Brand name: Opana
Drug class: Opiate Agonists
VA class: CN101
CAS number: 357-07-3

Medically reviewed by Drugs.com on Apr 19, 2023. Written by ASHP.

Introduction

Opiate agonist; phenanthrene derivative.^{500 501 502 a e}

Uses for oxyMORphone

Acute and Chronic Pain

Relief of moderate to severe pain.^{500 501 502}

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

Extended-release tablets 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.⁵⁰¹ The extended-release tablets are not intended for use on an as-needed (“prn”) basis.⁵⁰¹

In symptomatic treatment of acute pain, reserve opiate analgesics for pain resulting from severe injuries, severe medical conditions, or surgical procedures, or when nonopiate alternatives for relieving pain and restoring function are expected to be ineffective or are contraindicated.^{431 432 433 435} Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435} Optimize concomitant use of other appropriate therapies.^{432 434 435} (See Managing Opiate Therapy for Acute Pain under Dosage and Administration.)

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

Generally use opiates for management of chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing^{410 411 412 413} ) that is not associated with active cancer treatment, palliative care, or end-of-life care only if other appropriate nonpharmacologic and nonopiate pharmacologic strategies have been ineffective and expected benefits for both pain relief and functional improvement are anticipated to outweigh risks.^{411 412 413 414 422 429}

If used for chronic pain, opiate analgesics should be part of an integrated approach that also includes appropriate nonpharmacologic modalities (e.g., cognitive-behavioral therapy, relaxation techniques, biofeedback, functional restoration, exercise therapy, certain interventional procedures) and other appropriate pharmacologic therapies (e.g., nonopiate analgesics, analgesic adjuncts such as selected anticonvulsants and antidepressants for certain neuropathic pain conditions).^{411 412 413 422 429}

Available evidence insufficient to determine whether long-term opiate therapy for chronic pain results in sustained pain relief or improvements in function and quality of life^{411 423 431 432 436} or is superior to other pharmacologic or nonpharmacologic treatments.⁴³² Use is associated with serious risks (e.g., opiate use disorder [OUD], overdose).^{411 431 436} (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

Surgery

Used parenterally as a supplement to anesthesia.^{502 a}

Analgesia During Labor

Used parenterally for analgesia during labor.⁵⁰²

Acute Pulmonary Edema

Used in patients with acute pulmonary edema for its cardiovascular effects and to allay anxiety.^{502 a e} Should not be used in the treatment of pulmonary edema resulting from a chemical respiratory irritant.⁵⁰²

oxyMORphone Dosage and Administration

General

Managing Opiate Therapy for Acute Pain

• Optimize concomitant use of other appropriate therapies.^{432 434 435}

• When opiate analgesia required, use conventional (immediate-release) opiates in smallest effective dosage and for shortest possible duration, since long-term opiate use often begins with treatment of acute pain.^{411 431 434 435}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Depression under Cautions.)

• When sufficient for pain management, use lower-potency opiate analgesics given in conjunction with acetaminophen or an NSAIA on as-needed (“prn”) basis.⁴³²

• For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435} Do not prescribe larger quantities for use in case pain continues longer than expected;^{411 432} instead, reevaluate patient if severe acute pain does not remit.^{411 431 435}

• For moderate to severe postoperative pain, provide opiate analgesic as part of a multimodal regimen that also includes acetaminophen and/or NSAIAs and other pharmacologic (e.g., certain anticonvulsants, regional local anesthetic techniques) and nonpharmacologic therapy as appropriate.^{430 431 432}

• Oral administration of conventional opiate analgesics generally preferred over IV administration in postoperative patients who can tolerate oral therapy.^{430 431}

• Scheduled (around-the-clock) dosing frequently is required during immediate postoperative period or following major surgery.^{430 432} When repeated parenteral administration is required, IV patient-controlled analgesia (PCA) generally is recommended.^{430 431}

