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oxyMORphone

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

Medically reviewed by Drugs.com on Mar 29, 2021. Written by ASHP.

Warning

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

  • Potential for abuse in a manner similar to other legal or illicit opiates. 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.

    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.

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

    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.

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

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

    Concomitant Use with Benzodiazepines or Other CNS Depressants
  • Concomitant use of opiate agonists with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

  • Reserve concomitant use of opiate analgesics and benzodiazepines or other CNS depressants for patients in whom alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy and monitor closely for respiratory depression and sedation. (See Specific Drugs under Interactions.)

Risk Evaluation and Mitigation Strategy (REMS):

FDA approved a REMS for oxymorphone to ensure that the benefits outweigh the risk. The REMS may apply to one or more preparations of oxymorphone and consists of the following: medication guide and elements to assure safe use. See https://www.accessdata.fda.gov/scripts/cder/rems/.

Introduction

Opiate agonist; phenanthrene derivative.

Uses for oxyMORphone

Acute and Chronic Pain

Relief of moderate to severe pain.

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.

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

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. Use smallest effective dosage for shortest possible duration since long-term opiate use often begins with treatment of acute pain. Optimize concomitant use of other appropriate therapies. (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.

Generally use opiates for management of chronic pain (i.e., pain lasting >3 months or past the time of normal tissue healing ) 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.

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).

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 or is superior to other pharmacologic or nonpharmacologic treatments. Use is associated with serious risks (e.g., opiate use disorder [OUD], overdose). (See Managing Opiate Therapy for Chronic Noncancer Pain under Dosage and Administration.)

Surgery

Used parenterally as a supplement to anesthesia.

Analgesia During Labor

Used parenterally for analgesia during labor.

Acute Pulmonary Edema

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

oxyMORphone Dosage and Administration

General

Managing Opiate Therapy for Acute Pain

  • Optimize concomitant use of other appropriate therapies.

  • 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.

  • Consider prescribing naloxone concomitantly for patients who are at increased risk of opiate overdosage or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage. (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.

  • 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). Do not prescribe larger quantities for use in case pain continues longer than expected; instead, reevaluate patient if severe acute pain does not remit.

  • 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.

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

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

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.

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

  • 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.

  • Prior to and periodically during therapy, discuss with patients known risks and realistic benefits and patient and clinician responsibilities for managing therapy.

  • Some experts recommend initiating opiate therapy for chronic noncancer pain with conventional (immediate-release) opiate analgesics prescribed at lowest effective dosage. 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.

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

  • When repeated dosage increases required, evaluate potential causes and reassess relative benefits and risks. 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.

  • Higher dosages require particular caution, including more frequent and intensive monitoring or referral to specialist. 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).

  • 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. Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily. 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) or have mandated risk-management strategies (e.g., review of state prescription drug monitoring program [PDMP] data prior to prescribing).

  • 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.

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

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

Administration

Administer orally or by sub-Q, IM, or IV injection.

Oral Administration

Administer orally as conventional tablets or extended-release tablets.

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

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

IV Administration

Administer by direct IV injection.

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

IM Administration

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

Dosage

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

Use lowest effective dosage and shortest duration of therapy consistent with treatment goals of the patient.

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.

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

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. This calculation does not apply when switching to methadone; consult specific recommendations for methadone dosage.

When used concomitantly with other CNS depressants, use lowest effective dosages and shortest possible duration of concomitant therapy. (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.

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.

Adults

Pain (Oral Treatment)
Conventional Tablets
Oral

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

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. 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.

Extended-release Tablets
Oral

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

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.

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. 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.

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

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. Titrate dosage to provide adequate analgesia.

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.

Converting Daily Opiate Dosages to Oxymorphone Hydrochloride Extended-release Tablets (mg/day prior opiate × factor = approximate mg/day oral oxymorphone hydrochloride)501

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.

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

When converting from methadone to oxymorphone, monitor patients closely.

Pain (Parenteral Routes)
IV

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

Sub-Q or IM

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

Analgesia During Labor
IM

0.5–1 mg.

Prescribing Limits

Adults

Oral

Conventional tablet: Maximum initial dose is 20 mg.

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).

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. Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80–120 mg of morphine sulfate daily.

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).

Special Populations

Hepatic Impairment

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

Renal Impairment

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

Geriatric Patients

Select dosage with caution; use lower than usual initial dosages. (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.

  • Respiratory depression in the absence of resuscitative equipment.

  • Acute or severe asthma or hypercarbia.

