CENTER FOR DRUG EVALUATION AND
`
`CENTER FOR DRUG EVALUATION AND
`RESEARCH
`RESEARCH
`
`
`
`
`
`APPLICATION NUMBER:
`22-272
`22-272
`
`APPLICA TION NUMBER:
`
`REMS
`
`REMS
`
`
`
`
`
`

`

`
`
` NDA 22-272
`
`
` OxyContin® (oxycodone hydrochloride controlled-release) Tablets
`
`
`
`
`
`
`
` Opioid Agonist
`
`
` Purdue Pharma L.P.
`
`
` One Stamford Forum
`
`
` Stamford, CT 06901-3431
`
`
`
`
`
`
` RISK EVALUATION AND MITIGATION STRATEGY (REMS)
`
`
`
` I. GOALS
`
`
`
`
` Goal 1: To inform patients and healthcare professionals about the potential for abuse, misuse,
`
` overdose, and addiction of OxyContin®
`
`
`
`
`Goal 2: To inform patients and healthcare professionals about the safe use of OxyContin®
`
`
`
`
`II. REMS ELEMENTS
`
`
`
`A) Medication Guide
`
`In accordance with 21 CFR 208.24, a Medication Guide will be dispensed with each OxyContin®
`
`
`prescription. Purdue Pharma L.P. will ensure that the Medication Guide is available for distribution
`to patients receiving a prescription for OxyContin® by providing sufficient numbers to distributors
`
`
`
`
`and authorized dispensers.
`
`
`
`1. One copy of Full Prescribing Information, which includes the Medication Guide, will be
`
`packaged with each bottle of OxyContin®.
`
`
`
`
`
`
`
`2. Two separate additional Medication Guides will also be packaged with each bottle of
`
`OxyContin®.
`
`
`
`3. Per 21CFR 208.24(d) the label of each container or package of OxyContin® will include a
`
`
`
`
` prominent and conspicuous statement:
`
`
` a) instructing authorized dispensers to provide a Medication Guide to each patient to
` whom the drug is dispensed (eg, “Attention Dispenser: Accompanying Medication
`
` Guide must be provided to each patient upon dispensing”), and
`
`
`
`
`
` b) stating how the Medication Guide is provided.
`
`
`
`Page 1 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`

`

`
`
`
`
`4. Medication Guides will also be available via Purdue Pharma L.P. Field Sales
`
`
`representatives, through an Internet presence, and from Purdue’s Medical Services
`
`Department (1-888-726-7535).
`
`
`Please see appended Medication Guide.
`
`
`B. Elements to Assure Safe Use
`1. Healthcare providers who prescribe OxyContin® will receive training.
`
`
`
`
`
` a. Purdue will ensure that training will be provided to healthcare providers who prescribe
`
`
`
` OxyContin®. To become trained, each prescriber will be provided with the OxyContin®
`
`
` Educational materials.
`
` The Training includes the following:
`
`
`
`
`
`
`
`
`
`
`
` i) Proper patient selection;
`
` ii) Appropriate OxyContin® dosing and administration;
`
`
`
`
`iii) General principles of safe opioid use, including information about opioid abuse and how to
`
`
` identify patients who are at risk for addiction;
`
`iv) Potential abuse, misuse, overdose and addiction from exposure to opioids, including
`
`OxyContin®;
`
`
`v)
`
`
`
`
`
` Risks of OxyContin®, including:
`
`
`
`
` 1. The risk of overdose caused by exposure to an essentially immediate-release form of
`
`
` oxycodone by consuming broken, chewed, crushed or dissolved OxyContin® tablets;
`
`
`2. The risk of addiction from exposure to OxyContin®; and
`
`
`
`
`
` 3. The risk of overdose in patients who have not developed tolerance to the sedating or
`
` respiratory-depressant effects of opioids from exposure to a single dose of OxyContin
`
`
` greater than 40 mg;
`
`
`
`vi) Information to counsel patients and caregivers on the need to store opioid analgesics safely
`
`
`
`
` out of reach of children and household acquaintances and the need to properly dispose of
`
` unused drugs when no longer needed by the patient; and
`
` vii) Importance of providing each patient a Medication Guide with each prescription and
`
`
`instructing the patient to read the Medication Guide.
