` CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`022272Orig1s027
`LABELING
`
`
`
`

`

`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`OXYCONTIN® safely and effectively. See full prescribing information
`for OXYCONTIN.
`
`OXYCONTIN® (oxycodone hydrochloride) extended-release tablets, for
`oral use, CII
`Initial U.S. Approval: 1950
`
`
`WARNING: ADDICTION, ABUSE AND MISUSE; LIFE-
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
`and CYTOCHROME P450 3A4 INTERACTION
`See full prescribing information for complete boxed warning.
`• OXYCONTIN exposes users to risks of addictions, 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
`and 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 OXYCONTIN tablets whole to avoid
`exposure to a potentially fatal dose of oxycodone. (5.2)
`• Accidental ingestion of OXYCONTIN, especially in children, can
`result in a fatal overdose of oxycodone. (5.2)
`• Prolonged use of OXYCONTIN 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)
`• Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4
`inducers) can result in a fatal overdose of oxycodone from
`OXYCONTIN. (5.14)
`
`
`----------------------------RECENT MAJOR CHANGES--------------------------
`Indications and Usage (1)
`
`08/2015
`Dosage and Administration (2)
`
`08/2015
`
`----------------------------INDICATIONS AND USAGE---------------------------
`OXYCONTIN is an opioid agonist indicated for pain severe enough to require
`daily, around-the-clock, long-term opioid treatment and for which alternative
`treatment options are inadequate in:
`
`
`•
`•
`
`Adults; and
`Opioid-tolerant pediatric patients 11 years of age and older who are
`already receiving and tolerate a minimum daily opioid dose of at least
`20 mg oxycodone orally or its equivalent.
`
`
`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 formulations, reserve OXYCONTIN 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)
`• OXYCONTIN is not indicated as an as-needed (prn) analgesic. (1)
`
`----------------------DOSAGE AND ADMINISTRATION------------------------
`• To be prescribed only by health care providers knowledgeable in use of
`potent opioids for management of chronic pain. (2.1)
`• Must swallow tablets intact. Do not cut, break, chew, crush, or dissolve
`tablets (risk of potentially fatal dose). (2.1, 5.1)
`• Must take tablets one at a time, with enough water to ensure complete
`swallowing immediately after placing in mouth. (2.1, 5.9)
`• OXYCONTIN 60 mg and 80 mg tablets, a single dose greater than 40 mg,
`or a total daily dose greater than 80 mg are only for use in patients in whom
`tolerance to an opioid of comparable potency has been established. (2.1)
`• Do not abruptly discontinue OXYCONTIN in a physically dependent
`patient. (2.9)
`
`Adults: For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg
`tablets orally every 12 hours. See full prescribing information for instructions
`on conversion from opioids to OXYCONTIN, titration and maintenance of
`therapy. (2.2, 2.3, 2.5)
`Pediatric Patients 11 Years of Age and Older
`
`Reference ID: 3805894
`
`
`
`• For use only in pediatric patients 11 years and older already receiving and
`tolerating opioids for at least 5 consecutive days with a minimum of 20 mg
`per day of oxycodone or its equivalent for at least two days immediately
`preceding dosing with OXYCONTIN. (2.4)
`• See full prescribing information for instructions on conversion from
`opioids to OXYCONTIN, titration and maintenance of therapy. (2.4, 2.5)
`Geriatric Patients: In debilitated, opioid non-tolerant geriatric patients, initiate
`dosing at 1/3 to 1/2 the recommended starting dosage and titrate carefully.
`(2.7, 8.5)
`Patients with Hepatic Impairment: Initiate dosing at 1/3 to 1/2 the
`recommended staring dosage and titrate carefully. (2.8, 8.6)
`
`---------------------DOSAGE FORMS AND STRENGTHS----------------------
`Extended-release tablets: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80
`mg. (3)
`
`-------------------------------CONTRAINDICATIONS------------------------------
`• Significant respiratory depression. (4)
`• Acute or severe bronchial asthma in an unmonitored setting or in absence
`of resuscitative equipment. (4)
`• Known or suspected paralytic ileus and gastrointestinal obstruction. (4)
`• Hypersensitivity to oxycodone. (4)
`-----------------------WARNINGS AND PRECAUTIONS------------------------
`• Risk of life-threatening respiratory depression in elderly, cachectic, and
`debilitated patients, and in patients with chronic pulmonary disease:
`Monitor closely. (5.5, 5.6)
`• Severe hypotension: Monitor during dosage initiation and titration. Avoid
`use of OXYCONTIN in patients with circulatory shock. (5.7)
`• Risk of use in patients with increased intracranial pressure, brain tumors,
`head injury, or impaired consciousness: Monitor for sedation and
`respiratory depression. Avoid use of OXYCONTIN in patients with
`impaired consciousness or coma. (5.8)
`• Risk of obstruction in patients who have difficulty swallowing or have
`underlying GI disorders that may predispose them to obstruction: Consider
`use of an alternative analgesic. (5.9)
`
`------------------------------ADVERSE REACTIONS-------------------------------
`Most common adverse reactions (>5%) were constipation, nausea,
`somnolence, dizziness, vomiting, pruritus, headache, dry mouth, asthenia, and
`sweating. (6.1)
`
`To report SUSPECTED ADVERSE REACTIONS, contact Purdue
`Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`------------------------------DRUG INTERACTIONS-------------------------------
`• CNS depressants: Concomitant use may cause hypotension, profound
`sedation, respiratory depression, coma, and death. If decision to begin
`OXYCONTIN is made, start with 1/3 to 1/2 the recommended starting
`dosage and monitor closely. (2.6, 5.4, 7.1)
`• Mixed agonist/antagonist and partial agonist opioid analgesics: Avoid use
`with OXYCONTIN because they may reduce analgesic effect of
`OXYCONTIN or precipitate withdrawal symptoms. (7.3)
`
`-----------------------USE IN SPECIFIC POPULATIONS------------------------
`Nursing mothers: Oxycodone has been detected in human milk. Closely
`monitor infants of nursing women receiving OXYCONTIN. (8.3)
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide.
`
`
`
`
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`
`
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`
`
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`
`
`Revised: 08/2015
`
`

