` HIGHLIGHTS OF PRESCRIBING INFORMATION
` These highlights do not include all the information needed to use
`
`
`OXYCONTIN® safely and effectively. See full prescribing information
`
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`for OXYCONTIN.
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`
`OXYCONTIN® (oxycodone hydrochloride extended-release tablets), for
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` oral use, CII
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`Initial U.S. Approval: 1950
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`WARNING: ADDICTION, ABUSE and MISUSE; LIFE­
`THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL
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`
`
`INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME;
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`and CYTOCHROME P450 3A4 INTERACTION
`
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`See full prescribing information for complete boxed warning.
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`
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`• OXYCONTIN exposes users to risks of addictions, abuse and misuse,
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`which can lead to overdose and death. Assess each patient’s risk before
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`prescribing and monitor regularly for development of these behaviors
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`and conditions. (5.1)
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`• Serious, life-threatening, or fatal respiratory depression may occur.
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`Monitor closely, especially upon initiation or following a dose increase.
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`Instruct patients to swallow OXYCONTIN tablets whole to avoid
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`exposure to a potentially fatal dose of oxycodone. (5.2)
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`• Accidental ingestion of OXYCONTIN, especially in children, can
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`result in a fatal overdose of oxycodone. (5.2)
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`• Prolonged use of OXYCONTIN during pregnancy can result in
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`
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`neonatal opioid withdrawal syndrome, which may be life-threatening if
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`not recognized and treated. If opioid use is required for a prolonged
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`period in a pregnant woman, advise the patient of the risk of neonatal
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`opioid withdrawal syndrome and ensure that appropriate treatment
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`will be available. (5.3)
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`• Initiation of CYP3A4 inhibitors (or discontinuation of CYP3A4
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`inducers) can result in a fatal overdose of oxycodone from
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`OXYCONTIN. (5.14)
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`----------------------------RECENT MAJOR CHANGES-------------------------­
`Boxed Warning
`04/2014
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`Indications and Usage (1)
`04/2014
`
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`Dosage and Administration (2)
`04/2014
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`04/2014
`Warnings and precautions (5)
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`----------------------------INDICATIONS AND USAGE--------------------------­
`OXYCONTIN is an opioid agonist product indicated for the management of
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`pain severe enough to require daily, around-the-clock, long-term opioid
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`treatment and for which alternative treatment options are inadequate. (1)
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`Limitations of Use
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`• 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
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` otherwise inadequate to provide sufficient management of pain. (1)
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`
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`• OXYCONTIN is not indicated as an as-needed (prn) analgesic. (1)
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`
`----------------------DOSAGE AND ADMINISTRATION----------------------­
`
`• OXYCONTIN 60 mg and 80 mg tablets, a single dose greater than 40 mg,
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` or a total daily dose greater than 80 mg are only for use in patients in whom
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` tolerance to an opioid of comparable potency has been established. (2.1)
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`
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`• For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg
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` tablets orally every 12 hours. (2.1)
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`• Do not abruptly discontinue OXYCONTIN in a physically dependent
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` patient. (2.4)
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`• Tablets must be swallowed intact and are not to be cut, broken, chewed,
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` crushed, or dissolved (risk of potentially fatal dose). (2.5, 5.1)
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`• OXYCONTIN tablets should be taken one tablet at a time, with enough
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`
`
` water to ensure complete swallowing immediately after placing in the
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` mouth. (2.5, 5.9, 17)
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`FULL PRESCRIBING INFORMATION: CONTENTS*
