hydrocodone in combination with >325 mg of acetaminophen per dosage unit have been discontinued to minimize the risk of inadvertent acetaminophen overdosage; some of these preparations may have been reformulated to limit the amount of acetaminophen to ≤325 mg per dosage unit.288 289

Hydrocodone Bitartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, extended-release

10 mg

Zohydro ER (C-II)

Zogenix

15 mg

Zohydro ER (C-II)

Zogenix

20 mg

Zohydro ER (C-II)

Zogenix

30 mg

Zohydro ER (C-II)

Zogenix

40 mg

Zohydro ER (C-II)

Zogenix

50 mg

Zohydro ER (C-II)

Zogenix

Tablets, extended-release, film-coated

20 mg

Hysingla ER (C-II)

Purdue Pharma

30 mg

Hysingla ER (C-II)

Purdue Pharma

40 mg

Hysingla ER (C-II)

Purdue Pharma

60 mg

Hysingla ER (C-II)

Purdue Pharma

80 mg

Hysingla ER (C-II)

Purdue Pharma

100 mg

Hysingla ER (C-II)

Purdue Pharma

120 mg

Hysingla ER (C-II)

Purdue Pharma

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Hydrocodone Bitartrate Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

2.5 mg/5 mL with Acetaminophen 108 mg/5 mL*

Hydrocodone Bitartrate and Acetaminophen Oral Solution (C-II)

3.3 mg/5 mL with Acetaminophen 100 mg/5 mL*

Hydrocodone Bitartrate and Acetaminophen Oral Solution (C-II)

Lortab Elixir (C-II)

ECR

3.3 mg/5 mL with Acetaminophen 108 mg/5 mL*

Hydrocodone Bitartrate and Acetaminophen Oral Solution (C-II)

5 mg/5 mL with Chlorpheniramine Maleate 4 mg/5 mL

Vituz (C-II)

Hawthorn

5 mg/5 mL with Chlorpheniramine Maleate 4 mg/5 mL and Pseudoephedrine Hydrochloride 60 mg/5 mL*

Hydrocodone Bitartrate, Chlorpheniramine Maleate, and Pseudoephedrine Hydrochloride Oral Solution (C-II)

Zutripro (C-II)

Hawthorn

5 mg/5 mL with Homatropine Methylbromide 1.5 mg/5 mL*

Hydrocodone Bitartrate and Homatropine Methylbromide Syrup (C-II)

Hydromet Syrup (C-II)

Actavis

5 mg/5 mL with Pseudoephedrine Hydrochloride 60 mg/5 mL*

Hydrocodone Bitartrate and Pseudoephedrine Hydrochloride Oral Solution (C-II)

Rezira (C-II)

Hawthorn

Tablets

2.5 mg with Acetaminophen 325 mg*

Hydrocodone Bitartrate and Acetaminophen Tablets (C-II)

5 mg with Acetaminophen 300 mg*

Hydrocodone Bitartrate and Acetaminophen Tablets (C-II)

Vicodin (C-II; scored)

AbbVie

5 mg with Acetaminophen 325 mg*

Hydrocodone Bitartrate and Homatropine Methylbromide Tablets (C-II)

Lortab (C-II; scored)

UCB

Norco (C-II; scored)

Actavis

5 mg with Homatropine Methylbromide 1.5 mg*

Hydrocodone Bitartrate and Homatropine Methylbromide Tablets (C-II)

Tussigon (C-II; scored)

Pfizer

7.5 mg with Acetaminophen 300 mg*

Hydrocodone Bitartrate and Acetaminophen Tablets (C-II)

Vicodin ES (C-II; scored)

AbbVie

7.5 mg with Acetaminophen 325 mg*

Hydrocodone Bitartrate and Acetaminophen Tablets (C-II)

Lortab (C-II; scored)

UCB

Norco (C-II; scored)

Actavis

10 mg with Acetaminophen 300 mg*

Hydrocodone Bitartrate and Acetaminophen Tablets (C-II)

Vicodin HP (C-II; scored)

AbbVie

10 mg with Acetaminophen 325 mg*

Hydrocodone Bitartrate and Acetaminophen Tablets (C-II)

Lortab (C-II; scored)

UCB

Norco (C-II; scored)

Actavis

Tablets, film-coated

2.5 mg with Ibuprofen 200 mg*

Hydrocodone Bitartrate and Ibuprofen Film-coated Tablets (C-II)

Reprexain (C-II)

Gemini

5 mg with Ibuprofen 200 mg*

Hydrocodone Bitartrate and Ibuprofen Film-coated Tablets (C-II)

Reprexain (C-II)

Gemini

7.5 mg with Ibuprofen 200 mg*

Hydrocodone Bitartrate and Ibuprofen Film-coated Tablets (C-II)

Vicoprofen (C-II)

AbbVie

10 mg with Ibuprofen 200 mg*

Hydrocodone Bitartrate and Ibuprofen Film-coated Tablets (C-II)

Reprexain (C-II)

Gemini

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Hydrocodone Polistirex Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension, extended-release

equivalent to Hydrocodone Bitartrate 10 mg/5 mL with Chlorpheniramine Polistirex equivalent to Chlorpheniramine Maleate 8 mg/5 mL*

