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 controlled-release) Tablets, for
`oral use, CII
`
`Initial U.S. Approval: 1950
`
`
`WARNING: ABUSE POTENTIAL, LIFE-THREATENING
`
`RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE
`
`
`See full prescribing information for complete boxed warning.
`
`
`• OxyContin contains oxycodone, a Schedule II controlled substance.
`
`Monitor for signs of misuse, abuse, and addiction during OxyContin
`
`therapy (5.1, 9).
`
`• Fatal respiratory depression may occur, with highest risk at initiation
`and with dose increases. Instruct patients on proper administration of
`OxyContin tablets to reduce the risk (5.2).
`
`
`
`• Accidental ingestion of OxyContin can result in fatal overdose of
`
`
`oxycodone, especially in children (5.3).
`
`
`----------------------------RECENT MAJOR CHANGES--------------------------
`Boxed Warning
`
`
`07/2012
`Indications and Usage (1)
`07/2012
`
`Dosage and Administration (2)
`07/2012
`
`
`
`Contraindications (4)
`07/2012
`
`Warnings and Precautions (5)
`07/2012
`
`
`
`----------------------------INDICATIONS AND USAGE---------------------------
`OxyContin is an opioid agonist product indicated for the management of
`moderate to severe pain when a continuous, around-the-clock opioid analgesic
`is needed for an extended period of time. (1)
`
`
`Limitations of Use
`
`
`• OxyContin is not for use:
`
` As an as-needed (prn) analgesic (1)
`
` For pain that is mild or not expected to persist for an extended period of
`time (1)
`
` For acute pain (1)
`
`
` In the immediate postoperative period (1)
`
`
` For postoperative pain, unless the patient is already receiving chronic
`opioid therapy prior to surgery, or if the postoperative pain is expected
`
`
`to be moderate to severe and persist for an extended period of time (1)
`
`• OxyContin 60 mg and 80 mg tablets are only for patients in whom
`
`
`
` tolerance to an opioid of comparable potency is established. (1)
`
`
`
`----------------------DOSAGE AND ADMINISTRATION-----------------------
`
`• Individualize dosing based on patient’s prior analgesic treatment
`
`experience, and titrate as needed to provide adequate analgesia and
`minimize adverse reactions. (2.1, 2.2)
`
`• Do not abruptly discontinue OxyContin in a physically dependent patient.
`
`
`(2.4)
`
`• Tablets must be swallowed intact and are not to be cut, broken, chewed,
`
` crushed, or dissolved (risk of potentially fatal dose). (2.5, 5.1)
`
`
`• OxyContin tablets should be taken one tablet at a time, with enough water
`
`
`to ensure complete swallowing immediately after placing in the mouth.
`(2.5, 5.9, 17)
`
`---------------------DOSAGE FORMS AND STRENGTHS----------------------
`
`• Tablets: 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg, and 80 mg (3)
`
`
`-
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
` WARNING: ABUSE POTENTIAL, LIFE-THREATENING
`
`
` RESPIRATORY DEPRESSION, and ACCIDENTAL EXPOSURE
`
`
`INDICATIONS AND USAGE
`1
`
`
`2 DOSAGE AND ADMINISTRATION
`
`Initial Dosing
`2.1
`
`
`2.2 Titration and Maintenance of Therapy
`
`2.3 Patients with Hepatic Impairment
`
`2.4 Discontinuation of OxyContin
`
`2.5 Administration of OxyContin
`
`3 DOSAGE FORMS AND STRENGTHS
`
`4 CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Abuse Potential
`
`
`
`
`
`Reference ID: 3155030
`
`
`
`
`
`------------------------------CONTRAINDICATIONS------------------------------
`
`• Significant respiratory depression (4)
`
`• Acute or severe bronchial asthma (4)
`
`• Known or suspected paralytic ileus and GI obstruction (4)
`
`
`• Hypersensitivity to oxycodone (4)
`-----------------------WARNINGS AND PRECAUTIONS-----------------------­
`
`• Elderly, cachectic, and debilitated patients, and patients with chronic
`
`pulmonary disease: Monitor closely because of increased risk of respiratory
`
`depression. (5.4, 5.5)
`
`• Interaction with CNS depressants: Consider dose reduction of one or both
`
`drugs because of additive effects. (5.6, 7.1)
`
`• Hypotensive effects: Monitor during dose initiation and titration (5.7)
`
`• Patients with head injury or increased intracranial pressure: Monitor for
`
`sedation and respiratory depression. Avoid use of OxyContin in patients
`
`
`with impaired consciousness or coma susceptible to intracranial effects of
`CO2 retention. (5.8)
`
`• Use with caution in patients who have difficulty swallowing or have
`underlying GI disorders that may predispose them to obstruction. (5.9)
`
`
`• Concomitant use of CYP3A4 inhibitors may increase opioid effects. (5.14)
`
`
`
`
`------------------------------ADVERSE REACTIONS-------------------------------
`Most common adverse reactions (>5%) are 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-------------------------------
`
`• Muscle relaxants: Avoid use with OxyContin because of increased risk of
`
`
` respiratory depression. (7.2)
`
`• The CYP3A4 isoenzyme plays a major role in the metabolism of
`OxyContin, drugs that inhibit CYP3A4 activity may cause decreased
`clearance of oxycodone which could lead to an increase in oxycodone
`
`plasma concentrations. (7.3)
`
`• Mixed agonist/antagonist opioid analgesics: Avoid use with OxyContin
`because they may reduce analgesic effect of OxyContin or precipitate
`withdrawal symptoms. (7.4)
`
`-----------------------USE IN SPECIFIC POPULATIONS------------------------
`
`• Nursing mothers: Oxycodone has been detected in human milk. Closely
`
`
` monitor infants of nursing women receiving OxyContin. (8.3)
`
`• Geriatrics: The initial dose may need to be reduced to 1/3 to 1/2 of the
`usual doses. (8.5)
`
`
`• Hepatic impairment: Initiate therapy at 1/3 to 1/2 the usual doses and titrate
`carefully. (8.6)
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide.
`
`
`
`
`Revised: 07/2012
`
`
`
`5.2 Life-Threatening Respiratory Depression
`
`5.3 Accidental Exposure
`
`5.4 Elderly, Cachectic, and Debilitated Patients
`
`5.5 Use in Patients with Chronic Pulmonary Disease
`
`5.6
`Interactions with Alcohol, CNS Depressants, and Illicit Drugs
`
`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
`
`

