Oxymorphone

Oxymorphone is an Opioid receptor agonist belonging to the analgesic class.

Oxymorphone is an opioid analgesic used in the management of moderate-to-severe pain and for analgesic therapies.

Oxymorphone is absorbed from the GI tract. The onset of action occurs within 10-15 min (immediate release). The duration of action of Oxymorphone is 3-6 hours (immediate release); ≤12 hours (extended release). Oxymorphone crosses the placenta and enters breast milk. The volume of distribution is 1.94 to 4.22 L/kg (IV). Plasma protein binding is approx. 10-12%. Oxymorphone metabolised Hepatic via glucuronidation to active and inactive metabolites. Excretion via urine as unchanged drug. The Elimination half-life is about (Immediate release) 7 to 9 hours and (Extended release) 9 to 11 hours.

Oxymorphone shows side effects like Dry mouth, stomach pain or swelling, nausea, vomiting, gas, excessive sweating, flushing, fast heartbeat, red eyes, headache, feeling anxious or confused, itching.

Oxymorphone is available in the form of Oral Tablet.

Oxymorphone is available in India, US, Canada, Germany, Australia, China, Italy, Japan, and France.

Oxymorphone is an Analgesic belonging to the class Opioid receptor agonist.

Oxymorphone interacts predominantly with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, with high densities in the posterior amygdala, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical areas. They are also found on the terminal axons of primary afferents within laminae I and II (substantia gelatinosa) of the spinal cord and in the spinal nucleus of the trigeminal nerve. Also, it has been shown that oxymorphone binds to and inhibits GABA inhibitory interneurons via mu-receptors. These interneurons normally inhibit the descending pain inhibition pathway. So, without the inhibitory signals, pain modulation can proceed downstream.

The onset of action and duration of action of Oxymorphone is not clinically established.

Oxymorphone is available in the form of Oral Tablet.

Oxymorphone Tablet is administered on an empty stomach orally, 1 hour before or 2 hours after eating. Swallow tablet whole; do not break, crush, dissolve, or chew.

Oxymorphone is used to relieve moderate to severe pain in people whose pain is not controlled with other medications. Oxymorphone is a class of medications called opiate (narcotic) analgesics. It works by changing the way the body responds to pain.

Oxymorphone is an Opioid receptor agonist belonging to the analgesic class.

Oxymorphone is a potent opioid analgesic with uses like those of morphine. The drug is a semisynthetic derivative of morphine (phenanthrene derivative) and is closely related to hydromorphone chemically.

Oxymorphone is approved for use in the following clinical indications

• Oxymorphone is an opioid analgesic used in the management of moderate-to-severe pain and for analgesic therapies.

• Pain management

Oral: Immediate release: Acute pain:

Opioid-naive: Initial: 5 to 10 mg every 4 to 6 hours as needed (American Pain Society. Dosage adjustment should be based on level of analgesia, side effects, pain intensity, and patient comorbidities.

Conversion from other opioids: Use standard conversion chart to convert total daily dose of current opioid to oxymorphone equivalent. Generally, start with one-half (¹/₂) the calculated total daily oxymorphone dosage and administer in divided doses every 4 to 6 hours.

Oral: 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.

Oxymorphone is available in various strengths as 10 mg; 15 mg; 20 mg; 30 mg; 40 mg; 5 mg; 7.5 mg.

Oxymorphone is available in the form of Oral Tablet.

• Dosage Adjustment in Kidney Patient

CrCl ≥50 mL/minute: There are no dosage adjustments provided.

CrCl <50 mL/minute: Use with caution; bioavailability increased.

• Dosage Adjustment in Hepatic impairment Patient

Mild impairment: Use with caution.

Oral Extended release:

Opioid naive: Initial: 5 mg/dose; titrate slowly with careful monitoring.

Prior opioid therapy: Initiate oxymorphone ER at 50% lower than the starting dose for patients with normal hepatic function on prior opioids; titrate slowly.

Immediate release: Initial: 5 mg/dose; titrate slowly with careful monitoring.

Moderate to severe impairment: Use is contraindicated.

Oxymorphone is contraindicated in patients with

• Hypersensitivity (eg, anaphylaxis, angioedema) to oxymorphone or any component of the formulation; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment; GI obstruction, including paralytic ileus (known or suspected); moderate and severe hepatic impairment.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Constipation: May cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventive measures (eg, stool softener, increased fiber) to reduce the potential for constipation.
• Hyperalgesia: Opioid-induced hyperalgesia (OIH) occurred with short-term and prolonged use of opioid analgesics. Symptoms may include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily nonpainful stimuli; symptoms may be suggestive of OIH if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior.
• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute MI), or with drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.
• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (codeine, hydrocodone, hydromorphone, levorphanol, oxycodone).
• Respiratory depression: Fatal respiratory depression may occur. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Patients and caregivers should be educated on how to recognize respiratory depression and the importance of getting emergency assistance immediately (eg, calling 911) in the event of a known or suspected overdose.
• Thrombotic thrombocytopenic purpura (TTP): Cases of TTP resulting in kidney failure (requiring dialysis) and death have been reported because of misuse by drug abusers injecting the extended-release tablets intravenously. Tablets are intended for oral administration only.
• Obesity: Use with caution in patients who are morbidly obese.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.
• Psychosis: Use with caution in patients with toxic psychosis.
• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercarbia, or preexisting respiratory depression, particularly when initiating therapy and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

