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Included as part of the PRECAUTIONS section.

Information Essential for Safe Administration

OPANA ER tablets are to be swallowed whole, and are not to be cut, broken, chewed, crushed or dissolved. Taking cut, broken, chewed, dissolved, or crushed OPANA ER tablets could lead to the rapid release and absorption of a potentially fatal dose of oxymorphone [see BOXED WARNING].

Patients must not consume alcoholic beverages, or prescription or non-prescription medications containing alcohol, while on OPANA ER therapy. The co-ingestion of alcohol with OPANA ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone [see Pharmacokinetics].

Instruct patients against use by individuals other than the patient for whom OPANA ER was prescribed, as such inappropriate use may have severe medical consequences, including death.

Respiratory Depression

Respiratory depression is the chief hazard of OPANA ER. Respiratory depression is a potential problem 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 ER 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 ER only under careful medical supervision at the lowest effective dose in such patients.

Misuse, Abuse and Diversion of Opioids

OPANA ER 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 ER tablets may be abused by crushing, chewing, snorting or injecting the product. These practices will result in the less controlled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death [see Drug Abuse and Dependence].

OPANA ER 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 ER.

Healthcare professionals should advise patients to store OPANA ER 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.

Interactions with Alcohol and other CNS Depressants

Patients receiving other opioid analgesics, general anesthetics, phenothiazines or other tranquilizers, sedatives, hypnotics, or other CNS depressants (including alcohol) concomitantly with oxymorphone may experience respiratory depression, hypotension, profound sedation, coma and death [see DRUG INTERACTIONS]. Avoid concurrent use of alcohol and OPANA ER [see Pharmacokinetics].

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 possible 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 ER with extreme caution to 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.

Hypotensive Effect

OPANA ER 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 ER with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.

Hepatic Impairment

A study of oxymorphone hydrochloride extended-release tablets in patients with hepatic disease indicated greater plasma concentrations than those with normal hepatic function [see CLINICAL PHARMACOLOGY]. Use OPANA ER 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 ER is contraindicated in patients with moderate or severe hepatic impairment.

Special Risk Groups

Use OPANA ER 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.

Gastrointestinal Effects

OPANA ER decreases bowel motility. Opioids diminish propulsive peristaltic waves in the gastrointestinal tract. Monitor for decreased bowel motility in post-operative patients receiving opioids. The administration of OPANA ER may obscure the diagnosis or clinical course in patients with acute abdominal conditions. OPANA ER is contraindicated in patients with paralytic ileus.

Ambulatory Surgery and Post-Operative Use

OPANA ER is not indicated for pre-emptive analgesia (administration pre-operatively for the management of post-operative pain).

OPANA ER is only indicated for postoperative use in the patient if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time. Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate (see American Pain Society guidelines).

Patients who are already receiving OPANA ER as part of ongoing analgesic therapy may be safely continued on the drug if appropriate dosage adjustments are made considering the procedure, other drugs given, and the temporary changes in physiology caused by the surgical intervention.

Use in Pancreatic/Biliary Tract Disease

OPANA ER, like other opioids, may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis.

Driving and Operating Machinery

Opioid analgesics, including OPANA ER, may impair the mental and physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.

Patient Counseling Information

See FDA-Approved Medication Guide

• Advise patients that OPANA ER contains oxymorphone, a morphine-like pain medication, and should be taken only as directed.
• Advise patients that OPANA ER is designed to work properly only if swallowed whole. The extended-release tablets may release all their contents at once if broken, chewed or crushed, resulting in a risk of fatal overdose of oxymorphone.
• Advise patients they must not consume alcoholic beverages, or prescription or non-prescription medications containing alcohol, while on OPANA ER therapy. The co-ingestion of alcohol with OPANA ER may result in increased plasma levels and a potentially fatal overdose of oxymorphone.
• Advise patients that OPANA ER tablets should be taken on an empty stomach, at least one hour prior to or two hours after eating
• Advise patients that OPANA ER tablets should be taken one at a time.
• Advise patients not to pre-soak, lick or otherwise wet tablet prior to placing in the mouth.
• Advise patients to take each tablet with enough water to ensure complete swallowing immediately after placing in mouth.
• Appropriate pain management requires changes in the dose to maintain best pain control. Advise patients of the need to contact their physician if pain control is inadequate, but not to change the dose of OPANA ER without consulting their physician.
• Advise patients to report episodes of breakthrough pain and adverse experiences occurring during OPANA ER therapy to their doctor. Individualization of dosage is essential to make optimal use of this medication.
• Caution patients that OPANA ER may cause drowsiness, dizziness, or lightheadedness, and may impair mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car, operating machinery, etc.
• Instruct patients not to combine OPANA ER with central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because additive effects may occur, resulting in serious injury or death.
• Advise patients taking OPANA ER of the potential for severe constipation. Appropriate laxatives and/or stool softeners and other therapeutic approaches may be considered for use with the initiation of OPANA ER therapy.
• Advise patients not to adjust the dose of OPANA ER without consulting the prescribing professional.
• Advise patients that OPANA ER is a potential drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
• Advise women of childbearing potential who become, or are planning to become pregnant to consult their physician regarding the effects of opioid analgesics and other drug use during pregnancy on themselves and their unborn child.
• Advise patients that if they miss a dose, to take it as soon as possible. If it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Advise patients not to take more than the prescribed dose of OPANA ER. If the patient is not sure about dosing advise them to call their healthcare provider.
• If patients have been receiving treatment with OPANA ER for more than a few days to weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose and that abruptly discontinuing the medication could precipitate withdrawal symptoms. Provide patients with a dose schedule to accomplish a gradual discontinuation of the medication.
• As with any potent opioid, misuse of OPANA ER may result in serious adverse events. Instruct patients to keep OPANA ER in a secure place out of the reach of children and pets. Accidental consumption especially in children can result in overdose or death. When OPANA ER is no longer needed, instruct patients to destroy unused tablets by flushing down the toilet.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies have been completed to evaluate the carcinogenic potential of oxymorphone in both Sprague-Dawley rats and CD-1 mice. Oxymorphone HCl 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 in male rats was 0.34-fold and at the 25 mg/kg/day dose in female rats was 1.5-fold 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.

