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; RISK
`EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
`CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM
`CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS
`DEPRESSANTS
`See full prescribing information for complete boxed warning.
`• OXYCONTIN exposes users to risks of addiction, abuse and misuse,
`which can lead to overdose and death. Assess patient’s risk before
`prescribing and monitor regularly for these behaviors and conditions.
`(5.1)
`• To ensure that the benefits of opioid analgesics outweigh the risks of
`addiction, abuse, and misuse, the Food and Drug Administration
`(FDA) has required a Risk Evaluation and Mitigation Strategy
`(REMS) for these products. (5.2)
`• Serious, life-threatening, or fatal respiratory depression may occur.
`Monitor closely, especially upon initiation or following a dose increase.
`Instruct patients to swallow OXYCONTIN tablets whole to avoid
`exposure to a potentially fatal dose of oxycodone. (5.3)
`• Accidental ingestion of OXYCONTIN, especially by children, can
`result in a fatal overdose of oxycodone. (5.3)
`• Prolonged use of OXYCONTIN during pregnancy can result in
`neonatal opioid withdrawal syndrome, which may be life-threatening if
`not recognized and treated. If prolonged opioid use is required 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)
`• Concomitant use with CYP3A4 inhibitors (or discontinuation of
`CYP3A4 inducers) can result in a fatal overdose of oxycodone. (5.5, 7,
`12.3)
`• 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. (5.6, 7)
`
`
`----------------------------RECENT MAJOR CHANGES--------------------------
`Boxed Warning
`
`
`09/2018
`Warnings and Precautions (5.2)
`
`09/2018
`
`----------------------------INDICATIONS AND USAGE---------------------------
`OXYCONTIN 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 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, 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 healthcare providers knowledgeable in use of
`potent opioids for management of chronic pain. (2.1)
`
`Reference ID: 4326201
`
`• 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)
`• 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. (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)
`• Instruct patients to swallow tablets intact and not to cut, break, chew, crush,
`or dissolve tablets (risk of potentially fatal dose). (2.1, 5.1)
`• Instruct patients to take tablets one at a time, with enough water to ensure
`complete swallowing immediately after placing in mouth. (2.1, 5.10)
`• 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
`• 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 one third to one half the recommended starting dosage and titrate
`carefully. (2.7, 8.5)
`Patients with Hepatic Impairment: Initiate dosing at one third to one half the
`recommended starting 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 gastrointestinal obstruction, including paralytic ileus
`(4)
`• Hypersensitivity to oxycodone (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. (5.7)
`• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of
`corticosteroids, and wean patient off of the opioid. (5.8)
`• Severe Hypotension: Monitor during dosage initiation and titration. Avoid
`use of OXYCONTIN in patients with circulatory shock. (5.9)
`• 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 OXYCONTIN in patients with
`impaired consciousness or coma. (5.10)
`• 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. (5.11)
`
`------------------------------ADVERSE REACTIONS-------------------------------
`Most common adverse reactions (incidence >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.
`
`
`
`
`
`
`
`
`
`
`

`

`
`
`
`
`Revised: 09/2018
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`------------------------------DRUG INTERACTIONS-------------------------------
`• CNS Depressants: Concomitant use may cause hypotension, profound
`sedation, respiratory depression, coma, and death. If co-administration is
`required and the decision to begin OXYCONTIN is made, start with 1/3 to
`1/2 the recommended starting dosage, consider using a lower dosage of the
`concomitant CNS depressant, and monitor closely. (2.6, 5.6, 7)
`• Serotonergic Drugs: Concomitant use may result in serotonin syndrome.
`Discontinue OXYCONTIN if serotonin syndrome is suspected. (7)
`• Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid
`use with OXYCONTIN because they may reduce analgesic effect of
`OXYCONTIN or precipitate withdrawal symptoms. (5.14, 7)
`• Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects of
`morphine. 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)
`
`
`
`
`
`Reference ID: 4326201
`
`

`

`
`6 ADVERSE REACTIONS
`6.1 Clinical Trial Experience
`6.2 Postmarketing Experience
`7 DRUG INTERACTIONS
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`8.3 Females and Males of Reproductive Potential
`8.4 Pediatric Use
`8.5 Geriatric Use
`8.6 Hepatic Impairment
`8.7 Renal Impairment
`8.8 Sex 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; RISK EVALUATION
`AND MITIGATION STRATEGY (REMS); LIFE-THREATENING
`RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;
`NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME
`P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE
`WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
`
` 1
`
`INDICATIONS AND USAGE
`
`2 DOSAGE AND ADMINISTRATION
`Important Dosage and Administration Instructions
`2.1
`2.2
`Initial Dosage in Adults who are not 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 with Concomitant Use of Central Nervous
`System Depressants
`2.7 Dosage Modifications in Geriatric Patients who are Debilitated and
`not Opioid-Tolerant
`2.8 Dosage Modifications in Patients with Hepatic Impairment
`2.9 Discontinuation of OXYCONTIN
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1 Addiction, Abuse, and Misuse
`5.2 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS)
`5.3 Life-Threatening Respiratory Depression
`5.4 Neonatal Opioid Withdrawal Syndrome
`5.5 Risks of Concomitant Use or Discontinuation of Cytochrome P450
`3A4 Inhibitors and Inducers
`5.6 Risks from Concomitant Use with Benzodiazepines or Other CNS
`Depressants
`5.7 Life-Threatening Respiratory Depression in Patients with Chronic
`Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients
`5.8 Adrenal Insufficiency
`5.9 Severe Hypotension
`5.10 Risks of Use in Patients with Increased Intracranial Pressure, Brain
`Tumors, Head Injury, or Impaired Consciousness
`5.11 Difficulty in Swallowing and Risk for Obstruction in Patients at
`Risk for a Small Gastrointestinal Lumen
`5.12 Risks of Use in Patients with Gastrointestinal Conditions
`5.13 Increased Risk of Seizures in Patients with Seizure Disorders
`5.14 Withdrawal
`5.15 Risks of Driving and Operating Machinery
`5.16 Laboratory Monitoring
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4326201
`
`

