OPANA® ER – Pharmacokinetic Profile
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`Pharmacokinetic Profile
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`When compared in 3 studies
`OPANA® ER with INTAC®1 and the original formulation showed a similar oxymorphone plasma
`concentration at all time points over 12 hours2,*
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`Mean oxymorphone plasma concentrations under fasted conditions after single oral dose of original formulation and
`OPANA® ER with INTAC®
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`The correlation of pharmacokinetics to clinical effects has not been established
`With all doses and administration conditions (fasted or fed), the oxymorphone plasma concentration vs time profile was similar overall.2
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`In 3 open-label, randomized studies, healthy adults at a clinical research center received 2 single oral doses of original formulation and 2 single doses of OPANA® ER, each separated by a ≥7-day
`washout. Doses were administered under fasted conditions (study 1, 5 mg doses; study 2, 40 mg doses) or after a high-fat breakfast (study 3, 40 mg doses). Subjects administered 40 mg doses also
`received naltrexone. The primary endpoint was systemic oxymorphone exposure; the bioequivalence criterion was met if the 90% confidence intervals of the geometric mean ratio (OPANA ER/original
`formulation) for oxymorphone area under the curve from time 0 to the last measured concentration (AUC0–t), AUC from time 0 to infinity (AUC0–inf), and maximum plasma concentration (Cmax) were
`within 0.8–1.25.2
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`* *
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`IMPORTANT SAFETY INFORMATION
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`WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION,
`ACCIDENTAL EXPOSURE, and INTERACTION WITH ALCOHOL
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`Abuse Potential
`OPANA® ER contains oxymorphone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid
`agonists, legal or illicit. 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 depressive disorder). Routinely monitor all patients receiving OPANA® ER for signs of misuse, abuse, and addiction
`during treatment.
`Life-threatening Respiratory Depression
`Respiratory depression, including fatal cases, may occur with use of OPANA® ER, even when the drug has been used as recommended and
`not misused or abused. 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. Monitor for respiratory depression, especially
`during initiation of OPANA® ER or following a dose increase. Instruct patients to swallow OPANA® ER tablets whole. Crushing, dissolving,
`or chewing OPANA® ER can cause rapid release and absorption of a potentially fatal dose of oxymorphone.
`Accidental Exposure
`Accidental ingestion of OPANA® ER, especially in children, can result in a fatal overdose of oxymorphone.
`Interaction with Alcohol
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`http://www.opana.com/prescriber/product-information/pharmacokinetic-profile.aspx
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`OPANA® ER – Pharmacokinetic Profile
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`The co-ingestion of alcohol with OPANA® ER may result in an increase of plasma levels and potentially fatal overdose of oxymorphone.
`Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while on
`OPANA® ER.
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`LIMITATIONS OF USAGE
`OPANA® ER is not intended for use as an as-needed (PRN) analgesic; for pain that is mild or not expected to persist for an extended period of time; for acute
`pain; for postoperative pain unless the patient is already receiving chronic opioid therapy prior to surgery or if the postoperative pain is expected to be
`moderate to severe and persist for an extended period of time.
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`CONTRAINDICATIONS
`OPANA ER is contraindicated in patients with 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, any other ingredients in OPANA ER, or to
`morphine analogs such as codeine; and conditions that increase the risk of life-threatening respiratory depression.
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`WARNINGS AND PRECAUTIONS
`• Respiratory depression is the primary risk of OPANA ER. Respiratory depression, if not immediately recognized and treated, may lead to respiratory
`arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending
`on the patient's clinical status.
`• 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, following dose
`increases, and when OPANA ER is given concomitantly with other drugs that depress respiration. 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.
`• Monitor patients for respiratory depression who have significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a
`substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing 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.
`• 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). 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 hypotension, sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant.
`• 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). Monitor these patients for signs of hypotension after
`initiating or titrating the dose of OPANA ER.
`• 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. Opioids may obscure the
`clinical course in a patient with a head injury.
`• Avoid the use of OPANA ER in patients with circulatory shock; with impaired consciousness or coma; or with 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.
`• 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.
`• Do not abruptly discontinue OPANA ER. If OPANA ER is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur.
`Use a gradual downward titration of the dose every two to four days to prevent signs and symptoms of withdrawal.
`• Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal
`symptoms.
`• Chronic maternal use of oxymorphone during pregnancy can affect the fetus with subsequent withdrawal signs. 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.