Hydrocodone Polistirex and Chlorpheniramine Polistirex Extended-Release Suspension (C-II)

Tussionex Pennkinetic (C-II)

UCB

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 07/2015. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Hydrocod Polst-Chlorphen Polst 10-8MG/5ML Liquid (PAR): 60/$45.99 or 120/$80.98

Hydrocodone-Acetaminophen 10-325MG Tablets (WATSON LABS): 30/$17.99 or 90/$44.97

Hydrocodone-Acetaminophen 10-500MG Tablets (MALLINCKRODT PHARM): 30/$14.99 or 90/$39.97

Hydrocodone-Acetaminophen 10-650MG Tablets (MALLINCKRODT PHARM): 30/$14.99 or 90/$30.97

Hydrocodone-Acetaminophen 10-660MG Tablets (MALLINCKRODT PHARM): 30/$17.99 or 90/$37.97

Hydrocodone-Acetaminophen 10-750MG Tablets (MALLINCKRODT PHARM): 30/$32.99 or 90/$89.97

Hydrocodone-Acetaminophen 2.5-500MG Tablets (QUALITEST): 30/$12.99 or 90/$27.27

Hydrocodone-Acetaminophen 5-325MG Tablets (MALLINCKRODT PHARM): 30/$17.99 or 60/$29.98

Hydrocodone-Acetaminophen 5-500MG Tablets (WATSON LABS): 30/$12.99 or 60/$16.98

Hydrocodone-Acetaminophen 7.5-325MG Tablets (MALLINCKRODT PHARM): 30/$17.99 or 90/$51.97

Hydrocodone-Acetaminophen 7.5-500MG/15ML Solution (QUALITEST): 473/$60.98 or 1419/$182.95

Hydrocodone-Acetaminophen 7.5-500MG Tablets (WATSON LABS): 30/$13.99 or 60/$17.98

Hydrocodone-Acetaminophen 7.5-650MG Tablets (MALLINCKRODT PHARM): 100/$15.99 or 300/$35.97

Hydrocodone-Acetaminophen 7.5-750MG Tablets (MALLINCKRODT PHARM): 30/$12.99 or 90/$23.97

Hydrocodone-Ibuprofen 7.5-200MG Tablets (AMNEAL PHARMACEUTICALS): 30/$33.99 or 90/$82.97

Lorcet 10/650 10-650MG Tablets (FOREST): 30/$57.99 or 90/$159.97

Lorcet Plus 7.5-650MG Tablets (FOREST): 30/$48.49 or 90/$131.14

Lortab 5-500MG Tablets (UCB PHARMA): 30/$57.99 or 90/$155.98

Lortab 7.5-500MG/15ML Elixir (UCB PHARMA): 120/$47.99 or 360/$119.97

Lortab 10 10-500MG Tablets (UCB PHARMA): 30/$62.99 or 90/$165.97

Lortab 2.5 2.5-500MG Tablets (UCB PHARMA): 30/$30.99 or 90/$78.97

Lortab 7.5 7.5-500MG Tablets (UCB PHARMA): 30/$64.99 or 90/$173.97

Norco 10-325MG Tablets (WATSON LABS): 30/$69.95 or 90/$204.56

Norco 5-325MG Tablets (WATSON LABS): 30/$52.65 or 90/$132.76

Norco 7.5-325MG Tablets (WATSON LABS): 30/$57.23 or 90/$160.24

Reprexain 10-200MG Tablets (HAWTHORN PHARMACEUTICALS): 100/$110.85 or 300/$313.72

Reprexain 2.5-200MG Tablets (HAWTHORN PHARMACEUTICALS): 100/$75.81 or 300/$205.77

Reprexain 5-200MG Tablets (HAWTHORN PHARMACEUTICALS): 100/$79.44 or 300/$215.31

Stagesic 5-500MG Capsules (MAGNA PHARMACEUTICALS): 30/$24.99 or 90/$51.97

Tussionex Pennkinetic ER 10-8MG/5ML Liquid (UCB PHARMA): 115/$125.99 or 345/$349.97

Tussionex Pennkinetic ER 8-10MG/5ML Liquid (UCB PHARMA): 60/$50.99 or 120/$98.97

Vicodin 5-500MG Tablets (ABBOTT): 30/$50.99 or 90/$133.97

Vicodin ES 7.5-750MG Tablets (ABBOTT): 30/$54.99 or 90/$147.97

Vicodin HP 10-660MG Tablets (ABBOTT): 30/$53.99 or 90/$145.98

Vicoprofen 7.5-200MG Tablets (ABBOTT): 30/$91.99 or 90/$249.98

Xodol 10-300MG Tablets (SHIONOGI PHARMA): 100/$583.94 or 300/$1,646.45

Zamicet 10-325MG/15ML Solution (HAWTHORN PHARMACEUTICALS): 473/$164.88 or 1419/$468.25

Zydone 10-400MG Tablets (ENDO PHARMACEUTICALS): 30/$31.99 or 90/$83.97

Zydone 5-400MG Tablets (ENDO PHARMACEUTICALS): 30/$27.99 or 90/$65.97

Zydone 7.5-400MG Tablets (ENDO PHARMACEUTICALS): 30/$32.99 or 90/$72.58

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions June 24, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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Only references cited for selected revisions after 1984 are available electronically.

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