`

`
`6 ADVERSE REACTIONS
`6.1 Clinical Trial Experience
`6.2 Postmarketing Experience
`7 DRUG INTERACTIONS
`7.1 CNS Depressants
`7.2 Muscle Relaxants
`7.3 Drugs Affecting Cytochrome P450 Isoenzymes
`7.4 Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
`7.5 Diuretics
`7.6 Anticholinergics
`8 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
`8.8 Gender Differences
`9 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
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`WARNING: ADDICTION, ABUSE AND MISUSE; LIFE-
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and
`CYTOCHROME P450 3A4 INTERACTION
`INDICATIONS AND USAGE
`1
`2 DOSAGE AND ADMINISTRATION
`Important Dosage and Administration Instructions
`2.1
`2.2 Dosage in Adults who are Opioid Tolerant
`2.3 Conversion from Opioids to OXYCONTIN in Adults
`Initial Dosage in Pediatric Patients 11 Years and Older
`2.4
`2.5 Titration and Maintenance of Therapy in Adults and Pediatric
`Patients 11 Years and Older
`2.6 Dosage Modifications in Patients with Hepatic Impairment
`2.7 Discontinuation of OXYCONTIN
`2.8 Administration of OXYCONTIN
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1 Addiction, Abuse, and Misuse
`5.2 Life-Threatening Respiratory Depression
`5.3 Neonatal Opioid Withdrawal Syndrome
`Interactions with Central Nervous System Depressants
`5.4
`5.5 Use in Elderly, Cachectic, and Debilitated Patients
`5.6 Use in Patients with Chronic Pulmonary Disease
`5.7 Hypotensive Effects
`5.8 Use in Patients with Head Injury or Increased Intracranial Pressure
`5.9 Difficulty in Swallowing and Risk for Obstruction in Patients at
`Risk for a Small Gastrointestinal Lumen
`5.10 Use in Patients with Gastrointestinal Conditions
`5.11 Use in Patients with Convulsive or Seizure Disorders
`5.12 Avoidance of Withdrawal
`5.13 Driving and Operating Machinery
`5.14 Cytochrome P450 3A4 Inhibitors and Inducers
`5.15 Laboratory Monitoring
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 3805894
`
`

