`HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`
`These highlights do not include all the information needed to use
`OXYMORPHONE HYDROCHLORIDE EXTENDED-RELEASE
`
`
`
`TABLETS safely and effectively. See full prescribing information for
`
`OXYMORPHONE HYDROCHLORIDE EXTENDED-RELEASE
`
`TABLETS.
`OXYMORPHONE HYDROCHLORIDE extended-release tablets, for
`
`
`
`oral use, CII
`
`Initial U.S. Approval: 1959
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE­
` THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`
`
`
` INGESTION; NEONATAL OPIOID WITHDRAWAL
`
`
`
` SYNDROME; and INTERACTION WITH ALCOHOL
`
`
`
`
`See full prescribing information for complete boxed warning.
`
`
`
`• Oxymorphone hydrochloride extended-release tablets expose users
`
`
`
`
`to risks of addiction, abuse, and misuse, which can lead to
`
`overdose and death. Assess each patient’s risk before prescribing,
`
`
`
`and monitor regularly for development of these behaviors or
`
`conditions. (5.1)
`
`
`• Serious, life-threatening, or fatal respiratory depression may
`
`
`
`
`
`occur. Monitor closely, especially upon initiation or following a
`
`
`
`
`
`dose increase. Instruct patients to swallow oxymorphone
`
`
`
`hydrochloride extended-release tablets whole to avoid exposure to
`
`
`a potentially fatal dose of oxymorphone. (5.2)
`
`
`
`
`• Accidental ingestion of oxymorphone hydrochloride extended-
`
`
`
`
`release tablets, especially in children, can result in fatal overdose
`
`of oxymorphone. (5.2)
`
`
`• Prolonged use of oxymorphone hydrochloride extended-release
`
`
`
`
`
`tablets 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 (5.3).
`
`
`
`
`
`• Instruct patients not to consume alcohol or any product containing
`
`
`
`alcohol while taking oxymorphone hydrochloride extended-release
`
`
`
`
`tablets because co-ingestion can result in fatal plasma
` oxymorphone levels. (5.4)
`
`-----------------------------RECENT MAJOR CHANGES-------------------­
`
`
`
`
`
`
` Boxed Warning
`
` 4/2014
` Indications and Usage (1)
`
`
`
`
` 4/2014
`
`
`
`
`
` 4/2014
`
` Dosage and Administration (2)
`
`
`
`
` 4/2014
`
`
` Warnings and Precautions (5)
`
`----------------------------INDICATIONS AND USAGE--------------------------
`
`
`
`
` Oxymorphone hydrochloride extended-release tablets are 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 oxymorphone hydrochloride extended-release tablets 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)
`
`
`• Oxymorphone hydrochloride extended-release tablets are not
`
`
`
`
`indicated as an as-needed (prn) analgesic. (1)
`
`
`
`
`
`
`
`
`• 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). (2.2)
`
`
`
`
`
`
`• Administer on an empty stomach, at least 1 hour prior to or 2 hours
`
`
`
`after eating. (2.1)
`• Oxymorphone hydrochloride extended-release 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)
`
`• Do not abruptly discontinue oxymorphone hydrochloride extended-
`
`
`release tablets in a physically dependent patient. (2.3, 5.13)
`
`
`
`• Instruct patients to swallow oxymorphone hydrochloride extended-
`
`
`release tablets intact. (2.4)
`
`
