Oxymorphone Hydrochloride

Pronunciation

Class: Opiate Agonists
VA Class: CN101
CAS Number: 357-07-3
Brands: Opana

Warning(s)

  • Abuse Potential
  • Schedule II controlled substance with abuse liability similar to morphine.c

  • Potential for abuse in a manner similar to other legal or illicit opiates.c Consider abuse potential when prescribing or dispensing oxymorphone extended-release tablets in situations where the clinician or pharmacist is concerned about increased risk of misuse, abuse, or diversion.c

  • Intended Uses of Extended-release Tablets
  • Oxymorphone hydrochloride extended-release tablets are indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.c

  • Oxymorphone hydrochloride extended-release tablets are not intended for use as a prn analgesic.c

  • Overdose Risk with Improper Administration of Extended-release Tablets
  • Oxymorphone hydrochloride extended-release tablets are to be swallowed whole and are not to be broken, chewed, dissolved, or crushed.c

  • Chewing, crushing, or dissolving the extended-release tablets could result in rapid release and absorption of a potentially fatal dose of oxymorphone.c

  • Do not consume alcoholic beverages or prescription or nonprescription preparations containing alcohol during therapy with extended-release tablets.c Consuming alcohol while receiving extended-release tablets could result in increased plasma concentrations of oxymorphone and a potentially fatal dose of the drug.c

Introduction

Opiate agonist; phenanthrene derivative.a b c d e

Uses for Oxymorphone Hydrochloride

Acute and Chronic Pain

Relief of moderate to severe pain.b c d

Symptomatic relief of moderate to moderately severe pain such as that associated with acute and some chronic medical disorders including renal or biliary colic, acute trauma, postoperative pain, and cancer.e

Consider around-the-clock dosing of analgesics in the initial stages of acute pain to avoid wide swings in pain and sedation often associated with as-needed dosing regimens.e

In the management of chronic pain associated with a terminal illness such as cancer, the principal goal of analgesic therapy is to make the patient relatively pain-free while maintaining as good a quality of life as possible.e

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Analgesic therapy must be individualized and titrated according to patient response and tolerance.b c d e

Extended-release tablets (Opana ER) are used orally for management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.c The extended-release tablets are not intended for use on an as-needed (“prn”) basis, for preoperative administration to control postoperative pain, for pain in the immediate postoperative period (12–24 hours after surgery) in patients not previously exposed to opiates, or for postoperative pain that is expected to be mild or of short duration.c Patients who were receiving this preparation prior to surgery may reinitiate such use after they are able to resume oral therapy.c Extended-release tablets may be used postoperatively if pain is expected to be moderate to severe and persist for an extended period of time.c

Surgery

Used parenterally as a supplement to anesthesia.a d

Analgesia During Labor

Used parenterally for analgesia during labor.d

Acute Pulmonary Edema

Used in patients with acute pulmonary edema for its cardiovascular effects and to allay anxiety.a d e Should not be used in the treatment of pulmonary edema resulting from a chemical respiratory irritant.d

Oxymorphone Hydrochloride Dosage and Administration

Administration

Administer orally,b c or by sub-Q, IM, or IV injection.a d

Oral Administration

Administer orally as conventional tablets or extended-release tablets.b c

Administer conventional and extended-release tablets on an empty stomach, at least 1 hour before or 2 hours after food.b c Food affects oral absorption.b c (See Food under Pharmacokinetics.)

Extended-release tablets: Swallow tablets whole; do not divide, crush, or chew.c Do not administer with alcohol.c (See Boxed Warning.)

