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`•
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`•
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`•
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`•
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`•
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`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`OPANA® ER safely and effectively. See full prescribing information for
`OPANA® ER.
`OPANA® ER (oxymorphone hydrochloride) extended-release tablets,
`for oral use, CII
`Initial U.S. Approval: 1959
`
`WARNING: ADDICTION, ABUSE, AND MISUSE; RISK
`EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
`INTERACTION WITH ALCOHOL; and RISKS FROM
`CONCOMITANT USE WITH BENZODIAZEPINES AND OTHER
`CNS DEPRESSANTS
`See full prescribing information for complete boxed warning.
`• OPANA ER exposes users to risks of addiction, abuse, and
`misuse, which can lead to overdose and death. Assess patient’s
`risk before prescribing and monitor regularly for these behaviors
`and conditions. (5.1)
`To ensure that the benefits of opioid analgesics outweigh the risks
`of addiction, abuse, and misuse, the Food and Drug
`Administration (FDA) has required a Risk Evaluation and
`Mitigation Strategy (REMS) for these products. (5.2)
`Serious, life-threatening, or fatal respiratory depression may
`occur. Monitor closely, especially upon initiation or following a
`dose increase. Instruct patients to swallow OPANA ER tablets
`whole to avoid exposure to a potentially fatal dose of
`oxymorphone. (5.3)
`Accidental ingestion of OPANA ER, especially by children, can
`result in fatal overdose of oxymorphone. (5.3)
`Prolonged use of OPANA ER during pregnancy can result in
`neonatal opioid withdrawal syndrome, which may be life-
`threatening if not recognized and treated. If opioid use is
`required for a prolonged period in a pregnant woman, advise the
`patient of the risk of neonatal opioid withdrawal syndrome and
`ensure that appropriate treatment will be available (5.4).
`Instruct patients not to consume alcohol or any product
`containing alcohol while taking OPANA ER because co-ingestion
`can result in fatal plasma oxymorphone levels. (5.5)
`Concomitant use of opioids with benzodiazepines or other central
`nervous system (CNS) depressants, including alcohol, may result
`in profound sedation, respiratory depression, coma, and death.
`Reserve concomitant prescribing for use in patients for whom
`alternative treatment options are inadequate; limit dosages and
`durations to the minimum required; and follow patients for signs
`and symptoms of respiratory depression and sedation. (5.5, 7)
`
`
`
`-----------------------------RECENT MAJOR CHANGES--------------------
`Boxed Warning
`
`
`
`
` 09/2018
`Warnings and Precautions (5.2) 09/2018
`
`----------------------------INDICATIONS AND USAGE--------------------------
`OPANA ER is an opioid agonist indicated for the management of pain
`severe enough to require daily, around-the-clock, long-term opioid treatment
`and for which alternative treatment options are inadequate. (1)
`
`Limitations of Use
`• Because of the risks of addiction, abuse, and misuse with opioids,
`even at recommended doses, and because of the greater risks of
`overdose and death with extended-release opioid formulations,
`reserve OPANA ER for use in patients for whom alternative treatment
`options (e.g., non-opioid analgesics or immediate-release opioids) are
`ineffective, not tolerated, or would be otherwise inadequate to provide
`sufficient management of pain. (1)
`• OPANA ER is not indicated as an as-needed (prn) analgesic. (1)
`
`---------------------DOSAGE AND ADMINISTRATION--------------------
`• To be prescribed only by healthcare providers knowledgeable in use of
`potent opioids for management of chronic pain. (2.1)
`• Use the lowest effective dosage for the shortest duration consistent with
`individual patient treatment goals (2.1).
`• Individualize dosing based on the severity of pain, patient response, prior
`analgesic experience, and risk factors for addiction, abuse, and misuse.
