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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(oks i MOR fone)
Generic Available (U.S.)
Yes: Tablet
Index Terms
Controlled Substance
C-II
U.S. Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Parenteral: Management of moderate-to-severe acute pain; relief of anxiety in patients with dyspnea associated with pulmonary edema secondary to acute left ventricular failure
Oral, regular release: Management of moderate-to-severe acute pain
Oral, extended release: Management of moderate-to-severe pain in patients requiring around-the-clock opioid treatment for an extended period of time
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were not observed in animal studies; however, decreased fetal weight, decreased litter size, increased stillbirths, and increased neonatal death were noted. Chronic opioid use during pregnancy may lead to a withdrawal syndrome in the neonate. Symptoms include irritability, hyperactivity, loss of sleep pattern, abnormal crying, tremor, vomiting, diarrhea, weight loss, or failure to gain weight.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Some opioids can be found in breast milk. Withdrawal symptoms may be observed in breast-feeding infants when opioid analgesics are discontinued.
Contraindications
Hypersensitivity to oxymorphone, other morphine analogs (phenanthrene derivatives), or any component of the formulation; paralytic ileus (known or suspected); moderate-to-severe hepatic impairment; severe respiratory depression (unless in monitored setting with resuscitative equipment); acute/severe bronchial asthma; hypercarbia
Note: Injection formulation is also contraindicated in the treatment of upper airway obstruction and pulmonary edema due to a chemical respiratory irritant.
Warnings/Precautions
Boxed warnings:
• Abuse/misuse/diversion: See “Other warnings/precautions” below.
• Opana® ER: See “Dosage form specific issues” below.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Hypotension: May cause hypotension; use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or with drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics).
• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxymorphone).
Disease-related concerns:
• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.
• Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease.
• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction; acute pancreatitis may cause constriction of sphincter of Oddi.
• CNS depression/coma: Use with caution in patients with CNS depression or coma.
• Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.
• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.
• Hepatic impairment: Use with caution in patients with mild hepatic dysfunction; use is contraindicated in moderate-to-severe impairment.
• 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 renal impairment.
• Respiratory disease: Use with caution in patients with pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function; critical respiratory depression may occur, even at therapeutic dosages.
• Seizure disorders: Use with caution in patients with seizure disorders.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
• MAO inhibitors: Use not recommended within 14 days of MAO inhibitors; severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose.
Dosage form specific issues:
• Opana® ER: [U.S. Boxed Warnings]: Opana® ER is an extended release oral formulation of oxymorphone and is not suitable for use as an “as needed” analgesic. Tablets should not be broken, chewed, dissolved, or crushed; tablets should be swallowed whole. Opana® ER is intended for use in long-term, continuous management of moderate-to-severe chronic pain. It is not indicated for use in the immediate postoperative period (12-24 hours). [U.S. Boxed Warning]: The coingestion of ethanol or ethanol-containing medications with Opana® ER may result in accelerated release of drug from the dosage form, abruptly increasing plasma levels, which may have fatal consequences.
Other warnings/precautions:
• Abuse/misuse/diversion: [U.S. Boxed Warning]: Healthcare provider should be alert to problems of abuse, misuse, and diversion.
• 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.
• Withdrawal: Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.
Adverse Reactions
Incidence usually on higher end with extended release tablet.