`

`
`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 Agents Affecting Cytochrome P450 Isoenzymes
`
`
`
`7.4 Mixed Agonist/Antagonist 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
`
`
`8.9 Neonatal Opioid Withdrawal Syndrome
`
`
`
`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
`
`
`
`Reference ID: 3155030
`
`
`
`
`
`
`
`
`
`
`
`

`

`
`FULL PRESCRIBING INFORMATION
`
`
`
`WARNING: ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY
`
`DEPRESSION, and ACCIDENTAL EXPOSURE
`
`
`
` Abuse Potential
`
`OxyContin® contains oxycodone, an opioid agonist and Schedule II controlled substance
`with an abuse liability similar to other opioid agonists, legal or illicit [see Warnings and
`Precautions (5.1)]. Assess each patient’s risk for opioid abuse or addiction prior to
`prescribing OxyContin. The risk for opioid abuse is 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 depressive disorder). Routinely monitor all patients receiving
`OxyContin for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and
`Dependence (9)].
`
`Life-Threatening Respiratory Depression
`
`Respiratory depression, including fatal cases, may occur with use of OxyContin, even when
`the drug has been used as recommended and not misused or abused [see Warnings and
`Precautions (5.2)]. Proper dosing and titration are essential and OxyContin should be
`prescribed only by healthcare professionals who are knowledgeable in the use of potent
`opioids for the management of chronic pain. Monitor for respiratory depression, especially
`during initiation of OxyContin or following a dose increase. Instruct patients to swallow
`
`OxyContin tablets intact. Crushing, dissolving, or chewing the tablet can cause rapid
`release and absorption of a potentially fatal dose of oxycodone.
`
`Accidental Exposure
`
`Accidental ingestion of OxyContin, especially in children, can result in a fatal overdose of
`oxycodone [see Warnings and Precautions (5.3)].
`
`1 INDICATIONS AND USAGE
`
`OxyContin is indicated for the management of moderate to severe pain when a continuous,
`around-the-clock opioid analgesic is needed for an extended period of time.
`
`
`Limitations of Use
`
`OxyContin is not for use:
`
`
`
` As an as-needed (prn) analgesic
`
`  For pain that is mild or not expected to persist for an extended period of time
`
` For acute pain
`
` In the immediate postoperative period (the first 24 hours following surgery) for patients not
`
`previously taking the drug, because its safety in this setting has not been established.
` For postoperative pain unless the patient is already receiving chronic opioid therapy prior to
`
`surgery, or if the postoperative pain is expected to be moderate to severe and persist for an
`extended period of time.
`
`Reference ID: 3155030
`
`

