oxymorphone

Oxymorphone is a semisynthetic opioid pain reliever (analgesic) used as a substitute for morphine, an analgesic extracted from the opium plant. Oxymorphone immediate-release formulation is used to manage moderate-to-severe acute pain that is severe enough to require opioid therapy. The extended-release formulation was intended for the management of chronic severe pain that requires daily, long-term opioid treatment, but has been withdrawn from the market at the request of the FDA because of the significant risk for abuse and misuse.

The principal therapeutic effects of oxymorphone are analgesia and sedation. Oxymorphone inhibits the transmission of pain signals in the ascending pain pathways and alters pain perception and the body’s response to pain signals. Oxymorphone also causes respiratory depression by directly acting on the respiratory center in the brainstem, reducing its responsiveness to increases in carbon dioxide tension and to electrical stimulation.

Oxymorphone is a full opioid agonist that works by binding to mu opioid receptors in the central nervous system (CNS). Opioid receptors are protein molecules on nerve cell (neurons) membranes that mediate the body’s response to most hormones, and their functions include modulating pain, stress response, respiration, digestion, mood, and emotion. Oxymorphone binds selectively to mu opioid receptors, but at higher doses, it can bind to other types of opioid receptors as well.

As with all opioid medications, oxymorphone has a high potential for misuse, abuse, tolerance, dependence and addiction, and must be used with extreme caution. Treatment is individualized based on severity of pain, patient’s response to the drug, and risk factors for addiction, abuse, or misuse. In addition to analgesia and sedation, oxymorphone has many other effects on the body’s systems which include:

• Central nervous system: Works on the brainstem respiratory and cough centers, causing respiratory depression and cough suppression. Also causes constriction of pupils (miosis) even in complete darkness.
• Gastrointestinal (GI) system: Reduces gastric motility and peristalsis, the smooth muscle contractions that move the GI contents, which can result in constipation. Other GI effects include reduced pancreatic and biliary secretions, spasm of the sphincter of Oddi, and transient elevations in serum amylase, the enzyme that breaks down carbohydrates.
• Cardiovascular system: Causes dilation of peripheral blood vessels which may result in low blood pressure (hypotension), including from change in position (orthostatic hypotension), fainting, and histamine release that can cause opioid-induced itching, flushing, sweating and red eyes.
• Endocrine system: Inhibits secretion of luteinizing hormone by the pituitary gland and cortisol by the adrenal gland. Chronic opioid use can have deleterious effects on the reproductive system, including sexual dysfunction and infertility.
• Immune system: Animal studies indicate that oxymorphone has a variety of effects on components of the immune system, and overall, a modest immunosuppressive effect.