`• Reduce the dose of oxymorphone hydrochloride extended-release tablets
`
`
`
`in patients with mild hepatic impairment and patients with renal
`
`
`
`
`
`impairment. (2.5, 2.6)
`
`
`
`
`
`
`---------------------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 (4)
`
`
`• Known or suspected paralytic ileus and gastrointestinal obstruction (4)
`
`
`
`
`
`
`• Hypersensitivity to oxymorphone (4)
`
`
`
`
`• Moderate or severe hepatic impairment (4)
`
`
`
`
`
`
`
`------------------------WARNINGS AND PRECAUTIONS-------------------­
`See Boxed WARNINGS
`
`
`• Interaction with CNS depressants: Concomitant use may cause profound
`
`
`
`
`
`sedation, respiratory depression, and death. If coadministration is
`
`
`
`
`required, consider dose reduction of one or both drugs because of
`
`
`
`
`additive pharmacological effects. (5.4)
`
`
`• Elderly, cachectic, and debilitated patients and those with chronic
`
`
`
`
`
`pulmonary disease: Monitor closely because of increased risk for life-
`
`threatening respiratory depression. (5.5, 5.6)
`
`
`
`• Hypotensive effect: Monitor during dose initiation and titration. (5.8)
`
`
`
`
`
`
`• Patients with head injury or increased intracranial pressure: Monitor for
`
`
`
`
`sedation and respiratory depression. Avoid use of oxymorphone
`
`
`
`
`hydrochloride extended-release tablets in patients with impaired
`
`
`
`consciousness or coma susceptible to intracranial effects of CO2
`
`
`
`retention. (5.9)
`
`
`
`
`• Use with caution in patients who have difficulty in swallowing or have
`
`
`underlying GI disorders that may predispose them to obstruction. (5.10)
`
`
`
`
`
`
`
`
`
`
`-----------------------------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 [company
`
`
`
`
`name] at [phone number] or FDA at 1-800 FDA-1088 or
`www.fda.gov/medwatch.
`
`------------------------------DRUG INTERACTIONS---------------------------­
`Mixed agonist/antagonist and partial agonist opioid analgesics: Avoid use
`
`
`
`with oxymorphone hydrochloride extended-release tablets because they
`
`
`
`may reduce analgesic effect of oxymorphone hydrochloride extended-
`
`
`
`
`release tablets or precipitate withdrawal symptoms. (7.3)
`
`
`
`------------------------USE IN SPECIFIC POPULATIONS-------------------­
`• Pregnancy: Based on animal data, may cause fetal harm. (8.1)
`
`
`
`• Nursing mothers: Closely monitor infants of nursing women receiving
`
`
`oxymorphone hydrochloride extended-release tablets. (8.3)
`
`
`
`
`
`---------------------DOSAGE AND ADMINISTRATION-------------------­
`• For opioid-naïve and opioid non-tolerant patients, initiate with 5 mg
`
`
`
`
`
`tablets orally every 12 hours. (2.1)
`
`
`
`• To convert to oxymorphone hydrochloride extended-release tablets from
`
`
`
`another opioid, use available conversion factors to obtain estimated dose.
`
`
`(2.1)
`
`________________________________________________________________________________________________________________________________________
`
`
`See 17 for PATIENT COUNSELING INFORMATION and
`
`
`
`
`Medication Guide
`
`
`
`
`
`
`
`
`
`
`Revised: 01/2015
`
`
`
`
`Reference ID: 3693219
`
`
`
`
`
`1
`
`
`

