Numorphan

Uses

Tablet is used for treatment of moderate to severe pain like chronic cancer, arthritis, postoperative & low back pain.

Injection is used for the relief of moderate to severe pain. It is also used for pre-operative & post-operative 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.

Numorphan is also used to associated treatment for these conditions: Anxiety, Severe Pain, Moderate Pain, Perioperative analgesia, Obstetrical analgesia therapy

How Numorphan works

Numorphan 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.

Dosage

Numorphan dosage

Numorphan Tablet: This may be used as needed in the treatment of acute post-surgical pain with a dose of 5-10 mg every 4 hours. Administer Numorphan Tablet on an empty stomach at least one hour prior to or two hours after eating.

Numorphan Injection:

• Subcutaneous or Intramuscular Administration: Initially 1 mg to 1.5 mg, repeated every 4 to 6 hours as needed.
• Intravenous: 0.5 mg initially. For analgesia during labor 0.5 mg to 1 mg intramuscularly is recommended.

Conversion from Oral Numorphan to Numorphan Injection: Given the absolute oral bioavailability of approximately 10%, patients receiving oral Numorphan may be converted to Numorphan Hydrochloride injection by administering one-tenth the patient's total daily oral Numorphan dose as Numorphan Hydrochloride injectable in four or six equally divided doses (e.g., total daily oral dose/ [10X4]). For example, approximately 1 mg of Numorphan Hydrochloride injectable IM every 6 hours (4 mg total IM dose) may be required to provide pain relief equivalent to a total daily dose of 40 mg oral Numorphan. As with any opioid drug product, it is necessary to adjust the dosing regimen for each patient individually taking into account the patient's prior analgesic treatment experience.

Side Effects

General Disorders: Respiratory depression, Fatigue, Asthenia.

Metabolism and Nutrition Disorders: Anorexia.

Cardiac Disorders: Tachycardia, Bradycardia, Palpitations.

Eye Disorders: Miosis, Diplopia, Blurred vision.

Gastrointestinal Disorders: Vomiting, Constipation.

Psychiatric Disorders: Dysphoria, Euphoric mood, Nervousness, Restlessness, Insomnia, Agitation, Hallucination, Depression.

Vascular Disorders: Hypotension & Flushing.

Toxicity

Numorphan overdosage is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. Patients experiencing an overdose may develop apnea, circulatory collapse, and cardiac arrest. Intravenous mouse LD₅₀ is 172 mg/kg.

Precaution

Do not stop abruptly; taper gradually to stop treatment. Use caution in patients with acute pancreatitis, Addison disease, benign prostatic hyperplasia, cardiac arrhythmias, central nervous system (CNS) depression, drug abuse or dependence, emotional lability, gallbladder disease, gastrointestinal (Gl) disorder, pseudomembranous colitis, Gl surgery, head injury, hypothyroidism or untreated myxedema, intracranial hypertension, brain tumor, toxic psychosis, urethral stricture, urinary tract surgery, seizures, acute alcoholism, delirium tremens, shock, cor pulmonale, chronic pulmonary disease, emphysema, kyphoscoliosis, severe obesity, renal or hepatic impairment, elderly or debilitated patients.

Avoid alcohol. Reduce dosage if drug is coadministered with other CNS depressants. Thrombocytopenia purpura resulting in kidney failure or death has been reported when extended-release tablets are dissolved and injected IV. May obscure diagnosis of abdominal conditions.

Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death Assess each patient's risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions Life-threatening respiratory depression, life-threatening, or fatal respiratory depression may occur

Monitor for respiratory depression, especially during initiation or following a dose increase

Interaction

Clinical drug interaction studies with Numorphan showed no induction of CYP450 3A4 or 2C9 enzyme activity indicating that no dose adjustment for CYP 3A4 or 2C9 mediated drug-drug interactions is required.

Food Interaction

• Avoid alcohol. Ingesting alcohol has unpredictable effects on the pharmacokinetics of oxymorphone. Alcohol may also potentiate the CNS depressant effects of oxymorphone.
• Take on an empty stomach. Take oxymorphone at least one hour before or two hours after eating as food may increase the absorption of oxymorphone.

Numorphan Alcohol interaction

[Moderate] GENERALLY AVOID:

Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics.

Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills.

In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

Concomitant use of opioid analgesics with ethanol should be avoided.

Numorphan Drug Interaction

Major: zolpidem, hydromorphone, fentanyl, cyclobenzaprine, clonazepam, pregabalin, morphine, gabapentin, acetaminophen / hydrocodone, oxycodone, acetaminophen / oxycodone, quetiapine, carisoprodol, diazepam, alprazolamModerate: duloxetineUnknown: amphetamine / dextroamphetamine, aspirin, celecoxib, cholecalciferol

Numorphan Disease Interaction

Major: impaired GI motility, infectious diarrhea, liver disease, prematurity, acute alcohol intoxication, drug dependence, gastrointestinal obstruction, hypotension, intracranial pressure, respiratory depressionModerate: adrenal insufficiency, biliary spasm, hypothyroidism, renal dysfunction, seizure disorders, urinary retention, arrhythmias

Half Life

1.3 (+/-0.7) hours

Elimination Route

Numorphan is highly metabolized, principally in the liver, and undergoes reduction or conjugation with glucuronic acid to form both active and inactive products. Because oxymorphone is extensively metabolized, <1% of the administered dose is excreted unchanged in the urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. The safety of using Numorphan in pregnancy has not been established with regard to possible adverse effects on fetal development. The use of Numorphan in pregnancy, in nursing mothers, 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.

Contraindication

• Significant respiratory depression
• Acute or severe bronchial asthma or hypercarbia
• Known or suspected paralytic ileus
• Moderate and severe hepatic impairment
• Hypersensitivity (e.g. anaphylaxis) to oxymorphone

Special Warning

Pediatric use: Safety and effectiveness of Numorphan Hydrochloride tablet and injection in pediatric patients below the age of 18 years have not been established.

Geriatric use: Numorphan Hydrochloride tablet and injection should be used with caution in elderly patients. These adverse events included dizziness, somnolence, confusion and nausea.

Acute Overdose

Signs and Symptoms: Acute overdosage with Numorphan is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils and sometimes bradycardia and hypotension.

Treatment: In the treatment of Numorphan overdosage, primary attention should be given to the re-establishment of a patient airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. The opioid antagonist naloxone hydrochloride is a specific antidote against respiratory depression that may result from overdosage or unusual sensitivity to opioids including Numorphan

Storage Condition

Tablet: Store in a cool and dry place, protect from light.

Injection: Store at 25°C, protect from light.

Innovators Monograph

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