`
`• May cause respiratory depression. Use with extreme caution in patients
`at risk of respiratory depression, elderly and debilitated patients (5.4)
`
`• May aggravate convulsions in patients with convulsive disorders, and
`may induce or aggravate seizures in some clinical settings. (5.5)
`
`Use with caution in patients who have difficulty swallowing or have
`underlying GI disorders that may predispose them to obstruction. (5.6)
`
`Use with caution in patients at risk for ileus. Monitor for decreased
`bowel motility in postoperative patients. (5.6)
`
`• May worsen increased intracranial pressure and obscure its signs, such
`as level of consciousness or pupillary signs. (5.7)
`
`• May cause hypotension. Use with caution in patients at increased risk of
`
`hypotension and in patients in circulatory shock. (5.8)
`
`Concomitant use of CYP3A4 inhibitors may increase opioid effects (5.9)
`
`
`
`•
`
`• Mixed agonist/antagonist analgesics may precipitate withdrawal
`symptoms. (5.10)
`
`Use with caution in patients with biliary tract disease, including acute
`pancreatitis. (5.11)
`Tolerance may develop. (5.12)
`
`Use with caution in alcoholism; adrenocortical insufficiency;
`
`hypothyroidism; prostatic hypertrophy or urethral stricture; severe
`
`impairment of hepatic, pulmonary or renal function; and toxic psychosis.
`
`
`(5.13)
`
`
`• May impair the mental and physical abilities needed to perform
`
`potentially hazardous activities such as driving a car or operating
`
`machinery. (5.14)
`No approved use in the treatment of addiction. (5.15)
`
`Not every urine drug test for “opioids” or “opiates” detects oxycodone
`reliably. (5.16)
`
`
`------------------------------ADVERSE REACTIONS-------------------------------
`Most common adverse reactions (>5%) are constipation, nausea, somnolence,
`
`dizziness, vomiting, pruritus, headache, dry mouth, asthenia, and sweating.
`
`
`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-------------------------------
`
`OxyContin may enhance the neuromuscular blocking action of skeletal
`•
`muscle relaxants and produce an increased degree of respiratory
`
`
`depression. (7.1)
`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. (7.2)
`Concurrent use of other CNS depressants may cause respiratory
`
`depression, hypotension, and profound sedation or coma. (7.3)
`
`
`• Mixed agonist/antagonist analgesics may reduce the analgesic effect of
`oxycodone and may precipitate withdrawal symptoms in these patients.
`
`(7.4)
`
`
`-----------------------USE IN SPECIFIC POPULATIONS------------------------
`
`Labor and Delivery: Not recommended for use in women immediately
`•
`prior to and during labor and delivery; (8.2)
`
`Nursing Mothers: Nursing should not be undertaken while a patient is
`receiving OxyContin. (8.3)
`
`
`Pediatrics: Safety and effectiveness in pediatric patients below the age of
`
`18 have not been established. (8.4)
`
`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)
`Renal impairment: Dose initiation should follow a conservative
`
`approach. (8.7)
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`•
`
`
`•
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`•
`
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`
`Guide.
`
`Revised: xx/xxxx
`
`
`
`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 CII
`
`
`Initial U.S. Approval: 1950
`
` WARNING: IMPORTANCE OF PROPER PATIENT SELECTION
`
`
`
`AND POTENTIAL FOR ABUSE
`