IV Administration

Administer by direct IV injection.e

When administered IV, an opiate antagonist and facilities for administration of oxygen and control of respiration should be available.a e

Dosage

Available as oxymorphone hydrochloride; dosage expressed in terms of the salt.b c

Give the smallest effective dose as infrequently as possible to minimize the development of tolerance and physical dependence.a

Individualize dosage according to clinical status of the patient, desired therapeutic effect, degree of existing opiate tolerance, and age and weight; assess dosage at periodic intervals.b c d

Reduce dosage in poor-risk patients, in geriatric patients, and in patients receiving other CNS depressants.a (See Specific Drugs under Interactions)

Avoid abrupt withdrawal from relatively high dosages (e.g., in chronic pain patients) since precipitation of severe abstinence syndrome is likely.b c d

Extended-release tablets usually are administered twice daily in 2 equally divided doses; an asymmetric daily dosing regimen (i.e., different dose in the morning than in the evening) may be appropriate in some patients, depending on the pain pattern.c

Adults

Pain (Oral Treatment)
Conventional Tablets
Oral

Opiate-naive patients: Usually, initiate with 10–20 mg every 4–6 hours as needed.b Alternatively, use 5 mg every 4–6 hours.b Do not initiate with doses >20 mg.b Adjust according to response and tolerance.b

Switching from Parenteral Oxymorphone to Conventional Tablets
Oral

Calculate the total daily dosage of the parenteral preparation, multiply by a factor of 10 and administer as conventional tablets in 4 or 6 equally divided doses.b For example, 10 mg of oral oxymorphone hydrochloride given every 6 hours as conventional tablets can be substituted for a total daily IM oxymorphone hydrochloride dosage of 4 mg.b

Extended-release Tablets
Oral

Opiate-naive patients: Initiate with 5 mg every 12 hours.c Adjust according to response and tolerance.c Titrate in increments of 5–10 mg every 12 hours every 3–7 days to provide adequate analgesia.c

Switching from Conventional Oxymorphone Tablets to Extended-release Tablets
Oral

Calculate the total daily dosage of the conventional preparation and give as extended-release tablets in 2 divided doses at 12-hour intervals.c

Switching from Parenteral Oxymorphone to Extended-release Tablets
Oral

Calculate the total daily dosage of the parenteral preparation, multiply by a factor of 10 and administer as extended-release tablets in 2 equally divided doses.c For example, 20 mg of oral oxymorphone hydrochloride given every 12 hours as extended-release tablets can be substituted for a total daily IM oxymorphone hydrochloride dosage of 4 mg.c

Monitor closely to ensure adequate analgesia and to minimize side effects.c

Switching from Other Oral Opiates to Extended-release Tablets
Oral

The equivalent total daily dosage of oxymorphone hydrochloride should be calculated based on standard conversion factors suggested by the manufacturer (table below); initiate therapy with oxymorphone hydrochloride extended-release tablets by administering half the calculated dose in 2 divided doses at 12-hour intervals.c Titrate dosage to provide adequate analgesia.c

If patients are on a regimen of several opiates, calculate the approximate oral oxymorphone dose for each opiate and add the totals to estimate the total daily oxymorphone hydrochloride dosage.c

Converting Daily Opiate Dosages to Oxymorphone Hydrochloride Extended-release Tablets (mg/day prior opiate × factor = approximate mg/day oral oxymorphone hydrochloride)c

Prior Opiate

Approximate Oral Equivalent Dose

Factor Oral

Oxymorphone

10 mg

1

Hydrocodone

20 mg

0.5

Oxycodone

20 mg

0.5

Methadone

20 mg

0.5

Morphine

30 mg

0.333

Table to be used only for conversion to oxymorphone extended-release tablets.c

Refer to published relative potency information, keeping in mind that conversion ratios are only approximate.c

When converting from methadone to oxymorphone, monitor patients closely. c

Pain (Parenteral Routes)
IV

Initially, 0.5 mg.d Adjust according to response and tolerance.d

Sub-Q or IM

1–1.5 mg every 4 to 6 hours as necessary.d

Analgesia During Labor
IM

0.5–1 mg.d

Prescribing Limits

Adults

Oral

Conventional tablet: Maximum initial dose is 20 mg.b

Special Populations

Hepatic Impairment

In patients with mild hepatic impairment, initiate with lowest dosage and increase dose slowly.b c d (See Contraindications.)

Renal Impairment

In patients with Clcr <50 mL/minute, reduce dosage.b c d (See Special Populations under Pharmacokinetics.)

Geriatric Patients

Select dosage with caution; use lower than usual initial dosages.b c d (See Geriatric Use under Cautions and see Special Populations under Pharmacokinetics.)