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`WARNING: ADDICTION, ABUSE and MISUSE; LIFE-THREATENING
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`RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;
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`NEONATAL OPIOID WITHDRAWAL SYNDROME; and
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`CYTOCHROME P450 3A4 INTERACTION
`
`
`INDICATIONS AND USAGE
`1
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`2 DOSAGE AND ADMINISTRATION
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`2.1
`Initial Dosing
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`
`Reference ID: 3490236
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`---------------------DOSAGE FORMS AND STRENGTHS---------------------­
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`Extended-release tablets: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80
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`mg (3)
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`------------------------------CONTRAINDICATIONS-----------------------------­
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`• Significant respiratory depression (4)
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`• Acute or severe bronchial asthma (4)
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`• Known or suspected paralytic ileus and GI obstruction (4)
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`• Hypersensitivity to oxycodone (4)
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`-----------------------WARNINGS AND PRECAUTIONS-----------------------­
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`• Interactions with CNS depressants: Concomitant use may cause profound
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` sedation, respiratory depression and death. If coadminstration is required,
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` consider dose reduction of one or both drugs. (5.4)
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`• Elderly, cachectic, debilitated patients, and those with chronic pulmonary
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` disease: Monitor closely because of increased risk for life-threatening
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` respiratory depression. (5.5, 5.6)
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`• Hypotensive effects: Monitor during dose initiation and titration. (5.7)
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`• Patients with head injury or increased intracranial pressure: Monitor for
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` sedation and respiratory depression. Avoid use of OXYCONTIN in
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` patients with impaired consciousness or coma susceptible to intracranial
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`effects of CO2 retention. (5.8)
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`• Use with caution in patients who have difficulty swallowing or have
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` underlying GI disorders that may predispose them to obstruction. (5.9)
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`• Concomitant use of CYP3A4 inhibitors may increase opioid effects. (5.14)
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`------------------------------ADVERSE REACTIONS------------------------------­
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`Most common adverse reactions (>5%) are constipation, nausea, somnolence,
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`dizziness, vomiting, pruritus, headache, dry mouth, asthenia, and sweating.
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`(6.1)
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`To report SUSPECTED ADVERSE REACTIONS, contact Purdue
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`Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or
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`www.fda.gov/medwatch.
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`------------------------------DRUG INTERACTIONS------------------------------­
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`• Mixed agonist/antagonist and partial agonist opioid analgesics: Avoid use
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` with OXYCONTIN because they may reduce analgesic effect of
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` OXYCONTIN or precipitate withdrawal symptoms. (7.4)
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`-----------------------USE IN SPECIFIC POPULATIONS-----------------------­
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`• Nursing mothers: Oxycodone has been detected in human milk. Closely
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` monitor infants of nursing women receiving OXYCONTIN. (8.3)
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`• Geriatrics: The initial dose may need to be reduced to 1/3 to 1/2 of the
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` usual doses. (8.5)
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`• Hepatic impairment: Initiate therapy at 1/3 to 1/2 the usual doses and titrate
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` carefully. (8.6)
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`See 17 for PATIENT COUNSELING INFORMATION and Medication
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`Guide.
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`Revised: 04/2014
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`2.2 Titration and Maintenance of Therapy
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`2.3 Patients with Hepatic Impairment
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`2.4 Discontinuation of OXYCONTIN
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`2.5 Administration of OXYCONTIN
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`3 DOSAGE FORMS AND STRENGTHS
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`4 CONTRAINDICATIONS
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`