`

`FULL PRESCRIBING INFORMATION
`
`
`WARNING: ADDICTION, ABUSE AND MISUSE; LIFE-THREATENING
`RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID
`WITHDRAWAL SYNDROME; and CYTOCHROME P450 3A4 INTERACTION
`
`
`Addiction, Abuse, and Misuse
`OXYCONTIN® 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 OXYCONTIN 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
`OXYCONTIN. Monitor for respiratory depression, especially during initiation of
`OXYCONTIN or following a dose increase. Instruct patients to swallow OXYCONTIN
`tablets whole; crushing, chewing, or dissolving OXYCONTIN tablets can cause rapid
`release and absorption of a potentially fatal dose of oxycodone [see Warnings and
`Precautions (5.2)].
`
`Accidental Ingestion
`Accidental ingestion of even one dose of OXYCONTIN, especially by children, can result in
`a fatal overdose of oxycodone [see Warnings and Precautions (5.2)].
`
`Neonatal Opioid Withdrawal Syndrome
`Prolonged use of OXYCONTIN 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)].
`
`Cytochrome P450 3A4 Interaction
`The concomitant use of OXYCONTIN with all cytochrome P450 3A4 inhibitors may result
`in an increase in oxycodone plasma concentrations, which could increase or prolong
`adverse drug effects and may cause potentially fatal respiratory depression. In addition,
`discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an
`increase in oxycodone plasma concentration. Monitor patients receiving OXYCONTIN and
`any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.14) and Clinical
`Pharmacology (12.3)].
`
` 1
`
` INDICATIONS AND USAGE
`
`Reference ID: 3805894
`
`

`

`OXYCONTIN 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
`in:
`
`• Adults; and
`• Opioid-tolerant pediatric patients 11 years of age and older who are already receiving
`and tolerate a minimum daily opioid dose of at least 20 mg oxycodone orally or its
`equivalent.
`
`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 OXYCONTIN 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.
`• OXYCONTIN is not indicated as an as-needed (prn) analgesic.
`
` 2
`
` DOSAGE AND ADMINISTRATION
`
`2.1 Important Dosage and Administration Instructions
`
`OXYCONTIN 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 OXYCONTIN therapy [see Warnings and Precautions (5.2)].
`• Must take OXYCONTIN tablets whole, with enough water to ensure complete
`swallowing immediately after placing in the mouth. Must take OXYCONTIN tablets one
`tablet at a time and must not pre-soak, lick or otherwise wet the tablet prior to placing in
`the mouth [see Warnings and Precautions (5.9)]. Cutting, breaking, crushing, chewing,
`or dissolving OXYCONTIN tablets will result in uncontrolled delivery of oxycodone and
`can lead to overdose or death [see Warnings and Precautions (5.1)].
`• OXYCONTIN 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily
`dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of
`comparable potency has been established.
`
`
`2.2 Initial Dosage in Adults who are not Opioid-Tolerant
`
`The starting dosage for patients who are not opioid tolerant is OXYCONTIN 10 mg orally every
`12 hours. Adult patients who are opioid tolerant are those receiving, for one week or longer, at
`
`Reference ID: 3805894
`
`

`

`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 [see Warnings and Precautions (5.2)].
`2.3 Conversion from Opioids to OXYCONTIN in Adults
`
`Conversion from Other Oral Oxycodone Formulations to OXYCONTIN
`If switching from other oral oxycodone formulations to OXYCONTIN, administer one half of
`the patient's total daily oral oxycodone dose as OXYCONTIN every 12 hours
`
`Conversion from Other Opioids to OXYCONTIN
`There are no established conversion ratios for conversion from other opioids to OXYCONTIN
`defined by clinical trials. Discontinue all other around-the-clock opioid drugs when
`OXYCONTIN therapy is initiated and initiate dosing using OXYCONTIN 10 mg orally every 12
`hours.
`
`It is safer to underestimate a patient’s 24-hour oral oxycodone requirements and provide rescue
`medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone
`requirements which could result in adverse reactions. While useful tables of opioid equivalents
`are readily available, there is substantial inter-patient variability in the relative potency of
`different opioids.
`
`Conversion from Methadone to OXYCONTIN
`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.
`
`Conversion from Transdermal Fentanyl to OXYCONTIN
`If switching from transdermal fentanyl patch to OXYCONTIN, ensure that the patch has been
`removed for at least 18 hours prior to starting OXYCONTIN. Although there has been no
`systematic assessment of such conversion, start with a conservative conversion: substitute 10 mg
`of OXYCONTIN every 12 hours for each 25 mcg per hour fentanyl transdermal patch. Follow
`the patient closely during conversion from transdermal fentanyl to OXYCONTIN, as there is
`limited documented experience with this conversion.
`
`2.4 Initial Dosage in Pediatric Patients 11 Years and Older
`
`The following dosing information is for use only in pediatric patients 11 years and older already
`receiving and tolerating opioids for at least five consecutive days. For the two days immediately
`preceding dosing with OXYCONTIN, patients must be taking a minimum of 20 mg per day of
`oxycodone or its equivalent. OXYCONTIN is not appropriate for use in pediatric patients
`requiring less than a 20 mg total daily dose. Table 1, based on clinical trial experience, displays
`the conversion factor when switching pediatric patients 11 years and older (under the conditions
`described above) from opioids to OXYCONTIN.
`
`Reference ID: 3805894
`
`