`(2.1)
`
`•
`
`
`
`• Administer on an empty stomach, at least 1 hour prior to or 2 hours
`after eating. (2.1)
`• OPANA ER tablets should be taken one tablet at a time, with
`enough water to ensure complete swallowing immediately after
`placing in the mouth. (2.1, 17)
`• For opioid-naïve and opioid non-tolerant patients, initiate treatment with
`5 mg tablets orally every 12 hours. (2.2)
`• To convert to OPANA ER from another opioid, use available conversion
`factors to obtain estimated dose. (2.2)
`• Dose can be increased every 3 to 7 days, using increments of 5 to 10 mg
`every 12 hours (i.e., 10 to 20 mg per day). (2.3)
`• Do not abruptly discontinue OPANA ER in a physically dependent
`patient. (2.4, 5.15)
`• Mild Hepatic Impairment: For opioid-naïve patients, initiate treatment
`with 5 mg and titrate slowly. For patients on prior opioid therapy,
`reduce starting dose by 50% and titrate slowly. Monitor for signs of
`respiratory and central nervous system depression. (2.5)
`• Renal Impairment: For opioid-naïve patients, initiate treatment with 5
`mg and titrate slowly. For patients on prior opioid therapy, reduce
`starting dose by 50% and titrate slowly. Monitor for signs of respiratory
`and central nervous system depression. (2.6)
`• Geriatric Patients: Initiate dosing with 5 mg, titrate slowly, and monitor
`for signs of respiratory and central nervous system depression. (2.7)
`
`
`
`
`---------------------DOSAGE FORMS AND STRENGTHS-------------------
`Extended-release tablets: 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg, and
`40 mg
`------------------------------CONTRAINDICATIONS---------------------------
`• Significant respiratory depression (4)
`• Acute or severe bronchial asthma in an unmonitored setting or in
`absence of resuscitative equipment (4)
`• Hypersensitivity to oxymorphone (4)
`• Moderate or severe hepatic impairment (4)
`Known or suspected gastrointestinal obstruction, including paralytic
`ileus (4)
`
`------------------------WARNINGS AND PRECAUTIONS--------------------
`• Life-Threatening Respiratory Depression in Patients with Chronic
`Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients:
`Monitor closely, particularly during initiation and titration. (5.6, 5.7)
`• Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions: If
`symptoms occur, stop administration immediately, discontinue
`permanently, and do not rechallenge with any oxymorphone
`formulation. (5.7)
`• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement
`of corticosteroids, and wean patient off of the opioid. (5.8)
`• Severe Hypotension: Monitor during dose initiation and titration. Avoid
`use of OPANA ER in patients with circulatory shock. (5.10)
`• Risks of Use in Patients with Increased Intracranial Pressure, Brain
`Tumors, Head Injury or Impaired Consciousness: Monitor for sedation
`and respiratory depression. Avoid use of OPANA ER in patients with
`impaired consciousness or coma. (5.11)
`• Difficulty in Swallowing: Use with caution in patients who have
`difficulty in swallowing or have underlying GI disorders that may
`predispose them to obstruction. (5.12)
`
`
`-----------------------------ADVERSE REACTIONS-----------------------------
`Adverse reactions in ≥2% of patients in placebo-controlled trials: nausea,
`constipation, dizziness, somnolence, vomiting, pruritus, headache, sweating
`increased, dry mouth, sedation, diarrhea, insomnia, fatigue, appetite
`decreased, and abdominal pain. (6.1)
`
`To report SUSPECTED ADVERSE REACTIONS, contact Endo
`Pharmaceuticals Inc. at 1-800-462-3636 or FDA at 1-800 FDA-1088 or
`www.fda.gov/medwatch.
`
`------------------------------DRUG INTERACTIONS----------------------------
`• Serotonergic Drugs: Concomitant use may result in serotonin syndrome.