`
`
`
`
`
`
` b. Purdue will ensure that at least 3 weeks prior to first availability of OxyContin® to healthcare
`
`
`
`
`professionals, a Dear Healthcare Professional letter will be mailed to prescribers most
`
`Page 2 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`
`
`
`
`
`
`
`experienced in treating chronic pain with opioid agonists, including pain specialists, physiatrists,
`
` and primary care physicians. This letter is designed to convey and reinforce the risks of abuse,
` misuse, overdose and addiction of OxyContin® as well as the need to complete the OxyContin®
`
`
`REMS Educational Program. This letter will be available on the Purdue website
`
`(www.oxycontinrems.com) for 1 year from the date of mailing.
`
`
` c. The mailings will include the following OxyContin® REMS Educational Program materials:
`
`
` i) OxyContin® Medication Guide
`
`ii) Prescribing OxyContin® Tablets CII: A Guide for Healthcare Providers
`
`
`
`
`
`iii) OxyContin® Education Confirmation Form
`
`
`
`
`
`
`
`
`
`d. Additional printed educational material will be available through field-force distribution and by
`
`calling the toll-free number at Purdue (1-888-726-7535).
`
`
`e. The educational material will also be available for download at www.oxycontinrems.com.
`
`
`
`
`
`f. Purdue will maintain a list of all prescribers who have completed the OxyContin® REMS
`
`
`
`Educational Program.
`
`Prescribers will be re-trained every two years or following substantial changes to the OxyContin®
`
`
`REMS. Substantial changes may include changes in the OxyContin® Full Prescribing Information,
`
`
`OxyContin® Medication Guide, or OxyContin® REMS that require substantial modification of the
`
`
`
`educational materials.
`
`
`The following materials are part of the REMS and are appended:
`o Dear Healthcare Professional Letter
`
`
`
`o Medication Guide
`
`
`o The Healthcare Provider Guide, “Prescribing OxyContin® Tablets CII: A Training Guide for
`
`
`
`
`Healthcare Providers”
`
`o OxyContin® Education Confirmation Form
`
`
`
`
` C. Implementation System
` Because OxyContin® can be approved without the Elements to Assure Safe Use described under FDCA
`
`
` 505-1(f)(3) (B), (C), and (D) of the Act, an implementation system is not required.
`
`
`
`
`
`
`
`
`Page 3 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`
` D. Timetable for Submission of Assessments
`
` Purdue Pharma L.P. will submit REMS Assessments to FDA every 6 months for the first year from the
`
`
`
`
`
` date of approval of the REMS and annually thereafter. To facilitate inclusion of as much information as
` possible, while allowing reasonable time to prepare the submission, the reporting interval covered by
`
`
`
` each assessment will conclude no earlier than 60 days before the submission date for that assessment.
` Purdue L.P. will submit each assessment so that it will be received by the FDA on or before the due
`
`
` date.
`
`
`
`
`
`
`Page 4 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`REMS APPENDIX 1 – OXYCONTIN® MEDICATION GUIDE
`
`
`
`
`
`
`
`
` MEDICATION GUIDE
`
` OXYCONTIN (ox-e-KON-tin) (CII)
`
`
` (oxycodone hydrochloride controlled-release)
`
`
` Tablets
`
`
`
`
`Read this Medication Guide before you start taking OxyContin and each time you get a
`
`
`
`
`
`
`refill. There may be new information. This Medication Guide does not take the place of
`
`
`
`
`talking to your healthcare provider about your medical condition or your treatment.
`
`
`
`
`What is the most important information I should know about OxyContin?
`
`
`• OxyContin can cause serious side effects, including addiction or death.
`
`
`
`• Do not cut, break, chew, crush, or dissolve OxyContin before swallowing. If
`
`OxyContin is taken in this way, the medicine in the tablets will be released too
`
`fast. This is dangerous. It may cause you to stop breathing, and may lead to
`
`death.
`
`
`
`• OxyContin is not for use to treat pain that you only have once in a while (“as
`
`
`needed”).
`
`• Do not take OxyContin 60 mg or 80 mg tablets unless you are “opioid tolerant.”
`
`
`Opioid tolerant means that you regularly use OxyContin or another opioid medicine
`
`
`for your constant (around-the-clock) pain and your body is used to it.
`
`
`
`
`• Do not take more than 40 mg of OxyContin in one dose or more than 80 mg of
`
`
`OxyContin in one day unless you are “opioid tolerant.” This may cause you to
`
`
`stop breathing and may lead to death.
`
`
`• OxyContin is a federally controlled substance (CII) because it is a strong opioid
`
`
`
`pain medicine that can be abused by people who abuse prescription medicines or
`
`
`street drugs.
`
`• Prevent theft, misuse and abuse. Keep OxyContin in a safe place, to keep it from
`
`
`
`
`
`being stolen. OxyContin can be a target for people who misuse or abuse prescription
`
`medicines or street drugs.