`See full prescribing information for complete boxed warning.
`
`
`• OxyContin contains oxycodone which is an opioid agonist and a
`Schedule II controlled substance with an abuse liability similar to
`morphine. (9)
`
`
`
`
`
`• 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. (1)
`
`
`• OxyContin is NOT intended for use on an as-needed basis. (1)
`
`• OxyContin 60 mg and 80 mg Tablets, a single dose greater than 40
`mg, or a total daily dose greater than 80 mg are only for use in
`opioid-tolerant patients to avoid fatal respiratory depression. (2.7)
`
`
`Patients should be assessed for their clinical risks for opioid abuse
`
`or addiction prior to being prescribed opioids. (2.2)
`
`• OxyContin tablets must be swallowed whole and must not be cut,
`broken, chewed, crushed, or dissolved which can lead to rapid
`
`
`
`release and absorption of a potentially fatal dose of oxycodone. (2.1)
`
`The concomitant use with cytochrome P450 3A4 inhibitors such as
`macrolide antibiotics and protease inhibitors may result in an
`increase in oxycodone plasma concentrations and may cause
`
`potentially fatal respiratory depression. (7.2)
`
`
`•
`
`
`•
`
`
`---------------------------RECENT MAJOR CHANGES---------------------------
`Dosage and Administration (2.1)
`11/2010
`
`
`Warnings and Precautions (5.6)
`10/2011
`
`
`
`----------------------------INDICATIONS AND USAGE---------------------------
`OxyContin is an opioid agonist indicated for:
`
`
`• Management of moderate to severe pain when a continuous, around-the­
`clock opioid analgesic is needed for an extended period of time. (1)
`
`Not for use on an as-needed basis or in the immediate post-operative
`period. (1)
`
`
`•
`
`
`
`
`•
`
`
`•
`
`
`•
`
`----------------------DOSAGE AND ADMINISTRATION-----------------------
`
`
`Use low initial doses in patients who are not already opioid-tolerant,
`•
`especially those who are receiving concurrent treatment with muscle
`relaxants, sedatives, or other central nervous system (CNS) active
`
`medications. (2.2)
`
`For patients already receiving opioids, use standard conversion ratio
`estimates. (2.2)
`Tablets must be swallowed whole and are not to be cut, broken, chewed,
`
`crushed, or dissolved (risk of potentially fatal dose). (2.1)
`
`OxyContin tablets should be taken one tablet at a time, with enough
`water to ensure complete swallowing immediately after placing in the
`
`mouth.(2.1, 17.1)
`
`
`
`---------------------DOSAGE FORMS AND STRENGTHS----------------------
`
`Controlled-Release Tablets: 10 mg, 15 mg, 20 mg , 30 mg, 40 mg, 60
`
`•
`mg, and 80 mg (3)
`
`
`-------------------------------CONTRAINDICATIONS------------------------------
`
`in patients who have significant respiratory depression (4)
`
`•
`
`in patients who have or are suspected of having paralytic ileus (4)
`
`•
`
`in patients who have acute or severe bronchial asthma (4)
`
`
`•
`
`in patients with known hypersensitivity to oxycodone (4)
`•
`
`-----------------------WARNINGS AND PRECAUTIONS-----------------------­
`
`• Must be swallowed whole (5.1)
`
`
`• May cause somnolence, dizziness, alterations in judgment and
`alterations in levels of consciousness, including coma. (5.2)
`
`Additive CNS effects are expected when used with alcohol, other
`opioids, or illicit drugs. (5.1, 5.3, 7.3)
`Use with caution in patients who are receiving other CNS depressants.
`(5.1, 5.3, 7.3)
`
`
`
`
`•
`
`
`•
`
`Reference ID: 3024987
`
`