Mutagenesis

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 ≥ 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 hydrochloride did not affect reproductive function or sperm parameters in male rats at any dose tested ( ≤ 50 mg/kg/day). The highest dose tested is ~6-fold the human dose of 40 mg every 12 hours, based on body surface area. 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 1.2-fold the human dose of 40 mg every 12 hours based on a body surface area. The dose of oxymorphone that produced no adverse effects on reproductive findings in female rats is 0.6-fold the human dose of 40 mg every 12 hours on a body surface area basis.

Use In Specific Populations

Pregnancy

The safety of using oxymorphone in pregnancy has not been established with regard to possible adverse effects on fetal development. The use of OPANA ER 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.

Prolonged use of opioid analgesics including OPANA ER during pregnancy may cause fetal-neonatal physical dependence.

Teratogenic Effects - Pregnancy Category C

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

Oxymorphone hydrochloride administration did not cause malformations at any doses evaluated during developmental toxicity studies in rats ( ≤ 25 mg/kg/day) or rabbits ( ≤ 50 mg/kg/day). These doses are ~3fold and ~12-fold the human dose of 40 mg every 12 hours, based on body surface area. There were no developmental effects in rats treated with 5 mg/kg/day or rabbits treated with 25 mg/kg/day. Fetal weights were reduced in rats and rabbits given doses of ≥ 10 mg/kg/day and 50 mg/kg/day, respectively. These doses are ~1.2-fold and ~12-fold the human dose of 40 mg every 12 hours based on body surface area, respectively. There were no effects of oxymorphone hydrochloride on intrauterine survival in rats at doses ≤ 25 mg/kg/day, or rabbits at ≤ 50 mg/kg/day in these studies (see Non-teratogenic Effects, below). In a study that was 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 was reported to produce malformations in offspring of hamsters that received 15.5-fold the human dose of 40 mg every 12 hours based on body surface area. This dose also produced 20% maternal lethality.

Non-teratogenic Effects

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 increased incidence of stillborn pups. An increase in neonatal death occurred at ≥ 5 mg/kg/day. Post-natal survival of the pups was reduced throughout weaning following treatment of the dams with 25 mg/kg/day. Low pup birth weight and decreased postnatal weight gain occurred in pups born to oxymorphone-treated female rats given a dose of 25 mg/kg/day. This dose is ~3-fold higher than the human dose of 40 mg every 12 hours on a body surface area basis.

Labor and Delivery

Opioids cross the placenta and may produce respiratory depression in neonates. OPANA ER 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.

Upon delivery from a mother who received opioids for a long period of time, 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.

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 OPANA ER is administered to a nursing woman. Infants exposed to OPANA ER 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 OPANA ER in pediatric patients below the age of 18 years have not been established.

Geriatric Use

OPANA ER should be used with caution in elderly patients [see CLINICAL PHARMACOLOGY].

Of the total number of subjects in clinical studies of extended-release oxymorphone tablets, 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.

Hepatic Impairment

In a PK study of extended-release oxymorphone tablets, patients with mild hepatic impairment were shown to have an increase in bioavailability of 1.6 fold. Use OPANA ER with caution in patients with mild impairment. Start these patients on the lowest dose and titrate slowly while carefully monitoring for side effects. OPANA ER is contraindicated for patients with moderate and severe hepatic impairment [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and DOSAGE AND ADMINISTRATION].

Renal Impairment

In a PK 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]. Start these patients with the lowest dose of OPANA ER and titrate slowly while monitored for side effects [see DOSAGE AND ADMINISTRATION].

Last reviewed on RxList: 12/28/2011
This monograph has been modified to include the generic and brand name in many instances.