• Do not use oxymorphone in patients with hypersensitivity to any of the components in oxymorphone or with known hypersensitivity to morphine analogs such as codeine.
• Do not use oxymorphone in patients with any of the following conditions:
  • Significant respiratory depression, except in monitored settings and in the presence of resuscitative equipment
  • Acute or severe bronchial asthma, or high carbon dioxide levels (hypercarbia)
  • Suspected or confirmed gastrointestinal obstruction, or paralysis of the intestinal muscles (paralytic ileus)
  • Moderate or severe hepatic impairment
• Oxymorphone can cause serious, life-threatening, or fatal respiratory depression, monitor patients carefully, especially during initiation and dose increase.
• Advise patients and caregivers how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
• Patients with bronchial asthma, chronic obstructive pulmonary disease (COPD), cor pulmonale or other conditions with reduced respiratory drive are at higher risk for serious respiratory depression even with recommended doses. Monitor closely, especially when initiating and titration, or consider non-opioid analgesia.
• Oxymorphone has a high potential for addiction, abuse, and misuse similar to morphine and can lead to overdose and death. The risk is higher with extended-release formulations. Prescribe after carefully assessing the patient’s risk, and monitor regularly.
• Avoid concurrent use of oxymorphone with other central nervous system (CNS) depressants such as benzodiazepines. If no alternate drug is effective, limit dosages and durations to minimum required, and monitor the patient closely for respiratory depression and sedation.
• Concurrent use with alcohol or drugs containing alcohol can increase blood levels of oxymorphone and lead to a fatal overdose. Advise patients to avoid drinking alcohol while on oxymorphone therapy.
• Prolonged opioid use during pregnancy can cause opioid withdrawal syndrome in the newborn (neonatal opioid withdrawal syndrome), which may be life-threatening if not recognized and treated. If prolonged opioid treatment is required during pregnancy, advise the patient of the risks to the fetus and ensure appropriate treatment is available.
• Accidental consumption, especially in children, can result in a fatal overdose.
• Even therapeutic doses of oxymorphone can cause serious, life-threatening, or fatal respiratory depression in elderly and debilitated patients. Use with extreme caution.
• Use with caution in patients with head injury and high intracranial pressure. Oxymorphone can further increase intracranial pressure. Avoid use in patients with impaired consciousness or coma.
• Oxymorphone may increase frequency of seizures in patients with seizure disorders, monitor carefully.
• Oxymorphone can cause severe hypotension, particularly in patients with already compromised blood pressure stability due to reduced blood volume (hypovolemia) or concurrent use of certain CNS suppressant drugs. Use with caution and monitor such patients. Avoid use in patients with circulatory shock, because it can further reduce blood pressure and cardiac output.
• Use with caution in patients with biliary tract diseases such as acute pancreatitis and monitor for worsening of symptoms. Oxymorphone may reduce pancreatic and biliary secretions, cause sphincter of Oddi spasms and increase serum amylase.
• Oxymorphone can cause constipation, use preventive measures to reduce potential of constipation. Use with caution in patients with chronic constipation.
• Use with caution in patients with gastrointestinal disorders, pseudomembranous (Clostridium difficile) colitis, acute abdominal conditions or those at risk for developing ileus. Oxymorphone may obscure diagnosis or clinical course of patient.
• Use with caution in patients with mild liver function impairment, plasma concentration of oxymorphone can be higher than in those with normal liver function.
• Use oxymorphone with caution in patients with cardiac arrhythmia, untreated myxedema of hypothyroidism, adrenocortical insufficiency, morbid obesity, toxic psychoses, prostatic hypertrophy or urethral stricture, acute alcoholism, delirium tremens, or kyphoscoliosis associated with respiratory depression.
• Use oxymorphone with caution in patients with adrenocortical insufficiency (Addison’s disease), benign prostatic hypertrophy or urethral stricture, or severe impairment of pulmonary or kidney function.
• Opioids (dose-dependent) can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Taper and reduce if required.
• Oxymorphone may impair mental and physical abilities required to perform hazardous tasks, caution patients appropriately.
• When discontinuing oxymorphone, particularly in physically-dependent patients, gradually taper dosage; do not abruptly discontinue.
• Do not use oxymorphone concurrently or within 14 days of monoamine oxidase inhibitor (MAOI) antidepressant therapy.
• Concurrent use with anticholinergic drugs may increase the risk of urinary retention.
• Opioids may reduce efficacy of diuretics by inducing antidiuretic hormone release.
• Do not use oxymorphone concurrently with drugs that can increase serotonin levels. It can lead to serotonin syndrome, a potentially life-threatening condition.
• Avoid use of mixed opioid agonist/antagonist such as pentazocine, nalbuphine, and butorphanol or partial agonist such as buprenorphine analgesics in patients who are receiving oxymorphone, a full opioid agonist analgesic. May reduce analgesic effect and precipitate withdrawal symptoms.
• Healthcare workers are strongly encouraged to complete opioid analgesic risk evaluation and mitigation strategy (REMS) education program to be able to counsel patients and caregivers appropriately on safe use and disposal of opioid analgesics.

Common side effects of oxymorphone include:

• Nausea
• Vomiting
• High body temperature (pyrexia)
• Drowsiness (somnolence)
• Itching (pruritus)
• Dizziness
• Headache
• Sedation
• Confusion
• Anxiety
• Increased sweating
• Rapid heart rate (tachycardia)
• Low blood pressure (hypotension)
• Low oxygen in tissues (hypoxia)
• Dry mouth
• Abdominal distension
• Gas (flatulence)

Less common side effects of oxymorphone include:

