Numorphan

Name: Numorphan

Descriptions

Oxymorphone injection is used to treat moderate to severe pain, including labor pain. It may also be given before surgery or with a general anesthetic (medicine that puts you to sleep), and may be used to relieve anxiety for patients with breathing problems from pulmonary edema caused by heart disease.

Oxymorphone injection belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain.

When oxymorphone injection is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms:

  • Solution

Overdose

Signs and Symptoms

Serious overdosage with NUMORPHAN (oxymorphone) is characterized by respiratory depression, (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

Treatment

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The opioid antagonist naloxone hydrochloride (NARCAN®) is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to opioids including oxymorphone. Therefore, an appropriate dose of naloxone hydrochloride should be administered (usual initial adult dose 0.4 mg-2 mg) preferably by the intravenous route and simultaneously with efforts at respiratory resuscitation. Since the duration of action of oxymorphone may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.

Naloxone hydrochloride should not be administered in the absence of clinically significant respiratory or cardiovascular depression. In addition, it should be considered that the use of an opioid antagonist in patients physically dependent on opioids may precipitate an acute withdrawal syndrome that cannot be readily suppressed while the action of the antagonist persists. If respiratory depression is associated with muscular rigidity, administration of a neuromuscular blocking agent may be necessary to facilitate assisted or controlled ventilation. Muscular rigidity may also respond to opioid antagonist therapy.

Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.

Uses For Numorphan

Oxymorphone injection is used to treat moderate to severe pain, including labor pain. It may also be given before surgery or with a general anesthetic (medicine that puts you to sleep), and may be used to relieve anxiety for patients with breathing problems from pulmonary edema caused by heart disease.

Oxymorphone belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain.

When oxymorphone is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

This medicine is available only with your doctor's prescription.

Numorphan Description

Numorphan (oxymorphone hydrochloride, USP), a semi-synthetic opioid substitute for morphine, is a potent analgesic.

Oxymorphone hydrochloride is a white or slightly off-white, odorless powder, which is sparingly soluble in alcohol and ether, but freely soluble in water. The molecular weight of oxymorphone hydrochloride is 337.80. The pKa1 and pKa2 of oxymorphone at 37°C are 8.17 and 9.54, respectively. The octanol/aqueous partition coefficient at 37°C and pH 7.4 is 0.98.

Numorphan Injection is available in two concentrations, 1 mg/mL, 1 mL ampul and 1.5 mg/mL, 10 mL vial of oxymorphone hydrochloride. In addition, each 1 mg/mL ampul contains 8.0 mg/mL sodium chloride. Each 1.5 mg/mL vial contains 8.0 mg/mL sodium chloride, 1.8 mg/mL methylparaben and 0.2 mg/mL propylparaben. pH for both the ampul and vial is adjusted with hydrochloric acid.

The Numorphan Rectal Suppository is available in a concentration of 5 mg of oxymorphone hydrochloride in a base consisting of polyethylene glycol 1000 and polyethylene glycol 3350.

Indications and Usage for Numorphan

Numorphan Suppository is indicated for the relief of moderate to severe pain.

Numorphan Injection is indicated for the relief of moderate to severe pain. It is also indicated for preoperative medication, for support of anesthesia, for obstetrical analgesia, and for relief of anxiety in patients with dyspnea associated with pulmonary edema secondary to acute left ventricular dysfunction.

Precautions

General

Special Risk Patients

Numorphan should be used with caution in elderly and debilitated patients and in patients who are known to be sensitive to central nervous system depressants, such as those with cardiovascular, pulmonary, renal or hepatic disease. Caution should also be exercised in patients with hypothyroidism, acute alcoholism, delirium tremens, convulsive disorders, Addison’s disease, gallbladder disease or gallstones, prostatic hypertrophy or urethral stricture, recent gastrointestinal or genitourinary tract surgery, inflammatory bowel disease, diarrhea secondary to poisoning until the toxin is eliminated, diarrhea secondary to pseudomembranous colitis, cardiac arrhythmias, increased ocular pressure, and toxic psychosis. Debilitated and elderly patients and those with severe liver disease should receive smaller doses of Numorphan.

Hypotensive Effect

Opioid analgesics may cause severe hypotension in patients whose ability to maintain blood pressure has been compromised by a depleted blood volume or coadministration of drugs such as phenothiazines or general anesthetics. Administer with caution to patients in circulatory shock, since vasodilatation produced by the drug may further reduce cardiac output and blood pressure. Orthostatic hypotension may occur in ambulatory patients.

Information for Patients

Patients should be cautioned regarding the following:

Drowsiness, dizziness, or lightheadedness related to the use of this medication may impair mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car, operating machinery, etc.

This medication, like other opioid analgesics, will add to the effect of alcohol and other CNS depressants [such as antihistamines, sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, tricyclic antidepressants, and monoamine oxidase (MAO) inhibitors]. Alcohol should not be consumed while taking Numorphan.

Withdrawal side effects may be precipitated by suddenly stopping this drug after prolonged use (regular use for several weeks or more). The medication should be gradually reduced before completely discontinuing use.