`

`
`Discontinue all other around-the-clock opioid drugs when OXYCONTIN therapy is initiated.
`
`Although tables of oral and parenteral equivalents are readily available, there is substantial inter-
`patient variability in the relative potency of different opioid drugs and formulations. As such, it
`is preferable to underestimate a patient’s 24-hour oral oxycodone requirements and provide
`rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral
`oxycodone requirements and manage an adverse reaction.
`
`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 OXYCONTIN.
`
`• The table cannot be used to convert from OXYCONTIN to another opioid. Doing so
`will result in an over-estimation of the dose of the new opioid and may result in fatal
`overdose.
`
`• The formula for conversion from prior opioids, including oral oxycodone, to the daily
`dose of OXYCONTIN is mg per day of prior opioid x factor = mg per day of
`OXYCONTIN. Divide the calculated total daily dose by 2 to get the every-12-hour
`OXYCONTIN dose. If rounding is necessary, always round the dose down to the
`nearest OXYCONTIN tablet strength available.
`
`
`Table 1: Conversion Factors When Switching Pediatric Patients 11 Years and Older to
`OXYCONTIN
`
` Prior Opioid
`
`Conversion Factor
`
`Parenteral*
`Oral
`
`--
`1
`Oxycodone
`--
`0.9
`Hydrocodone
`20
`4
`Hydromorphone
`3
`0.5
`Morphine
`0.2
`0.17
`Tramadol
`*For patients receiving high-dose parenteral opioids, a more conservative conversion is
`warranted. For example, for high-dose parenteral morphine, use 1.5 instead of 3 as a
`multiplication factor.
`
`Step #1: To calculate the estimated total OXYCONTIN daily dosage using Table 1:
`
`Reference ID: 3805894
`
`

`

`• For pediatric patients taking a single opioid, sum the current total daily dosage of the
`opioid and then multiply the total daily dosage by the approximate conversion factor to
`calculate the approximate OXYCONTIN daily dosage.
`
`• For pediatric patients on a regimen of more than one opioid, calculate the approximate
`oxycodone dose for each opioid and sum the totals to obtain the approximate
`OXYCONTIN daily dosage.
`
`• For pediatric patients on a regimen of fixed-ratio opioid/non-opioid analgesic products,
`use only the opioid component of these products in the conversion.
`
`Step #2: If rounding is necessary, always round the dosage down to the nearest OXYCONTIN
`tablet strength available and initiate OXYCONTIN therapy with that dose. If the calculated
`OXYCONTIN total daily dosage is less than 20 mg, there is no safe strength for conversion and
`do not initiate OXYCONTIN.
`
`Example conversion from a single opioid (e.g., hydrocodone) to OXYCONTIN: Using the
`conversion factor of 0.9 for oral hydrocodone in Table 1, a total daily hydrocodone dosage of
`50 mg is converted to 45 mg of oxycodone per day or 22.5 mg of OXYCONTIN every 12
`hours. After rounding down to the nearest strength available, the recommended
`OXYCONTIN starting dosage is 20 mg every 12 hours.
`
`Step #3: Close observation and titration are warranted until pain management is stable on the
`new opioid. Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-
`sedation/toxicity after converting patients to OXYCONTIN. See Dosage and Administration
`(2.4) for important instructions on titration and maintenance of therapy.
`
`There is limited experience with conversion from transdermal fentanyl to OXYCONTIN in
`pediatric patients 11 years and older. If switching from transdermal fentanyl patch to
`OXYCONTIN, ensure that the patch has been removed for at least 18 hours prior to starting
`OXYCONTIN. Although there has been no systematic assessment of such conversion, start with
`a conservative conversion: substitute 10 mg of OXYCONTIN every 12 hours for each 25 mcg
`per hour fentanyl transdermal patch. Follow the patient closely during conversion from
`transdermal fentanyl to OXYCONTIN.
`
`If using asymmetric dosing, instruct patients to take the higher dose in the morning and the lower
`dose in the evening
`
`2.5 Titration and Maintenance of Therapy in Adults and Pediatric Patients 11 Years and
`Older
`
`Individually titrate OXYCONTIN to a dosage that provides adequate analgesia and minimizes
`adverse reactions. Continually reevaluate patients receiving OXYCONTIN to assess the
`maintenance of pain control, signs and symptoms of opioid withdrawal, and 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
`
`Reference ID: 3805894
`
`

