"Today, the U.S. Food and Drug Administration approved Kanuma (sebelipase alfa) as the first treatment for patients with a rare disease known as lysosomal acid lipase (LAL) deficiency.
Patients with LAL deficiency (also known as Wolman disea"...
Respiratory depression is the chief hazard of OPANA (oxymorphone hydrochloride) . Respiratory depression may occur more frequently in elderly or debilitated patients as well as in those suffering from conditions accompanied by hypoxia or hypercapnia, when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.
Administer OPANA (oxymorphone hydrochloride) with extreme caution to patients with conditions accompanied by hypoxia, hypercapnia, or decreased respiratory reserve such as: asthma, chronic obstructive pulmonary disease or cor pulmonale, severe obesity, sleep apnea syndrome, myxedema, kyphoscoliosis, CNS depression, or coma. In these patients, even usual therapeutic doses of oxymorphone may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Consider alternative non-opioid analgesics and use OPANA (oxymorphone hydrochloride) only under careful medical supervision at the lowest effective dose in such patients.
Misuse, Abuse, and Diversion of Opioids
OPANA (oxymorphone hydrochloride) contains oxymorphone, a mu opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Oxymorphone can be abused in a manner similar to other opioid agonists, legal or illicit. This issue should be considered when prescribing or dispensing oxymorphone in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
OPANA (oxymorphone hydrochloride) tablets may be abused by crushing, chewing, snorting, or injecting the product. These practices pose a significant risk to the abuser that could result in overdose and death [see Drug Abuse and Dependence].
OPANA (oxymorphone hydrochloride) may be targeted for theft and diversion. Healthcare professionals should contact their State Medical Board, State Board of Pharmacy, or State Control Board for information on how to detect or prevent diversion of this product, and security requirements for storing and handling of OPANA (oxymorphone hydrochloride) .
Healthcare professionals should advise patients to store OPANA (oxymorphone hydrochloride) in a secure place, preferably locked and out of the reach of children and other non-caregivers.
Concerns about abuse, misuse, diversion and addiction should not prevent the proper management of pain.
Additive CNS Depressant Effects
The concomitant use of other CNS depressants including other opioids, general anesthetics, phenothiazines, other tranquilizers, sedatives, hypnotics, and alcohol with oxymorphone may produce increased depressant effects including hypoventilation, hypotension, profound sedation, coma and death [see DRUG INTERACTIONS].
Use in Patients with Head Injury and Increased Intracranial Pressure
In the presence of head injury, intracranial lesions or a preexisting increase in intracranial pressure, the respiratory depressant effects of opioid analgesics and their potential to elevate cerebrospinal fluid pressure (resulting from vasodilation following CO2 retention) may be markedly exaggerated. Furthermore, opioid analgesics can produce effects on papillary response and consciousness, which may obscure neurologic signs of further increases in intracranial pressure in patients with head injuries.
Administer OPANA (oxymorphone hydrochloride) with extreme caution in patients who may be particularly susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or impaired consciousness.
Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.
OPANA (oxymorphone hydrochloride) , like all opioid analgesics, may cause severe hypotension in a patient whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents that compromise vasomotor tone. Administer OPANA (oxymorphone hydrochloride) with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.
A study of extended-release oxymorphone tablets in patients with hepatic disease indicated greater plasma concentrations than in those with normal hepatic function [see CLINICAL PHARMACOLOGY]. Use OPANA (oxymorphone hydrochloride) with caution in patients with mild impairment, starting with the lowest dose and titrating slowly while carefully monitoring for side effects [see DOSAGE AND ADMINISTRATION]. OPANA (oxymorphone hydrochloride) is contraindicated in patients with moderate or severe hepatic impairment.
Special Risk Groups
Use OPANA (oxymorphone hydrochloride) with caution in the following conditions: adrenocortical insufficiency (e.g., Addison's disease), prostatic hypertrophy or urethral stricture, severe impairment of pulmonary or renal function, and toxic psychosis.
Opioids may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings.
Opioids diminish propulsive peristaltic waves in the gastrointestinal tract. Monitor for decreased bowel motility in post-operative patients receiving opioids. The administration of OPANA (oxymorphone hydrochloride) may obscure the diagnosis or clinical course in patients with acute abdominal conditions. OPANA (oxymorphone hydrochloride) is contraindicated in patients with paralytic ileus.
Use in Pancreatic/Biliary Tract Disease
Driving and Operating Machinery
Opioid analgesics impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies have been completed to evaluate the carcinogenic potential of oxymorphone in both Sprague-Dawley rats and CD-1 mice. Oxymorphone was administered to Sprague-Dawley rats (2.5, 5, and 10 mg/kg/day in males and 5, 10, and 25 mg/kg/day in females) for 2 years by oral gavage. The systemic drug exposure (AUC ng•h/mL) at the 10 mg/kg/day dose in male rats was 0.34-fold and at the 25 mg/kg/day dose in female rats was 1.5fold the human exposure at a dose of 260 mg/day. No evidence of carcinogenic potential was observed in rats. Oxymorphone was administered to CD-1 mice (10, 25, 75 and 150 mg/kg/day) for 2 years by oral gavage. The systemic drug exposure (AUC ng•h/mL) at the 150 mg/kg/day dose in mice was 14.5-fold (in males) and 17.3-fold (in females) times the human exposure at a dose of 260 mg/day. No evidence of carcinogenic potential was observed in mice.
