Oxymorphone (Opana) is a semisynthetic opioid that has strong analgesic properties. It is used in the treatment of moderate or severe pain that is not responsive to NSAIDs or other anagesic medications.

Oxymorphone Uses:

• Pain management:

  • Parenteral:
    • Management of pain severe enough to warrant an opioid analgesic and for which alternative treatments are not adequate;
    • Obstetrical analgesia;
    • Preoperative medication;
    • Anesthesia support;
    • Relief of anxiety in patients with dyspnea associated with pulmonary edema secondary to acute left ventricular dysfunction.
  • Oral, immediate-release:
    • Management of acute pain severe enough to warrant an opioid analgesic and for which alternative treatments are inadequate.
  • Oral, extended-release:
    • Management of pain severe enough to warrant daily, around-the clock, long-term opioid treatment, and for which alternative treatment options are inadequate.

  • Limitations of use:

    • Use oxymorphone only in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient pain management.
    • Oxymorphone ER is not indicated as an as-needed analgesic.

Oxymorphone (Opana) Dose in Adults

Note: Opana injection has been discontinued in the United States for more than 1 year.

Oxymorphone (Opana) Dose in pain management:

Note: Dosage must be individualized.

• Parenteral:

  • IM, SubQ: Initial: 1 to 1.5 mg; may repeat every 4 to 6 hours as needed
  • Labor analgesia: IM: 0.5 to 1 mg
  • IV: Initial: 0.5 mg

• Conversion from oral oxymorphone to parenteral oxymorphone:

  • Start parenteral oxymorphone with approximately one-tenth of the total daily oral dose and administer in 4 or 6 equally divided doses.
  • Because of patient variability, closely monitor the patient for analgesia and adverse reactions upon conversion.

Oral:

• Immediate release: Acute pain:

  • Opioid-naive: Initial: 5 to 10 mg every 4 to 6 hours as required.
  • Dosage adjustment should be based on the level of analgesia, side effects, pain intensity, and patient comorbidities.
  • Conversion from a stable dose of parenteral oxymorphone:
    • Start oral oxymorphone with approximately 10 times the total daily parenteral requirement administered in 4 to 6 equally divided doses.
  • Conversion from other opioids:
    • Use standard conversion chart to convert total daily dose of current opioid to oxymorphone equivalent.
    • Generally, initiate with one-half the calculated total daily oxymorphone dosage and administer in divided doses every 4 to 6 hours.

• Extended-release: Chronic pain:

  • Opioid-naive (use as the first opioid analgesic or in patients who are not opioid-tolerant):
    • Initial: 5 mg every 12 hours.

Note:

• Opioid tolerance is defined as:
  • Patients already on least 60 mg of oral morphine daily, 25 mcg of transdermal fentanyl per hour, 30 mg of oral oxycodone daily, 8 mg oral hydromorphone daily, 25 mg oral oxymorphone daily, or an equivalent dose of another opioid for at least 1 week.

Conversion from a stable dose of parenteral oxymorphone to extended-release oxymorphone:

• Start extended-release oxymorphone with approximately 10 times the total daily parenteral requirement administered in 2 equally divided doses.
• Because of patient variability, closely monitor the patient for analgesia and adverse reactions upon conversion.

Conversion of a stable dose of immediate-release oxymorphone to extended-release oxymorphone:

• Using the same total daily dose, administer one-half of the daily dose of immediate-release oxymorphone as the extended-release formulation every 12 hours

Conversion from other oral opioids to extended-release oxymorphone:

• Stop all other around-the-clock opioids when extended-release oxymorphone is started.
• Substantial interpatient variability exists in the relative potency of opioids. Therefore, it is safer to underestimate a patient’s daily oral oxymorphone need and provide breakthrough pain relief with rescue medication (eg, immediate-release opioid) than to overestimate requirements.
• The conversion factors, per the manufacturer, in the chart (see table) provide an estimate to convert the daily dose of current opioid to an oxymorphone equivalent.
• Select the previous oral opioid, add the current total daily dose, multiply by the conversion factor on the table to calculate the approximate oral oxymorphone daily dose, then divide daily dose by 2 to give every 12 hours as oxymorphone extended-release.
• Round down, if suitable, to the nearest strength available. For patients on a regimen of more than one opioid, calculate the approximate oral oxymorphone dose for each opioid and add the totals to get the approximate total oxymorphone daily dose.
• For patients on a regimen of fixed-ratio opioid/non-opioid analgesic medications, only the opioid component of these medications must be used in the conversion.
  • Note:
    • The conversion factors in this conversion table are only to be used for the conversion from current opioid therapy to oxymorphone ER.
    • Conversion factors in this table cannot be used to convert from oxymorphone ER to another opioid (doing so may result in fatal overdose because of overestimation of the new opioid).
    • This is not a table of equianalgesic doses. When converting from methadone to extended-release oxymorphone, close monitoring is needed.
    • The ratio between methadone and other opioid agonists varies based on prior dose exposure. Methadone has a long half-life and can accumulate in the plasma.