Managing Opiate Therapy for Chronic Noncancer Pain

• Although specific recommendations may vary, common elements in clinical guideline recommendations include risk mitigation strategies, upper dosage thresholds, careful dosage titration, and consideration of risks associated with particular opiates and formulations, coexisting diseases, and concomitant drug therapy.^{410 411 414 415 423}

• Prior to initiating therapy, thoroughly evaluate patient; assess risk factors for misuse, abuse, and addiction;^{411 412 413 415 422 429} establish treatment goals (including realistic goals for pain and function); and consider how therapy will be discontinued if benefits do not outweigh risks.^{411 415}

• Regard initial opiate therapy for chronic noncancer pain as a therapeutic trial that will be continued only if there are clinically meaningful improvements in pain and function that outweigh treatment risks.^{411 412 413}

• Prior to and periodically during therapy, discuss with patients known risks and realistic benefits and patient and clinician responsibilities for managing therapy.^{411 412 413 414 415}

• Some experts recommend initiating opiate therapy for chronic noncancer pain with conventional (immediate-release) opiate analgesics prescribed at lowest effective dosage.^{411 415} Individualize opiate selection, initial dosage, and dosage titration based on patient’s health status, prior opiate use, attainment of therapeutic goals, and predicted or observed harms.^{412 413}

• Evaluate benefits and harms within 1–4 weeks following initiation of therapy or dosage increase^{411 413} and reevaluate on ongoing basis (e.g., at least every 3 months⁴¹¹ ) throughout therapy.^{411 412 413} Document pain intensity and level of functioning and assess progress toward therapeutic goals, presence of adverse effects, and adherence to prescribed therapies.^{412 413 422 423} Anticipate and manage common adverse effects (e.g., constipation, nausea and vomiting, cognitive and psychomotor impairment).^{412 413 415} If benefits do not outweigh harms, optimize other therapies and taper opiate to lower dosage or taper and discontinue opiate.^{411 412 413 415}

• When repeated dosage increases required, evaluate potential causes and reassess relative benefits and risks.^{412 413} Although evidence is limited, some experts state that opiate rotation may be considered in patients with intolerable adverse effects or inadequate benefit despite dosage increases.^{412 413 415}

• Higher dosages require particular caution,^{410 412 415} including more frequent and intensive monitoring or referral to specialist.^{411 412 413} Greater benefits of high-dose opiates for chronic pain not established in controlled clinical studies; higher dosages associated with increased risks (motor vehicle accidents, overdosage, OUD).^{411 415 423 424 425 426}

• CDC states that primary care clinicians should carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately ≥17 mg of oxymorphone hydrochloride daily) for chronic pain and should avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately ≥30 mg of oxymorphone hydrochloride daily) or carefully justify decision to prescribe such dosages.⁴¹¹ Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.^{423 431} Some states have established opiate dosage thresholds (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with specialist is mandated or recommended)^{411 420 421 423} or have mandated risk-management strategies (e.g., review of state prescription drug monitoring program [PDMP] data prior to prescribing).^{411 419 423}

• Recommended strategies for managing risks include written treatment agreements or plans (e.g., “contracts”), urine drug testing, review of state PDMP data, and risk assessment and monitoring tools.^{410 411 412 413 414 415 422 423 429}

• Taper and discontinue opiate therapy if patient engages in serious or repeated aberrant drug-related behaviors or drug abuse or diversion.^{412 413 415} Offer or arrange treatment for patients with OUD.^{411 412 413}

• Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ (See Respiratory Depression under Cautions.)

Administration

Administer orally^{500 501} or by sub-Q, IM, or IV injection.^{502 a}

Oral Administration

Administer orally as conventional tablets or extended-release tablets.^{500 501}

Administer conventional and extended-release tablets on an empty stomach, at least 1 hour before or 2 hours after food.^{500 501} Food affects oral absorption.^{500 501} (See Food under Pharmacokinetics.)

