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Numorphan (Oxymorphone Hydrochloride) - Description and Clinical Pharmacology

 
 



NUMORPHAN®
(Oxymorphone Hydrochloride Injection, USP) CII
(Oxymorphone Hydrochloride Suppositories, USP)
Opioid
Analgesic

Rx only

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.

CLINICAL PHARMACOLOGY

NUMORPHAN is a potent opioid analgesic. Administered parenterally, 1 mg of NUMORPHAN is approximately equivalent in analgesic activity to 10 mg of morphine sulfate.

Many of the effects described below are common to the class of opioid analgesics, including NUMORPHAN.

Central Nervous System (CNS)

Opioid analgesics exert their principal pharmacologic effects on the CNS and the gastrointestinal tract. The principal actions of therapeutic value are analgesia and sedation. The precise mechanism of the analgesic action is unknown. However, specific CNS opiate receptors have been identified and likely play a role in the expression of analgesic effects.

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. Opioids depress the cough reflex by direct action on the cough center in the medulla. Opioids cause miosis. Pinpoint pupils are a common sign of opioid overdose but are not pathognomonic. Marked mydriasis may be seen with worsening hypoxia.

Gastrointestinal Tract and Other Smooth Muscle

Opioids decrease gastric, biliary, and pancreatic secretions. These drugs cause a reduction in motility associated with an increase in tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased while tone is increased to the point of spasm. The end result is constipation. Opioids can cause a marked increase in biliary tract pressure as a result of spasm of the sphincter of Oddi.

Opioids increase smooth muscle tone in the urinary tract and can induce spasms. Urinary urgency and difficulty with urination may result. These effects, in conjunction with the central effect of these drugs on release of vasopressin, may produce oliguria.

Pharmacokinetics

The onset of action of parenterally administered NUMORPHAN is rapid; initial effects are usually perceived within 5 to 10 minutes. Its duration of action is approximately 3 to 6 hours.

Distribution
After an IV dose, the steady state volume of distribution was 3.08 ± 1.14 L/kg in healthy male and female subjects.

Metabolism
Oxymorphone undergoes extensive hepatic metabolism in humans. After a 10 mg oral dose, 49% was excreted over a five-day period in the urine. Of this, 82% was excreted in the first 24 hours after administration. The recovered drug-related products contained the oxymorphone (1.9%), the conjugate of oxymorphone (44.1%), the 6β-carbinol produced by 6-keto reduction of oxymorphone (0.3%), and the conjugates of 6β-carbinol (2.6%) and 6α-carbinol (0.1%).

Elimination
In healthy subjects, the mean terminal half-life of oxymorphone was 1.3 ± 0.7 hours. The mean systemic clearance was 2.0 ± 0.5 L/min.

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