  • Known or suspected paralytic ileus.

  • Moderate or severe hepatic impairment.

  • 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.

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

Warnings/Precautions

Warnings

Dependence and Abuse

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

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

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

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

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.

Respiratory Depression

The major toxicity associated with oxymorphone.

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.

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

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

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) or who have household members, including children, or other close contacts who are at risk for accidental ingestion or overdosage. 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).

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. Substantial proportion of fatal opiate overdoses involve concurrent benzodiazepine use.

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

Adrenal Insufficiency

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

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. 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. In some patients, switching to a different opiate improved symptoms.

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.

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

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).

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

General Precautions

Acute Abdominal Conditions

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

Seizures

May aggravate preexisting seizures in patients with seizure disorders. May induce seizures.

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.

Pancreatic and Biliary Disease

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

GI Effects

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

Contraindicated in patients with known or suspected paralytic ileus.

Hypogonadism

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

Specific Populations

Pregnancy

Category C.

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

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

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

Lactation

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

Pediatric Use

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

Geriatric Use

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

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

Parenteral preparation not systematically evaluated in geriatric adults.

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.

Hepatic Impairment

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

Contraindicated in patients with moderate or severe hepatic impairment.

Renal Impairment

Use with caution in patients with moderate or severe renal impairment. Dosage adjustment needed in these patients. (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.

Interactions for oxyMORphone

Drugs Associated with Serotonin Syndrome

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

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

Specific Drugs

Drug

Interaction

Comments

Anticholinergic agents

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

Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline), SNRIs (e.g., desvenlafaxine, duloxetine, milnacipran, venlafaxine), tricyclic antidepressants (TCAs), mirtazapine, nefazodone, trazodone, vilazodone

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, the antidepressant, and/or any concurrently administered opiates or serotonergic agents

Antiemetics, 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron)

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, the 5-HT3 receptor antagonist, and/or any concurrently administered opiates or serotonergic agents

Antipsychotics (e.g., aripiprazole, asenapine, cariprazine, chlorpromazine, clozapine, fluphenazine, haloperidol, iloperidone, loxapine, lurasidone, molindone, olanzapine, paliperidone, perphenazine, pimavanserin, quetiapine, risperidone, thioridazine, thiothixene, trifluoperazine, ziprasidone)

Risk of profound sedation, respiratory depression, hypotension, coma, or death

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy

In patients receiving oxymorphone, initiate antipsychotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response

In patients receiving an antipsychotic, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response

Monitor closely for respiratory depression and sedation

Benzodiazepines (e.g., alprazolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flurazepam, lorazepam, midazolam, oxazepam, quazepam, temazepam, triazolam)

Risk of profound sedation, respiratory depression, hypotension, coma, or death

Whenever possible, avoid concomitant use

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy

In patients receiving oxymorphone, initiate benzodiazepine, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response

In patients receiving a benzodiazepine, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response

Monitor closely for respiratory depression and sedation

Consider prescribing naloxone for patients receiving opiates and benzodiazepines concomitantly

Buspirone

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, buspirone, and/or any concurrently administered opiates or serotonergic agents

Cimetidine

Adverse CNS effects (confusion, disorientation, respiratory depression, apnea, seizures) reported with opiates

Caution

CNS depressants (e.g., other opiate agonists, anxiolytics, general anesthetics, tranquilizers, phenothiazines, alcohol)

Additive CNS effects; increased risk of profound sedation, respiratory depression, hypotension, coma, or death

Alcohol: Increased or decreased plasma oxymorphone concentrations reported in patients receiving oxymorphone extended-release tablets

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy

In patients receiving oxymorphone, initiate CNS depressant, if required for any indication other than epilepsy, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response

In patients receiving a CNS depressant, initiate oxymorphone, if required, using 1/3 to ½ the usual dosage and titrate based on clinical response

Monitor closely for respiratory depression and sedation

Consider prescribing naloxone for patients receiving opiates and other CNS depressants concomitantly

Avoid alcohol use

Dextromethorphan

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, dextromethorphan, and/or any concurrently administered opiates or serotonergic agents

5-HT1 receptor agonists (triptans; e.g., almotriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, zolmitriptan)

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, the triptan, and/or any concurrently administered opiates or serotonergic agents

Lithium

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, lithium, and/or any concurrently administered opiates or serotonergic agents

MAO inhibitors (e.g., isocarboxazid, linezolid, methylene blue, phenelzine, selegiline, tranylcypromine)

