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Opana ER

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Opana ER

Opana ER

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Abuse Potential

OPANA ER contains oxymorphone, an opioid agonist and a Schedule II controlled substance. Oxymorphone can be abused in a manner similar to other opioid agonists, legal or illicit. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing OPANA ER in situations where there is concern about increased risks of misuse, abuse, or diversion. Concerns about abuse, addiction, and diversion should not, however, prevent the proper management of pain.

Assess each patient's risk for opioid abuse or addiction prior to prescribing OPANA ER. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients at increased risk may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction. Routinely monitor all patients receiving opioids for signs of misuse, abuse, and addiction because these drugs carry a risk for addiction even under appropriate medical use.

Misuse or abuse of OPANA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the opioid and pose a significant risk that could result in overdose and death [see OVERDOSAGE].

Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Life Threatening Respiratory Depression

Respiratory depression is the primary risk of OPANA ER. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with a “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see OVERDOSAGE].

While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of OPANA ER, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with OPANA ER and following dose increases. Instruct patients against use by individuals other than the patient for whom OPANA ER was prescribed and to keep OPANA ER out of the reach of children, as such inappropriate use may result in fatal respiratory depression.

To reduce the risk of respiratory depression, proper dosing and titration of OPANA ER are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the OPANA ER dose when converting patients from another opioid product can result in fatal overdose with the first dose. Respiratory depression has also been reported with use of modified-release opioids when used as recommended and not misused or abused.

To further reduce the risk of respiratory depression, consider the following:

  • Proper dosing and titration are essential and OPANA ER should only be prescribed by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
  • Instruct patients to swallow OPANA ER tablets intact. The tablets are not to be crushed, dissolved, or chewed. The resulting oxymorphone dose may be fatal, particularly in opioid-na´ve individuals.
  • OPANA ER is contraindicated in patients with respiratory depression and in patients with conditions that increase the risk of life-threatening respiratory depression [see CONTRAINDICATIONS].

Accidental Exposure

Accidental consumption of OPANA ER, especially in children, can result in a fatal overdose of oxymorphone.

Interaction with Alcohol

The co-ingestion of alcohol with OPANA ER can result in an increase of oxymorphone plasma levels and potentially fatal overdose of oxymorphone. Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products containing alcohol while on OPANA ER therapy [see CLINICAL PHARMACOLOGY].

Elderly, Cachectic, and Debilitated Patients

Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance compared to younger, healthier patients. Therefore, monitor such patients closely, particularly when initiating and titrating OPANA ER and when OPANA ER is given concomitantly with other drugs that depress respiration.

Use in Patients with Chronic Pulmonary Disease

Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression for respiratory depression, particularly when initiating therapy and titrating with OPANA ER, as in these patients, even usual therapeutic doses of OPANA ER may decrease respiratory drive to the point of apnea. Consider the use of alternative non-opioid analgesics in these patients if possible.

Interactions with CNS Depressants and Illicit Drugs

Hypotension, profound sedation, coma, or respiratory depression may result if OPANA ER is used concomitantly with other CNS depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of OPANA ER in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient's response, including the degree of tolerance that has developed to CNS depression. Additionally, consider the patient's use, if any, of alcohol or illicit drugs that cause CNS depression. If OPANA ER therapy is to be initiated in a patient taking a CNS depressant, start with a lower OPANA ER dose than usual and monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant [see DRUG INTERACTIONS].

Use in Patients with Hepatic Impairment

A study of OPANA ER in patients with hepatic disease indicated greater plasma concentrations than those with normal hepatic function [see CLINICAL PHARMACOLOGY]. OPANA ER is contraindicated in patients with moderate or severe hepatic impairment. In patients with mild hepatic impairment reduce the starting dose to the lowest dose and monitor for signs of respiratory and central nervous system depression [see DOSAGE AND ADMINISTRATION].

Hypotensive Effect

OPANA ER may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is an increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g. phenothiazines or general anesthetics) [see DRUG INTERACTIONS]. Monitor these patients for signs of hypotension after initiating or titrating the dose of OPANA ER. In patients with circulatory shock, OPANA ER may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of OPANA ER in patients with circulatory shock.

Use in Patients with Head Injury or Increased Intracranial Pressure

Monitor patients taking OPANA ER who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with OPANA ER. OPANA ER may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of OPANA ER in patients with impaired consciousness or coma.

Use in Patients with Gastrointestinal Conditions

OPANA ER is contraindicated in patients with paralytic ileus. Avoid the use of OPANA ER in patients with other GI obstruction.

The oxymorphone in OPANA ER may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase.

Use in Patients with Convulsive or Seizure Disorders

The oxymorphone in OPANA ER may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during OPANA ER therapy.

Avoidance of Withdrawal

Avoid the use of mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) in patients who have received or are receiving a course of therapy with an opioid agonist analgesic, including OPANA ER. In these patients, mixed agonists/antagonists analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.