`

`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE­
`
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`
`INGESTION; NEONATAL OPIOID WITHDRAWAL
`
`SYNDROME; and INTERACTION WITH ALCOHOL
`
`
`Boxed Warning
`
`INDICATIONS AND USAGE
`1
`
`
`2
`DOSAGE AND ADMINISTRATION
`
`
`2.1
`Initial Dosing
`
`
`
`
`2.2 Titration and Maintenance of Therapy
`
`
`
`2.3 Discontinuation of oxymorphone hydrochloride extended-
`
`
`
`release tablets
`
`
`2.4 Administration of oxymorphone hydrochloride extended-
`
`
`
`release tablets
`
`
`2.5 Patients with Hepatic Impairment
`
`
`
`
`2.6 Patients with Renal Impairment
`
`
`
`2.7 Geriatric Patients
`
`
`
`DOSAGE FORMS AND STRENGTHS
`3
`
`
`CONTRAINDICATIONS
`4
`
`
`5 WARNINGS AND PRECAUTIONS
`
`
`
`
`5.1 Addiction, Abuse, and Misuse Potential
`
`
`
`5.2 Life Threatening Respiratory Depression
`
`
`
`5.3 Neonatal Opioid Withdrawal Syndrome
`
`
`
`
`5.4
`Interaction with Central Nervous System Depressants
`
`
`
`
`5.5 Use in Elderly, Cachectic, and Debilitated Patients
`
`
`
`
`5.6 Use in Patients with Chronic Pulmonary Disease
`
`
`
`5.7 Use in Patients with Hepatic Impairment
`
`
`
`5.8 Hypotensive Effect
`
`
`
`
`
`
`5.9 Use in Patients with Head Injury or Increased Intracranial
`
`
`
`Pressure
`
`
`5.10 Difficulty in Swallowing and Risk for Obstruction in Patients
`
`
`
`at Risk for a Small Gastrointestinal Lumen
`
`
`
`5.11 Use in Patients with Gastrointestinal Conditions
`
`
`
`
`
`5.12 Use in Patients with Convulsive or Seizure Disorders
`
`
`
`
`5.13 Avoidance of Withdrawal
`
`
`
`5.14 Driving and Operating Machinery
`
`
`
`_________________________________________________________________________________________________________________________________
`
`8
`
`
`9
`
`
`6
`
`
`7
`
`
`
`
`ADVERSE REACTIONS
`
`6.1 Clinical Trial Experience
`
`
`
`
`6.2 Post-marketing Experience
`
`
`DRUG INTERACTIONS
`
`
`7.1 Alcohol
`
`
`
`7.2 CNS Depressants
`
`
`
`
`7.3
`Interactions with Mixed Agonist/Antagonist and Partial
`
`
`Agonist Opioid Analgesics
`
`
`
`7.4 Muscle Relaxants
`
`
`
`7.5 Cimetidine
`
`
`
`7.6 Anticholinergics
`
`
`USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`
`
`
`8.2 Labor and Delivery
`
`
`
`8.3 Nursing Mothers
`
`
`
`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.
`
`
`
`
`
`Reference ID: 3693219
`
`
`
`
`
`
`
`
`
`

`

`
`
` FULL PRESCRIBING INFORMATION
`
`
` WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION;
`
`
`
`
`
`
`ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and
`
`
`INTERACTION WITH ALCOHOL
`
`
`
`
`
`Addiction, Abuse, and Misuse
`
`
`
`
`Oxymorphone hydrochloride extended-release tablets expose 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
`
`
`oxymorphone hydrochloride extended-release tablets, and monitor all patients regularly for the development of these
`
`behaviors or conditions [see Warnings and Precautions (5.1)].
`
`
`Life-threatening Respiratory Depression
`
`
`
`Serious, life-threatening, or fatal respiratory depression may occur with use of oxymorphone hydrochloride extended-
`
`
`
`release tablets. Monitor for respiratory depression, especially during initiation of oxymorphone hydrochloride
`
`
`
`extended-release tablets or following a dose increase. Instruct patients to swallow oxymorphone hydrochloride
`
`
`extended-release tablets whole; crushing, chewing, or dissolving oxymorphone hydrochloride extended-release tablets
`
`can cause rapid release and absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions
`
`
`
`(5.2)].
`
`
`
`
`Accidental Ingestion
`
`
`
`
`
`
`Accidental ingestion of even one dose of oxymorphone hydrochloride extended-release tablets, especially by children,
`
`can result in a fatal overdose of oxymorphone [see Warnings and Precautions (5.2)].
`
`
`
`
`
`Neonatal Opioid Withdrawal Syndrome
`
`
`
`
`Prolonged use of oxymorphone hydrochloride extended-release tablets 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 (5.3)].
`
`
`
`Interaction with Alcohol
`
`Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain
`
`
`
`alcohol while taking oxymorphone hydrochloride extended-release tablets. The co-ingestion of alcohol with
`
`
`
`oxymorphone hydrochloride extended-release tablets may result in increased plasma levels and a potentially fatal
`
`
`overdose of oxymorphone [see Warnings and Precautions (5.4)].
`
`
`
`INDICATIONS AND USAGE
`1
`
`
`
`
`
`
`
`Oxymorphone hydrochloride extended-release tablets are 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, reserve oxymorphone hydrochloride extended-release tablets
`
`
`
`
`
`
`
`
`
`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.
`
`
`
`
`
`
`• Oxymorphone hydrochloride extended-release tablets are not indicated as an as-needed (prn) analgesic.
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`
`2.1 Initial Dosing
`
`
`
`To avoid medication errors, prescribers and pharmacists must be aware that oxymorphone is available as both immediate-release 5 mg
`and 10 mg tablets and extended-release 5 mg and 10 mg tablets [see Dosage Forms and Strengths (3)].
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Oxymorphone hydrochloride extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable in
`
`
`
`
`
`
`
`
`the use of potent opioids for the management of chronic pain.
`
`
`
`Initiate the dosing regimen for each patient individually, taking into account the patient's 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 with oxymorphone hydrochloride extended-release tablets [see Warnings
`
`
`
`
`
`and Precautions (5.2)].
`
`
`
`
`
`
`
`Oxymorphone hydrochloride extended-release tablets must be taken 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
`
`
`
`Reference ID: 3693219
`
`
`
`
`
`
`
`
`
`
`