`• OPANA ER is not recommended during labor and delivery, pregnancy, or nursing.
`• 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.
`• Patients 65 years of age or older, patients with mild hepatic impairment, and patients with moderate to severe renal impairment have an increase in
`oxymorphone bioavailability. For these patients on prior opioid therapy, start at 50% of the starting dose for a younger patient or a patient with normal
`hepatic or renal function and titrate slowly and monitor closely for respiratory and central nervous system depression.
`• In opioid-naïve patients initiate OPANA ER using the 5 mg dose and monitor closely for respiratory and central nervous system depression.
`• OPANA ER can be abused and is subject to criminal diversion. The high drug content in extended release formulations adds to the risk of adverse
`outcomes from abuse and misuse. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper
`dispensing and storage are appropriate measures that help to reduce abuse of opioid drugs. Careful record-keeping of prescribing information, including
`quantity, frequency, and renewal requests as required by state law, is strongly advised.
`• OPANA ER is administered at a frequency of twice daily (every 12 hours). Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.
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`Risks Specific to Abuse of OPANA ER
`• OPANA ER is for oral use only. Abuse of OPANA ER poses a risk of overdose and death. This risk is increased with concurrent abuse of OPANA ER with
`alcohol and other substances. OPANA ER tablets must be taken whole, one tablet at a time, with enough water to ensure complete swallowing
`immediately after placing in the mouth. Taking cut, broken, chewed, crushed, or dissolved OPANA ER enhances drug release and increases the risk of
`overdose and death.
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`ADVERSE REACTIONS
`• Adverse reactions reported at (≥2%) in placebo-controlled trials were: nausea, constipation, dizziness, somnolence, vomiting, pruritus, headache,
`sweating increased, dry mouth, sedation, diarrhea, insomnia, fatigue, appetite decreased, and abdominal pain.
`• In clinical trials 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.
`• Post-marketing Experience - The following adverse reactions have been identified during post approval use of OPANA ER. Because these reactions are
`reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to
`drug exposure. Nervous system disorder: amnesia, convulsion, memory impairment.
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`DRUG INTERACTIONS
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`OPANA® ER – Pharmacokinetic Profile
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`• Concurrent use of OPANA ER and other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other
`opioids, and alcohol can increase the risk of respiratory depression, hypotension, profound sedation, or coma. Monitor patients receiving CNS
`depressants and OPANA ER for signs of respiratory depression and hypotension. When such combined therapy is contemplated, reduce the initial dose
`of one or both agents.
`• Mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, or buprenorphine) may reduce the analgesic effect of OPANA ER or may
`precipitate withdrawal symptoms in these patients. Avoid the use of mixed agonist/antagonist analgesics in patients receiving OPANA ER.
`• Cimetidine can potentiate opioid-induced respiratory depression. Monitor patients for respiratory depression when OPANA ER and cimetidine are used
`concurrently.
`• Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary
`retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of respiratory and central nervous system depression
`when OPANA ER is used concurrently with anticholinergic drugs.
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`Please see full Prescribing Information, including boxed WARNING and Medication Guide for OPANA® ER.
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`Oxymorphone is also available in immediate release tablets and injectable form. For more information, please see full Prescribing Information for
`OPANA® Tablets and OPANA® Injection.
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`Vermont prescribers, please see additional information for OPANA® ER.
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`References
`1. OPANA® ER (Oxymorphone Hydrochloride) Extended-Release tablets CII [Prescribing Information]. Endo Pharmaceuticals Inc.
`2. Benedek IH, Jobes J, Xiang Q, Fiske WD. Bioequivalence of oxymorphone extended release and crush-resistant oxymorphone extended
`release. Drug Des Devel Ther. 2011;5:455-463.
`3. Adams MP, Ahdieh H. Pharmacokinetics and dose-proportionality of oxymorphone extended release and its metabolites: results of a
`randomized crossover study. Pharmacotherapy. 2004;24(4):468-476.
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`Intended for U.S. Residents Only
`
`Rx Only
`DEA Order Form Required.
`OPANA® is a registered trademark of Endo Pharmaceuticals Inc.
`INTAC® is a registered trademark of the Grünenthal Group.
`© 2013 Endo Pharmaceuticals Inc. All Rights Reserved. Malvern, PA 19355
`Privacy/Legal OP-02671b/May 2013 www.opana.com 1-800-462-ENDO (3636)
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