`Discontinue OPANA ER if serotonin syndrome is suspected. (7)
`• Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics:
`Avoid use with OPANA ER because they may reduce analgesic effect of
`OPANA ER or precipitate withdrawal symptoms. (7)
`
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`Reference ID: 4321317
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`• Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects of
`oxymorphone. Avoid concomitant use in patients receiving MAOIs or
`within 14 days of stopping treatment with an MAOI. (7)
`
`
`
`6
`
`
`
`• Lactation: Not Recommended. (8.2)
`See 17 for PATIENT COUNSELING INFORMATION and
`Medication Guide
`
`Revised: 09/2018
`
`
`------------------------USE IN SPECIFIC POPULATIONS--------------------
`• Pregnancy: May cause fetal harm. (8.1)
`________________________________________________________________________________________________________________________________________
`FULL PRESCRIBING INFORMATION: CONTENTS*
`5.12 Difficulty in Swallowing and Risk for Obstruction in Patients
`
`at Risk for a Small Gastrointestinal Lumen
`WARNING: ADDICTION, ABUSE, AND MISUSE; RISK
`5.13 Risks of Use in Patients with Gastrointestinal Conditions
`EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-
`5.14 Increased Risk of Seizures in Patients with Seizure Disorders
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`5.15 Withdrawal
`INGESTION; NEONATAL OPIOID WITHDRAWAL
`5.16 Risks of Driving and Operating Machinery
`ADVERSE REACTIONS
`SYNDROME; INTERACTION WITH ALCOHOL; and
`RISKS FROM CONCOMITANT USE WITH
`6.1 Clinical Trial Experience
`BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
`6.2 Post-marketing Experience
`DRUG INTERACTIONS
`USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`8.3 Females and Males Reproductive Potential
`8.4 Pediatric Use
`8.5 Geriatric Use
`8.6 Hepatic Impairment
`8.7 Renal Impairment
`DRUG ABUSE AND DEPENDENCE
`9.1 Controlled Substance
`9.2 Abuse
`9.3 Dependence
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`14 CLINICAL STUDIES
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing
`information are not listed.
`
`
`7
`8
`
`9
`
`INDICATIONS AND USAGE
`DOSAGE AND ADMINISTRATION
`Important Dosage and Administration Instructions
`2.1
`2.2
`Initial Dosing
`2.3 Titration and Maintenance of Therapy
`2.4 Discontinuation of OPANA ER
`2.5 Dosage Modifications in Patients with Hepatic Impairment
`2.6 Dosage Modifications in Patients with Renal Impairment
`2.7 Dosage Modifications in Geriatric Patients
`DOSAGE FORMS AND STRENGTHS
`3
`CONTRAINDICATIONS
`4
`5 WARNINGS AND PRECAUTIONS
`5.1 Addiction, Abuse, and Misuse Potential
`5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy
`(REMS)
`5.3 Life Threatening Respiratory Depression
`5.4 Neonatal Opioid Withdrawal Syndrome
`5.5 Risks from Concomitant Use with Benzodiazepines or Other
`CNS Depressants
`5.6 Risk of Life-Threatening Respiratory Depression in Patients
`with Chronic Pulmonary Disease or in Elderly, Cachectic, or
`Debilitated Patients
`5.7 Anaphylaxis, Angioedema, and Other Hypersensitivity
`Reactions
`5.8 Adrenal Insufficiency
`5.9 Use in Patients with Hepatic Impairment
`5.10 Severe Hypotension
`5.11 Risks of Use in Patients with Increased Intracranial Pressure,
`Brain Tumors, Head Injury, or Impaired Consciousness
`_________________________________________________________________________________________________________________________________
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`Reference ID: 4321317
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`FULL PRESCRIBING INFORMATION
`
`
`WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY
`(REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL
`OPIOID WITHDRAWAL SYNDROME; INTERACTION WITH ALCOHOL; and RISKS FROM
`CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
`Addiction, Abuse, and Misuse
`OPANA ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to
`overdose and death. Assess each patient’s risk prior to prescribing OPANA ER, and monitor all patients regularly
`for the development of these behaviors and conditions [see Warnings and Precautions (5.1)].
`Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS):
`To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug
`Administration (FDA) has required a REMS for these products [see Warnings and Precautions (5.2)]. Under the
`requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant
`education programs available to healthcare providers. Healthcare providers are strongly encouraged to
` • complete a REMS-compliant education program,
` • counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal
`of these products,
` • emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is
`provided by their pharmacist, and
` • consider other tools to improve patient, household, and community safety.