`• Never give OxyContin to anyone else, even if they have the same symptoms you
`
`
`
`
`
`have. It may harm them and even cause death.
`
`• Before taking OxyContin, tell your doctor if you or a family member have been
`
`
` addicted to or abused other medicines, street drugs, or alcohol, or if you have a
`
`
`history of mental illness.
`
`
`
`• Do not drink alcohol while using OxyContin. Using alcohol with OxyContin may
`
`
`increase your risk of dangerous side effects, including death.
`
`
`
`
`Page 5 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`• Certain medicines can interact with OxyContin and cause you to have high levels
`
`
`
`of oxycodone in your blood. This may cause you to stop breathing and lead to
`
`
`death. Before taking OxyContin, tell your healthcare provider if you take an
`
`antibiotic, an antifungal medicine, or an anti-HIV medicine.
`
`
`
`
`
`
`
`
`
`
` •
`
`
`
`
` What is OxyContin?
`
`• OxyContin is a prescription medicine used when an opioid medicine is needed to
`
`
` manage moderate to severe pain that continues around-the-clock and is expected to
`
` last for a long period of time.
`
` It is not known if OxyContin is safe and effective in children younger than 18 years.
`
`
` •
`
`
` • OxyContin is not for use:
`
`o
` to manage pain “as needed”
`
`
`o before surgery to manage any pain from your surgery
`
`
`o
` to manage pain after surgery if the pain is mild and is not expected to last for a
`
`
`
` long period of time
` If you already take OxyContin, it may be used to manage your pain after surgery if:
`o
`
` it has been at least 12 to 24 hours after your surgery, and
`
`o your pain from surgery is expected to be moderate to severe, and last for a
`
`
`long period of time.
`
`
` Who should not take OxyContin?
` Do not take OxyContin if you:
`
` • are allergic to any of its ingredients. See the end of this Medication Guide for a list of
`
`
` the ingredients in OxyContin.
`
` • have had a severe allergic reaction to a medicine that contains oxycodone. Ask your
`
`
` healthcare provider if you are not sure.
`
` • are having an asthma attack or have severe asthma, trouble breathing, or lung
`
`
`
` problems
` • have a bowel blockage called paralytic ileus
`
`
`
`
`What should I tell my healthcare provider before taking OxyContin?
` OxyContin may not be right for you. Before taking OxyContin, tell your doctor if
`
`
`
` you:
` • have trouble breathing or lung problems
`
` • have had a head injury
`
`
`
` • have liver or kidney problems
`
` • have adrenal gland problems, such as Addison’s disease
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Page 6 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
` • have severe scoliosis that affects your breathing
`
` • have thyroid problems
`
`
` • have enlargement of your prostate or a urethral stricture
`
` • have or had convulsions or seizures
`
`
`
` • have a past or present drinking problem or alcoholism
`
`
` • have hallucinations or other severe mental problems
`
`
` • have past or present substance abuse or drug addiction
`
`
`
` • have any other medical conditions
`
`
` • are pregnant or plan to become pregnant. If you take OxyContin regularly before
`
`
`
`
` your baby is born, your newborn baby may have signs of withdrawal because
`their body has become used to the medicine. Signs of withdrawal in a newborn
`
`baby can include:
`
`irritability
`•
`
`
`• crying more than usual
`
`
`shaking (tremors)
`•
`
`
`jitteriness
`•
`
`
`• breathing faster than normal
`
`
`• diarrhea or more stools than normal
`
`
`
`
`sneezing
`•
`
`
`• yawning
`
`
`• vomiting
`
`
`fever
`•
`
`If you take OxyContin right before your baby is born, your baby could have
`
`
`
`breathing problems at birth.
`
`• are breast-feeding. You should not take OxyContin if you are nursing. Some
`
`
`
`oxycodone from OxyContin passes into breast milk. A nursing baby could
`
`become very drowsy or have difficulty breathing or feeding well.
`
`
`Tell your healthcare provider about all the medicines you take, including prescription
`and non-prescription medicines, vitamins, and herbal supplements. Sometimes the doses
`
`
`
`of medicines that you take with OxyContin may need to be changed if used together.
`
`• See “What is the most important information I should know about
`
`
`
`
`OxyContin?”