Cautions for Oxymorphone Hydrochloride

Contraindications

  • Known hypersensitivity to oxymorphone, morphine analogs such as codeine, or any ingredient in the formulation.b c d

  • Respiratory depression in the absence of resuscitative equipment.b c d

  • Acute or severe asthma or hypercarbia.b c d

  • Known or suspected paralytic ileus.b c d

  • Moderate or severe hepatic impairment.b c d

  • Extended-release preparation contraindicated in the management of immediate postoperative pain (first 12–24 hours following surgery), in patients with mild pain, and in those who are expected to require analgesia for a short period of time.c

  • Parenteral use contraindicated in the treatment of pulmonary edema resulting from a chemical respiratory irritant.d

Warnings/Precautions

Warnings

Dependence and Abuse

Possible tolerance, psychologic dependence, and physical dependence following prolonged administration.b c Use only with careful surveillance in patients with a history of drug or alcohol dependence or abuse.b c Clinicians should consider abuse potential when prescribing or dispensing oxymorphone in situations where they are concerned about an increased risk of misuse, abuse, or diversion.d However, concerns about abuse, addiction, and diversion should not prevent the proper management of pain.c d

Oxymorphone tablets can be abused by crushing, chewing, “snorting” the powder, or dissolving the contents in water and injecting.c d

Breaking, chewing, or crushing of extended-release tablets results in immediate release of the opiate and the risk of a potentially fatal overdose.c (See Boxed Warning.)

Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms.b c d After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.b c d

Health-care professionals should contact the professional licensing board or controlled substance authority in their states for information about prevention and detection of abuse or diversion.c d

Respiratory Depression

The major toxicity associated with oxymorphone.c d e

Occurs most frequently in geriatric or debilitated patients and in those with conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic opiate dosages may dangerously decrease pulmonary ventilation.c d e

Use with extreme caution in patients with hypoxia, hypercapnia, or substantially decreased respiratory reserve (e.g., asthma, COPD, cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression, coma).c d e In such patients, even therapeutic oxymorphone doses may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.c d e Consider use of non-opiate analgesics.c d e Use oxymorphone only with careful medical supervision and at lowest effective dosage.c d e

Interactions with Other CNS Depressants

Additive depressant effects may occur with concomitant use of other CNS depressants including other opiates, sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers, illicit drugs associated with CNS depression, and alcohol.c d e (See Specific Drugs under Interactions.)

Hypoventilation, hypotension, and profound sedation or coma may occur.c d e

Head Injury and Increased Intracranial Pressure

Respiratory depressant effects of oxymorphone (with CO2 retention and secondary elevation of CSF pressure) may be markedly exaggerated in the presence of head injury, other intracranial lesions, or preexisting increase in intracranial pressure.c d e

Opiates produce effects (e.g., pupillary changes) that may obscure neurologic signs of further increase in pressure in patients with head injuries.c d e

Hypotensive Effects

Possible severe hypotension in individuals whose ability to maintain their BP is compromised by depleted blood volume or concomitant drugs that compromise vasculature tone (e.g., phenothiazines, general anesthetics).b c d e

Use with caution in patients in circulatory shock, because vasodilation produced by the drug may further reduce cardiac output and BP.b c d

General Precautions

Acute Abdominal Conditions

Administration may complicate assessment of patients with acute abdominal conditions.b c d (See GI Effects under Cautions.)

Seizures

May aggravate preexisting seizures in patients with seizure disorders.c d e May induce seizures.b c d

Debilitated and Special-Risk Patients.

Use with caution in debilitated patients, those sensitive to CNS depressants, patients with Addison's disease, CNS depression or coma, kyphoscoliosis, myxedema or hypothyroidism, prostatic hypertrophy, urethral stricture, severe impairment of pulmonary function, toxic psychosis, acute alcoholism, delirium tremens, or following GI surgery.b c d

Pancreatic and Biliary Disease

May cause spasm of the sphincter of Oddi.b c d Use with caution in patients with biliary tract disease, including acute pancreatitis, and patients undergoing biliary tract surgery.b c d

GI Effects

Monitor for decreased bowel motility in post-operative patients.b c d (See Acute Abdominal Conditions under Cautions.)