`

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` 5 WARNINGS AND PRECAUTIONS
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` 5.1 Addiction, Abuse, and Misuse
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` 5.2 Life-Threatening Respiratory Depression
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` 5.3 Neonatal Opioid Withdrawal Syndrome
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`5.4
` Interactions with Central Nervous System Depressants
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` 5.5 Use in Elderly, Cachectic, and Debilitated Patients
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` 5.6 Use in Patients with Chronic Pulmonary Disease
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` 5.7 Hypotensive Effects
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` 5.8 Use in Patients with Head Injury or Increased Intracranial Pressure
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` 5.9 Difficulty in Swallowing and Risk for Obstruction in Patients at
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` Risk for a Small Gastrointestinal Lumen
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` 5.10 Use in Patients with Gastrointestinal Conditions
`
` 5.11 Use in Patients with Convulsive or Seizure Disorders
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` 5.12 Avoidance of Withdrawal
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` 5.13 Driving and Operating Machinery
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` 5.14 Cytochrome P450 3A4 Inhibitors and Inducers
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` 5.15 Laboratory Monitoring
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` 6 ADVERSE REACTIONS
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` 6.1 Clinical Trial Experience
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` 6.2 Postmarketing Experience
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` 7 DRUG INTERACTIONS
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` 7.1 CNS Depressants
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` 7.2 Muscle Relaxants
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` 7.3 Drugs Affecting Cytochrome P450 Isoenzymes
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` 7.4 Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
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` 7.5 Diuretics
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`7.6 Anticholinergics
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`8 USE IN SPECIFIC POPULATIONS
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`8.1 Pregnancy
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`8.2 Labor and Delivery
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`8.3 Nursing Mothers
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`8.4 Pediatric Use
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`8.5 Geriatric Use
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`8.6 Hepatic Impairment
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`8.7 Renal Impairment
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`8.8 Gender Differences
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`9 DRUG ABUSE AND DEPENDENCE
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`9.1 Controlled Substance
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`
`9.2 Abuse
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`9.3 Dependence
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`
`10 OVERDOSAGE
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`
`11 DESCRIPTION
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`12 CLINICAL PHARMACOLOGY
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`
`12.1 Mechanism of Action
`
`
`12.2 Pharmacodynamics
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`
`12.3 Pharmacokinetics
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`
`13 NONCLINICAL TOXICOLOGY
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`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
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`14 CLINICAL STUDIES
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`16 HOW SUPPLIED/STORAGE AND HANDLING
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`17 PATIENT COUNSELING INFORMATION
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`
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`*Sections or subsections omitted from the full prescribing information are not
`listed
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` FULL PRESCRIBING INFORMATION
`
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`
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`
`
`
`
` WARNING: ADDICTION, ABUSE and MISUSE; LIFE-THREATENING
`
`
` RESPIRATORY DEPRESSION; ACCIDENTALINGESTION; 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)].
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`
`
`Accidental Ingestion
`
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`
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`
`
`
`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
`
`
`
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`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
`
`
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`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)].
`
`
`
`Reference ID: 3490236
`
`

`

` Cytochrome P450 3A4 Interaction
`
`The concomitant use of OXYCONTIN with all cytochrome P450 3A4 inhibitors may result
`
`
`
`
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`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
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`
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`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)].
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`
`
`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.
`
`
`
`
`
`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.
` • OXYCONTIN is not indicated as an as-needed (prn) analgesic
`
`
`
`
`
`
`
`
`
`
` 2 DOSAGE AND ADMINISTRATION
`
`
`
` 2.1 Initial Dosing
`
`
`
` 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. Patients considered opioid tolerant are those receiving, for one
`
`
` week or longer, at least 60 mg oral morphine/day, 25 mcg transdermal fentanyl/hour, 30 mg oral
`
`
`oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day, or an
`
`equianalgesic dose of another opioid.
`
`
` 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 OXYCONTIN [see Warnings and Precautions (5.2)].
`
`
`
`
`
`
`
`
`
`
`
`
` OXYCONTIN 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 OXYCONTIN tablets will result in
`
`
`
`
`
`
`Reference ID: 3490236
`
`

`

`
` uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and
`
` Precautions (5.1)].
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`
`
`Use of OXYCONTIN as the First Opioid Analgesic
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` Initiate treatment with OXYCONTIN with one 10 mg tablet orally every 12 hours.
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` Use of OXYCONTIN in Patients who are not Opioid Tolerant
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`The starting dose for patients who are not opioid tolerant is OXYCONTIN 10 mg orally every 12
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`
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`hours. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg
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`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.
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`
`
`Conversion from other Oral Oxycodone Formulations to OXYCONTIN
`
`Patients receiving other oral oxycodone formulations may be converted to OXYCONTIN by
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`
`administering one-half of the patient's total daily oral oxycodone dose as OXYCONTIN every 12
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`
`
`
`hours.
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`
`Conversion from other Opioids to OXYCONTIN
`
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`Discontinue all other around-the-clock opioid drugs when OXYCONTIN therapy is initiated.
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`
`
`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
`
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`
`
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`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 opioid drugs and products.
`
`
`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
`
`
`
`
`
`Reference ID: 3490236
`
`