>10%:
Central nervous system: Somnolence (9% to 19%), dizziness (7% to 18%), fever (1% to 14%), headache (7% to 12%)
Dermatologic: Pruritus (8% to 15%)
Gastrointestinal: Nausea (19% to 33%), constipation (4% to 28%), vomiting (9% to 16%)
1% to 10%:
Cardiovascular: Hypotension (<10%), tachycardia (<10%), edema (<10%), flushing (<10%), hypertension (<10%)
Central nervous system: Anxiety (1% to <10%), sedation (1% to <10%), depression (<10%), disorientation (<10%), lethargy (<10%), nervousness (<10%), restlessness (<10%), fatigue (≤4%), insomnia (≤4%), confusion (3%)
Endocrine & metabolic: Dehydration (<10%)
Gastrointestinal: Abdominal distension (<10%), flatulence (1% to <10%), xerostomia (1% to <10%), dyspepsia (<10%), weight loss (<10%), diarrhea (≤4%), abdominal pain (≤3%), appetite decreased (≤3%)
Neuromuscular & skeletal: Weakness (<10%)
Ocular: Blurred vision (<10%)
Respiratory: Hypoxia (<10%), dyspnea (<10%)
Miscellaneous: Diaphoresis (1% to <10%)
<1%, postmarketing, and/or case reports: Agitation, allergic reaction, apnea (injection), atelectasis (injection), biliary colic, bradycardia, bronchospasm (injection), clamminess, dermatitis, diplopia (injection), dysphoria, euphoric mood, hallucination, hot flashes, hypersensitivity, ileus, injection site reaction, micturition difficulty, miosis, oliguria (injection), palpitation, physical and psychological dependence, postural hypotension, respiratory depression, syncope, uretral spasm (injection), urinary retention, urticaria
Drug Interactions
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alvimopan: Analgesics (Opioid) 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
Ammonium Chloride: May increase the excretion of Analgesics (Opioid). Risk C: Monitor therapy
Amphetamines: May enhance the analgesic effect of Analgesics (Opioid). Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Analgesics (Opioid). Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Exceptions: Levocabastine (Nasal). Risk C: Monitor therapy
Desmopressin: Analgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin. 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 (e.g., opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: For patients being treated with hydroxyzine, a reduction in the dose of any other CNS depressants that are to be used in combination is recommended. With concurrent use, monitor patients closely for excessive response to the combination. Risk D: Consider therapy modification
MAO Inhibitors: Oxymorphone may enhance the adverse/toxic effect of MAO Inhibitors. Risk X: Avoid combination
Mixed Agonist / Antagonist Opioids: May diminish the analgesic effect of Analgesics (Opioid). 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 D: Consider therapy modification
Pegvisomant: Analgesics (Opioid) may diminish the therapeutic effect of Pegvisomant. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: Analgesics (Opioid) may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Risk C: Monitor therapy
Succinylcholine: May enhance the bradycardic effect of Analgesics (Opioid). Risk C: Monitor therapy
Thiazide Diuretics: Analgesics (Opioid) may enhance the orthostatic hypotensive effect of Thiazide Diuretics. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Ethanol ingestion with extended-release tablets is specifically contraindicated due to possible accelerated release and potentially fatal overdose. Ethanol may also increase CNS depression; monitor for increased effects with coadministration. Caution patients about effects.
Food: When taken orally with a high-fat meal, peak concentration is 38% to 50% greater. Both immediate-release and extended-release tablets should be taken 1 hour before or 2 hours after eating.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Injection solution, tablet: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect injection from light.
Compatibility
Compatibility in syringe: Compatible: Glycopyrrolate, hydroxyzine, ranitidine.
Mechanism of Action
Oxymorphone hydrochloride is a potent narcotic analgesic with uses similar to those of morphine. The drug is a semisynthetic derivative of morphine (phenanthrene derivative) and is closely related to hydromorphone chemically (Dilaudid®).
Pharmacodynamics/Kinetics
Onset of action: Parenteral: 5-10 minutes
Duration: Analgesic: Parenteral: 3-6 hours
Distribution: Vd: I.V.: 1.94-4.22 L/kg
Protein binding: 10% to 12%
Metabolism: Hepatic via glucuronidation to active and inactive metabolites
Bioavailability: Oral: ~10%
Half-life elimination: Oral: Immediate release: 7-9 hours; Extended release: 9-11 hours
Excretion: Urine (<1% as unchanged drug); feces
Dosage
Adults: Note: Dosage must be individualized.
I.M., SubQ: Initial: 1-1.5 mg; may repeat every 4-6 hours as needed
Labor analgesia: I.M.: 0.5-1 mg
I.V.: Initial: 0.5 mg
Oral:
Immediate release:
Opioid-naive: 10-20 mg every 4-6 hours as needed. Initial dosages as low as 5 mg may be considered in selected patients and/or patients with renal impairment. Dosage adjustment should be based on level of analgesia, side effects, and pain intensity. Initiation of therapy with initial dose >20 mg is not recommended.