When discontinuing OPANA ER, gradually taper the dose [see DOSAGE AND ADMINISTRATION]. Do not abruptly discontinue OPANA ER.

Driving and Operating Machinery

OPANA ER may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of OPANA ER and know how they will react to the medication.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide)

Abuse Potential

Inform patients that OPANA ER contains oxymorphone, a Schedule II controlled substance that is subject to abuse. Instruct patients not to share OPANA ER with others and to take steps to protect OPANA ER from theft or misuse.

Life-threatening Respiratory Depression

Discuss the risk of respiratory depression with patients, explaining that the risk is greatest when starting OPANA ER or when the dose is increased. Advise patients how to recognize respiratory depression and to seek medical attention if they are experiencing breathing difficulties.

Accidental Exposure

Instruct patients to take steps to store OPANA ER securely. Accidental exposure, especially in children, may results in serious harm or death. Advise patients to dispose of unused OPANA ER by flushing the tablets down the toilet.

Risks from Concomitant Use of Alcohol and other CNS Depressants

Inform patients that the concomitant use of alcohol with OPANA ER can increase the risk of life-threatening respiratory depression. Instruct patients not to consume alcoholic beverages, as well as prescription and over-thecounter drug products that contain alcohol, during treatment with OPANA ER.

Inform patients that potentially serious additive effects may occur if OPANA ER is used with other CNS depressants, and not to use such drugs unless supervised by a health care provider.

Important Administration Instructions

Instruct patients how to properly take OPANA ER, including the following:

  • Swallowing OPANA ER tablets whole
  • Not crushing, chewing, or dissolving the tablets
  • Using OPANA ER exactly as prescribed to reduce the risk of life-threatening adverse reactions (e.g., respiratory depression)
  • Not discontinuing OPANA ER without first discussing the need for a tapering regimen with the prescriber
Hypotension

Inform patients that OPANA ER may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position).

Driving or Operating Heavy Machinery

Inform patients that OPANA ER may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication.

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention.

Anaphylaxis

Inform patients that anaphylaxis has been reported with ingredients contained in OPANA ER. Advise patients how to recognize such a reaction and when to seek medical attention.

Pregnancy

Advise female patients that OPANA ER can cause fetal harm and to inform the prescriber if they are pregnant or plan to become pregnant.

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 17.3fold (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 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 ~3-fold 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 pregnant 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

OPANA ER is not for use in women during and immediately prior to labor, where shorter acting analgesics or other analgesic techniques are more appropriate [see INDICATIONS AND USAGE]. Occasionally, opioid analgesics may prolong labor through by temporarily reducing the strength, duration, and frequency of uterine contractions. However, these effects are not consistent and may be offset by an increased rate of cervical dilatation which tends to shorten labor.

Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. Closely observe neonates whose mothers received opioid analgesics during labor for signs of respiratory depression. An opioid antagonist, such as naloxone, should be available for reversal of opioid-induced respiratory depression in the neonate in such situations.

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. Monitor infants who may be exposed to OPANA ER through breast milk 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

The safety and effectiveness of OPANA ER in patients below the age of 18 years have not been established.

Geriatric Use

Of the total number of subjects in clinical studies of OPANA ER, 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. On average, age greater than 65 years was associated with a 1.4-fold increase in oxymorphone AUC and a 1.5-fold increase in Cmax. Initiate dosing with OPANA ER in patients 65 years of age and over using the 5 mg dose and monitor closely for signs of respiratory and central nervous system depression when initiating and titrating OPANA ER. For patients on prior opioid therapy, start at 50% of the starting dose for a younger patient on prior opioids and titrate slowly.

Hepatic Impairment

Patients with mild hepatic impairment have an increase in oxymorphone bioavailability of 1.6-fold. In opioid-na´ve patients with mild hepatic impairment, initiate OPANA ER using the 5 mg dose and monitor closely for respiratory and central nervous system depression. OPANA ER is contraindicated for patients with moderate and severe hepatic impairment [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and DOSAGE AND ADMINISTRATION]. For patients on prior opioid therapy, start at the 50% of the dose for that a patient with normal hepatic function on prior opioids and titrate slowly.

Renal Impairment

Patients with moderate to severe renal impairment were shown to have an increase in oxymorphone bioavailability ranging from 57-65% [see CLINICAL PHARMACOLOGY]. Start opioid-na´ve patients with the 5 mg dose of OPANA ER and titrate slowly while closely monitoring for respiratory and central nervous system depression [see DOSAGE AND ADMINISTRATION]. For patients on prior opioid therapy, start at 50% of the dose for a patient with normal renal function on prior opioids and titrate slowly.

Neonatal Opioid Withdrawal Syndrome

Chronic maternal use of oxymorphone during pregnancy can affect the fetus with subsequent withdrawal signs. Neonatal withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration and severity of neonatal withdrawal syndrome vary based on the drug used, duration of use, the dose of last maternal use, and rate of elimination of the drug by the newborn. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts.

Last reviewed on RxList: 7/27/2012
This monograph has been modified to include the generic and brand name in many instances.

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