`

`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.
`
`Patients who experience breakthrough pain may require a dosage increase of OXYCONTIN 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 the OXYCONTIN dosage. Because steady-state plasma concentrations are
`approximated in 1 day, OXYCONTIN dosage may be adjusted every 1 to 2 days. If unacceptable
`opioid-related adverse reactions are observed, the subsequent dose may be reduced. Adjust the
`dosage to obtain an appropriate balance between management of pain and opioid-related adverse
`reactions.
`
`There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more
`frequently than every 12 hours. As a guideline for pediatric patients 11 years and older, the total
`daily oxycodone dosage usually can be increased by 25% of the current total daily dosage. As a
`guideline for adults, the total daily oxycodone dosage usually can be increased by 25% to 50% of
`the current total daily dosage, each time an increase is clinically indicated.
`
`2.6 Dosage Modifications with Concomitant Use of Central Nervous System Depressants
`
`If the patient is currently taking a central nervous system (CNS) depressant and the decision is
`made to begin OXYCONTIN, start with 1/3 to 1/2 the recommended starting dosage of
`OXYCONTIN and monitor patients for signs of respiratory depression, sedation, and
`hypotension [see Warnings and Precautions (5.4), Drug Interactions (7.1)].
`
`2.7 Dosage Modifications in Geriatric Patients who are Debilitated and not Opioid-
`Tolerant
`
`For geriatric patients who are debilitated and not opioid tolerant, start dosing patients at 1/3 to
`1/2 the recommended starting dosage and titrate the dosage cautiously [see Use in Specific
`Populations (8.5)].
`
`2.8 Dosage Modifications in Patients with Hepatic Impairment
`
`For patients with hepatic impairment, start dosing patients at 1/3 to 1/2 the recommended starting
`dosage followed by careful dosage titration [see Clinical Pharmacology (12.3)].
`
`2.9 Discontinuation of OXYCONTIN
`
`When the patient no longer requires therapy with OXYCONTIN, gradually titrate the dosage
`downward to prevent signs and symptoms of withdrawal in the physically dependent patient. Do
`not abruptly discontinue OXYCONTIN.
`
`3 DOSAGE FORMS AND STRENGTHS
`
`Reference ID: 3805894
`
`