Conversion Factors to Oxymorphone ER

• Titration and maintenance:

  • Adjust therapy incrementally by 5 to 10 mg every 12 hours at intervals of every 3 to 7 days. Breakthrough pain may warrant a dose increase or rescue medication with an immediate-release analgesic.

• Discontinuation of therapy:

  • When discontinuing chronic opioid therapy, the dose should be slowly tapered down.
  • An optimal universal tapering schedule for all patients has not been established.
  • Proposed schedules range from slow (eg, 10% reductions per week) to rapid (eg, 25% to 50% reduction every few days).
  • Tapering schedules should be customized to minimize opioid withdrawal while considering patient-specific goals and concerns as well as the pharmacokinetics of the opioid being tapered.
  • An even slower taper may be used in patients who have been receiving opioids for a long duration (eg, years), particularly in the final stage of tapering, whereas more rapid tapers may be appropriate in patients experiencing severe adverse events.
  • Monitor carefully for signs/symptoms of withdrawal.
  • If the patient develops withdrawal symptoms, consider slowing the taper schedule; alterations may include increasing the interval between dose reductions, decreasing the amount of daily dose reduction, pausing the taper and restarting when the patient is ready, and/or coadministration of an alpha-2 agonist (eg, clonidine) to blunt withdrawal symptoms.
  • Continue to offer nonopioid analgesics as required for pain management during the taper; consider nonopioid adjunctive treatments for withdrawal symptoms (eg, GI complaints, muscle spasms) as needed.

Use in Children:

Not indicated.

Oxymorphone Pregnancy Category: C

[US Boxed Warning]

• A neonatal withdrawal syndrome can develop from prolonged maternal opioid use during pregnancy. If not treated and recognized by neonatologists, it could be fatal.
• Pregnant women who require prolonged opioid therapy should be notified and ensure that the treatment is available.
  • Opioids can cross the placenta. Opioids can cross the placenta and cause birth defects, poor fetal development, stillbirths, and preterm deliveries.
  • A pregnant woman may experience withdrawal symptoms if they are exposed to chronic opioids.
  • Symptoms of neonatal Abstinence Syndrome (NAS) may include autonomic symptoms (eg. fever, temperature instability, diarrhea, vomiting), gastrointestinal symptoms (eg. diarrhea, vomiting), or neurologic (eg. high-pitched crying and hyperactivity, increased muscle tone/abnormal wakefulness, increased wakefulness/abnormal sleeping pattern, irritability/sneezing), seizure.
  • Opioids can cause physical dependence in mothers who give birth to children who are also dependent. 
  • Opioids can cause respiratory depression in newborns and psycho-physiologic side effects in neonates. Mothers who have received opioids during labor must be monitored.
  • Other than oxymorphone, agents are often used to treat pain in the maternity during labor and postpartum.
  • They can also be used to treat chronic noncancer pain in pregnant women who are pregnant or may become pregnant.

Use of oxymorphone while breastfeeding

• It is not known if breast milk contains oxymorphone.
• To limit adverse reactions in mother and baby, opioids should only be administered to breastfeeding mothers who are not allergic to them. 
• A single, occasional dose of opioid analgesics may be acceptable for breastfeeding.
• Breastfeeding mothers who are using opioids to treat postpartum pain and chronic maternal pain should monitor their infants for signs of drowsiness or sedation, feeding difficulties, and/or limpness.
• According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.
• When breastfeeding is interrupted or stopped, withdrawal symptoms can occur.

Oxymorphone (Opana) Dose in Kidney Disease:

• CrCl ≥50 mL/minute:

  • No dosage adjustments provided in the manufacturer’s labeling.

• CrCl <50 mL/minute:

  • Use cautiously; bioavailability increased.

Oral:

• Extended-release:

  • Opioid naive:
    • Initial: 5 mg/dose; titrate gradually with careful monitoring.
  • Previous opioid therapy:
    • Start oxymorphone ER at 50% lower than the starting dose for patients with normal renal function on previous opioids; titrate gradually.

• Immediate release:

  • Initial: 5 mg/dose; titrate gradually with careful observation.
  • IM, IV, SubQ: Start with reduced dose and titrate slowly with careful monitoring.