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, the MAO inhibitor, and/or any concurrently administered opiates or serotonergic agents

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

Possible reduced analgesic effect and/or withdrawal symptoms

Avoid concomitant use

Sedative/hypnotic agents (e.g., butabarbital, eszopiclone, pentobarbital, ramelteon, secobarbital, suvorexant, zaleplon, zolpidem)

Risk of profound sedation, respiratory depression, hypotension, coma, or death

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy

In patients receiving oxymorphone, initiate sedative/hypnotic, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response

In patients receiving a sedative/hypnotic, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response

Monitor closely for respiratory depression and sedation

Skeletal muscle relaxants (e.g., baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, tizanidine)

Risk of profound sedation, respiratory depression, hypotension, coma, or death

Cyclobenzaprine: Risk of serotonin syndrome

Use concomitantly only if alternative treatment options are inadequate; use lowest effective dosages and shortest possible duration of concomitant therapy

In patients receiving oxymorphone, initiate skeletal muscle relaxant, if required, at lower dosage than indicated in the absence of opiate therapy and titrate based on clinical response

In patients receiving a skeletal muscle relaxant, initiate oxymorphone, if required, at reduced dosage and titrate based on clinical response

Monitor closely for respiratory depression and sedation

Cyclobenzaprine: If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, cyclobenzaprine, and/or any concurrently administered opiates or serotonergic agents

St. John’s wort (Hypericum perforatum)

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, St. John’s wort, and/or any concurrently administered opiates or serotonergic agents

Tryptophan

Risk of serotonin syndrome

If concomitant use warranted, monitor for serotonin syndrome, particularly during initiation of therapy and dosage increases

If serotonin syndrome suspected, discontinue oxymorphone, tryptophan, and/or any concurrently administered opiates or serotonergic agents

oxyMORphone Pharmacokinetics

Absorption

Bioavailability

Absolute oral bioavailability is 10%.

Onset

5–10 minutes following IV administration.

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

Duration

3–6 hours following parenteral administration.

Food

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

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

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.

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.

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

Distribution

Plasma Protein Binding

10–12%.

Elimination

Metabolism

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

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.

Half-life

Extended-release tablets: 9.4–11.3 hours.

Stability

Storage

Oral

Conventional Tablets

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

Extended-release Tablets

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

Parenteral

Injection

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

Actions

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

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

  • 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).

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

  • 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.

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

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

  • 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.

Advice to Patients

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

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

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

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

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

  • Importance of informing patients that oxymorphone should never be given to anyone other than the individual for whom it was prescribed.

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

  • 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. Advise patients that oxymorphone should not be combined with alcohol.

  • 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.

  • Potential risk of serotonin syndrome with concurrent use of oxymorphone and other serotonergic agents. 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.

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

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

  • Risk of dizziness and other adverse events.

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

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

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

  • Importance of informing patients of other important precautionary information. (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.

In July 2017, Endo voluntarily agreed to comply with FDA request to remove Opana ER extended-release tablets from US market. FDA's request was based on data indicating that route of Opana ER abuse shifted from nasal to injection abuse following reformulation with properties intended to deter nasal and injection abuse in 2012. FDA stated that abuse by injection of the reformulated preparation had been associated with a serious outbreak of HIV and HCV infection, as well as cases of thrombotic microangiopathy. FDA concluded that the benefits associated with the reformulated preparation may no longer outweigh its risks.

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

oxyMORphone Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

5 mg*

Opana ( C-II)

Endo

oxyMORphone Hydrochloride Tablets ( C-II)

10 mg*

Opana ( C-II)

Endo

oxyMORphone Hydrochloride Tablets ( C-II)

Tablet, extended-release

5 mg*

oxyMORphone Hydrochloride Extended-release Tablets ( C-II)

7.5 mg*

oxyMORphone Hydrochloride Extended-release Tablets ( C-II)

10 mg*

oxyMORphone Hydrochloride Extended-release Tablets ( C-II)

15 mg*

oxyMORphone Hydrochloride Extended-release Tablets ( C-II)

20 mg*

oxyMORphone Hydrochloride Extended-release Tablets ( C-II)

30 mg*

oxyMORphone Hydrochloride Extended-release Tablets ( C-II)

40 mg*

oxyMORphone Hydrochloride Extended-release Tablets ( C-II)

Parenteral

Injection

1 mg/mL

Opana ( C-II)

Endo

AHFS DI Essentials™. © Copyright 2021, Selected Revisions March 29, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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