`

`FULL PRESCRIBING INFORMATION
`
`
`WARNING: ADDICTION, ABUSE AND MISUSE; RISK EVALUATION AND
`MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY
`DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL
`SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM
`CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
`
`•
`
`
`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 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
`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 (5.3)].
`
`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 (5.3)].
`
`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
`
`Reference ID: 4326201
`
`

`

`neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be
`available [see Warnings and Precautions (5.4)].
`
`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 (5.5), Drug Interactions
`(7), Clinical Pharmacology (12.3)].
`
`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 (5.6), Drug Interactions (7)].
`
` •
`
`
`
`Reserve concomitant prescribing of OXYCONTIN and benzodiazepines or other
`CNS depressants for use in patients for whom alternative treatment options are
`inadequate.
`Limit dosages and durations to the minimum required.
`Follow patients for signs and symptoms of respiratory depression and sedation.
`
`•
`•
`
` 1
`
` INDICATIONS AND USAGE
`
`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.
`
`
`Reference ID: 4326201
`
`

`

`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.
`
`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. Adult 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, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.
`• 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 OXYCONTIN and adjust the
`dosage accordingly [see Warnings and Precautions (5.3)].
`
`
`Instruct patients to swallow OXYCONTIN tablets whole, one tablet at a time, with enough water
`to ensure complete swallowing immediately after placing in the mouth [see Patient Counseling
`Information (17)]. Instruct patients not to pre-soak, lick, or otherwise wet the tablet prior to
`placing in the mouth [see Warnings and Precautions (5.11)]. 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 is administered orally every 12 hours.
`
`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.
`
`Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory
`depression [see Warnings and Precautions (5.3)].
`
`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.
`
`Reference ID: 4326201
`
`

`

`
`Conversion from Other Opioids to OXYCONTIN
`Discontinue all other around-the-clock opioid drugs when OXYCONTIN therapy is initiated.
`
`There are no established conversion ratios for conversion from other opioids to OXYCONTIN
`defined by clinical trials. 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
`dosage and manage an adverse reaction due to an overdose. While useful tables of opioid
`equivalents are readily available, there is substantial inter-patient variability in the relative
`potency of different opioids.
`
`Close observation and frequent titration are warranted until pain management is stable on the
`new opioid. Monitor patients for signs and symptoms of opioid withdrawal and for signs of
`oversedation/toxicity after converting patients to OXYCONTIN.
`
`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
`Treatment with OXYCONTIN can be initiated after the transdermal fentanyl patch has been
`removed for at least 18 hours. 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.
`
`Discontinue all other around-the-clock opioid drugs when OXYCONTIN therapy is initiated.
`
`There is substantial inter-patient variability in the relative potency of different opioid drugs and
`formulations. Therefore, a conservative approach is advised when determining the total daily
`dosage of OXYCONTIN. It is safer to underestimate a patient’s 24-hour oral oxycodone
`requirements and provide rescue medication (e.g., immediate-release opioid) than to
`
`Reference ID: 4326201
`
`

`

`overestimate the 24-hour oral oxycodone requirements and manage an adverse reaction due to an
`overdose.
`
`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:
`
`• 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.
`
`Reference ID: 4326201
`
`

`

`• 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
`(2.5)] 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 [see Warnings and
`Precautions (5.1)]. 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.
`
`Patients who experience breakthrough pain may require a dosage adjustment 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
`
`Reference ID: 4326201
`
`

`

`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, consider reducing the dosage.
`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
`aily 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 one-third to one-half the recommended starting dosage
`of OXYCONTIN, consider using a lower dosage of the concomitant CNS depressant, and
`monitor patients for signs of respiratory depression, sedation, and hypotension [see Warnings
`and Precautions (5.6), Drug Interactions (7)].
`
`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 one-third
`to one-half 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 one-third to one-half the
`recommended starting dosage and titrate the dosage carefully. Monitor for signs of respiratory
`depression, sedation, and hypotension [see Use in Specific Populations, (8.6), Clinical
`Pharmacology (12.3)].
`
`2.9 Discontinuation of OXYCONTIN
`
`When the patient no longer requires therapy with OXYCONTIN, taper the dosage gradually, by
`25% to 50% every 2 to 4 days, while monitoring for signs and symptoms of withdrawal. If a
`patient develops these signs or symptoms, raise the dose to the previous level and taper more
`slowly, either by increasing the interval between decreases, decreasing the amount of change in
`dose, or both. Do not abruptly discontinue OXYCONTIN [see Warnings and Precautions
`(5.14), Drug Abuse and Dependence (9.3)].
`
`
`
`Reference ID: 4326201
`
`

`

`3 DOSAGE FORMS AND STRENGTHS
`
`Extended-release tablets: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg.
`
` 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 [see Warnings and Precautions (5.3)]
`• Acute or severe bronchial asthma in an unmonitored setting or in the absence
`of resuscitative equipment [see Warnings and Precautions (5.7)]
`• Known or suspected gastrointestinal obstruction, including paralytic ileus [see
`Warnings and Precautions (5.12)]
`• 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. Because extended-
`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