`

` Eighteen hours following the removal of the transdermal fentanyl patch, OXYCONTIN
`
`
` treatment can be initiated. Although there has been no systematic assessment of such
` conversion, a conservative oxycodone dose, approximately 10 mg every 12 hours of
`
`
`
`
` OXYCONTIN, should be initially substituted for each 25 mcg/hr fentanyl transdermal patch.
` Follow the patient closely during conversion from transdermal fentanyl to OXYCONTIN, as
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`
`
`
`
` there is limited documented experience with this conversion.
`
`
`
` 2.2 Titration and Maintenance of Therapy
`
`
`
`
`
` Individually titrate OXYCONTIN to a dose that provides adequate analgesia and minimizes
` adverse reactions. Continually reevaluate patients receiving OXYCONTIN 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.
`
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`
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`
`
`
`
` Patients who experience breakthrough pain may require a dose increase of OXYCONTIN or may
`
`
`
`
`
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`
`
`
`
`
`
` 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 dose. 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
`
`
`
`dose 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, the total daily oxycodone dose usually can be
` increased by 25% to 50% of the current dose, each time an increase is clinically indicated.
`
`
`
`
` 2.3 Patients with Hepatic Impairment
`
`
`
` For patients with hepatic impairment, start dosing patients at 1/3 to 1/2 the usual starting dose
`
` followed by careful dose titration [see Clinical Pharmacology (12.3)].
`
`
`
`
`
`
`
`
`
` 2.4 Discontinuation of OXYCONTIN
`
`
`
`
`
` When the patient no longer requires therapy with OXYCONTIN tablets, use a gradual downward
`
`
`
`
`
` titration of the dose to prevent signs and symptoms of withdrawal in the physically dependent
` patient. Do not abruptly discontinue OXYCONTIN.
`
`
`
`
`
`
` 2.5 Administration of OXYCONTIN
`
`
`
`
`
` Instruct patients to swallow OXYCONTIN 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
`
`
`
` oxycodone [see Warnings and Precautions (5.1)].
`
`
`
`
`Reference ID: 3490236
`
`

`

` Instruct patients to take OXYCONTIN one tablet at a time and with enough water to ensure
`
`
`
`
` complete swallowing immediately after placing in the mouth [see Warnings and Precautions
`
` (5.9) and Patient Counseling Information (17)].
`
`
`
`
`
`
`
` 3 DOSAGE FORMS AND STRENGTHS
`
`
`
`
`
`
`
`
`
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`
`
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`
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`
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`
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`
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`
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` 10 mg film-coated extended-release tablets (round, white-colored, bi-convex tablets
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` debossed with OP on one side and 10 on the other)
` 15 mg film-coated extended-release tablets (round, gray-colored, bi-convex tablets
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` 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
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` debossed with OP on one side and 30 on the other)
` 40 mg film-coated extended-release tablets (round, yellow-colored, bi-convex tablets
`
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` debossed with OP on one side and 40 on the other)
` 60 mg film-coated extended-release tablets* (round, red-colored, bi-convex tablets
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` debossed with OP on one side and 60 on the other)
` 80 mg film-coated extended-release tablets* (round, green-colored, bi-convex tablets
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` debossed with OP on one side and 80 on the other)
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` * 60 mg and 80 mg tablets for use in opioid-tolerant patients only
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` 4 CONTRAINDICATIONS
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`
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` OXYCONTIN is contraindicated in patients with:
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` • Significant respiratory depression
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` • Acute or severe bronchial asthma in an unmonitored setting or in the absence of
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` resuscitative equipment
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` • Known or suspected paralytic ileus and gastrointestinal obstruction
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` • Hypersensitivity (e.g., anaphylaxis) to oxycodone [see Adverse Reactions (6.2)]
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` 5 WARNINGS AND PRECAUTIONS
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` 5.1 Addiction, Abuse, and Misuse
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` OXYCONTIN contains oxycodone, a Schedule II controlled substance. As an opioid,
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` OXYCONTIN exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and
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`
` Dependence (9)]. As modified-release products such as OXYCONTIN deliver the opioid over an
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` extended period of time, there is a greater risk for overdose and death due to the larger amount of
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` oxycodone present [see Drug Abuse and Dependence (9)].
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`
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` 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
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`
` drug is misused or abused.
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`
`
`
`
`
`
`Reference ID: 3490236
`
`