`

`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
` WARNING: IMPORTANCE OF PROPER PATIENT SELECTION
`AND POTENTIAL FOR ABUSE
`
`
`INDICATIONS AND USAGE
`1
`
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1 Safe Administration Instructions
`
`
`2.2
`Initiating Therapy with OxyContin
`
`
`2.3 Conversion from Transdermal Fentanyl to OxyContin
`
`
`2.4 Hepatic Impairment
`
`
`2.5 Managing Expected Opioid Adverse Reactions
`
`
`2.6
`Individualization of Dosage
`
`
`2.7 Special Instructions for Patients who are not Opioid Tolerant
`
`
`2.8 Continuation of Therapy
`
`
`
`2.9 Cessation of Therapy
`
`
`
`2.10 Conversion from OxyContin to Parenteral Opioids
`
`
`
`3 DOSAGE FORMS AND STRENGTHS
`
`4 CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1
`Information Essential for Safe Administration
`
`
`5.2 CNS Depression
`
`
`5.3
`Interactions with Alcohol, CNS Depressants and Illicit Drugs
`
`
`5.4 Respiratory Depression
`
`
`5.5 Seizures
`
`
`5.6 Difficulty Swallowing and Gastrointestinal Effects
`
`
`5.7 Head Injury
`
`
`5.8 Hypotensive Effect
`
`
`5.9 Cytochrome P450 3A4 Inhibitors and Inducers
`
`
`
`5.10 Interactions with Mixed Agonist/Antagonist Opioid Analgesics
`
`
`5.11 Use in Pancreatic/Biliary Tract Disease
`
`
`5.12 Tolerance
`
`
`5.13 Special Risk Groups
`
`
`5.14 Driving and Operating Machinery
`
`
`
`5.15 Use in Addiction Treatment
`
`
`5.16 Laboratory Monitoring
`
`
`6 ADVERSE REACTIONS
`
`6.1 Clinical Trial Experience
`
`
`6.2 Postmarketing Experience
`
`
`7 DRUG INTERACTIONS
`
`7.1 Neuromuscular Junction Blocking Agents
`
`
`7.2 Agents Affecting Cytochrome P450 Isoenzymes
`
`
`
`7.3 CNS Depressants
`
`
`7.4
`Interactions with Mixed Agonist/Antagonist Opioid Analgesics
`
`
`8 USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`
`
`
`8.2 Labor and Delivery
`
`
`
`8.3 Nursing Mothers
`
`
`8.4 Pediatric Use
`
`
`8.5 Geriatric Use
`
`
`8.6 Hepatic Impairment
`
`
`8.7 Renal Impairment
`
`
`8.8 Gender Differences
`
`
`9 DRUG ABUSE AND DEPENDENCE
`9.1 Controlled Substance
`9.2 Abuse
`9.3 Dependence
`10 OVERDOSAGE
`
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`
`
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`
`
`
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`
`
`14 CLINICAL STUDIES
`15 REFERENCES
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`17 PATIENT COUNSELING INFORMATION
`17.1
`Information for Patients and Caregivers
`
`
`
`
`
`*Sections or subsections omitted from the full prescribing information are not
`
`listed.
`
`
`
`
`
`Reference ID: 3024987
`
`
`
`
`
`
`
`
`
`
`
`

`

`
`FULL PRESCRIBING INFORMATION
`
`
`
`WARNING: IMPORTANCE OF PROPER PATIENT SELECTION AND
`
`POTENTIAL FOR ABUSE
`
`
`
`OxyContin contains oxycodone which is an opioid agonist and a Schedule II
`controlled substance with an abuse liability similar to morphine. (9)
`
`OxyContin can be abused in a manner similar to other opioid agonists, legal or
`illicit. This should be considered when prescribing or dispensing OxyContin in
`situations where the physician or pharmacist is concerned about an increased risk of
`misuse, abuse, or diversion. (9.2)
`
`OxyContin is a controlled-release oral formulation of oxycodone hydrochloride
`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)
`
`OxyContin is not intended for use on an as-needed basis. (1)
`
`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. (2.7)
`
`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 opioid-tolerant patients, as they
`may cause fatal respiratory depression when administered to patients who are not
`tolerant to the respiratory-depressant or sedating effects of opioids. (2.7)
`
`
`Persons at increased risk for opioid abuse include those with a personal or family
`history of substance abuse (including drug or alcohol abuse or addiction) or mental
`illness (e.g., major depression). Patients should be assessed for their clinical risks
`for opioid abuse or addiction prior to being prescribed opioids. All patients
`receiving opioids should be routinely monitored for signs of misuse, abuse and
`addiction. (2.2)
`
`
`OxyContin must be swallowed whole and must not be cut, broken, chewed, crushed,
`or dissolved. Taking cut, broken, chewed, crushed or dissolved OxyContin tablets
`leads to rapid release and absorption of a potentially fatal dose of oxycodone. (2.1)
`
`The concomitant use of OxyContin with all cytochrome P450 3A4 inhibitors such as
`macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g.,
`ketoconazole), and protease inhibitors (e.g., ritonavir) may result in an increase in
`oxycodone plasma concentrations, which could increase or prolong adverse effects
`and may cause potentially fatal respiratory depression. Patients receiving
`
`Reference ID: 3024987
`
`

