`
`
`
`
`
`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;
`and 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 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----------------------
`
`Dosage and Administration (2.2)
`03/2021
`
`
`Warnings and Precautions (5.1, 5.3, 5.5)
`03/2021
`
`
`
`----------------------------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)
`
`
`
`
`
`Reference ID: 4756482
`
`
` Administer on an empty stomach, at least 1 hour prior to or 2 hours
`
`
`
`
`
`
`
`
`after eating. (2.1)
`
` Discuss availability of naloxone with the patient and caregiver and
`
`assess each patient’s need for access to naloxone, both when initiating
`and renewing treatment with OPANA ER. Consider prescribing
`
`naloxone based on the patient’s risk factors for overdose (2.2, 5.1, 5.3,
`
`
`
`5.5).
`
` For opioid-naïve and opioid non-tolerant patients, initiate treatment
`with 5 mg tablets orally every 12 hours. (2.3)
`
`
`
` To convert to OPANA ER from another opioid, use available conversion
`
`
`
`
`
`
`factors to obtain estimated dose. (2.3)
`
` 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). (2.4)
`
` Do not abruptly discontinue OPANA ER in a physically dependent patient
`
`
`because rapid discontinuation of opioid analgesics has resulted in serious
`
`withdrawal symptoms, uncontrolled pain, and suicide. (2.5, 5.14)
`
`
` 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. (2.6)
`
`
`
`
` 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. (2.7)
`
`
`
` Geriatric Patients: Initiate dosing with 5 mg, titrate slowly, and monitor for
`
`
`
`signs of respiratory and central nervous system depression. (2.8)
`
`
`
`
`---------------------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)
`
`
` Anaphylaxis, Angioedema, and Other Hypersensitivity Reactions: If
`
`
`symptoms occur, stop administration immediately, discontinue permanently,
`
`
`
`and do not rechallenge with any other 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)
`
`-----------------------------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)
`
` 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)
`
`
`
`
`
`------------------------USE IN SPECIFIC POPULATIONS--------------------
`
`
` Pregnancy: May cause fetal harm. (8.1)
`
` Lactation: Not recommended. (8.2)
`
`
`
`
`
` 1
`
`

`

`Revised: 03/2021
`
`
`
`6
`
`
`7
`
`8
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`
`Guide
`
`________________________________________________________________________________________________________________________________________
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`5.10 Severe Hypotension
`
`
`
`5.11 Risks of Use in Patients with Increased Intracranial Pressure,
`
`WARNING: ADDICTION, ABUSE, AND MISUSE; RISK
`
`Brain Tumors, Head Injury, or Impaired Consciousness
`
`
`
`EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-
`
`
`5.12 Risks of Use in Patients with Gastrointestinal Conditions
`
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`
`
`
`5.13 Increased Risk of Seizures in Patients with Seizure Disorders
`
`
`INGESTION; NEONATAL OPIOID WITHDRAWAL
`
`5.14 Withdrawal
`
`SYNDROME; INTERACTION WITH ALCOHOL; and RISKS
`
`
`5.15 Risks of Driving and Operating Machinery
`ADVERSE REACTIONS
`FROM CONCOMITANT USE WITH BENZODIAZEPINES OR
`
`
`OTHER CNS DEPRESSANTS
`
`
`6.1 Clinical Trial Experience
`
`
`6.2 Post-marketing Experience
`
`DRUG INTERACTIONS
`INDICATIONS AND USAGE
`1
`
`
`
`
`USE IN SPECIFIC POPULATIONS
`DOSAGE AND ADMINISTRATION
`2
`
`
`8.1 Pregnancy
`Important Dosage and Administration Instructions
`2.1
`
`
`8.2 Lactation
`2.2 Patient Access to Naloxone for the Emergency Treatment of
`
`
`8.3 Females and Males Reproductive Potential
`Opioid Overdose
`
`
`
`8.4 Pediatric Use
`Initial Dosage
`2.3
`
`
`
`
`8.5 Geriatric Use
`2.4 Titration and Maintenance of Therapy
`
`
`
`8.6 Hepatic Impairment
`2.5 Safe Reduction or Discontinuation of OPANA ER
`
`
`
`
`
`8.7 Renal Impairment
`2.6 Dosage Modifications in Patients with Hepatic Impairment
`DRUG ABUSE AND DEPENDENCE
`
`2.7 Dosage Modifications in Patients with Renal Impairment
`
`
`9.1 Controlled Substance
`2.8 Dosage Modifications in Geriatric Patients
`
`DOSAGE FORMS AND STRENGTHS
`3
`
`
`
`9.2 Abuse
`
`CONTRAINDICATIONS
`4
`
`
`9.3 Dependence
`
`
`10 OVERDOSAGE
`5 WARNINGS AND PRECAUTIONS
`
`
`
`11 DESCRIPTION
`
`
`5.1 Addiction, Abuse, and Misuse
`
`
`
`12 CLINICAL PHARMACOLOGY
`
`
`5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy
`
`12.1
` Mechanism of Action
`(REMS)
`
`
`
`
`12.2 Pharmacodynamics
`5.3 Life Threatening Respiratory Depression
`
`
`
`
`12.3 Pharmacokinetics
`5.4 Neonatal Opioid Withdrawal Syndrome
`
`13 NONCLINICAL TOXICOLOGY
`
`
`5.5 Risks from Concomitant Use with Benzodiazepines or Other
`
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`CNS Depressants
`
`
`14 CLINICAL STUDIES
`
`5.6 Risk of Life-Threatening Respiratory Depression in Patients
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`with Chronic Pulmonary Disease or in Elderly, Cachectic, or
`
`
`
`
`
`17 PATIENT COUNSELING INFORMATION
`
`Debilitated Patients
`
`
`5.7 Anaphylaxis, Angioedema, and Other Hypersensitivity
`*Sections or subsections omitted from the full prescribing
`
`Reactions
`information are not listed.
`
`
`5.8 Adrenal Insufficiency
`
`5.9 Use in Patients with Hepatic Impairment
`
`_________________________________________________________________________________________________________________________________
`
`
`9
`
`
`
`
`
`2
`
`
`Reference ID: 4756482
`
`