Contraindicated in patients with known or suspected paralytic ileus.b c d

Specific Populations

Pregnancy

Category C.b c d

Use parenteral preparation with caution during labor.d Administration during labor may cause neonatal respiratory depression.d An opiate antagonist and resuscitative equipment for reversal of opiate-induced respiratory depression should be readily available when opiates are administered during labor and delivery.d

Use of oxymorphone tablets and extended-release tablets not recommended during or immediately prior to labor.b c

Infants born to women regularly taking opiates during pregnancy may be physically dependent.b c d

Lactation

Not known whether oxymorphone is distributed into human milk.b c d Women receiving oxymorphone generally should not nurse.b c d

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.b c d

Geriatric Use

No substantial difference in efficacy of oral preparations in geriatric patients relative to younger adults.b c Dizziness, somnolence, confusion, nausea reported more frequently in geriatric adults than in younger adults.b c

Following oral administration, plasma concentrations of oxymorphone are higher in geriatric patients ≥65 years of age than in younger patients.b c d (See Special Populations under Pharmacokinetics.)

Parenteral preparation not systematically evaluated in geriatric adults.d

Select dose with caution, starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.b c d

Hepatic Impairment

Use with caution in patients with mild hepatic impairment.b c d (See Hepatic Impairment under Dosage and Administration.)

Contraindicated in patients with moderate or severe hepatic impairment.b c d

Renal Impairment

Use with caution in patients with moderate or severe renal impairment.b c d Dosage adjustment needed in these patients.b c d (See Renal Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Common Adverse Effects

Nausea, constipation, pyrexia, somnolence, vomiting, pruritus, headache, dizziness, confusion.b c d

Interactions for Oxymorphone Hydrochloride

Specific Drugs

Drug

Interaction

Comments

Alcohol

Additive CNS effectsb c d

Oxymorphone extended-release tablets: Increased or decreased plasma oxymorphone concentrations reportedc

Avoid concomitant useb c

Anticholinergic agents

Increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileusb c d

Cimetidine

Adverse CNS effects (confusion, disorientation, respiratory depression, apnea, seizures) reported with opiatesb c d

Cautionb c d

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

Additive CNS effects.b d

Reduce dosage of one or both agents; initiate oxymorphone therapy using (1/3) to ½ the usual doseb c d

MAO inhibitors

Use with cautionb c d

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

Possible reduced analgesic effect and/or withdrawal symptomsb c d

Avoid concomitant useb c d

Oxymorphone Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is 10%.b c

Onset

5–10 minutes following IV administration.a d

10–15 minutes following sub-Q or IM administration.a

Duration

3–6 hours following parenteral administration.a d

Food

Conventional tablets with high-fat meal: Peak plasma concentration and AUC increase 38%.b

Extended-release tablets with food: Peak plasma concentrations increase 50%; time to peak plasma concentrations delayed; no change in AUC or small increase.c

Special Populations

Oxymorphone extended-release tablets: Bioavailability increased 26, 57, or 65% in patients with mild (Clcr 51–80 mL/minute), moderate (Clcr 30–50 mL/minute), or severe renal impairment (Clcr <30 mL/minute), respectively.c

Oxymorphone extended-release tablets: Based on information from a few individuals with hepatic impairment, bioavailability increased 1.6-, 3.7-, or 12.2-fold in patients with mild, moderate, or severe hepatic impairment, respectively.c

Oxymorphone extended-release tablets: Plasma concentrations increased 40% in geriatric individuals.c

Distribution

Plasma Protein Binding

10–12%.b c

Elimination

Metabolism

Extensively metabolized in the liver; undergoes reduction or conjugation with glucuronic acid to form oxymorphone-3-glucuronide and 6-OH-oxymorphone.b c d

Elimination Route

33–38% excreted in the urine as oxymorphone-3-glucuronide, <1% excreted in urine as 6-OH-oxymorphone, <1% excreted unchanged in the urine.b c d