`

`OxyContin and a CYP3A4 inhibitor should be carefully monitored for an extended
`period of time and dosage adjustments should be made if warranted. (7.2)
`
`1 INDICATIONS AND USAGE
`
`OxyContin is a controlled-release oral formulation of oxycodone hydrochloride 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 Usage
`
`
`OxyContin is not intended for use on an as-needed basis.
`
`OxyContin is not indicated for the management of pain in the immediate postoperative
`period (the first 12-24 hours following surgery), or if the pain is mild, or not expected to
`persist for an extended period of time. OxyContin is indicated for postoperative use
`following the immediate post-operative period only if the patient is already receiving the
`drug prior to surgery or if the postoperative pain is expected to be moderate to severe and
`persist for an extended period of time. Physicians should individualize treatment, moving
`from parenteral to oral analgesics as appropriate (see American Pain Society guidelines).
`
`OxyContin is not indicated for pre-emptive analgesia (preoperative administration for the
`management of postoperative pain).
`
`OxyContin is not indicated for rectal administration.
`
`2 DOSAGE AND ADMINISTRATION
`
`
`2.1 Safe Administration Instructions
`
`
`OxyContin tablets must be swallowed whole and must not be cut, broken, chewed,
`crushed or dissolved. Taking cut, broken, chewed, crushed or dissolved OxyContin
`tablets leads to rapid release and absorption of a potentially fatal dose of oxycodone.
`
`
`OxyContin tablets should be taken one tablet at a time. Take each tablet with enough
`water to ensure complete swallowing immediately after placing in the mouth [see Patient
`Counseling Information (17.1)].
`
`
`Selection of patients for treatment with OxyContin should be governed by the same
`principles that apply to the use of similar opioid analgesics. Physicians should
`individualize treatment using a progressive plan of pain management such as outlined by
`the World Health Organization, Federation of State Medical Boards Model Policy, and
`the American Pain Society. Healthcare professionals should follow appropriate pain
`
`management principles of careful assessment and ongoing monitoring.
`
`2.2 Initiating Therapy with OxyContin
`
`
`Reference ID: 3024987
`
`

`

`
`It is critical to initiate the dosing regimen for each patient individually. Attention should
`be given to:
`
`
`
`•
`
`
`•
`
`•
`
`•
`
`•
`
`•
`
`risk factors for abuse or addiction; including whether the patient has a previous or
`current substance abuse problem, a family history of substance abuse, or a history
`of mental illness or depression;
`the age, general condition and medical status of the patient;
`the patient's opioid exposure and opioid tolerance (if any);
`the daily dose, potency, and kind of the analgesic(s) the patient has been taking;
`the reliability of the conversion estimate used to calculate the dose of oxycodone;
`the special instructions for OxyContin 60 mg and 80 mg tablets, a single dose
`greater than 40 mg, or total daily doses greater than 80 mg [see Dosage and
`Administration (2.7)]; and
`the balance between pain control and adverse reactions.
`
`
`•
`
`
`Use low initial doses of OxyContin in patients who are not already opioid-tolerant [see
`Dosage and Administration (2.7)], especially those who are receiving concurrent
`
` treatment with muscle relaxants, sedatives, or other CNS active medications [see
`
` Warnings and Precautions (5.1, 5.3) and Drug Interactions (7.1, 7.3)].
`
`
`
`Experience indicates a reasonable starting dose of OxyContin for patients who are taking
`non-opioid analgesics and require continuous around-the-clock therapy for an extended
`period of time is 10 mg every 12 hours. Individually titrate OxyContin to a dose that
`provides adequate analgesia and minimizes adverse reactions while maintaining an every-
`twelve-hour dosing regimen.
`
`For initiation of OxyContin therapy for patients previously taking opioids, the conversion
`ratios found in Table 1 are a reasonable starting point, although not verified in well-
`controlled, multiple-dose trials. No fixed conversion ratio is likely to be satisfactory in all
`patients, especially patients receiving large opioid doses. A reasonable approach for
`converting from existing opioid therapy to OxyContin is as follows:
`
`
`
`• Discontinue all other around-the-clock opioid drugs when OxyContin therapy is
`initiated.
`
`
`
`• Using standard conversion ratio estimates (see Table 1), multiply the mg/day of
`
`each of the current opioids to be converted by their appropriate multiplication
`factor to obtain the equivalent total daily dose of oral oxycodone.
`
`
`• Divide the calculated 24-hour oxycodone dose in half to approximate the every
`12-hour dose of OxyContin.
`
`
`
`• Round down, if necessary, to the appropriate OxyContin tablet strengths
`
`available.
`
`
`
`
`
`
`
`
`Reference ID: 3024987
`
`