Extended-release tablets: Swallow tablets whole; do not divide, crush, or chew.⁵⁰¹ Do not administer with alcohol.⁵⁰¹ (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}

IM Administration

IM administration of opiate analgesics is discouraged; IM injections can cause pain and are associated with unreliable absorption, resulting in inconsistent analgesia.⁴³⁰

Dosage

Available as oxymorphone hydrochloride; dosage expressed in terms of the salt.^{500 501}

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.^{411 413 431 432 435}

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.^{500 501 502}

Reduce dosage in poor-risk patients and in geriatric patients.^a

When switching patients receiving chronic opiate therapy from one opiate analgesic to another, generally reduce the calculated equianalgesic dosage of the new opiate agonist by about 25–50% to avoid inadvertent overdosage.^{410 412} This calculation does not apply when switching to methadone; consult specific recommendations for methadone dosage.⁴¹²

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy.^{700 703} (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.^{500 501 502}

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.⁵⁰¹

Adults

Pain (Oral Treatment)

Conventional Tablets

Oral

Opiate-naive patients: Usually, initiate with 10–20 mg every 4–6 hours as needed.⁵⁰⁰ Alternatively, use 5 mg every 4–6 hours.⁵⁰⁰ Do not initiate with doses >20 mg.⁵⁰⁰ Adjust according to response and tolerance.⁵⁰⁰

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.⁵⁰⁰ 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.⁵⁰⁰

Extended-release Tablets

Oral

Opiate-naive patients: Initiate with 5 mg every 12 hours.⁵⁰¹ Adjust according to response and tolerance.⁵⁰¹ Titrate in increments of 5–10 mg every 12 hours every 3–7 days to provide adequate analgesia.⁵⁰¹

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.⁵⁰¹

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.⁵⁰¹ 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.⁵⁰¹

Monitor closely to ensure adequate analgesia and to minimize side effects.⁵⁰¹

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.⁵⁰¹ Titrate dosage to provide adequate analgesia.⁵⁰¹

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.⁵⁰¹

Table to be used only for conversion to oxymorphone extended-release tablets.⁵⁰¹

Refer to published relative potency information, keeping in mind that conversion ratios are only approximate.⁵⁰¹

When converting from methadone to oxymorphone, monitor patients closely.⁵⁰¹

Pain (Parenteral Routes)

IV

Initially, 0.5 mg.⁵⁰² Adjust according to response and tolerance.⁵⁰²

Sub-Q or IM

1–1.5 mg every 4 to 6 hours as necessary.⁵⁰²

Analgesia During Labor

IM

0.5–1 mg.⁵⁰²

Prescribing Limits

Adults

Oral

Conventional tablet: Maximum initial dose is 20 mg.⁵⁰⁰

For acute pain not related to trauma or surgery, limit prescribed quantity to amount needed for the expected duration of pain severe enough to require opiate analgesia (generally ≤3 days and rarely >7 days).^{411 433 434 435}

CDC recommends that primary care clinicians carefully reassess individual benefits and risks before prescribing dosages equivalent to ≥50 mg of morphine sulfate daily (approximately 17 mg of oxymorphone hydrochloride daily) for chronic pain and avoid dosages equivalent to ≥90 mg of morphine sulfate daily (approximately 30 mg of oxymorphone hydrochloride daily) or carefully justify their decision to prescribe such dosages.⁴¹¹ Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.^{423 431}

Some states have set prescribing limits (e.g., maximum daily dosages that can be prescribed, dosage thresholds at which consultation with a specialist is mandated or recommended).^{411 420 421 423}

Special Populations

Hepatic Impairment

In patients with mild hepatic impairment, initiate with lowest dosage and increase dose slowly.^{500 501 502} (See Contraindications.)

Renal Impairment

In patients with Cl_cr <50 mL/minute, reduce dosage.^{500 501 502} (See Special Populations under Pharmacokinetics.)

Geriatric Patients

Select dosage with caution; use lower than usual initial dosages.^{500 501 502} (See Geriatric Use under Cautions and see Special Populations under Pharmacokinetics.)