`

`
`
`
` 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
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`
`
` behaviors or conditions. Risks are increased in patients with a personal or family history of
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` substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major
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` depression). The potential for these risks should not, however, prevent the proper management of
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` pain in any given patient. Patients at increased risk may be prescribed modified-release opioid
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` formulations such as OXYCONTIN, but use in such patients necessitates intensive counseling
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` about the risks and proper use of OXYCONTIN along with intensive monitoring for signs of
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` addiction, abuse, and misuse.
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` Abuse, or misuse of OXYCONTIN by crushing, chewing, snorting, or injecting the dissolved
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` product will result in the uncontrolled delivery of oxycodone and can result in overdose and
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` death [see Overdosage (10)].
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` Opioid agonists are sought by drug abusers and people with addiction disorders and are subject
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`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
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` and advising the patient on the proper disposal of unused drug [see Patient Counseling
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` Information (17)]. Contact local state professional licensing board or state controlled substances
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`
` authority for information on how to prevent and detect abuse or diversion of this product.
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` 5.2 Life-Threatening Respiratory Depression
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` Serious, life-threatening, or fatal respiratory depression has been reported with the use modified-
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` 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
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` 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
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`from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
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`While serious, life-threatening, or fatal respiratory depression can occur at any time during the
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`use of OXYCONTIN, the risk is greatest during the initiation of therapy or following a dose
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`increase. Closely monitor patients for respiratory depression when initiating therapy with
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`OXYCONTIN and following dose increases.
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`To reduce the risk of respiratory depression, proper dosing and titration of OXYCONTIN are
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`essential [see Dosage and Administration (2)]. Overestimating the OXYCONTIN dose when
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`converting patients from another opioid product can result in a fatal overdose with the first dose.
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`Accidental ingestion of even one dose of OXYCONTIN, especially by children, can result in
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`respiratory depression and death due to an overdose of oxycodone.
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`5.3 Neonatal Opioid Withdrawal Syndrome
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`Prolonged use of OXYCONTIN during pregnancy can result in withdrawal signs in the neonate.
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`Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be
`
`Reference ID: 3490236
`
`

`

`
`
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` 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
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` woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that
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` appropriate treatment will be available.
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` Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep
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`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
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`used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug
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`by the newborn.
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`5.4 Interactions with Central Nervous System Depressants
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`Hypotension and profound sedation, coma, or respiratory depression may result if OXYCONTIN
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`is used concomitantly with other central nervous system (CNS) depressants (e.g., sedatives,
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`anxiolytics, hypnotics, neuroleptics, other opioids).
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`When considering the use of OXYCONTIN in a patient taking a CNS depressant, assess the
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`duration of use of the CNS depressant and the patient’s response, including the degree of
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`tolerance that has developed to CNS depression. Additionally, evaluate the patient’s use of
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`alcohol or illicit drugs that can cause CNS depression. If the decision to begin OXYCONTIN
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`therapy is made, start with 1/3 to 1/2 the usual dose of OXYCONTIN, monitor patients for signs
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`of sedation and respiratory depression and consider using a lower dose of the concomitant CNS
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`depressant [see Drug Interactions (7.1) and Dosage and Administration (2.2)].
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`5.5 Use in Elderly, Cachectic, and Debilitated Patients
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`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,
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`healthier patients. Monitor such patients closely, particularly when initiating and titrating
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`OXYCONTIN and when OXYCONTIN is given concomitantly with other drugs that depress
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`respiration [see Warnings and Precautions (5.2)].
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`5.6 Use in Patients with Chronic Pulmonary Disease
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`Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and
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`patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre­
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`existing respiratory depression for respiratory depression, particularly when initiating therapy
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`and titrating with OXYCONTIN, as in these patients, even usual therapeutic doses of
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`OXYCONTIN may decrease respiratory drive to the point of apnea [see Warnings and
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`
`Precautions (5.2)]. Consider the use of alternative non-opioid analgesics in these patients if
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`possible.
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`5.7 Hypotensive Effects
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`
`Reference ID: 3490236
`
`

