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 that is severe enough to require an opioid analgesic but that cannot be adequately treated with other methods;
    • 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 that is sufficiently severe to require an opioid analgesic and for which no other treatment is effective.
  • Oral, extended-release:
    • Treatment of pain that is severe enough to require long-term, daily, round-the-clock opioid medication and for which there are no effective alternative treatments.

  • Limitations of use:

    • Only administer oxymorphone to patients when other treatment choices (such as nonopioid analgesics and opioid combination medications) are ineffective, poorly tolerated, or would otherwise fall short of meeting the patient's needs for acceptable pain management.
    • As-needed analgesia is not advised for use with oxymorphone ER.

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: Every 12 hours, 5 mg.

Note:

• Opioid tolerance is defined as:
  • Those who have been taking an equivalent amount of another opioid for at least a week or at least 60 mg of oral morphine daily, 25 mcg of transdermal fentanyl hourly, 30 mg of oral oxycodone daily, 8 mg of oral hydromorphone daily, or 25 mg of oral oxymorphone daily.

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:

• Provide immediate-release oxymorphone half as often every 12 hours as the extended-release version while using the same total daily dose.

Conversion from other oral opioids to extended-release oxymorphone:

• When extended-release oxymorphone is started, stop using all other 24-hour opioids.
• The relative potency of opioids varies significantly amongst patients. As a result, it is safer to provide breakthrough pain relief with rescue medication (such as an immediate-release opioid) than to overestimate a patient's daily oral oxymorphone needs.
• According to the manufacturer, the conversion parameters in the chart (see table) give an estimate for changing the daily opioid dose to an oxymorphone equivalent.
• To determine the approximate oral oxymorphone daily dose, choose the previous oral opioid, add the current total daily dose, multiply by the conversion factor in the table, split the daily dose by 2, and administer as oxymorphone extended-release every 12 hours.
• If necessary, round down to the next available strength. Calculate the approximate oral oxymorphone dose for each opioid in a patient's regimen, then sum the results to get the approximate daily dose of oxymorphone.
• Just the opioid component of these drugs must be administered as directed to patients taking a fixed-ratio regimen of opioid/non-opioid analgesics.
  • Note:
    • Just the conversion from current opioid medication to oxymorphone ER should be done using the conversion parameters in this conversion table.
    • It is not possible to convert from oxymorphone ER to another opioid using the conversion parameters in this table (doing so may result in fatal overdose because of overestimation of the new opioid).
    • This is not a dose comparison chart for analgesics. Close monitoring is required when switching from methadone to extended-release oxymorphone.
    • 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 the dosage of your medication gradually over the course of three to seven days, every 12 hours. Increased dosage or rescue therapy with an immediate-release analgesic may be necessary for severe pain.

• Discontinuation of therapy:

  • The dose should be gradually reduced before stopping long-term opioid medication.
  • There is now a recommended uniform tapering schedule for all patients.
  • The suggested timetables range from gradual (10% reductions weekly, for example) to abrupt (25–50% reductions every few days).
  • The pharmacokinetics of the opioid being tapered should be taken into account as well as the patient's individual goals and concerns when designing tapering regimens to reduce opioid withdrawal.
  • In the last stages of tapering, patients who have been taking opioids for a long time (years, for example) may benefit from an even slower reduction, whereas those who are having serious side events may benefit from more fast tapering.
  • Watch out for withdrawal symptoms and indicators.
  • Consider delaying the taper schedule if the patient experiences withdrawal symptoms; modifications may include lengthening the time between dose decreases, reducing the amount of daily dose drop, suspending the taper and restarting when the patient no longer experiences 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 may also be used to treat pregnant women who are or may become pregnant with persistent noncancer pain.

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).
• Acute or severe bronchial asthma, significant respiratory depression, and these conditions occur unattended, without the use of resuscitative equipment.
• 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:

  • Usage with caution in patients who have had hypersensitivity to other opioid agonists derived from phenanthrene (codeine, hydrocodone, hydromorphone, levorphanol, oxycodone).

• Respiratory depression [US Boxed Warning]

  • You should keep a close eye on your respiratory depression, particularly at the start and finish 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:

• Consume on an empty stomach, one hour prior to, or two hours following a meal.
• Do not chew, crush, dissolve, or break an ER pill; instead, swallow it whole.

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.