It is not known whether oxymorphone is excreted in human milk. Because many drugs, including some opioids, are excreted in human milk, caution should be exercised when Oxymorphone is administered to a nursing woman. Infants exposed to Oxymorphone through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

There are no adequate and well-controlled studies of oxymorphone in pregnant women. Oxymorphone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Common

Nausea, constipation, vomiting, resp depression, headache, pruritus, insomnia, dizziness, asthenia, somnolence, abdominal pain, chills and fever, hypotension, anorexia, diarrhea, dyspepsia, dysphagia, anxiety, nervousness, tremor, vasodilation, cough, dyspnoea, rash.

Use with CNS Depressants

The concomitant use of other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol may produce additive CNS depressant effects. Oxymorphone should be started at 1/3 to 1/2 of the usual dose in patients who are concurrently receiving other central nervous system depressants because respiratory depression, hypotension, and profound sedation, coma and death may result, and titrated slowly as necessary for adequate pain relief. When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced.

Interactions with Mixed Agonist/Antagonist Opioid Analgesics

Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, or buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic, such as oxymorphone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxymorphone and/or may precipitate withdrawal symptoms.

Cimetidine

CNS side effects have been reported (e.g., confusion, disorientation, respiratory depression, apnea, seizures) following coadministration of cimetidine with opioid analgesics; a causal relationship has not been established.

Anticholinergics

Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

MAO Inhibitors

Oxymorphone is not recommended for use in patients who have received MAO inhibitors within 14 days, because severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. No specific interaction between oxymorphone and MAO inhibitors has been observed, but caution in the use of any opioid in patients taking this class of drugs is appropriate.

The common side effects of Oxymorphone include the following

• Common side effects

Dry mouth, stomach pain or swelling, nausea, vomiting, gas, excessive sweating, flushing, fast heartbeat, red eyes, headache, feeling anxious or confused, itching.

• Rare side effects

Rash, agitation, hallucinations (seeing things or hearing voices that do not exist), fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea, nausea, vomiting, loss of appetite, weakness, or dizziness, inability to get or keep an erection, irregular menstruation, decreased sexual desire, changes in heartbeat, seizures, rash, hives, itching, nausea, vomiting, hoarseness, difficulty breathing or swallowing, chest pain. or swelling of the hands, eyes, face, lips, mouth, tongue or throat, extreme drowsiness, fainting.

• Pregnancy

Pregnancy Category C

Teratogenic Effects

There are no adequate and well-controlled studies of oxymorphone in pregnant women. Oxymorphone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

It is not known whether oxymorphone is excreted in human milk. Because many drugs, including some opioids, are excreted in human milk, caution should be exercised when Oxymorphone is administered to a nursing woman. Infants exposed to Oxymorphone through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

• Pediatric Use

Safety and effectiveness of Oxymorphone in pediatric patients below the age of 18 years have not been established.

• Geriatric Use

Oxymorphone should be used with caution in elderly patients. Of the total number of subjects in clinical studies of OPANA ER, 27% were 65 and over, while 9% were 75 and over. No overall differences in effectiveness were observed between these subjects and younger subjects. There were several adverse events that were more frequently observed in subjects 65 and over compared to younger subjects. These adverse events included dizziness, somnolence, confusion, and nausea.

Symptoms: Pin-point pupils, resp depression, hypotension. Circulatory failure and somnolence progressing to stupor or deepening coma, skeletal muscle flaccidity, bradycardia, and death may occur in more severe cases.

Management: Maintain adequate respiration and employ supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation. Naloxone may be used as an antidote.

• Pharmacodynamic

Oxymorphone is a semi-synthetic opioid substitute for morphine. It is a potent analgesic. Opioid analgesics exert their principal pharmacologic effects on the CNS and the gastrointestinal tract. The principal actions of therapeutic value are analgesia and sedation. Opioids produce respiratory depression by direct action on brain stem respiratory centers. The mechanism of respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.

• Pharmacokinetics

Absorption

Oxymorphone is absorbed from the GI tract. The onset of action occurs within 10-15 min (immediate release). The duration of action of Oxymorphone is 3-6 hours (immediate release); ≤12 hours (extended release).

Distribution

Oxymorphone crosses the placenta and enters breast milk. The volume of distribution is 1.94 to 4.22 L/kg (IV). Plasma protein binding is approx. 10-12%.

Metabolism and Excretion

Oxymorphone metabolized Hepatic via glucuronidation to active and inactive metabolites.

Excretion via urine as unchanged drug. The Elimination half-life is about (Immediate release) 7 to 9 hours and (Extended release) 9 to 11 hours.

• https://www.uptodate.com/contents/oxymorphone-drug-information#F205287
• https://medlineplus.gov/druginfo/meds/a610022.html#:~:text=Oxymorphone is used to relieve,the body responds to pain.
• https://www.drugs.com/mtm/oxymorphone.html#dosage
• https://go.drugbank.com/drugs/DB01192