`

` 10 mg film-coated extended-release tablets (round, white-colored, bi-convex tablets
`debossed with OP on one side and 10 on the other)
` 15 mg film-coated extended-release tablets (round, gray-colored, bi-convex tablets
`debossed with OP on one side and 15 on the other)
` 20 mg film-coated extended-release tablets (round, pink-colored, bi-convex tablets
`debossed with OP on one side and 20 on the other)
` 30 mg film-coated extended-release tablets (round, brown-colored, bi-convex tablets
`debossed with OP on one side and 30 on the other)
` 40 mg film-coated extended-release tablets (round, yellow-colored, bi-convex tablets
`debossed with OP on one side and 40 on the other)
` 60 mg film-coated extended-release tablets (round, red-colored, bi-convex tablets
`debossed with OP on one side and 60 on the other)
` 80 mg film-coated extended-release tablets (round, green-colored, bi-convex tablets
`debossed with OP on one side and 80 on the other)
`
`4 CONTRAINDICATIONS
`
`OXYCONTIN is contraindicated in patients with:
`
`• Significant respiratory depression
`• Acute or severe bronchial asthma in an unmonitored setting or in the absence of
`resuscitative equipment
`• Known or suspected paralytic ileus and gastrointestinal obstruction
`• Hypersensitivity (e.g., anaphylaxis) to oxycodone [see Adverse Reactions (6.2)]
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Addiction, Abuse, and Misuse
`
`OXYCONTIN contains oxycodone, a Schedule II controlled substance. As an opioid,
`OXYCONTIN exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and
`Dependence (9)]. As modified-release products such as OXYCONTIN deliver the opioid over an
`extended period of time, there is a greater risk for overdose and death due to the larger amount of
`oxycodone present [see Drug Abuse and Dependence (9)].
`
`Although the risk of addiction in any individual is unknown, it can occur in patients
`appropriately prescribed OXYCONTIN. 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
`OXYCONTIN, and monitor all patients receiving OXYCONTIN 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 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 modified-release opioid
`formulations such as OXYCONTIN, but use in such patients necessitates intensive counseling
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`Reference ID: 3805894
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`about the risks and proper use of OXYCONTIN along with intensive monitoring for signs of
`addiction, abuse, and misuse.
`
`Abuse, or misuse of OXYCONTIN by crushing, chewing, snorting, or injecting the dissolved
`product will result in the uncontrolled delivery of oxycodone and can result in overdose and
`death [see Overdosage (10)].
`
`Opioid agonists are sought by drug abusers and people with addiction disorders and are subject
`to criminal diversion. Consider these risks when prescribing or dispensing OXYCONTIN.
`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 Life-Threatening Respiratory Depression
`
`Serious, life-threatening, or fatal respiratory depression has been reported with the use of
`modified-release opioids, even when used as recommended. Respiratory depression, if not
`immediately recognized and treated, may lead to respiratory arrest and death. Management of
`respiratory depression may include close observation, supportive measures, and use of opioid
`antagonists, depending on the patient’s clinical status [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 OXYCONTIN, the risk is greatest during the initiation of therapy or following a dose
`increase. Closely monitor patients for respiratory depression when initiating therapy with
`OXYCONTIN and following dose increases.
`
`To reduce the risk of respiratory depression, proper dosing and titration of OXYCONTIN are
`essential [see Dosage and Administration (2)]. Overestimating the OXYCONTIN dose when
`converting patients from another opioid product can result in a fatal overdose with the first dose.
`
`Accidental ingestion of even one dose of OXYCONTIN, especially by children, can result in
`respiratory depression and death due to an overdose of oxycodone.
`
`5.3 Neonatal Opioid Withdrawal Syndrome
`
`Prolonged use of OXYCONTIN during pregnancy can result in withdrawal signs in the neonate.
`Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, 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.
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`Reference ID: 3805894
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`

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`Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep
`pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset,
`duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid
`used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug
`by the newborn.
`
`5.4 Interactions with Central Nervous System Depressants
`
`Hypotension and profound sedation, coma, or respiratory depression may result if OXYCONTIN
`is used concomitantly with other central nervous system (CNS) depressants (e.g., sedatives,
`anxiolytics, hypnotics, neuroleptics, other opioids).
`
`When considering the use of OXYCONTIN in a patient taking a CNS depressant, assess the
`duration of use of the CNS depressant and the patient’s response, including the degree of
`tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of
`alcohol or illicit drugs that can cause CNS depression. If the decision to begin OXYCONTIN
`therapy is made, start with 1/3 to 1/2 the usual dose of OXYCONTIN, monitor patients for signs
`of sedation and respiratory depression and consider using a lower dose of the concomitant CNS
`depressant [see Drug Interactions (7.1) and Dosage and Administration (2.6)].
`
`5.5 Use in Elderly, Cachectic, and Debilitated Patients
`
`Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated
`patients as they may have altered pharmacokinetics or altered clearance compared to younger,
`healthier patients. Monitor such patients closely, particularly when initiating and titrating
`OXYCONTIN and when OXYCONTIN is given concomitantly wi