Half-life

Extended-release tablets: 9.4–11.3 hours.c

Stability

Storage

Oral

Conventional Tablets

Tight container at 25°C (may be exposed to 15–30°C).b

Extended-release Tablets

Tight container at 25°C (may be exposed to 15–30°C).c

Parenteral

Injection

25°C (may be exposed to 15°–30°C).d Protect from light.d

Actions

  • A potent analgesic; shares the actions of the opiate agonists.b c d

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

  • 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).e

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

  • 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.e

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

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

  • 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.e

Advice to Patients

  • Importance of not breaking, crushing, or chewing extended-release tablets; potentially fatal overdose can occur.c

  • Conventional and extended-release tablets: Advise patients to take tablets on an empty stomach, at least 1 hour before or 2 hours after food.b c

  • Importance of taking only as prescribed; do not increase dosage or abruptly discontinue without consulting a clinician.b c d

  • Advise patients to report any episodes of breakthrough pain or adverse experiences to their clinician.b c d

  • Advise patients that oxymorphone should not be combined with alcohol or other CNS depressants (e.g., sleep medications, tranquilizers).b c d

  • Potential for severe constipation.b c d Counsel patients on appropriate laxatives and/or stool softeners and other therapeutic approaches.b c d

  • Importance of informing patients that oxymorphone may impair mental and/or physical ability required for performance of potentially hazardous tasks; avoid driving or operating heavy machinery until effects on individual are known.b c d

  • Risk of dizziness and other adverse events.b c d

  • Importance of informing patients that this is a drug of potential abuse and should be protected from theft.b c d

  • Importance of informing patients that this medication should never be given to anyone other than the individual for whom it was prescribed.b c d

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.b c d

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.b c d

  • Importance of informing patients of other important precautionary information.b c d (See Cautions.)

Preparations

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

Oxymorphone hydrochloride is subject to control under the Federal Controlled Substances Act of 1970 as a schedule II (C-II) drug.

Oxymorphone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

5 mg

Opana (C-II)

Endo

10 mg

Opana (C-II)

Endo

Tablet, extended-release

5 mg

Opana ER (C-II)

Endo

10 mg

Opana ER (C-II)

Endo

20 mg

Opana ER (C-II)

Endo

40 mg

Opana ER (C-II)

Endo

Parenteral

Injection

1 mg/mL

Opana (C-II; preservative-free)

Endo

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2013. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Opana 5MG Tablets (ENDO PHARMACEUTICALS): 20/$71.99 or 30/$105.97

Opana ER 10MG 12-hr Tablets (ENDO PHARMACEUTICALS): 20/$84.99 or 30/$127.49

Opana ER 15MG 12-hr Tablets (ENDO PHARMACEUTICALS): 20/$114.99 or 30/$170.97

Opana ER 20MG 12-hr Tablets (ENDO PHARMACEUTICALS): 20/$145.99 or 30/$217.97

Opana ER 40MG 12-hr Tablets (ENDO PHARMACEUTICALS): 20/$250.00 or 30/$373.97

Opana ER 5MG 12-hr Tablets (ENDO PHARMACEUTICALS): 20/$47.99 or 30/$71.98

Opana ER 7.5MG 12-hr Tablets (ENDO PHARMACEUTICALS): 20/$65.99 or 30/$93.99

Opana ER (Crush Resistant) 40MG 12-hr Tablets (ENDO PHARMACEUTICALS): 20/$269.99 or 30/$404.99

Oxymorphone HCl 10MG Tablets (ROXANE): 20/$100.00 or 30/$150.00

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2013, Selected Revisions November 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS drug information 2007. McEvoy GK, ed. Oxymorphone. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2154-5.

b. Endo Pharmaceuticals Inc. Opana (oxymorphone hydrochloride) tablets prescribing information. Chadds Ford, PA; 2006 Jul.

c. Endo Pharmaceuticals Inc. Opana ER (oxymorphone hydrochloride) extended-release tablets prescribing information. Chadds Ford, PA; 2007 June.

d. Endo Pharmaceuticals Inc. Opana (oxymorphone hydrochloride) injection prescribing information. Chadds Ford, PA; 2006 Sept.

e. AHFS drug information 2007. McEvoy GK, ed. Opioid Agonists General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2007:2123-8.

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