Note: The American Pain Society recommends an initial dose of 5-10 mg for adult patients with severe pain.
Currently on stable dose of parenteral oxymorphone: ~10 times the daily parenteral requirement. The calculated amount should be divided and given in 4-6 equal doses.
Currently on other opioids: Use standard conversion chart to convert daily dose to oxymorphone equivalent. Generally start with 1/2 the calculated daily oxymorphone dosage and administered in divided doses every 4-6 hours.
Extended release (Opana® ER):
Opioid-naive: Initial: 5 mg every 12 hours. Supplemental doses of immediate-release oxymorphone may be used as “rescue” medication as dosage is titrated.
Note: Continued requirement for supplemental dosing may be used to titrate the dose of extended-release continuous therapy. Adjust therapy incrementally, by 5-10 mg every 12 hours at intervals of every 3-7 days. Ideally, basal dosage may be titrated to generally mild pain or no pain with the regular use of fewer than 2 supplemental doses per 24 hours.
Currently on stable dose of parenteral oxymorphone: Approximately 10 times the daily parenteral requirement. The calculated amount should be given in 2 divided doses (every 12 hours).
Currently on opioids: Use conversion chart (see "Note") to convert daily dose to oxymorphone equivalent. Generally start with 1/2 the calculated daily oxymorphone dosage. Divide daily dose in 2 (for every 12-hour dosing) and round down to nearest dosage form. Note: Per manufacturer, the following approximate oral dosages are equivalent to oxymorphone 10 mg:
Hydrocodone 20 mg
Oxycodone 20 mg
Methadone 20 mg
Morphine 30 mg
Conversion of stable dose of immediate-release oxymorphone to extended-release oxymorphone: Administer 1/2 of the daily dose of immediate-release oxymorphone (Opana®) as the extended-release formulation (Opana® ER) every 12 hours
Elderly: Initiate dosing at the lower end of the dosage range
Dosing adjustment in renal impairment: Clcr <50 mL/minute: Reduce initial dosage of oral formulations (bioavailability increased 57% to 65%). Begin therapy at lowest dose and titrate carefully.
Dosing adjustment in hepatic impairment: Generally, contraindicated for use in patients with moderate-to-severe liver disease. Initiate with lowest possible dose and titrate slowly in mild impairment.
Administration: Oral
Administer immediate release and extended release tablets 1 hour before or 2 hours after eating. Opana® ER tablet should be swallowed; do not break, crush, or chew.
Administration: I.V. Detail
pH: 2.7-4.5
Monitoring Parameters
Respiratory rate, heart rate, blood pressure, CNS activity
Test Interactions
Some quinolones may produce a false-positive urine screening result for opiates using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opiate screens by more specific methods should be considered. May cause elevation in amylase (due to constriction of the sphincter of Oddi).
Dietary Considerations
Immediate release and extended release tablets should be taken 1 hour before or 2 hours after eating.
Patient Education
May cause physical and/or psychological dependence. Do not break, chew, dissolve, or crush extended release tablets. Swallow whole. While using this medication, do not use alcohol and other prescription or OTC medications (especially sedatives, tranquilizers, antihistamines, or pain medications) without consulting prescriber. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause hypotension, dizziness, drowsiness, impaired coordination, or blurred vision; nausea, vomiting, or dry mouth; or constipation. Report chest pain, slow or rapid heartbeat, dizziness, or persistent headache; confusion or respiratory difficulties; or severe constipation.
Geriatric Considerations
Elderly may be particularly susceptible to the CNS depressant and constipating effects of narcotics. Plasma levels of oxymorphone were about 40% higher in elderly patients as compared to younger patients.