Elderly patients are more sensitive to opioid analgesics, especially the respiratory depressant effects and opioid induced urinary retention. Lower doses or longer dosing intervals may be required.

Orthostatic hypotension may occur with the use of this medication, especially in ambulatory patients. Patients should get up slowly from a lying or sitting position.

Numorphan (oxymorphone hydrochloride, USP) may be habit forming and has the potential for being abused. Tolerance, psychological and physical dependence can occur.

Safe use in pregnancy has not been established. Prolonged use of opioid analgesics during pregnancy may cause fetal-neonatal physical dependence, and neonatal withdrawal may occur.

Laboratory Tests

Opioids may increase biliary tract pressure with resultant increases in plasma amylase or lipase.

Drug Interactions

The concomitant use of other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, tricyclic antidepressants, monoamine oxidase (MAO) inhibitors, and alcohol may produce additive CNS depressant effects. When such combined therapy is contemplated, the dose of one or both agents should be reduced (see WARNINGS).

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.

It has been reported that the incidence of bradycardia was increased when oxymorphone was combined with propofol for induction of anesthesia.

In addition, CNS toxicity has been reported (confusion, disorientation, respiratory depression, apnea, seizures) following coadministration of cimetidine with opioid analgesics; no clear-cut cause and effect relationship was established.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies have not been performed in animals to evaluate the carcinogenic potential of Numorphan. Studies to evaluate the mutagenic potential of Numorphan have not been conducted. There have been no studies to evaluate the effect of Numorphan on fertility.

Usage in Pregnancy

Teratogenic Effects: Pregnancy Category C: Numorphan was reported to produce malformations in offspring of hamsters that received 1,500 times the recommended human dose on Day 8 of gestation. There have been no adequate and well-controlled studies of reproductive toxicity in other laboratory animals or in pregnant women. It is not known whether Numorphan can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. As with other opioid analgesics, the use of Numorphan in pregnancy or in women of child-bearing potential requires that the possible benefits of the drug be weighed against the possible hazards to the mother and the child.

Non-teratogenic Effects
Prolonged use of opioid analgesics during pregnancy may cause fetal-neonatal physical dependence. Neonatal withdrawal may occur. Symptoms usually appear during the first days of life and may include convulsions, irritability, excessive crying, tremors, hyperactive reflexes, fever, vomiting, diarrhea, sneezing, yawning, and increased respiratory rate.

Labor and Delivery

Numorphan should be used with caution during labor. Sinusoidal fetal heart rate patterns may occur with the use of opioid analgesics.

Opioid analgesics in therapeutic doses may prolong labor. Generally, the effect of opioids on the pregnant uterus appears to depend on the time of administration; administration of the drugs during the latent phase of the first stage of labor, or before cervical dilation of 4-5 cm has occurred, may hamper the progress of labor.

Opioid analgesics, including Numorphan, may cause respiratory depression in the newborn. The effect of Numorphan, if any, on the later growth, development, and functional maturation of the child is unknown.

Nursing Mothers

It is not known whether Numorphan is excreted in human milk. Because many drugs, including some opioids, are excreted in human milk, caution should be exercised when Numorphan is administered to a nursing woman.

Pediatric Use

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

Adverse Reactions

As with all potent opioid analgesics, possible side effects when using Numorphan include:

Central Nervous System
Drowsiness, sedation, lightheadedness, unusual tiredness or weakness, headache, dysphoria, euphoria, miosis, diplopia, blurred vision, nervousness, restlessness, confusion, mental clouding, trouble sleeping, paradoxical CNS stimulation, hallucinations, mental depression.

Gastrointestinal System
Nausea, vomiting, dry mouth, constipation, biliary tract spasm, cramps or pain, loss of appetite, paralytic ileus or toxic megacolon in patients with inflammatory bowel disease.

Cardiovascular System
Hypotension, orthostatic hypotension particularly in ambulatory patients, tachycardia, bradycardia, palpitations, flushing.

Respiratory System
Respiratory depression, atelectasis, allergic bronchospastic reaction, allergic laryngeal edema, allergic laryngospasm.

Genitourinary System
Ureteral spasm, urinary hesitancy or retention, antidiuretic effect.

Dermatologic
Itching, sweating, injection site reaction, allergic reaction (such as skin rash, hives, and/or itching, swelling of the face).

For the Consumer

Applies to oxymorphone: oral tablet, oral tablet extended release

Other dosage forms:

  • injection solution

Along with its needed effects, oxymorphone (the active ingredient contained in Numorphan) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking oxymorphone:

Less common
  • Blurred vision
  • confusion
  • decreased urination
  • difficult or labored breathing
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • dry mouth
  • fast, pounding, racing, or irregular heartbeat or pulse
  • headache
  • nervousness
  • pounding in the ears
  • rapid breathing
  • sunken eyes
  • sweating
  • swelling of the hands, ankles, or feet
  • thirst
  • tightness in the chest
  • unusual tiredness or weakness
  • wrinkled skin
Rare
  • Abdominal or stomach pain
  • chest pain or discomfort
  • chills
  • cold sweats
  • cough
  • decrease in consciousness
  • decrease in urine volume
  • difficulty in passing urine (dribbling)
  • difficulty with sleeping
  • difficulty with swallowing
  • disorientation
  • drowsiness to profound coma
  • fever
  • hallucination
  • hives, itching, or skin rash
  • hyperventilation
  • hoarseness
  • irregular, slow, or shallow breathing
  • irritability
  • irritation
  • joint pain, stiffness, or swelling
  • lethargy
  • painful urination
  • pale or blue lips, fingernails, or skin
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • redness of the skin
  • restlessness
  • severe constipation
  • severe vomiting
  • shaking
  • trouble in holding or releasing urine