Cautions for oxyMORphone

Contraindications

• Known hypersensitivity to oxymorphone, morphine analogs such as codeine, or any ingredient in the formulation.^{500 501 502}

• Respiratory depression in the absence of resuscitative equipment.^{500 501 502}

• Acute or severe asthma or hypercarbia.^{500 501 502}

• Known or suspected paralytic ileus.^{500 501 502}

• Moderate or severe hepatic impairment.^{500 501 502}

• 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.⁵⁰¹

• Parenteral use contraindicated in the treatment of pulmonary edema resulting from a chemical respiratory irritant.⁵⁰²

Warnings/Precautions

Warnings

Dependence and Abuse

Possible tolerance, psychologic dependence, and physical dependence following prolonged administration.^{500 501} Use only with careful surveillance in patients with a history of drug or alcohol dependence or abuse.^{500 501} 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.⁵⁰² However, concerns about abuse, addiction, and diversion should not prevent the proper management of pain.^{501 502}

Oxymorphone tablets can be abused by crushing, chewing, “snorting” the powder, or dissolving the contents in water and injecting.^{501 502}

Breaking, chewing, or crushing of extended-release tablets results in immediate release of the opiate and the risk of a potentially fatal overdose.⁵⁰¹ (See Boxed Warning.)

Abrupt cessation of therapy or sudden reduction in dosage after prolonged use may result in withdrawal symptoms.^{500 501 502} After prolonged exposure to opiate analgesics, if withdrawal is necessary, it must be undertaken gradually.^{500 501 502}

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.^{501 502}

Respiratory Depression

The major toxicity associated with oxymorphone.^{501 502 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.^{501 502 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).^{501 502 e} In such patients, even therapeutic oxymorphone doses may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea.^{501 502 e} Consider use of non-opiate analgesics.^{501 502 e} Use oxymorphone only with careful medical supervision and at lowest effective dosage.^{501 502 e}

Routinely discuss availability of the opiate antagonist naloxone with all patients receiving new or reauthorized prescriptions for opiate analgesics, including oxymorphone.⁷⁵⁰

Consider prescribing naloxone for patients receiving opiate analgesics who are at increased risk of opiate overdosage (e.g., those receiving concomitant therapy with benzodiazepines or other CNS depressants, those with history of opiate or substance use disorder, those with medical conditions that could increase sensitivity to opiate effects, those who have experienced a prior opiate overdose)^{411 431 750} or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage.⁷⁵⁰ Even if patients are not receiving an opiate analgesic, consider prescribing naloxone if the patient is at increased risk of opiate overdosage (e.g., those with current or past diagnosis of OUD, those who have experienced a prior opiate overdose).⁷⁵⁰

Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opiates, including oxymorphone, and benzodiazepines or other CNS depressants (e.g., anxiolytics, sedatives, hypnotics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opiate agonists, alcohol) may result in profound sedation, respiratory depression, coma, and death.^{416 417 418 700 701 702 703} Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.^{416 417 418 435 700 701}

Reserve concomitant use of oxymorphone and other CNS depressants for patients in whom alternative treatment options are inadequate.^{700 703} (See Specific Drugs under Interactions.)

Adrenal Insufficiency

Adrenal insufficiency reported in patients receiving opiate agonists or opiate partial agonists.⁴⁰⁰ Manifestations are nonspecific and may include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and hypotension.⁴⁰⁰

If adrenal insufficiency is suspected, perform appropriate laboratory testing promptly and provide physiologic (replacement) dosages of corticosteroids; taper and discontinue the opiate agonist or partial agonist to allow recovery of adrenal function.⁴⁰⁰ If the opiate agonist or partial agonist can be discontinued, perform follow-up assessment of adrenal function to determine if corticosteroid replacement therapy can be discontinued.⁴⁰⁰ In some patients, switching to a different opiate improved symptoms.⁴⁰⁰

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.^{501 502 e}

Opiates produce effects (e.g., pupillary changes) that may obscure neurologic signs of further increase in pressure in patients with head injuries.^{501 502 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).^{500 501 502 e}

Use with caution in patients in circulatory shock, because vasodilation produced by the drug may further reduce cardiac output and BP.^{500 501 502}

General Precautions

Acute Abdominal Conditions

Administration may complicate assessment of patients with acute abdominal conditions.^{500 501 502} (See GI Effects under Cautions.)