`

`
` oxymorphone hydrochloride extended-release tablets will result in uncontrolled delivery of oxymorphone and can lead to overdose or
`
` death [see Warnings and Precautions (5.2)].
`
`
`
`
` Oxymorphone hydrochloride extended-release tablets are 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.
`
`
`
`
`
`
` Use of Oxymorphone Hydrochloride Extended-Release Tablets as the First Opioid Analgesic
`Initiate treatment with oxymorphone hydrochloride extended-release tablets with the 5 mg tablet orally every 12-hours.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Use of Oxymorphone Hydrochloride Extended-Release Tablets in Patients who are not Opioid Tolerant
`
`
`
`
`
`
`
`
`
`
`
`
`The starting dose for patients who are not opioid tolerant is oxymorphone hydrochloride extended-release tablets 5 mg orally every 12
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`hours. Patients who are opioid tolerant are those receiving, 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, 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 Oxymorphone Hydrochloride Extended-Release Tablets
`
`
`
`
`Patients receiving OPANA may be converted to oxymorphone hydrochloride extended-release tablets by administering half the
`
`
`patient's total daily oral OPANA dose as oxymorphone hydrochloride extended-release tablets, every 12 hours.
`
`
`Conversion from Parenteral Oxymorphone to Oxymorphone Hydrochloride Extended-Release Tablets
`
`
`
`
`
`The absolute oral bioavailability of oxymorphone hydrochloride extended-release tablets are approximately 10%. Convert patients
`
`
`
`receiving parenteral oxymorphone to oxymorphone hydrochloride extended-release tablets by administering 10 times the patient's total
`
`
`
`daily parenteral oxymorphone dose as oxymorphone hydrochloride extended-release tablets 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 Oxymorphone Hydrochloride Extended-Release Tablets
`
`
`
`
`
`
`Discontinue all other around-the-clock opioid drugs when oxymorphone hydrochloride extended-release tablets 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 oxymorphone hydrochloride extended-release tablets clinical trial with an
`
`
`
`
`
`
`open-label titration period, patients were converted from their prior opioid to oxymorphone hydrochloride extended-release tablets
`
`
`
`
`
`
`
`
`
`using Table 1 as a guide for the initial oxymorphone hydrochloride extended-release tablets 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 oxymorphone
`
`
`
`
`
`hydrochloride extended-release tablets.
`
` • This table cannot be used to convert from oxymorphone hydrochloride extended-release tablets 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 OXYMORPHONE
`
` HYDROCHLORIDE EXTENDED-RELEASE TABLETS
`
`
`
` Approximate Oral
` Prior Oral Opioid
`
` Conversion Factor
`
` 1
`
` 0.5
`
` 0.5
`
` 0.5
` 0.333
`
`
`
` Oxymorphone
`
` Hydrocodone
`
` Oxycodone
`
` Methadone
`
` Morphine
`
`
`To calculate the estimated oxymorphone hydrochloride extended-release tablets 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
`
`
`Reference ID: 3693219
`
`
`
`
`
`
`
`
`
`
`