`

`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 patients in whom tolerance to an opioid of comparable potency is
`established. Patients considered opioid tolerant are those who are taking 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
`for one week or longer.
`
`
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1 Initial Dosing
`
`Initiate the dosing regimen for each patient individually, taking into account the patient's prior
`analgesic treatment experience. Monitor patients closely for respiratory depression, especially
`within the first 24-72 hours of initiating therapy with OxyContin [see Warnings and Precautions
`(5.2)].
`
`
`Consider the following factors when selecting an initial dose of OxyContin:
`
`
` Total daily dose, potency, and any prior opioid the patient has been taking previously;
`
` Reliability of the relative potency estimate used to calculate the equivalent dose of
`oxycodone needed (Note: potency estimates may vary with the route of administration);
`
` Patient's degree of opioid experience and opioid tolerance;
`
` General condition and medical status of the patient;
`
` Concurrent medication;
`
` Type and severity of the patient's pain.
`
`Use of OxyContin as the First Opioid Analgesic
`
`
`Initiate therapy with 10 mg every 12 hours.
`
`Conversion from other Oral Oxycodone Formulations to OxyContin
`
`
`Patients receiving other oral oxycodone formulations may be converted to OxyContin by
`administering one-half of the patient's total daily oral oxycodone dose as OxyContin every 12
`hours.
`
`Conversion from other Opioids to OxyContin
`
`
`While there are useful tables of oral and parenteral equivalents, there is substantial inter-patient
`variation in the relative potency of different opioid drugs and formulations. Specific
`recommendations are not available because of a lack of systematic evidence for these types of
`analgesic substitutions. As such, it is safer to underestimate a patient's 24-hour oral oxycodone
`requirement and provide rescue medication (e.g., immediate-release oxycodone) than to
`overestimate and precipitate an adverse reaction. In general, begin with half of the estimated
`
`Reference ID: 3155030
`
`

`

`daily oxycodone requirement as the initial dose, managing inadequate analgesia by
`supplementation with immediate-release oxycodone.
`
`Published relative potency data are available and may be referred to in clinical practice
`guidelines such as those published by authorities in the field of pain medicine, but such ratios are
`approximations. Consider contacting your specific state medical or pharmacy professional
`societies for further information on how to safely convert patients from one opioid to another.
`
`
`Conversion from Transdermal Fentanyl to OxyContin
`
`
`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 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. During chronic therapy, especially
`for non-cancer-related pain (or pain associated with other terminal illnesses), periodically
`reassess the continued need for the use of opioid analgesics.
`
`If the level of pain increases, attempt to identify the source of increased pain, while adjusting the
`OxyContin dose to decrease the level of pain. Because steady-state plasma concentrations are
`approximated in 1 day, OxyContin dosage adjustments may be done every 1 to 2 days. Patients
`who experience breakthrough pain may require dosage adjustment or rescue medication with an
`appropriate dose of an immediate-release opioid and non-opioid medication.
`
`If signs of excessive opioid-related adverse reactions are observed, the next 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.
`
`During chronic, around-the-clock opioid therapy, especially for non-cancer pain syndromes,
`reassess the continued need for around-the-clock opioid therapy regularly (e.g., every 6 to 12
`months) as appropriate.
`
`2.3 Patients with Hepatic Impairment
`
`Reference ID: 3155030
`
`