Oxymorphone (Opana) Dose in Liver Disease:

• Mild impairment:

  • Use cautiously.

Oral:

• Extended-release:

  • Opioid naive:
    • Initial: 5 mg/dose; titrate slowly with careful monitoring.
  • Prior opioid therapy:
    • Start oxymorphone ER at 50% lower than the starting dose for patients with normal hepatic function on previous opioids; titrate gradually.

• Immediate release:

  • Initial: 5 mg/dose; titrate gradually with careful observation.
  • IM, IV, SubQ: Start with reduced dose and titrate slowly with careful monitoring.

• Moderate to severe impairment:

  • Use is contraindicated.

Incidence of side effects usually on higher-end with extended-release (ER) tablet.

Common Side Effects of Oxymorphone (Opana):

• Central Nervous System:

  • Dizziness
  • Drowsiness
  • Headache

• Dermatologic:

  • Pruritus

• Gastrointestinal:

  • Nausea
  • Constipation
  • Vomiting

• Miscellaneous:

  • Fever

Less Common Side Effects Of Oxymorphone (Opana):

• Cardiovascular:

  • Edema
  • Flushing
  • Hypertension
  • Hypotension
  • Tachycardia

• Central Nervous System:

  • Fatigue
  • Insomnia
  • Confusion
  • Anxiety
  • Depression
  • Disorientation
  • Lethargy
  • Nervousness
  • Restlessness

• Dermatologic:

  • Diaphoresis

• Endocrine & Metabolic:

  • Dehydration
  • Weight Loss

• Gastrointestinal:

  • Xerostomia
  • Abdominal Pain
  • Decreased Appetite
  • Abdominal Distention
  • Diarrhea
  • Dyspepsia
  • Flatulence

• Neuromuscular & Skeletal:

  • Asthenia

• Ophthalmic:

  • Blurred Vision

• Respiratory:

  • Dyspnea
  • Hypoxia

Side effects of Oxymorphone (Opana) Frequency Not Defined:

• Central Nervous System:

  • Agitation
  • Cognitive Dysfunction
  • Drug Abuse
  • Opioid Dependence
  • Sedation

• Dermatologic:

  • Allergic Dermatitis

• Endocrine & Metabolic:

  • Adrenocortical Insufficiency

• Gastrointestinal:

  • Anorexia
  • Biliary Colic
  • Paralytic Ileus

• Genitourinary:

  • Oliguria
  • Ureteral Spasm
  • Urinary Hesitancy

• Local:

  • Injection Site Reaction

• Ophthalmic:

  • Diplopia

• Respiratory:

  • Apnea
  • Atelectasis
  • Bronchospasm
  • Laryngeal Edema
  • Laryngospasm

Contraindications to Oxymorphone (Opana):

• Hypersensitivity to oxymorphone and any other component of the formulation (eg anaphylaxis or angioedema).
• Significant respiratory depression, acute or severe bronchial asthma in an unobserved setting and in the absence or use of resuscitative devices.
• GI obstruction, including paralytic ileus (known and suspected).
• Moderate and severe hepatic dysfunction.
• There is not much data on the possibility of cross-reactivity between opioids and allergenic opioids. 
• Cross-sensitivity is possible due to chemical similarities and/or pharmacologic interactions.

Warnings and precautions

• CNS depression:

  • CNS depression can lead to impairment of mental or physical abilities.
  • Patients should be aware that driving or operating machinery requires mental alertness.

• Constipation

  • Constipation can be a problem in patients with unstable angina or post-myocardial injury patients.
  • To reduce constipation, consider preventive measures such as stool softener or increased fiber.

• Hypotension

  • This medication can cause severe hypotension, including orthostatic hypotension, syncope, and heart disease.
  • Patients with hypovolemia, cardiac disease (including acute MI), and drugs that may increase hypotension (such as phenothiazines and general anesthetics) should be cautious.
  • After starting or increasing the dose, monitor for hypotension.
  • Avoid using in the presence of circulatory shock.

• Phenanthrene hypersensitivity:

  • Use cautiously in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxycodone).

• Respiratory depression [US Boxed Warning]

  • Severe, life-threatening or fatal respiratory depression can occur. You should monitor your respiratory depression closely, especially at the beginning or end of dose escalation.
  • Take ER tablets whole. Do not crush or chew them. This could lead to rapid release and potentially fatal doses.
  • The sedative effects of opioids can be exacerbated by carbon dioxide retention due to opioid-induced respiratory depression.