Cardiovascular Considerations
Oxymorphone may cause constipation which may be problematic in patients with unstable angina, and patients after myocardial infarction. The hemodynamic responses to valsalva-like maneuvers due to straining may have adverse cardiovascular consequences in patients with critical coronary artery disease.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation). Anticholinergic side effects can cause a reduction of saliva production or secretion, contributing to discomfort and dental disease (ie, caries, oral candidiasis, and periodontal disease).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness and dizziness are common; may cause nervousness, restlessness or confusion; may rarely cause depression or hallucinations
Mental Health: Effects on Psychiatric Treatment
Psychotropics may alter the analgesic effects of opioids; monitor for change in pain relief
Nursing: Physical Assessment/Monitoring
If used to control diarrhea, monitor stools. Monitor for therapeutic effectiveness at beginning of therapy and periodically thereafter. Monitor blood pressure, CNS and respiratory status, and degree of sedation. Assess patient's physical and/or psychological dependence. For inpatients, implement safety measures to prevent falls. Discontinue slowly after prolonged use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution, as hydrochloride:
Opana®: 1 mg/mL (1 mL)
Tablet, oral, as hydrochloride: 5 mg, 10 mg
Opana®: 5 mg, 10 mg
Tablet, extended release, oral, as hydrochloride:
Opana® ER: 5 mg, 7.5 mg [DSC], 10 mg, 15 mg [DSC], 20 mg, 30 mg, 40 mg
Pricing: U.S. (www.drugstore.com)
Tablet, 12-hour (Opana ER)
5 mg (20): $47.99
7.5 mg (20): $65.99
10 mg (20): $84.99
15 mg (20): $114.99
20 mg (20): $143.99
40 mg (20): $248.98
Tablets (Opana)
5 mg (20): $71.99
References
Adams MP and Ahdieh H, “Pharmacokinetics and Dose-Proportionality of Oxymorphone Extended Release and its Metabolites: Results of a Randomized Crossover Study,” Pharmacotherapy, 2004, 24(4):468-76.
Adams MP and Ahdieh H, “Single- and Multiple-Dose Pharmacokinetic and Dose-Proportionality Study of Oxymorphone Immediate-Release Tablets,” Drugs R D, 2005, 6(2):91-9.
“Drugs for Pain,” Med Lett Drugs Ther, 2000, 42(1085):73-8.
Gabrail NY, Dvergsten C, and Ahdieh H, “Establishing the Dosage Equivalency of Oxymorphone Extended Release and Oxycodone Controlled Release in Patients With Cancer Pain: A Randomized Controlled Study,” Curr Med Res Opin, 2004, 20(6):911-8.
Gimbel J and Ahdieh H, “The Efficacy and Safety of Oral Immediate-Release Oxymorphone for Postsurgical Pain,” Anesth Analg, 2004, 99(5):1472-7.
Gimbel J, Walker D, Ma T, et al, “Efficacy and Safety of Oxymorphone Immediate Release for the Treatment of Mild to Moderate Pain After Ambulatory Orthopedic Surgery: Results of a Randomized, Double-Blind, Placebo-Controlled Trial,” Arch Phys Med Rehabil, 2005, 86(12):2284-9
Matsumoto AK, Babul N, and Ahdieh H, “Oxymorphone Extended-Release Tablets Relieve Moderate to Severe Pain and Improve Physical Function in Osteoarthritis: Results of a Randomized, Double-Blind, Placebo- and Active-Controlled Phase III Trial,” Pain Med, 2005, 6(5):357-66.
McIlwain H and Ahdieh H, “Safety, Tolerability, and Effectiveness of Oxymorphone Extended Release for Moderate to Severe Osteoarthritis Pain: A One-Year Study,” Am J Ther, 2005, 12(2):106-12.
“Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain,” 6th ed, Glenview, IL: American Pain Society, 2008.
Prommer E, “Oxymorphone: A Review,” Support Care Cancer, 2006, 14(2):109-15.
Rathmell JP, Viscomi CM, and Ashburn MA, “Management of Nonobstetric Pain During Pregnancy and Lactation,” Anesth Analg, 1997, 85(5):1074-87.
Sinatra RS and Harrison DM, “Oxymorphone in Patient-Controlled Analgesia,” Clin Pharm, 1989, 8(8):541, 544.
Zacher JL and Givone DM, “False-Positive Urine Opiate Screening Associated With Fluoroquinolone Use,” Ann Pharmacother, 2004, 38:1525-28.
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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