`

`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, 5.2)].
`
`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
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`10 mg film-coated tablets (round, white-colored, bi-convex tablets debossed with OP on
`one side and 10 on the other)
`15 mg film-coated tablets (round, gray-colored, bi-convex tablets debossed with OP on
`one side and 15 on the other)
`20 mg film-coated tablets (round, pink-colored, bi-convex tablets debossed with OP on
`one side and 20 on the other)
`30 mg film-coated tablets (round, brown-colored, bi-convex tablets debossed with OP on
`one side and 30 on the other)
`40 mg film-coated tablets (round, yellow-colored, bi-convex tablets debossed with OP on
`one side and 40 on the other)
`60 mg film-coated tablets* (round, red-colored, bi-convex tablets debossed with OP on
`one side and 60 on the other)
`80 mg film-coated tablets* (round, green-colored, bi-convex tablets debossed with OP on
`one side and 80 on the other)
`
`* 60 mg and 80 mg tablets for use in opioid-tolerant patients only
`
`
`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
`
`
`Reference ID: 3155030
`
`

`

` • Hypersensitivity (e.g., anaphylaxis) to oxycodone [see Adverse Reactions (6.2)]
`
`
`
`
`
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Abuse Potential
`
`OxyContin contains oxycodone, an opioid agonist and a Schedule II controlled substance.
`Oxycodone can be abused in a manner similar to other opioid agonists legal or illicit. 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 in situations
`where there is concern about increased risks of misuse, abuse, or diversion. Concerns about
`abuse, addiction, and diversion should not, however, prevent the proper management of pain.
`
`Assess each patient’s risk for opioid abuse or addiction prior to prescribing OxyContin. The risk
`for opioid abuse is 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). Patients
`at increased risk may still be appropriately treated with modified-release opioid formulations;
`however these patients will require intensive monitoring for signs of misuse, abuse, or addiction.
`Routinely monitor all patients receiving opioids for signs of misuse, abuse, and addiction
`because these drugs carry a risk for addiction even under appropriate medical use.
`
`Misuse or abuse of OxyContin by crushing, chewing, snorting, or injecting the dissolved product
`will result in the uncontrolled delivery of the opioid and pose a significant risk that could result
`in overdose and death [see Overdosage (10)].
`
`
`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
`
`Respiratory depression is the chief hazard of opioid agonists, including OxyContin. Respiratory
`depression if not immediately recognized and treated, may lead to respiratory arrest and death.
`Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased
`rate of respiration, often associated with a “sighing” pattern of breathing (deep breaths separated
`by abnormally long pauses). Carbon dioxide (CO2) retention from opioid-induced respiratory
`depression can exacerbate the sedating effects of opioids. 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)].
`
`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. Instruct patients against use by individuals other than
`the patient for whom OxyContin was prescribed and to keep OxyContin out of the reach of
`children, as such inappropriate use may result in fatal respiratory depression.
`
`Reference ID: 3155030
`
`

`

`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 fatal overdose with the first dose.
`Respiratory depression has also been reported with use of modified-release opioids when used as
`recommended and not misused or abused.
`
`To further reduce the risk of respiratory depression, consider the following:
`
` Proper dosing and titration are essential and OxyContin should only be prescribed 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 are for use in opioid-tolerant patients only. Ingestion of
`
`these strengths of OxyContin tablets may cause fatal respiratory depression when
`administered to patients not already tolerant to high doses of opioids.
`  Instruct patients to swallow OxyContin tablets intact. The tablets are not to be crushed,
`
`
`
`dissolved, or chewed. The resulting oxycodone dose may be fatal, particularly in opioid-
`
`naïve individuals.
`
` OxyContin is contraindicated in patients with respiratory depression and in patients with
`
`
`conditions that increase the risk of life-threatening respiratory depression [see
`
`Contraindications (4)].
`
`
`
`
` 5.3 Accidental Exposure
`
`Accidental ingestion of OxyContin, especially in children, can result in a fatal overdose of
`oxycodone.
`
`5.4 Elderly, Cachectic, and Debilitated Patients
`
`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.
`Therefore, monitor such patients closely, particularly when initiating and titrating OxyContin
`
`and when OxyContin is given concomitantly with other drugs that depress respiration [see
`Warnings and Precautions (5.2)].
`
`5.5 Use in Patients with Chronic Pulmonary Disease
`
`Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and
`patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre­
`existing respiratory depression for respiratory depression, particularly when initiating therapy
`and titrating with OxyContin, as in these patients, even usual therapeutic doses of OxyContin
`may decrease respiratory drive to the point of apnea [see Warnings and Precautions (5.2)].
`
`Consider the use of alternative non-opioid analgesics in these patients if possible.
`
`5.6 Interactions with Alcohol, CNS Depressants, and Illicit Drugs
`
`Reference ID: 3155030
`
`