Seizures

May aggravate preexisting seizures in patients with seizure disorders.^{501 502 e} May induce seizures.^{500 501 502}

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.^{500 501 502}

Pancreatic and Biliary Disease

May cause spasm of the sphincter of Oddi.^{500 501 502} Use with caution in patients with biliary tract disease, including acute pancreatitis, and patients undergoing biliary tract surgery.^{500 501 502}

GI Effects

Monitor for decreased bowel motility in post-operative patients.^{500 501 502} (See Acute Abdominal Conditions under Cautions.)

Contraindicated in patients with known or suspected paralytic ileus.^{500 501 502}

Hypogonadism

Hypogonadism or androgen deficiency reported in patients receiving long-term opiate agonist or opiate partial agonist therapy;^{400 401 402 403 404} causality not established.⁴⁰⁰ Manifestations may include decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility.⁴⁰⁰ Perform appropriate laboratory testing in patients with manifestations of hypogonadism.⁴⁰⁰

Specific Populations

Pregnancy

Category C.^{500 501 502}

Use parenteral preparation with caution during labor.⁵⁰² Administration during labor may cause neonatal respiratory depression.⁵⁰² 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.⁵⁰²

Use of oxymorphone tablets and extended-release tablets not recommended during or immediately prior to labor.⁵⁰¹

Infants born to women regularly taking opiates during pregnancy may be physically dependent.^{500 501 502}

Lactation

Not known whether oxymorphone is distributed into human milk.^{500 501 502} Women receiving oxymorphone generally should not nurse.^{500 501 502}

Pediatric Use

Safety and efficacy not established in pediatric patients <18 years of age.^{500 501 502}

Geriatric Use

No substantial difference in efficacy of oral preparations in geriatric patients relative to younger adults.^{500 501} Dizziness, somnolence, confusion, nausea reported more frequently in geriatric adults than in younger adults.^{500 501}

Following oral administration, plasma concentrations of oxymorphone are higher in geriatric patients ≥65 years of age than in younger patients.^{500 501 502} (See Special Populations under Pharmacokinetics.)

Parenteral preparation not systematically evaluated in geriatric adults.⁵⁰²

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.^{500 501 502}

Hepatic Impairment

Use with caution in patients with mild hepatic impairment.^{500 501 502} (See Hepatic Impairment under Dosage and Administration.)

Contraindicated in patients with moderate or severe hepatic impairment.^{500 501 502}

Renal Impairment

Use with caution in patients with moderate or severe renal impairment.^{500 501 502} Dosage adjustment needed in these patients.^{500 501 502} (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.^{500 501 502}

Drug Interactions

Drugs Associated with Serotonin Syndrome

Risk of serotonin syndrome when used with other serotonergic drugs.⁴⁰⁰ May occur at usual dosages.⁴⁰⁰ Symptom onset generally occurs within several hours to a few days of concomitant use, but may occur later, particularly after dosage increases.⁴⁰⁰ (See Advice to Patients.)

If concomitant use of other serotonergic drugs is warranted, monitor patients for serotonin syndrome, particularly during initiation of therapy and dosage increases.⁴⁰⁰

If serotonin syndrome is suspected, discontinue oxymorphone, other opiate therapy, and/or any concurrently administered serotonergic agents.⁴⁰⁰

Specific Drugs

oxyMORphone Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is 10%.^{500 501}

Onset

5–10 minutes following IV administration.^{502 a}

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

Duration

3–6 hours following parenteral administration.^{502 a}

Food

Conventional tablets with high-fat meal: Peak plasma concentration and AUC increase 38%.⁵⁰⁰