`

`
`Always round the dose down, if necessary, to the appropriate oxymorphone hydrochloride extended-release tablets strength(s)
`
`
`
`
`
`
`
`
`available.
`
`
`Example conversion from a single opioid to oxymorphone hydrochloride extended-release tablets:
`
`
`
`
`
`
`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 oxymorphone hydrochloride extended-release tablets to be given every 12
`
`
`
`
`
`
`
`
`
`
`
`
`hours. Round down, if necessary, to the appropriate oxymorphone hydrochloride extended-release tablet strengths
`
`
`
`
`
`
`
`
`available.
`
`10 mg oxymorphone hydrochloride extended-release tablets every 12 hours
`
`
`
`
`
`
`
`
`Conversion from Methadone to Oxymorphone Hydrochloride Extended-Release Tablets
`
`
`
`
`
`
`
`
`
`
`
`
`
`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.
`
`
`
`2.2 Titration and Maintenance of Therapy
`
`
`
`
`Individually titrate oxymorphone hydrochloride extended-release tablets to a dose that provides adequate analgesia and minimizes
`
`
`adverse reactions. Continually reevaluate patients receiving oxymorphone hydrochloride extended-release tablets 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 oxymorphone hydrochloride
`
`
`
`
`extended-release tablets dose to decrease the level of pain. Because steady-state plasma concentrations are approximated within 3
`
`
`
`
`
`
`days, oxymorphone hydrochloride extended-release tablets 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 oxymorphone hydrochloride extended-release tablets, 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 oxymorphone hydrochloride extended-release tablets
`
`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.
`
`
`
`2.3 Discontinuation of oxymorphone hydrochloride extended-release tablets
`
`
`
`
`When a patient no longer requires therapy with oxymorphone hydrochloride extended-release tablets, use a gradual downward
`
`
`
`
`titration of the dose every two to four days, to prevent signs and symptoms of withdrawal in the physically-dependent patient. Do not
`
`
`
`abruptly discontinue oxymorphone hydrochloride extended-release tablets.
`
`
`
`2.4 Administration of oxymorphone hydrochloride extended-release tablets
`
`
`Instruct patients to swallow oxymorphone hydrochloride extended-release tablets intact. The tablets are not to be crushed, dissolved,
`
`or chewed due to the risk of rapid release and absorption of a potentially fatal dose of oxymorphone [see Warnings and Precautions
`
`
`(5.2)]. Administer on an empty stomach, at least 1 hour prior to or 2 hours after eating.
`
`
`
`
`
`2.5 Patients with Hepatic Impairment
`
`
`
`
`
`
`Oxymorphone hydrochloride extended-release tablets are 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
`
`
`
`oxymorphone hydrochloride extended-release tablets 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 (5.2), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].
`
`
`
`
`
`2.6 Patients with Renal Impairment
`
`
`
`
`
`In patients with creatinine clearance rates less than 50 mL/min, start oxymorphone hydrochloride extended-release tablets in the
`
`
`
`
`
`
`opioid-naïve patient with the 5 mg dose. For patients on prior opioid therapy, start oxymorphone hydrochloride extended-release
`
`
`
`
`
`tablets at 50% lower than the starting dose for a patient with normal renal function on prior opioids and titrate slowly. Monitor patients
`Reference ID: 3693219
`
`
`
`
`
`
`
`
`
`
`