Get emergency help immediately if any of the following symptoms of overdose occur while taking oxymorphone:

Symptoms of overdose
  • Cold and clammy skin
  • constricted, pinpoint, or small pupils (black part of the eye)
  • decreased awareness or responsiveness
  • low blood pressure or pulse
  • muscle weakness
  • severe sleepiness or unusual drowsiness
  • very slow breathing

Some side effects of oxymorphone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Difficulty having a bowel movement (stool)
  • feeling of constant movement of self or surroundings
  • increased sweating
  • nausea or vomiting
  • relaxed and calm
  • sensation of spinning
  • sleepiness
Less common
  • Acid or sour stomach
  • belching
  • decreased appetite
  • decreased weight
  • diarrhea
  • discouragement
  • excess air or gas in the stomach or intestines
  • feeling of warmth
  • feeling sad or empty
  • full or bloated feeling
  • heartburn
  • indigestion
  • lack of appetite
  • loss of interest or pleasure
  • passing gas
  • pressure in the stomach
  • redness of the face, neck, arms, and occasionally, upper chest
  • stomach discomfort or upset
  • swelling of the abdominal or stomach area
  • tiredness
  • trouble concentrating
Rare
  • Blistering, crusting, irritation, itching, or reddening of the skin
  • cracked, dry, scaly skin
  • difficulty with thinking or concentrating
  • disturbed color perception
  • double vision
  • false or unusual sense of well-being
  • feeling jittery
  • halos around lights
  • loss of vision
  • mental depression
  • night blindness
  • nightmares or unusually vivid dreams
  • overbright appearance of lights
  • sudden sweating
  • tunnel vision
  • welts

For Healthcare Professionals

Applies to oxymorphone: injectable solution, oral tablet, oral tablet extended release, rectal suppository

General

The most commonly reported adverse reactions included nausea, pyrexia, somnolence, vomiting, pruritus, headache, dizziness, constipation, and confusion. Additionally, the following adverse events were reported with the extended release tablet, diarrhea, insomnia, fatigue, decreased appetite and abdominal pain.[Ref]

Gastrointestinal

Very common (10% or more): Constipation (up to 26%), nausea (up to 33%), vomiting (up to 16%)
Common (1% to 10%): Dry mouth, abdominal distention, flatulence, abdominal pain, diarrhea, dyspepsia
Frequency not reported: Paralytic ileus, ileus
Postmarketing reports: Difficulty swallowing tablets[Ref]

Respiratory

Common (1% to 10%): Hypoxia, dyspnea
Frequency not reported: Respiratory depression, atelectasis, bronchospasm, decreased oxygen saturation, respiratory distress, respiratory rate decreased
laryngospasm, laryngeal edema, apnea[Ref]

Nervous system

Very common (10% or more): Somnolence (up to 19%), dizziness (excluding vertigo; up to 18%)
Common (1% to 10%): Headache, confusion
Frequency not reported: Sedation, CNS depression
Postmarketing reports: Amnesia, convulsion, memory impairment[Ref]

Hypersensitivity

Frequency not reported: Hypersensitivity including dermatitis allergic, urticaria, pruritus, face swelling[Ref]

Cardiovascular

Common (1% to 10%): Tachycardia, hypotension, edema, flushing, hypertension
Frequency not reported: Bradycardia, palpitations, orthostatic hypotension, syncope[Ref]

Psychiatric

Common (1% to 10%): Anxiety, insomnia, confusion, disorientation, restlessness, nervousness, depression
Frequency not reported: Mental impairment, dysphoria, euphoric mood, agitation, hallucination, drug dependence, drug abuse, feeling jittery[Ref]

Genitourinary

Frequency not reported: Ureteral spasm, urinary hesitation, urinary retention, oliguria, difficult micturition[Ref]

Dermatologic

Very common (10% or more): Pruritus (up to 15%)
Common (1% to 10%): Increased sweating
Frequency not reported: Dermatitis[Ref]

Metabolic

Common (1% to 10%): Decreased appetite, dehydration, decreased weight
Frequency not reported: Anorexia[Ref]

Hepatic

Frequency not reported: Biliary colic[Ref]

Other

Very common (10% or more): Pyrexia (14%)
Frequency not reported: Fatigue, asthenia, hot flashes, clamminess, weakness[Ref]

Ocular

Common (1% to 10%): Vision blurred
Frequency not reported: Miosis, diplopia, visual disturbances[Ref]

Local

Frequency not reported: Injection site reaction[Ref]

Some side effects of Numorphan may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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