• TTP:Thrombotic thrombocytopenic purpura

  • TTP can lead to kidney failure and even death. This is due to drug abusers injecting extended-release tablets intravenously. Tablets should only be used for oral consumption.

• Conditions abdominales:

  • Patients with acute abdominal conditions may not be diagnosed or treated appropriately.

• Adrenocortical Insufficiency

  • Patients with adrenal insufficiency (including Addison disease) should be cautious.
  • Long-term opioid abuse can lead to secondary hypogonadism. This could cause infertility, sexual dysfunction, mood disorders, and osteoporosis.

• Insufficiency of the biliary tract:

  • Patients with biliary dysfunction, including acute pancreatitis, should be cautious. Opioids may cause constriction to the sphincter.

• CNS depression/coma:

  • Patients with altered consciousness and coma should not be used as they are more at risk of experiencing intracranial CO2 retention.

• Delirium tremens:

  • Patients with delirium-tremens should be cautious.

• Head trauma

  • Patients with intracranial injuries, intracranial lesions or an elevated intracranial pressure (ICP) should be cautious. A marked increase in ICP could occur.

• Hepatic impairment

  • Patients with mild hepatic impairment should be cautious; moderate to severe impairments are contraindicated.

• Mental health conditions

  • Patients with mental disorders (eg depression, anxiety disorders and post-traumatic stress disorder), should be treated cautiously.
  • There is an increased risk of opioid overdose and opioid use disorder. It is recommended to have more frequent monitoring.

• Obesity:

  • Patients who are obese or morbid should be treated with caution.

• Prostatic hyperplasia/urinary restriction:

  • Patients with prostatic hyperplasia or urinary stricture should be cautious.

• Psychosis:

  • Patients with toxic psychosis should be treated cautiously

• Renal impairment

  • Patients with impaired renal function should be cautious.

• Respiratory disease

  • Patients with severe chronic obstructive lung disease (or cor pulmonale) should be treated with caution.
  • Also, patients with hypoxia, hypercarbia, significant respiratory impairment, and preexisting respiratory depression should be screened for potential respiratory depression.
  • These patients may benefit from non-opioid analgesics.

• Seizure disorders:

  • Patients with seizure disorders should be cautious; it may exaggerate or cause preexisting seizures.

• Sleep-disordered breathing

  • Patients with sleep-disordered sleeping disorders, such as HF or obesity, should be treated cautiously. Patients with severe or moderate sleep-disordered breath should avoid opioids

• Thyroid dysfunction:

  • Patients with thyroid dysfunction should be cautious.

Oxymorphone: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring Parameters:

• Pain relief
• Mental and respiratory health
• Blood pressure and heart rate
• Bowel function
• Signs and symptoms of abuse, misuse, or addiction
• Signs and symptoms of hypogonadism/hypoadrenalism

Alternate suggestions:

• Chronic pain is long-term treatment that does not include end-of life or palliative care. It can also be active cancer treatment, sickle cells disease or medication-assisted opioid abuse disorder treatment.
  • Within 1 to 4 weeks after starting treatment, and with increasing doses, you can assess the benefits and risks of opioid therapy.
  • Patients at greater risk for overdose or those with opioid use disorders should have their benefits and risks reevaluated every three months. Before starting treatment, it is recommended that urine drug testing be done. Re-checking should occur at least once a year (includes prescription controlled medications and illicit drugs).
  • Clinicians should review state prescription drug monitoring program data (PDMP) before starting therapy and periodically throughout treatment (frequency ranging between every prescription and every 3 months).

How to administer Oxymorphone (Opana)?

Oral:

• Take with an empty stomach, 1 hour before or 2 hours after eating.
• Swallow ER tablet whole; do not break, crush, dissolve, or chew.

Injectable:

• Administer IV, IM, or SubQ.

Mechanism of action of Oxymorphone (Opana):

• The strong opioid analgesic Oxymorphone has similar uses to morphine.
• It is a semi-synthetic derivative (phenanthrene derivative), of morphine and closely related chemically to hydromorphone.

The onset of action when administered parenteral:

• 5 to 10 minutes

Duration of analgesia when administered parenteral:

• 3 to 6 hours

Protein binding:

• 10% to 12%

Metabolism:

• Hepatic via glucuronidation to active and inactive metabolites

Bioavailability: Oral:

• About 10%

Half-life elimination: Oral:

• Immediate-release: 7 to 9 hours;
• Extended-release: 9 to 11 hours

Excretion:

• Urine (<1% as unchanged drug); feces

International Brand Names of Oxymorphone:

• Opana
• Opana ER

Oxymorphone Brand Names in Pakistan:

No Brands Available in Pakistan.