• Misuse, abuse, addiction, and dependence
• Respiratory depression
• Respiratory distress
• Shortness of breath (dyspnea)
• Increased respiratory rate
• Reduced oxygen saturation
• Slow heart rate (bradycardia)
• High blood pressure (hypertension)
• Palpitations
• Postural (orthostatic) hypotension
• Fainting (syncope)
• Swelling (edema)
• Fatigue
• Lethargy
• Weakness
• Clamminess
• Flushing
• Hot flashes
• Dehydration
• Central nervous system (CNS) depression
• Depressed level of consciousness
• Feeling jittery
• Nervousness
• Restlessness
• Disorientation
• Agitation
• Mental impairment
• Mental status changes
• Euphoria
• Feeling of unease (dysphoria)
• Insomnia
• Hallucination
• Memory impairment
• Loss of memory (amnesia)
• Convulsions
• Contracted pupils (miosis)
• Blurred vision
• Visual disturbances
• Indigestion (dyspepsia)
• Diarrhea
• Abdominal pain
• Temporary paralysis of intestinal muscles (ileus)
• Decrease in appetite
• Weight loss
• Difficulty in urination
• Urinary retention
• Hypersensitivity reactions
• Swelling of tissue under the skin and mucous membranes (angioedema)
• Allergic reactions including anaphylaxis
• Dermatitis
• Hives (urticaria)
• Adrenal insufficiency
• Androgen deficiency
• Serotonin syndrome, a life-threatening drug reaction with concomitant administration of serotonergic drugs

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet, Immediate-Release: Schedule II

• 5 mg
• 10 mg

Tablet, Extended-Release: Schedule II

• 5 mg
• 7.5 mg
• 10 mg
• 15 mg
• 20 mg
• 30 mg
• 40 mg

Reformulated Extended-Release Tablet (Opana ER)

• Opana ER was discontinued from the market at the request of FDA owing to a significant shift in route of abuse from nasal to injection following the product’s reformulation Injection abuse of reformulated
• Opana ER has been associated with a serious outbreak of human immunodeficiency virus (HIV) infection, hepatitis C, and thrombotic microangiopathy

Adult:

Moderate-to-Severe Pain

Acute pain

• Immediate-release tablets are indicated for acute moderate-to-severe pain where pain is severe enough to require an opioid analgesic and for which alternative therapies are inadequate
• Opioid-naive patients (immediate-release): 10-20 mg orally every 4-6 hours as needed initially, then titrated as warranted (may start with 5-mg increments)

Chronic Severe Pain

• Extended-release oxymorphone is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Extended-release tablet initial dosing

• Patients who are opioid-naive or not opioid-tolerant
  • 5 mg orally every 12 hours initially, then titrated in increments of 5-10 mg every 12 hours every 3-7 days to level that provides adequate analgesia and minimizes side effects
• Patients who are opioid-tolerant
  • Opioid-tolerant definition: Patients who are receiving, for 1 week or longer, at least 60 mg/day oral morphine, 25 mcg/hour transdermal fentanyl, 30 mg/day oral oxycodone, 8 mg/day oral hydromorphone, 25 mg/day oral oxymorphone, or an equianalgesic dose of another opioid
  • Conversion from immediate-release to extended-release oxymorphone: Administer one-half of total immediate-release daily dose as extended-release every 12 hours
  • Conversion from other opioids: Refer to equianalgesic recommendations within the prescribing information

Dosage Modifications

Renal impairment

• Immediate-release tablet
  • Creatinine clearance (CrCl) less than 50 mL/min: Initiate therapy at lowest dose (e.g., 5 mg); titrate to effect slowly; monitor
• Extended-release tablet
  • CrCl less than 50 mL/min (opioid-naïve): Initiate with 5 mg orally every 12 hours
  • CrCl less than 50 mL/min (prior opioid therapy): Initiate at 50% lower than the starting dose for a patient with normal hepatic function and titrate slowly

Hepatic impairment

• Mild: Immediate-release or injection: Initiate therapy at lowest dose; titrate to effect slowly; monitor
• Moderate to severe: Contraindicated
• Extended-release
  • Mild (opioid-naïve): Initiate with 5 mg orally every 12 hours
  • Mild (prior opioid therapy): Initiate at 50% lower than the starting dose for a patient with normal hepatic function and titrate slowly
  • Moderate or severe: Contraindicated

Dosing Considerations

Immediate-release tablets

Limitations of use

• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve use when alternative treatment options (e.g., nonopioid analgesics, opioid/opioid antagonist combination products) have not been tolerated, or are not expected to be tolerated, or have not provided adequate analgesia, or are not expected to provide adequate analgesia

Extended-release tablets

Limitations of use

• Because of risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release formulations, reserve for use in patients for whom alternative treatment options (e.g., nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient pain management
• Extended-release formulations are not indicated as an as-needed analgesic

Access to naloxone for opioid overdose

• Assess the need for naloxone upon initiating and renewing treatment
• Consider prescribing naloxone
  • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
  • Household members (including children) or other close contacts at risk for accidental ingestion or overdose
• Consult patients and caregivers on the following:
  • Availability of naloxone for emergency treatment of opioid overdose
  • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, as part of a community-based program)