`

`Hypotension, and profound sedation, coma or respiratory depression may result if OxyContin is
`used concomitantly with other CNS depressants (e.g., sedatives, anxiolytics, hypnotics,
`neuroleptics, muscle relaxants, 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, consider the patient’s use, if any, of alcohol and/or illicit drugs that can cause CNS
`depression. If OxyContin therapy is to be initiated in a patient taking a CNS depressant, start
`with a lower OxyContin dose than usual and 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)].
`
`5.7 Hypotensive Effects
`
`OxyContin may cause severe hypotension including orthostatic hypotension and syncope in
`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
`of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug
`Interactions (7.1)]. Monitor these patients for signs of hypotension after initiating or titrating the
`dose of OxyContin. In patients with circulatory shock, OxyContin may cause vasodilation that
`can further reduce cardiac output and blood pressure. Avoid the use of OxyContin in patients
`with circulatory shock.
`
`5.8 Use in Patients with Head Injury or Increased Intracranial Pressure
`
`Monitor patients taking OxyContin who may be susceptible to the intracranial effects of CO2
`
`retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs
`of sedation and respiratory depression, particularly when initiating therapy with OxyContin.
`OxyContin may reduce respiratory drive, and the resultant CO2 retention can further increase
` intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury.
`
`
`Avoid the use of OxyContin in patients with impaired consciousness or coma.
`
`5.9 Difficulty in Swallowing and Risk for Obstruction in Patients at Risk for a Small
`Gastrointestinal Lumen
`
`
`There have been post-marketing reports of difficulty in swallowing OxyContin tablets. These
`reports included choking, gagging, regurgitation and tablets stuck in the throat. Instruct patients
`not to pre-soak, lick or otherwise wet OxyContin tablets prior to placing in the mouth, and to
`take one tablet at a time with enough water to ensure complete swallowing immediately after
`placing in the mouth.
`
`There have been rare post-marketing reports of cases of intestinal obstruction, and exacerbation
`of diverticulitis, some of which have required medical intervention to remove the tablet. Patients
`with underlying GI disorders such as esophageal cancer or colon cancer with a small
`gastrointestinal lumen are at greater risk of developing these complications. Consider use of an
`
`Reference ID: 3155030
`
`

`

`alternative analgesic in patients who have difficulty swallowing and patients at risk for
`underlying GI disorders resulting in a small gastrointestinal lumen.
`
`5.10 Use in Patients with Gastrointestinal Conditions
`
`OxyContin is contraindicated in patients with GI obstruction, including paralytic ileus. The
`oxycodone in OxyContin may cause spasm of the sphincter of Oddi. Monitor patients with
`biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause
`increases in the serum amylase.
`
`5.11 Use in Patients with Convulsive or Seizure Disorders
`
`The oxycodone in OxyContin may aggravate convulsions in patients with convulsive 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.
`
`5.12 Avoidance of Withdrawal
`
`Avoid the use of mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and
`butorphanol) in patients who have received or are receiving a course of therapy with a full opioid
`agonist analgesic, including OxyContin. In these patients, mixed agonists/antagonists analgesics
`may reduce the analgesic effect and/or may precipitate withdrawal symptoms.
`
`When discontinuing OxyContin, gradually taper the dose [see Dosage and Administration (2.4)].
`Do not abruptly discontinue OxyContin.
`
`5.13 Driving and Operating Machinery
`
`OxyContin may impair the mental or physical abilities needed to perform potentially hazardous
`activities such as driving a car or operating machinery. Warn patients not to drive or operate
`dangerous machinery unless they are tolerant to the effects of OxyContin and know how they
`will react to the medication.
`
`5.14 Cytochrome P450 3A4 Inhibitors and Inducers
`
`Since the CYP3A4 isoenzyme plays a major role in the metabolism of OxyContin, drugs that
`alter CYP3A4 activity may cause changes in clearance of oxycodone which could lead to
`changes in oxycodone plasma concentrations.
`
`Inhibition of CYP3A4 activity by its inhibitors, such as macrolide antibiotics (e.g.,
`erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g.,
`ritonavir), may increase plasma concentrations of oxycodone and prolong opioid effects.
`
`CYP450 inducers, such as rifampin, carbamazepine, and phenytoin, may induce the metabolism
`
`of oxycodone and, therefore, may cause increased clearance of the drug which could lead to a
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`Reference ID: 3155030
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`