`

`
`
` FULL PRESCRIBING INFORMATION
`
`
`
` WARNING: ADDICTION, ABUSE, AND MISUSE; 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.
`
`
`
`
`
`Reference ID: 4756482
`
`

`

`
`
`
`INDICATIONS AND USAGE
`1
` 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 Usage
`
` 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 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.
`
`
`
`
`
`
`DOSAGE AND ADMINISTRATION
`2
`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 [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 twice daily (every 12 hours).
`
`
`
`2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose
`
`
`
`
`Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver
`
`
`
`and assess the potential need for access to naloxone, both when initiating and renewing treatment with OPANA ER
`
`[see Warnings and Precautions (5.3) and Patient Counseling Information (17)].
`
`
`
`
`
`Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone
`
`
`
`dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of
`a community-based program).
`
`
`
`Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS
`
`
`
`
`
`
`
`depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose
`
`
`
`
`
`
`
`should not prevent the proper management of pain in any given patient [see Warnings and Precautions (5.1, 5.3,
`
`5.5)].
`
`
`
`
`
`
`
`Consider prescribing naloxone if the patient has household members (including children) or other close contacts at
`
`risk for accidental ingestion or overdose.
`
`2.3 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.
`
`
`
`
`Reference ID: 4756482
`
`

`

` 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.
`
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`Consider the following when using the information in the below Table 1:
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` This is not a table of equianalgesic doses.
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` The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics
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`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 over-
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`estimation of the dose of the new opioid and may result in fatal overdose.
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`Table 1: CONVERSION FACTORS TO OPANA ER
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`Approximate Oral
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`Conversion Factor
`1
`0.5
`0.5
`0.5
`0.333
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`Prior Oral Opioid
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` Oxymorphone
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` Hydrocodone
`Oxycodone
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`Methadone
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`Morphine
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`To calculate the estimated OPANA ER dose using the above table:
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` For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the total
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`daily dose by the conversion factor to calculate the approximate oral (active opioid) daily dose.
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` For patients on a regimen of more than one opioid, calculate the approximate oral (active opioid) dose for
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`each opioid and sum the totals to obtain the approximate total (active opioid) daily dose.
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` For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid
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`component of these products in the conversion
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`Always round the dose down, if necessary, to the appropriate OPANA ER strength(s) available.
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`Reference ID: 4756482
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` Example conversion from a single opioid to OPANA ER:
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` Step 1: Sum the total daily dose of the opioid oxycodone 20 mg twice daily
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` 20 mg former opioid 2 times daily = 40 mg total daily dose of former opioid
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` Step 2: Calculate the approximate equivalent dose of oral (active opioid) based on the total daily dose of the
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` current opioid using Table 1
` 40 mg total daily dose of former opioid x 0.5 mg Conversion Factor = 20 mg of oral (active opioid)
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` daily
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` Step 3: Calculate the approximate starting dose of OPANA ER to be given every 12 hours. Round down, if
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` necessary, to the appropriate OPANA ER TABLETS strengths available.
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` 10 mg OPANA ER every 12 hours
` Conversion from Methadone to OPANA ER
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`Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio
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`between methadone and other opioid agonists may vary widely as a function of previous dose exposure.
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`Methadone has a long half-life and can accumulate in the plasma.
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`2.4 Titration and Maintenance of Therapy
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`Individually titrate OPANA ER to a dose that provides adequate analgesia and minimizes adverse reactions.
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`Continually reevaluate patients receiving OPANA ER to assess the maintenance of pain control and the relative
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`incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, and misuse. Frequent
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`communication is important among the prescriber, other members of the healthcare team, the patient, and the
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`caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic
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`therapy, periodically reassess the continued need for the use of opioid analgesics.
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`If the level of pain increases, attempt to identify the source of increased pain, while adjusting the OPANA ER dose
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`to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3 days, OPANA
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`ER dosage adjustments, preferably at increments of 5-10 mg every 12 hours, may be done every 3 to 7 days.
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`Patients who experience breakthrough pain may require a dose increase of OPANA ER, or may need rescue
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`medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose
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`stabilization, attempt to identify the source of increased pain before increasing OPANA ER dose.
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`If unacceptable opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the dose
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`to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