`

`
`• Close observation and frequent titration are indicated until patients are stable on
`the new therapy.
`
`
`TABLE 1
`
`Multiplication Factors for Converting the Daily Dose
` of Current Opioids to the Daily Dose of Oral Oxycodone1*
`
`(mg/Day Opioid x Factor = mg/Day Oral Oxycodone)
`
`
`Parenteral Opioid
`Oral Opioid
`1
`--
`Oxycodone
`0.15
`--
`Codeine
`0.9
`--
`Hydrocodone
`4
`20
`Hydromorphone
`7.5
`15
`Levorphanol
`0.1
`0.4
`Meperidine
`1.5
`3
`Methadone
`0.5
`3
`Morphine
`* To be used only for conversion to oral oxycodone. 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.
`
`2.3 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.
`
`2.4 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)].
`
`2.5 Managing Expected Opioid Adverse Reactions
`
`
`Most patients receiving OxyContin, especially those who are opioid-naive, will
`
`experience adverse reactions. Patients do not usually become tolerant to the constipating
`effects of opioids, therefore, anticipate constipation and treat aggressively and
`prophylactically with a stimulant laxative with or without a stool softener. If nausea
`persists and is unacceptable to the patient, consider treatment with antiemetics or other
`modalities to relieve these symptoms.
`
`2.6 Individualization of Dosage
`
`
`
`Reference ID: 3024987
`
`
`

`

` Once therapy is initiated, assess pain relief and other opioid effects frequently. Titrate
`
`patients to adequate effect (generally mild or no pain with the regular use of no more than
`two doses of supplemental analgesia per 24 hours). Patients who experience
`breakthrough pain may require dosage adjustment or rescue medication. Because steady-
`state plasma concentrations are approximated within 24 to 36 hours, dosage adjustment
`may be carried out every 1 to 2 days.
`
`There are no well-controlled clinical studies evaluating the safety and efficacy with
`dosing more frequently than every 12 hours. Increase the OxyContin dose by increasing
`the total daily dose, not by changing the 12-hour dosing interval. 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.
`
`If signs of excessive opioid-related adverse reactions are observed, the next dose may be
`reduced. If this adjustment leads to inadequate analgesia, a supplemental dose of
`immediate-release oxycodone may be given. Alternatively, non-opioid analgesic
`adjuvants may be employed. Adjust the dose to obtain an appropriate balance between
`
`pain relief and opioid-related adverse reactions.
`
`During periods of changing analgesic requirements, including initial titration, maintain
`frequent contact between physician, other members of the healthcare team, the patient
`and, with proper consent, the caregiver/family.
`
`2.7 Special Instructions for Patients who are not Opioid Tolerant
`
`Do not begin treatment with OxyContin 60 mg and 80 mg Tablets, a single dose greater
`than 40 mg, or a total daily dose greater than 80 mg in patients who are not already
`tolerant to the respiratory-depressant and sedating effects of opioids. Use of these doses
`in patients who are not opioid tolerant may cause fatal respiratory depression. These
`doses are only for use in opioid-tolerant patients.
`
`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.
`
`Instruct patients not to share or permit use by individuals other than the patient for
`whom OxyContin was prescribed, as such inappropriate use may have severe
`medical consequences, including death.
`
`2.8 Continuation of Therapy
`
`
`During chronic 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.
`
`
`
`
`Reference ID: 3024987
`
`