`Life-threatening Respiratory Depression
`Serious, life-threatening, or fatal respiratory depression may occur with use of OPANA ER. Monitor for respiratory
`depression, especially during initiation of OPANA ER or following a dose increase. Instruct patients to swallow
`OPANA ER tablets whole; crushing, chewing, or dissolving OPANA ER tablets can cause rapid release and
`absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions (5.3)].
`Accidental Ingestion
`Accidental ingestion of even one dose of OPANA ER, especially by children, can result in a fatal overdose of
`oxymorphone [see Warnings and Precautions (5.3)].
`Neonatal Opioid Withdrawal Syndrome
`Prolonged use of OPANA ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be
`life-threatening if not recognized and treated, and requires management according to protocols developed by
`neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the
`risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings
`and Precautions (5.4)].
`Interaction with Alcohol
`Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain
`alcohol while taking OPANA ER. The co-ingestion of alcohol with OPANA ER may result in increased plasma levels
`and a potentially fatal overdose of oxymorphone [see Warnings and Precautions (5.5)].
`Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
`Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including
`alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions
`(5.5), Drug Interactions (7)].
`• Reserve concomitant prescribing of OPANA ER and benzodiazepines or other CNS depressants for use in patients
`for whom alternative treatment options are inadequate.
`• Limit dosages and durations to the minimum required.
`• Follow patients for signs and symptoms of respiratory depression and sedation.
`
`
` 1
`
`INDICATIONS AND USAGE
`
`OPANA ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and
`for which alternative treatment options are inadequate.
`Limitations of Use
`• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks
`of overdose and death with extended-release opioid formulations [see Warnings and Precautions (5.1)], reserve OPANA ER
`
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`Reference ID: 4321317
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`•
`
`for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are
`ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
`• OPANA ER is not indicated as an as-needed (prn) analgesic.
`2 DOSAGE AND ADMINISTRATION
`2.1 Important Dosage and Administration Instructions
`OPANA ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the
`management of chronic pain.
`• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and
`Precautions (5)].
`Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response,
`prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)].
`• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following
`dosage increases with OPANA ER and adjust the dosage accordingly [see Warnings and Precautions (5.3)].
`Instruct patients to swallow OPANA ER tablets whole, one tablet at a time, with enough water to ensure complete swallowing
`immediately after placing in the mouth [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving OPANA ER
`tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or death [see Warnings and Precautions (5.3)].
`Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.
`OPANA ER is administered orally every 12 hours.
`2.2
`Initial Dosage
`Use of OPANA ER as the First Opioid Analgesic
`Initiate treatment with OPANA ER with the 5 mg tablet orally every 12-hours.
`Use of OPANA ER in Patients who are not Opioid Tolerant
`The starting dose for patients who are not opioid tolerant is OPANA ER 5 mg orally every 12 hours.
`Patients considered opioid tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal
`fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral
`hydrocodone per day, or an equianalgesic dose of another opioid.
`Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.
`Conversion from OPANA to OPANA ER
`Patients receiving OPANA may be converted to OPANA ER by administering half the patient's total daily oral OPANA dose as
`OPANA ER, every 12 hours.
`Conversion from Parenteral Oxymorphone to OPANA ER
`The absolute oral bioavailability of OPANA ER is approximately 10%. Convert patients receiving parenteral oxymorphone to
`OPANA ER by administering 10 times the patient's total daily parenteral oxymorphone dose as OPANA ER in two equally divided
`doses (e.g., [IV dose x 10] divided by 2). Due to patient variability with regards to opioid analgesic response, upon conversion
`monitor patients closely to evaluate for adequate analgesia and side effects.
`Conversion from Other Oral Opioids to OPANA ER
`Discontinue all other around-the-clock opioid drugs when OPANA ER therapy is initiated.