`
`
`• Be especially careful about taking other medicines that make you sleepy such as:
`
`
`• pain medicines
`
`
`
`
`
`
`Page 7 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`
`
`
`
`
`•
`
`
`sleeping pills
`
` •
`
`
` • anxiety medicines
`
` • antihistamines
`
`
`
` • anti-depressants
`
`
` tranquilizers
` •
`
`
` • anti-nausea medicine
`
`
` Do not take other medicines without talking to your healthcare provider. Your healthcare
`
` provider will tell you if it is safe to take other medicines while you take OxyContin.
`
` Know the medicines you take. Keep a list of your medicines to show your healthcare
`
`
`
`
`
`provider and pharmacist.
`
`How should I take OxyContin?
`
`
`• See “What is the most important information I should know about OxyContin?”
`
`
`• Take OxyContin exactly as prescribed. Do not change your dose unless your
`
`
`healthcare provider tells you to.
`
`• Swallow OxyContin tablets whole. Do not cut, break, chew, crush, or dissolve
`
`
`before swallowing.
`
`• Take OxyContin every 12 hours
`
`
`• You can take OxyContin with or without food.
`
`If you miss a dose, take it as soon as possible. Take your next dose 12 hours later.
`•
`
`Do not take more than your prescribed dose of OxyContin. Call your healthcare
`
`
`provider if you are not sure about your dose of OxyContin or when to take it.
`
`
`
`If you take more OxyContin than prescribed, or overdose, call your local
`emergency number (such as 911) or your local Poison Control Center right away,
`
`
`or get emergency help.
`
`• Talk with your healthcare provider regularly about your pain to see if you
`
`
`
`still need to take OxyContin.
`
`
`
`What should I avoid while taking OxyContin?
`
`• Do not drink alcohol while using OxyContin. See “What is the most
`
`
`important information I should know about OxyContin?” Do not drive,
`
`operate heavy machinery, or do other dangerous activities, especially when
`
`you start taking OxyContin and when your dose is changed, until you know
`
`
`how you react to this medicine. OxyContin can make you sleepy, and also
`
`cause you to feel dizzy. Ask your healthcare provider to tell you when it is
`okay to do these activities.
`
`
`What are the possible side effects of OxyContin?
`
`
`
`
`
`Page 8 of 37
`
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`
`
`OxyContin can cause serious side effects, including:
`
`
`• See “What is the most important information I should know about OxyContin?”
`
`• OxyContin can cause serious breathing problems that can become life-
`
`
`
`threatening, especially if OxyContin is used the wrong way. Call your
`
`healthcare provider or get medical help right away if:
`
`• your breathing slows down
`
`
`• you have shallow breathing (little chest movement with breathing)
`
`
`• you feel faint, dizzy, confused, or
`
`
`• you have any other unusual symptoms
`
`
`
`
`These can be signs or symptoms that you have taken too much OxyContin (overdose)
`
`or the dose is too high for you. These symptoms may lead to serious problems or
`
`
`death if not treated right away.
`• Central nervous system effects, including sleepiness, dizziness, passing out,
`
`
`becoming unconscious, or coma.
`
`
`
`• OxyContin may cause a worsening of seizures in people who already have
`
`seizures.
`
`• OxyContin can cause your blood pressure to drop. This can make you feel dizzy
`
`
`
`and faint if you get up too fast from sitting or lying down. Low blood pressure is also
`more likely to happen if you take other medicines that can also lower your blood
`
`
`pressure. Severe low blood pressure can happen if you lost blood or take certain
`
`other medicines.
`• OxyContin can cause physical dependence. Do not stop taking OxyContin or any
`
`
`other opioid without talking to your healthcare provider about how to slowly stop
`
`
`
`your medicine. You could become sick with uncomfortable withdrawal symptoms
`because your body has become used to these medicines. Physical dependence is not
`
`
`
`the same as drug addiction. Tell your healthcare provider if you have any of these
`
`signs or symptoms of withdrawal while slowly stopping OxyContin:
`o feel restless
`
`
`o
`
`tearing eyes
`
`o runny nose
`
`
`o yawning
`
`o sweating
`
`
`o chills or hair on your arms “standing up”
`
`
`o muscle aches, backache
`
`
`o dilated pupils of your eyes
`
`
`o feel irritable or anxious
`
`
`o nausea, loss of appetite, vomiting, diarrhea
`
`
`
`Page 9 of 37
`
`
`
`CONFIDENTIAL
`
`
`
`
`
`1 April 2010
`
`
`
`
`

`

`
`
`
`
`o increase in your blood pressure, breathing faster, or your heart beats faster
`
`
` • There is a chance of abuse or addiction with OxyContin. The chance is higher if
`
`
`
` you are or have been addicted to or abused other medicines, street drugs, or alcohol,
`
`
` or if you have a history of mental problems.