`

`2.9 Cessation of Therapy
`
`
`When the patient no longer requires therapy with OxyContin, taper the dose gradually to
`prevent signs and symptoms of withdrawal in the physically-dependent patient.
`
`2.10 Conversion from OxyContin to Parenteral Opioids
`
`To avoid overdose, follow conservative dose conversion ratios. When converting from
`OxyContin to parenteral opioids, it is advisable to calculate an equivalent parenteral dose
`
`and then initiate treatment at half of this calculated value.
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`
`ƒ 10 mg film-coated tablets (round, white-colored, bi-convex tablets debossed with
`OP on one side and 10 on the other)
`
`ƒ 15 mg film-coated tablets (round, gray-colored, bi-convex tablets debossed with
`OP on one side and 15 on the other)
`
`ƒ 20 mg film-coated tablets (round, pink-colored, bi-convex tablets debossed with
`OP on one side and 20 on the other)
`
`ƒ 30 mg film-coated tablets (round, brown-colored, bi-convex tablets debossed with
`OP on one side and 30 on the other)
`
`ƒ 40 mg film-coated tablets (round, yellow-colored, bi-convex tablets debossed
`with OP on one side and 40 on the other)
`
`ƒ 60 mg film-coated tablets* (round, red-colored, bi-convex tablets debossed with
`OP on one side and 60 on the other)
`
`ƒ 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:
`
`
`
`ƒ patients who have significant respiratory depression
`
`ƒ patients who have or are suspected of having paralytic ileus
`
`
`ƒ patients who have acute or severe bronchial asthma
`
`ƒ patients who have known hypersensitivity to any of its components or the active
`ingredient, oxycodone.
`
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Information Essential for Safe Administration
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`Reference ID: 3024987
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`OxyContin tablets must be swallowed whole and must not be cut, broken, chewed,
`crushed, or dissolved. Taking cut, broken, chewed, crushed or dissolved OxyContin
`tablets leads to rapid release and absorption of a potentially fatal dose of oxycodone.
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`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 opioid-tolerant patients. Use of these doses in
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`patients who are not opioid tolerant may cause fatal respiratory depression.
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`Instruct patients against use by individuals other than the patient for whom
`OxyContin was prescribed, as such inappropriate use may have severe medical
`consequences, including death.
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`Opioid analgesics have a narrow therapeutic index in certain patient populations,
`especially when combined with CNS depressant drugs, and should be reserved for cases
`where the benefits of opioid analgesia outweigh the known risks of respiratory
`depression, altered mental state, and postural hypotension.
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`5.2 CNS Depression
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`OxyContin may cause somnolence, dizziness, alterations in judgment and alterations in
`levels of consciousness, including coma.
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`5.3 Interactions with Alcohol, CNS Depressants and Illicit Drugs
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`Hypotension, profound sedation, coma or respiratory depression may result if OxyContin
`is added to a regimen that includes other CNS depressants (e.g., sedatives, anxiolytics,
`hypnotics, neuroleptics, other opioids). Therefore, use caution when deciding to initiate
`therapy with OxyContin in patients who are taking other CNS depressants. Take into
`account the types of other medications being taken, the duration of therapy with them,
`and the patient’s response to those medicines, including the degree of tolerance that has
`developed to CNS depression. Consider the patient’s use, if any, of alcohol and/or illicit
`drugs that cause CNS depression. If the decision to begin OxyContin is made, start with a
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`lower OxyContin dose than usual [see Drug Interactions (7.3)].
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`Consider using a lower initial dose of a CNS depressant when given to a patient currently
`taking OxyContin due to the potential of additive CNS depressant effects.
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`5.4 Respiratory Depression
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`Decreased respiratory drive resulting in respiratory depression is the chief hazard from
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`the use or abuse of opioid agonists, including OxyContin. The risk of opioid-induced
`respiratory depression is increased, for example, in elderly [see Use In Specific
`Populations (8.5)] or debilitated patients; following large initial doses in any patient who
`is not tolerant to the respiratory-depressant or sedating effects of opioids; or when opioids
`are given in conjunction with other agents that either depress respiratory drive or
`consciousness.
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`Reference ID: 3024987
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`Use OxyContin with extreme caution in patients with any of the following:
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`significant chronic obstructive pulmonary disease or cor pulmonale