`While there are useful tables of opioid equivalents readily available, there is substantial inter- patient variability in the relative
`potency of different opioid drugs and products. As such, it is preferable to underestimate a patient’s 24-hour oral oxymorphone
`requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxymorphone
`requirements which could result in adverse reactions. In an OPANA ER clinical trial with an open-label titration period, patients
`were converted from their prior opioid to OPANA ER using Table 1 as a guide for the initial OPANA ER dose.
`Consider the following when using the information in Table 1:
`• This is not a table of equianalgesic doses.
`• The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to OPANA ER.
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`• This table cannot be used to convert from OPANA ER to another opioid. Doing so will result in an overestimation of the dose of
`the new opioid and may result in fatal overdose.
`CONVERSION FACTORS TO OPANA ER
`Prior Oral Opioid
`Approximate Oral
`Conversion Factor
`1
`Oxymorphone
`0.5
`Hydrocodone
`0.5
`Oxycodone
`0.5
`Methadone
`0.333
`Morphine
`To calculate the estimated OPANA ER dose using Table 1:
`• For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the total daily dose by the
`conversion factor to calculate the approximate oral oxymorphone daily dose.
`• For patients on a regimen of more than one opioid, calculate the approximate oral oxymorphone dose for each opioid and sum the
`totals to obtain the approximate total oxymorphone daily dose.
`• For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in
`the conversion
`Always round the dose down, if necessary, to the appropriate OPANA ER strength(s) available.
`Example conversion from a single opioid to OPANA ER:
`Step 1: Sum the total daily dose of the opioid oxycodone 20 mg BID
`20 mg former opioid 2 times daily = 40 mg total daily dose of former opioid
`Step 2: Calculate the approximate equivalent dose of oral oxymorphone based on the total daily dose of the current opioid using
`Table 1
`40 mg total daily dose of former opioid x 0.5 mg Conversion Factor = 20 mg of oral oxymorphone daily
`Step 3: Calculate the approximate starting dose of OPANA ER to be given every 12 hours. Round down, if necessary, to the
`appropriate OPANA ER TABLETS strengths available.
`10 mg OPANA ER every 12 hours
`Conversion from Methadone to OPANA ER
`Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between
`methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and
`can accumulate in the plasma.
`
`2.3 Titration and Maintenance of Therapy
`Individually titrate OPANA ER to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate
`patients receiving OPANA ER to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as
`monitoring for the development of addiction, abuse, and misuse. Frequent communication is important among the prescriber, other
`members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including
`initial titration. During chronic therapy, periodically reassess the continued need for the use of opioid analgesics.
`If the level of pain increases, attempt to identify the source of increased pain, while adjusting the OPANA ER dose to decrease the
`level of pain. Because steady-state plasma concentrations are approximated within 3 days, OPANA ER dosage adjustments, preferably
`at increments of 5-10 mg every 12 hours, may be done every 3 to 7 days.
`Patients who experience breakthrough pain may require a dose increase of OPANA ER, or may need rescue medication with an
`appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source
`of increased pain before increasing OPANA ER dose.
`If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the dose to obtain an
`appropriate balance between management of pain and opioid-related adverse reactions.
`2.4 Discontinuation of OPANA ER
`When a patient no longer requires therapy with OPANA ER, taper the dose gradually, by 25% to 50% every 2 to 4 days, while
`monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the
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`previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or
`both. Do not abruptly discontinue OPANA ER [see Warnings and Precautions (5.15), Drug Abuse and Dependence (9.3)].
`
`2.5 Dosage Modification in Patients with Mild Hepatic Impairment
`OPANA ER is contraindicated in patients with moderate or severe hepatic impairment.
`In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose. For patients on prior opioid therapy, start
`OPANA ER at 50% lower than the starting dose for a patient with normal hepatic function on prior opioids and titrate slowly.
`Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.3), Use in
`Specific Populations (8.6) and Clinical Pharmacology (12.3)].