Oxymorphone hydrochloride was not mutagenic when tested in the in vitro bacterial reverse mutation assay (Ames test) at concentrations of ≤ 5270 μg/plate, or in an in vitro mammalian cell chromosome aberration assay performed with human peripheral blood lymphocytes at concentrations ≤ 5000 μg/ml with or without metabolic activation. Oxymorphone hydrochloride tested positive in both the rat and mouse in vivo micronucleus assays. An increase in micronucleated polychromatic erythrocytes occurred in mice given doses of ≥ 250 mg/kg and in rats given doses of 20 and 40 mg/kg. A subsequent study demonstrated that oxymorphone hydrochloride was not aneugenic in mice following administration of up to 500 mg/kg. Additional studies indicate that the increased incidence of micronucleated polychromatic erythrocytes in rats may be secondary to increased body temperature following oxymorphone administration. Doses associated with increased micronucleated polychromatic erythrocytes also produce a marked, rapid increase in body temperature. Pretreatment of animals with sodium salicylate minimized the increase in body temperature and prevented the increase in micronucleated polychromatic erythrocytes after administration of 40 mg/kg oxymorphone.
Impairment of fertility
Oxymorphone did not affect reproductive function or sperm parameters in male rats at any dose tested ( ≤ 50 mg/kg/day). In female rats, an increase in the length of the estrus cycle and decrease in the mean number of viable embryos, implantation sites and corpora lutea were observed at doses of oxymorphone ≥ 10 mg/kg/day. The dose of oxymorphone associated with reproductive findings in female rats is 0.8 times a total human daily dose of 120 mg based on a body surface area. The dose of oxymorphone that produced no adverse effects on reproductive findings in female rats (i.e., NOAEL) is 0.4-times a total human daily dose of 120 mg based on body surface area.
Use In Specific Populations
The safety of using oxymorphone in pregnancy has not been established with regard to possible adverse effects on fetal development. The use of OPANA (oxymorphone hydrochloride) in pregnancy, in nursing mothers, or in women of child-bearing potential requires that the possible benefits of the drug be weighted against the possible hazards to the mother and the child.
Teratogenic Effects - Pregnancy Category C
There are no adequate and well-controlled studies of oxymorphone in pregnant women. In animal studies, oxymorphone caused decreased fetal and pup weights, an increase in stillbirth, and a decrease in postnatal pup survival at maternal oxymorphone doses equivalent to 0.4 to 4 times the human daily dose of 120 mg (Based on body surface area). OPANA (oxymorphone hydrochloride) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In embryo-fetal developmental toxicity studies, pregnant rats and rabbits received oxymorphone hydrochloride at doses up to about 2 times (rats) and 8 times (rabbits) total human daily dose of 120 mg (based on body surface area). No malformations occurred, but reduced fetal weights occurred at maternal doses of 0.8 (rat) and 4 (rabbit) times the total human daily dose of 120 mg (based on body surface area). There were no adverse developmental effects in rats that received 0.4 times or rabbits that received less than 4 times the total human dose. There were no effects of oxymorphone hydrochloride on intrauterine survival at doses in rats ≤ 2 times, or in rabbits at ≤ 8 times the human dose (see Non-teratogenic Effects, below). In a study conducted prior to the establishment of Good Laboratory Practices (GLP) and not according to current recommended methodology, a single subcutaneous injection of oxymorphone hydrochloride on gestation day 8 produced malformations in offspring of hamsters that received a dose equivalent to 10 times the total human daily dose of 120 mg (based on body surface area). This dose also produced 83% maternal lethality.
Oxymorphone hydrochloride administration to female rats during gestation in a pre- and postnatal developmental toxicity study reduced mean litter size (18%) at a dose of 25 mg/kg/day, attributed to an increase in the incidence of stillborn pups. An increase in neonatal death occurred at doses ≥ 5 mg/kg/day (0.4 times a total human daily dose of 120 mg, based on body surface area). Low pup birth weight, decreased post-natal weight gain, and reduced post-natal survival of pups occurred following treatment of the dams with 25 mg/kg/day (about 2 times a total human daily dose of 120 mg, based on body surface area).
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
Opioids cross the placenta and may produce respiratory depression in neonates. OPANA (oxymorphone hydrochloride) is not recommended for use in women during and immediately prior to labor, when use of shorter acting analgesics or other analgesic techniques are more appropriate. Occasionally, opioid analgesics may prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor. Neonates whose mothers received opioid analgesics during labor should be observed closely for signs of respiratory depression. A specific opioid antagonist, such as naloxone or nalmefene, should be available for reversal of opioid-induced respiratory depression in the neonate.
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 OPANA (oxymorphone hydrochloride) is administered to a nursing woman. Infants exposed to OPANA (oxymorphone hydrochloride) 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.
Safety and effectiveness of OPANA (oxymorphone hydrochloride) in pediatric patients below the age of 18 years have not been established.
OPANA (oxymorphone hydrochloride) should be used with caution in elderly patients [see CLINICAL PHARMACOLOGY].
Of the total number of subjects in clinical studies of OPANA (oxymorphone hydrochloride) , 31% were 65 and over, while 7% 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. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy
In a study of extended-release oxymorphone tablets, patients with mild hepatic impairment were shown to have an increase in bioavailability of 1.6 fold. OPANA (oxymorphone hydrochloride) should be used with caution in patients with mild impairment. These patients should be started with the lowest dose and titrated slowly while carefully monitoring for side effects. OPANA (oxymorphone hydrochloride) is contraindicated for patients with moderate and severe hepatic impairment [see CONTRAINDICATIONS, and DOSAGE AND ADMINISTRATION].
In a study of extended-release oxymorphone tablets, patients with moderate to severe renal impairment were shown to have an increase in bioavailability ranging from 57-65% [see CLINICAL PHARMACOLOGY]. Such patients should be started cautiously with lower doses of OPANA (oxymorphone hydrochloride) and titrated slowly while monitoring for side effects [see DOSAGE AND ADMINISTRATION].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 3/28/2011
Additional Opana Information
Opana - User Reviews
Opana User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.