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`2.5 Safe Reduction or Discontinuation of OPANA ER
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`Do not abruptly discontinue OPANA ER in patients who may be physically dependent on opioids. Rapid
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`discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious
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`withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts
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`to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also
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`attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances.
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`When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking
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`OPANA ER, there are a variety of factors that should be considered, including the dose of OPANA ER the patient
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`has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological
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`attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering
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`schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid
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`analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer
`for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches,
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`such as medication assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance
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`use disorders may benefit from referral to a specialist.
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`There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a
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`patient-specific plan to taper the dose of the opioid gradually. For patients on OPANA ER who are physically
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`opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily
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`Reference ID: 4756482
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`dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients
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`who have been taking opioids for briefer periods of time may tolerate a more rapid taper.
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`It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the
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`patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms
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`include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and
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`symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps,
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`insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If
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`withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid
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`analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in
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`mood, emergence of suicidal thoughts, or use of other substances.
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`When managing patients taking opioid analgesics, particularly those who have been treated for a long duration
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`and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental
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`health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain
`management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid
`analgesic [see Warnings and Precautions (5.14) and Drug Abuse and Dependence (9.3)].
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`2.6 Dosage Modification in Patients with Mild Hepatic Impairment
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`OPANA ER is contraindicated in patients with moderate or severe hepatic impairment.
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`In opioid-naïve patients with mild hepatic impairment, initiate treatment with the 5 mg dose. For patients on prior
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`opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient with normal hepatic function on
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`prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or central nervous system
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`depression [see Warnings and Precautions (5.3), Use in Specific Populations (8.6), and Clinical Pharmacology
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`(12.3)].
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`2.7 Dosage Modification in Patients with Renal Impairment
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`In patients with creatinine clearance rates less than 50 mL/min, start OPANA ER in the opioid-naïve patient with the
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`5 mg dose. For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a patient
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`with normal renal function on prior opioids and titrate slowly. Monitor patients closely for signs of respiratory or
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`central nervous system depression [see Warnings and Precautions (5.3), Use in Specific Populations (8.7), and
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`Clinical Pharmacology (12.3)].
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`2.8 Dosage Modification in Geriatric Patients
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`The steady-state plasma concentrations of oxymorphone are higher in elderly subjects than in young subjects.
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`Initiate dosing with OPANA ER in patients 65 years of age and over using the 5 mg dose and monitor closely for
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`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
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`(12.3)]. For patients on prior opioid therapy, start OPANA ER at 50% lower than the starting dose for a younger
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`patient on prior opioids and titrate slowly.
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`DOSAGE FORMS AND STRENGTHS
`3
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`Extended Release Tablets 5 mg: pink, octagon shape, film coated, convex extended-release tablets debossed with
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`“5” on one side and plain on the other.
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`Extended Release Tablets 7.5 mg: gray, octagon shape, film coated, convex extended-release tablets debossed with
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`“7 ½” on one side and plain on the other.
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`Extended Release Tablets 10 mg: light orange, octagon shape, film coated, convex extended-release tablets debossed
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`with “10” on one side and plain on the other.
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`Extended Release Tablets 15 mg: white, octagon shape, film coated, convex extended-release tablets debossed wit