`

`OXYCONTIN may cause severe hypotension, including orthostatic hypotension and syncope in
`
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`ambulatory patients. There is an increased risk in patients whose ability to maintain blood
`pressure has already been compromised by a reduced blood volume or concurrent administration
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`of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug
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`Interactions (7.1)]. Monitor these patients for signs of hypotension after initiating or titrating the
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`dose of OXYCONTIN. In patients with circulatory shock, OXYCONTIN may cause
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`vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of
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`OXYCONTIN in patients with circulatory shock.
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`5.8 Use in Patients with Head Injury or Increased Intracranial Pressure
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`Monitor patients taking OXYCONTIN who may be susceptible to the intracranial effects of CO2
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`retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs
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`of sedation and respiratory depression, particularly when initiating therapy with OXYCONTIN.
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`OXYCONTIN may reduce respiratory drive, and the resultant CO2 retention can further increase
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`intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury.
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`Avoid the use of OXYCONTIN in patients with impaired consciousness or coma.
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`5.9 Difficulty in Swallowing and Risk for Obstruction in Patients at Risk for a Small
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`Gastrointestinal Lumen
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`There have been post-marketing reports of difficulty in swallowing OXYCONTIN tablets. These
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`reports included choking, gagging, regurgitation and tablets stuck in the throat. Instruct patients
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`not to pre-soak, lick or otherwise wet OXYCONTIN tablets prior to placing in the mouth, and to
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`take one tablet at a time with enough water to ensure complete swallowing immediately after
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`placing in the mouth.
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`There have been rare post-marketing reports of cases of intestinal obstruction, and exacerbation
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`of diverticulitis, some of which have required medical intervention to remove the tablet. Patients
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`with underlying GI disorders such as esophageal cancer or colon cancer with a small
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`gastrointestinal lumen are at greater risk of developing these complications. Consider use of an
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`alternative analgesic in patients who have difficulty swallowing and patients at risk for
`
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`underlying GI disorders resulting in a small gastrointestinal lumen.
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`5.10 Use in Patients with Gastrointestinal Conditions
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`OXYCONTIN is contraindicated in patients with GI obstruction, including paralytic ileus. The
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`oxycodone in OXYCONTIN may cause spasm of the sphincter of Oddi. Monitor patients with
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`biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause
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`increases in the serum amylase.
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`5.11 Use in Patients with Convulsive or Seizure Disorders
`
`Reference ID: 3490236
`
`

`

` The oxycodone in OXYCONTIN may aggravate convulsions in patients with convulsive
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`disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with
`a history of seizure disorders for worsened seizure control during OXYCONTIN therapy.
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`5.12 Avoidance of Withdrawal
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`Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or
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`partial agonist (buprenorphine) analgesics in patients who have received or are receiving a
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`course of therapy with a full opioid agonist analgesic, including OXYCONTIN. In these
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`patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect
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`and/or may precipitate withdrawal symptoms.
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`When discontinuing OXYCONTIN, gradually taper the dose [see Dosage and Administration
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`(2.4)]. Do not abruptly discon