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`ƒ other risk of substantially decreased respiratory reserve
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`ƒ hypoxia
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`ƒ hypercapnia
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`ƒ pre-existing respiratory depression
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`Respiratory depression induced by opioids typically follows a pattern entailing first a
`shift in CO2 responsiveness of the CNS respiratory drive center, which results in a
`decrease in the urge to breathe, despite the presence of hypercapnia. The increase in
`brain CO2 can result in sedation that can accentuate the sedation from the opioid itself.
`Profound sedation, unresponsiveness, infrequent deep (“sighing”) breaths or atypical
`snoring frequently accompany opioid-induced respiratory depression. Eventually,
`hypoxia ensues. In addition to further decreasing consciousness, hypoxia, along with
`hypercapnia, can predispose to life-threatening cardiac arrhythmias.
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`5.5 Seizures
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`Oxycodone, as with other opioids, may aggravate convulsions in patients with convulsive
`disorders, and may induce or aggravate seizures in some clinical settings. Use OxyContin
`with caution in patients with a history of seizure disorders.
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`5.6 Difficulty Swallowing and Gastrointestinal Effects
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`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.
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`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.
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`Use caution when prescribing OxyContin for patients who have difficulty swallowing or
`have underlying GI disorders that may predispose them to obstruction.
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`The administration of OxyContin may obscure the diagnosis or clinical course in patients
`with acute abdominal conditions. Use OxyContin with caution in patients who are at risk
`of developing ileus.
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`5.7 Head Injury
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`Reference ID: 3024987
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`The respiratory depressant effects of opioids include carbon dioxide retention, which can
`lead to an elevation of cerebrospinal fluid pressure. This effect may be exaggerated in
`the presence of head injury, intracranial lesions, or other sources of pre-existing increased
`intracranial pressure. Oxycodone may produce miosis that is independent of ambient
`light, and altered consciousness, either of which may obscure neurologic signs associated
`with increased intracranial pressure in persons with head injuries.
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`5.8 Hypotensive Effect
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`OxyContin may cause severe hypotension. There is an added risk to individuals whose
`ability to maintain blood pressure has been compromised by a depleted blood volume, or
`after concurrent administration with drugs such as phenothiazines or other agents which
`compromise vasomotor tone. Oxycodone may produce orthostatic hypotension in
`ambulatory patients. Administer OxyContin with caution to patients in circulatory shock,
`since vasodilation produced by the drug may further reduce cardiac output and blood
`pressure.
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`5.9 Cytochrome P450 3A4 Inhibitors and Inducers
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`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.
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`The expected clinical results with CYP3A4 inhibitors would be an increase in oxycodone
`plasma concentrations and possibly increased or prolonged opioid effects. The expected
`clinical results with CYP3A4 inducers would be a decrease in oxycodone plasma
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`concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a
`patient who had developed physical dependence to oxycodone.
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`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
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`are achieved [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].
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`5.10 Interactions with Mixed Agonist/Antagonist Opioid Analgesics
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`It is generally not advisable to administer mixed agonist/antagonist analgesics (i.e.,
`pentazocine, nalbuphine, and butorphanol) to a patient receiving OxyContin. In this
`situation, mixed agonist/antagonist analgesics may reduce the analgesic effect and may
`precipitate withdrawal symptoms in these patients.
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`5.11 Use in Pancreatic/Biliary Tract Disease
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`Oxycodone may cause spasm of the sphincter of Oddi and should be used with caution in
`patients with biliary tract disease, including acute pancreatitis. Opioids may cause
`increases in the serum amylase.
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`Reference ID: 3024987
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`5.12 Tolerance
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`Tolerance to opioids is demonstrated by the need for increasing doses to