`
`2.6 Dosage Modification in Patients with Renal Impairment
`In patients with creatinine clearance rates less than 50 mL/min, start OPANA ER in the opioid-naïve patient with the 5 mg dose. For
`patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal renal function on prior
`opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system depression [see Warnings and
`Precautions (5.3), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
`
`2.7 Dosage Modification in Geriatric Patients
`The steady-state plasma concentrations of oxymorphone are higher in elderly subjects than in young subjects. 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 to adequate analgesia [see Warnings and Precautions (5.3), Use in
`Specific Populations (8.5) and Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start OPANA ER at 50% lower
`than the starting dose for a younger patient on prior opioids and titrate slowly.
`
`3 DOSAGE FORMS AND STRENGTHS
`Extended Release Tablets 5 mg: pink, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a
`“5” on the other side.
`Extended Release Tablets 7.5 mg: gray, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a
`“7 ½” on the other side.
`Extended Release Tablets 10 mg: light orange, round, film-coated, biconcave extended-release tablet debossed with an “E” on one
`side and a “10” on the other side.
`Extended Release Tablets 15 mg: white, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a
`“15” on the other side.
`Extended Release Tablets 20 mg: light green, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side
`and a “20” on the other side.
`Extended Release Tablets 30 mg: red, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a
`“30” on the other side.
`Extended Release Tablets 40 mg: light yellow to pale yellow, round, film-coated, biconcave extended-release tablet debossed with an
`“E” on one side and a “40” on the other side.
`
`4 CONTRAINDICATIONS
`OPANA ER is contraindicated in patients with:
`• Significant respiratory depression [see Warnings and Precautions (5.3)]
`• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings
`and Precautions (5.6)]
`• Hypersensitivity to oxymorphone, (e.g. anaphylaxis) [see Warnings and Precautions (5.7), Adverse Reactions (6)]
`• Moderate and severe hepatic impairment [see Warnings and Precautions (5.9), Clinical Pharmacology (12.3)]
`• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12)]
`5 WARNINGS AND PRECAUTIONS
`5.1 Addiction, Abuse, and Misuse
`OPANA ER contains oxymorphone, a Schedule II controlled substance. As an opioid, OPANA ER exposes users to the risks of
`addiction, abuse, and misuse. Because extended-release products such as OPANA ER deliver the opioid over an extended period of
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`time, there is a greater risk for overdose and death due to the larger amount of oxymorphone present [see Drug Abuse and Dependence
`(9)].
`Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OPANA ER. Addiction
`can occur at recommended doses and if the drug is misused or abused.
`Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing OPANA ER, and monitor all patients receiving
`OPANA ER for the development of these behaviors and conditions. Risks are 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). The potential for these risks
`should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed
`opioids such as OPANA ER, but use in such patients necessitates intensive counseling about the risks and proper use of OPANA ER
`along with intensive monitoring for signs of addiction, abuse, and misuse.
`Abuse or misuse of OPANA ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled
`delivery of the oxymorphone and can result in overdose and death [see Overdosage (10)].
`Opioids 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. Strategies to reduce these risks include prescribing the drug in the smallest appropriate
`quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. 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.
`5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
`To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration
`(FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug
`companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers.
`Healthcare providers are strongly encouraged to do all of the following:
`• Complete a REMS-compliant education program offered by an accredited provider of continuing education (CE) or
`another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers
`Involved in the Management or Support of Patients with Pain.
`• Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their
`caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link:
`www.fda.gov/OpioidAnalgesicREMSPCG.
`• Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from
`their pharmacist every time an opioid analgesic is dispensed to them.
`• Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements
`that reinforce patient-prescriber responsibilities.
`To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log
`on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint.
`
`5.3 Life Threatening Respiratory Depression
`Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
`Respiratory depression from opioid use, 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 [see Overdosage (10)]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can
`exacerbate the sedating effects of opioids.
`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 dosage increase. Monitor patients closely for respiratory depression, especially within
`24-72 hours of initiating therapy with and following dose increases of OPANA ER.
`To reduce the risk of respiratory depression, proper dosing and titration of OPANA ER are essential [see Dosage and Adminis