`

`decrease in oxycodone plasma concentrations, lack of efficacy or, possibly, development of an
`abstinence syndrome in a patient who had developed physical dependence to oxycodone.
`
`If co-administration is necessary, caution is advised when initiating OxyContin treatment in
`patients currently taking, or discontinuing, CYP3A4 inhibitors or inducers. Evaluate these
`patients at frequent intervals and consider dose adjustments until stable drug effects are achieved
`
`[see Drug Interactions (7.3), and Clinical Pharmacology (12.3)].
`
`
`5.15 Laboratory Monitoring
`
`Not every urine drug test for “opioids” or “opiates” detects oxycodone reliably, especially those
`designed for in-office use. Further, many laboratories will report urine drug concentrations below
`
`a specified “cut-off” value as “negative”. Therefore, if urine testing for oxycodone is considered
`in the clinical management of an individual patient, ensure that the sensitivity and specificity of
`
`the assay is appropriate, and consider the limitations of the testing used when interpreting results.
`
`
`
`6 ADVERSE REACTIONS
`
`The following adverse reactions described elsewhere in the labeling include:
`
`
` Respiratory depression [see Boxed Warning, Warnings and Precautions (5.2, 5.5), and
`Overdosage (10)]
`
`
` CNS depression [see Drug Interactions (7.1), and Overdosage (10)]
`
`
` Hypotensive effects [see Warning and Precautions (5.7), and Overdosage (10)]
`
`
` Drug abuse, addiction, and dependence [see Drug Abuse and Dependence (9.2, 9.3)]
`
`
` Gastrointestinal Effects [see Warnings and Precautions (5.9, 5.10)]
`
`
` Seizures [see Warnings and Precautions (5.11)]
`
`
`6.1 Clinical Trial Experience
`
`Because clinical trials are conducted under widely varying conditions, adverse reaction rates
`observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
`of another drug and may not reflect the rates observed in practice.
`
`The safety of OxyContin was evaluated in double-blind clinical trials involving 713 patients with
`moderate to severe pain of various etiologies. In open-label studies of cancer pain, 187 patients
`received OxyContin in total daily doses ranging from 20 mg to 640 mg per day. The average
`total daily dose was approximately 105 mg per day.
`
`OxyContin may increase the risk of serious adverse reactions such as those observed with other
`opioid analgesics, including respiratory depression, apnea, respiratory arrest, circulatory
`
`depression, hypotension, or shock [see Overdosage (10)].
`
`Reference ID: 3155030
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`

`

`The most common adverse reactions (>5%) reported by patients in clinical trials comparing
`OxyContin with placebo are shown in Table 2 below:
`
`TABLE 2: Common Adverse Reactions (>5%)
`
`Adverse
`Reaction
`
`Constipation
`Nausea
`Somnolence
`Dizziness
`Pruritus
`Vomiting
`Headache
`Dry Mouth
`Asthenia
`Sweating
`
`
`OxyContin
`
`(n=227)
`(%)
`(23)
`(23)
`(23)
`(13)
`(13)
`(12)
`(7)
`(6)
`(6)
`(5)
`
`
`
`
`
`
`
`
`
`
`
`
`
`Placebo
`(n=45)
`(%)
`(7)
`(11)
`(4)
`(9)
`(2)
`(7)
`(7)
`(2)
`