Extended-release tablets with food: Peak plasma concentrations increase 50%; time to peak plasma concentrations delayed; no change in AUC or small increase.⁵⁰¹

Special Populations

Oxymorphone extended-release tablets: Bioavailability increased 26, 57, or 65% in patients with mild (Cl_cr 51–80 mL/minute), moderate (Cl_cr 30–50 mL/minute), or severe renal impairment (Cl_cr <30 mL/minute), respectively.⁵⁰¹

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.⁵⁰¹

Oxymorphone extended-release tablets: Plasma concentrations increased 40% in geriatric individuals.⁵⁰¹

Distribution

Plasma Protein Binding

10–12%.^{500 501}

Elimination

Metabolism

Extensively metabolized in the liver; undergoes reduction or conjugation with glucuronic acid to form oxymorphone-3-glucuronide and 6-OH-oxymorphone.^{500 501 502}

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.^{500 501 502}

Half-life

Extended-release tablets: 9.4–11.3 hours.⁵⁰¹

Stability

Storage

Oral

Conventional Tablets

Tight container at 25°C (may be exposed to 15–30°C).⁵⁰⁰

Extended-release Tablets

Tight container at 25°C (may be exposed to 15–30°C).⁵⁰¹

Parenteral

Injection

25°C (may be exposed to 15°–30°C).⁵⁰² Protect from light.⁵⁰²

Actions

• A potent analgesic; shares the actions of the opiate agonists.^{500 501 502}

• 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.⁵⁰¹

• Conventional and extended-release tablets: Advise patients to take tablets on an empty stomach, at least 1 hour before or 2 hours after food.^{500 501}

• Importance of taking only as prescribed; do not increase dosage or abruptly discontinue without consulting a clinician.^{500 501 502}

• Advise patients to report any episodes of breakthrough pain or adverse experiences to their clinician.^{500 501 502}

• Importance of informing patients that this is a drug of potential abuse and should be protected from theft.^{500 501 502}

• Importance of informing patients that oxymorphone should never be given to anyone other than the individual for whom it was prescribed.^{500 501 502}

• Risk of respiratory depression following overdosage.⁷⁵⁰ Advise patients of the benefits of naloxone following opiate overdose and of their options for obtaining the drug.⁷⁵⁰

• Risk of potentially fatal additive effects (e.g., profound sedation, respiratory depression, coma) if used concomitantly with benzodiazepines or other CNS depressants, including alcohol and other opiates, either therapeutically or illicitly; avoid concomitant use unless such use is supervised by clinician.^{700 703} Advise patients that oxymorphone should not be combined with alcohol.^{500 501 502 700}

• 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.^{500 501 502}

• Potential risk of serotonin syndrome with concurrent use of oxymorphone and other serotonergic agents.⁴⁰⁰ Importance of immediately contacting clinician if manifestations of serotonin syndrome (e.g., agitation, hallucinations, tachycardia, labile BP, fever, excessive sweating, shivering, shaking, muscle stiffness, twitching, loss of coordination, nausea, vomiting, diarrhea) develop.⁴⁰⁰

• Potential risk of adrenal insufficiency.⁴⁰⁰ Importance of contacting clinician if manifestations of adrenal insufficiency (e.g., nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, hypotension) develop.⁴⁰⁰

• Potential for severe constipation.^{500 501 502} Counsel patients on appropriate laxatives and/or stool softeners and other therapeutic approaches.^{500 501 502}

• Risk of dizziness and other adverse events.^{500 501 502}

• Possible risk (although causality not established) of hypogonadism or androgen deficiency with long-term opiate agonist or partial agonist use.⁴⁰⁰ Importance of informing clinician if decreased libido, impotence, erectile dysfunction, amenorrhea, or infertility occurs.⁴⁰⁰

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{500 501 502}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{500 501 502}

• Importance of informing patients of other important precautionary information.^{500 501 502} (See Cautions.)

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.

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

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

Frequently asked questions

• Oxymorphone vs Hydromorphone - How do they compare?

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