Geriatric:

• Steady-state plasma concentrations are 40% higher in elderly individuals
• Initiate with lowest dose; consider less frequent dosing
• Carefully monitor for respiratory or CNS depression

Pediatric:

• Safety and efficacy not established

• Oxymorphone has a high potential for addiction, abuse, and misuse and can lead to overdose. Physical tolerance and dependence can develop with chronic opioid use and cause withdrawal symptoms upon discontinuation of the drug.
• Oxymorphone overdose can cause respiratory depression, constricted pupils, cold and clammy skin, skeletal muscle flaccidity, extreme drowsiness leading to stupor or coma, and sometimes, hypotension and slow heart rate (bradycardia). Severe overdose can result in respiratory arrest, circulatory collapse, cardiac arrest, and death.
• Intravenous drug abuse is commonly associated with the transmission of infectious diseases, such as hepatitis and human immunodeficiency virus (HIV) infection, which can lead to clot formation in small blood vessels (thrombotic microangiopathy).
• Opioid overdose treatment includes:
  • Supportive care to maintain respiration with assisted ventilation, oxygen, intravenous fluids, and medication to increase arterial pressure.
  • Advanced life-support techniques such as cardiac massage and defibrillation if arrhythmia or cardiac arrest occurs.
  • Administration of an opioid antagonist such as naloxone hydrochloride or nalmefene, antidotes used to reverse opioid effects, if there is significant respiratory and circulatory depression.
  • The duration of opioid antagonist is usually shorter than the duration of oxymorphone. Patient should be monitored till spontaneous respiration is established. Additional naloxone doses may be administered, if necessary.
  • Patients with physical dependence may have severe withdrawal symptoms and opioid antagonist should be initiated and titrated with caution.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Severe interactions of oxymorphone include:
  • alvimopan
• Oxymorphone has serious interactions with at least 38 different drugs.
• Oxymorphone has moderate interactions with at least 209 different drugs.
• Mild interactions of oxymorphone include:
  • brimonidine
  • dextroamphetamine
  • eucalyptus
  • lidocaine
  • sage
  • ziconotide

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Chronic use of opioids may reduce fertility in both men and women of reproductive potential. It is not known whether these effects are reversible.
• Oxymorphone may cause fetal harm. Use oxymorphone in pregnancy only if benefits clearly outweigh the potential risks to the fetus.
• Chronic opioid use by the mother during pregnancy can result in physical dependence and opioid withdrawal syndrome in the newborn.
• Opioid analgesics may prolong labor by temporarily reducing the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by the increased rate of cervical dilation.
• Maternal use of oxymorphone during labor and delivery may produce respiratory depression and other effects in the newborn; monitor newborn closely; keep an opioid antagonist, such as naloxone, available for reversal of opioid-induced respiratory depression in the newborn.
• It is not known if oxymorphone is present in breast milk, however, most drugs, including opioids are present in breast milk. Oxymorphone should be used with caution in nursing mothers.
• If opioids are used in a nursing mother, the breastfeeding infant should be monitored for adverse effects such as feeding difficulties, drowsiness, sedation or limpness. When maternal opioid use is discontinued or breastfeeding is stopped, the infant may have withdrawal symptoms.

• Oxymorphone is a Schedule II controlled substance; diversion of Schedule II products is subject to criminal penalty.
• Oxymorphone has a high potential for addiction, abuse, misuse, and dependence, even with prescribed dose, and can lead to a fatal overdose. Use with extreme caution.
• Take oxymorphone exactly as prescribed. Do not take a higher or more frequent dosage, and do not discontinue abruptly without consulting with your physician.
• Do not drink alcohol or take other drugs that can depress the central nervous system, while taking oxymorphone. It increases the risk for sedation, respiratory depression, coma, and death.
• Oxymorphone can impair mental and physical abilities. Avoid driving, operating heavy machinery, or performing other potentially hazardous tasks while on oxymorphone therapy.
• Store oxymorphone well out of reach of children in a safe location not accessible to others. Accidental consumption, especially in children, can result in a fatal overdose.
• In case of known or suspected overdose, seek emergency medical help or contact Poison Control.
• Dispose of expired, unwanted, or unused oxymorphone tablets and oral liquid by flushing down the toilet, if a drug take-back option is not readily available.