`

`closely for signs of respiratory or central nervous system depression [see Warnings and Precautions (5.2), Use in Specific Populations
`
`
`
`
`
`(8.7) and Clinical Pharmacology (12.3)].
`
`
`
`2.7 Geriatric Patients
`
`
`The steady-state plasma concentrations of oxymorphone are approximately 40% higher in elderly subjects than in young subjects.
`
`
`
`
`
`Initiate dosing with oxymorphone hydrochloride extended-release tablets 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 oxymorphone
`
`
`
`
`
`hydrochloride extended-release tablets to adequate analgesia [see Warnings and Precautions (5.2), Use in Specific Populations (8.5)
`
`
`
`and Clinical Pharmacology (12.3)]. For patients on prior opioid therapy, start oxymorphone hydrochloride extended-release tablets at
`
`
`
`
`
`50% lower than the starting dose for a younger patient on prior opioids and titrate slowly.
`
`
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`The 5 mg dosage form is a pink, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a “5” on
`
`
`
`the other side.
`
`
`The 7.5 mg dosage form is a gray, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a “7
`
`
`
`
`
`½” on the other side.
`
`
`The 10 mg dosage form is a light orange, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and
`
`
`a “10” on the other side.
`
`
`The 15 mg dosage form is a white, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a “15”
`
`
`
`
`on the other side.
`
`
`The 20 mg dosage form is a light green, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a
`
`
`
`
`“20” on the other side.
`
`
`The 30 mg dosage form is a red, round, film-coated, biconcave extended-release tablet debossed with an “E” on one side and a “30”
`
`
`
`on the other side.
`
`
`The 40 mg dosage form is a 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
`
`
`
`Oxymorphone hydrochloride extended-release tablets are contraindicated in patients with:
`
`
`
`
`
`
`
`Significant respiratory depression
`
`
`
` Acute or severe bronchial asthma or hypercarbia
`
`
`
`
` Known or suspected paralytic ileus and gastrointestinal obstruction
`
`
`
` Moderate and severe hepatic impairment [see Clinical Pharmacology (12.3), Warnings and Precautions (5.7)].
`
`
`
`
` Hypersensitivity (e.g. anaphylaxis) to oxymorphone, any other ingredients in oxymorphone hydrochloride extended-release
`
`
`
`
`tablets, or to morphine analogs such as codeine [see Adverse Reactions (6.1)].
`
`
`
`
`5 WARNINGS AND PRECAUTIONS
`
`
`5.1 Addiction, Abuse, and Misuse
`
`
`
`Oxymorphone hydrochloride extended-release tablets contain oxymorphone, a Schedule II controlled substance. As an opioid,
`
`
`
`
`
`oxymorphone hydrochloride extended-release tablets expose users to the risks of addiction, abuse, and misuse [see Drug Abuse and
`
`
`
`Dependence (9)]. As modified-release products such as oxymorphone hydrochloride extended-release tablets deliver the opioid over
`
`
`
`
`
`
`an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxymorphone present.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed oxymorphone
`
`
`
`
`
`
`
`
`
`hydrochloride extended-release tablets and in those who obtain the drug illicitly. Addiction can occur at recommended doses and if
`
`
`
`
`the drug is misused or abused.
`
`
`
`
`
`Assess each patient’s risk for opioid abuse or addiction, abuse, or misuse prior to prescribing oxymorphone hydrochloride extended-
`
`
`
`
`release tablets, and monitor all patients receiving oxymorphone hydrochloride extended-release tablets for the development of these
`
`
`
`behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol
`
`
`
`
`
`
`
`addiction or abuse) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the
`
`
`prescribing of oxymorphone hydrochloride extended-release tablets for the proper management of pain in any given patient. Patients
`
`
`
`
`
`
`
`
`
`
`
`at increased risk may be prescribed modified-release opioid formulations such as oxymorphone hydrochloride extended-release
`
`
`
`
`
`
`
`
`
`tablets, but use in such patients necessitates intensive counseling about the risks and proper use of oxymorphone hydrochloride
`
`
`
`
`
`
`
`extended-release tablets along with intensive monitoring for signs of addiction, abuse, and misuse.
`
`
`
`
`Abuse or misuse of oxymorphone hydrochloride extended-release tablets 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)].
`
`
`
`
`
`
`Reference ID: 3693219
`
`
`
`
`
`
`
`
`
`
`

`

`
`Opioid agonists such as oxymorphone hydrochloride extended-release tablets are sought by drug abusers and people with addiction
`
`
`
`
`
`
`
`
`
`disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing oxymorphone hydrochloride
`
`
`
`
`
`
`
`
`
`
`extended-release tablets. 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 substance