`
`
` The most common side effects of OxyContin include:
`o constipation
`
`
`o nausea
`
`
`o drowsiness
`
`
`o dizziness
`
`
`o
`
` itching
`
`o vomiting
`
`
`o headache
`
`
`o dry mouth
`
`
`o weakness
`
`
`
`o sweating
`
`
`
`Some of these side effects may decrease with continued use. Talk with your healthcare
`
`
`
` provider if you continue to have these side effects. These are not all the possible side
` effects of OxyContin. For a complete list, ask your healthcare provider or pharmacist.
`
`
` Constipation (not often enough or hard bowel movements) is a very common side effect
`
`
` of pain medicines (opioids) including OxyContin, and is unlikely to go away without
`
` treatment. Talk to your healthcare provider about dietary changes, and the use of
`
`
`
` laxatives (medicines to treat constipation) and stool softeners to prevent or treat
`
`constipation while taking OxyContin.
`
`
` Call your doctor for medical advice about side effects. You may report side effects to
`
` FDA at 1–800–FDA–1088.
`
`
`
`
`
`
`
`
`
`
`Page 10 of 37
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`How should I store OxyContin?
`
`• Keep OxyContin out of the reach of children. Accidental overdose by a child is dangerous and
`
`
`can lead to death.
`• Store OxyContin at 59o F to 86oF (15o C to 30o C)
`
`
`
` • Keep OxyContin in the container it comes in.
`
`
`
`
` • Keep the container tightly closed and away from light.
`
`• After you stop taking OxyContin, flush the unused tablets down the toilet.
`
`
`
`
`General information about OxyContin
`
`
`Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not
`
`use OxyContin for a condition for which it was not prescribed. Never give your OxyContin to other
`
`
`people even if they have the same symptoms you have.
`
`
`
`
`Selling or giving away OxyContin may harm others, even causing death, and is against the law.
`
`
`This Medication Guide summarizes the most important information about OxyContin. If you would like
`
`more information, talk with your healthcare provider. You can ask your healthcare provider or
`
`pharmacist for information about OxyContin that is written for health professionals. For more
`
`
` information about OxyContin, go to www.purduepharma.com or call 1-888-726-7535.
`
` What are the ingredients of OxyContin?
`
` Active ingredient: oxycodone hydrochloride
`
` Inactive ingredients in all strengths: butylated hydroxytoluene (BHT), hypromellose, polyethylene
`
` glycol 400, polyethylene oxide, magnesium stearate, titanium dioxide
` • The 10 mg tablets also contain: hydroxypropyl cellulose.
`
`
` • The 15 mg tablets also contain: black iron oxide, yellow iron oxide, and red iron oxide.
`
` • The 20 mg tablets also contain: polysorbate 80 and red iron oxide.
`
`
`• The 30 mg tablets also contain: polysorbate 80, red iron oxide, yellow iron oxide, and black iron
`
`
` oxide.
`
` • The 40 mg tablets also contain: polysorbate 80 and yellow iron oxide.
`
`
` • The 60 mg tablets also contain: polysorbate 80, red iron oxide and black iron oxide
`
` • The 80 mg tablets also contain: hydroxypropyl cellulose, yellow iron oxide and FD&C Blue
`
`
` #2/Indigo Carmine Aluminum Lake
`
`
`
`
` Always check to make sure that the medicine you are taking is the correct one. The dosage
` strength and appearance of each OxyContin tablet are as follows:
`
`
` • 10 mg: white-colored with “OP” on one side and “10” on the other
`
`
` • 15 mg: gray-colored with “OP” on one side and “15” on the other
`
`
`
` • 20 mg: pink-colored with “OP” on one side and “20” on the other
`
`
`
`
` • 30 mg: brown-colored with “OP” on one side and “30” on the other
`
`
`
` • 40 mg: yellow-colored with “OP” on one side and “40” on the other
`
`
` • 60 mg: red-colored with “OP” on one side and “60” on the other
`
`
`
`Page 11 of 37
`
`
`CONFIDENTIAL
`
`
`
`
`
`
`
`
`
`1 April 2010
`
`
`
`
`

`

`• 80 mg: green-colored with “OP” on one side and “80” on the other
`
`
`
`
`
`
`
`Purdue Pharma L.P.
`
`Stamford, CT 06901-3431
`
`
` This Medication Guide has been approved by the U.S. Food and Drug Administration.
`
`
`
`©2010, Purdue Pharma L.P.
`
`
`March 22, 2010
`
`301734-0A
`
`
`
`
`
`
`
`
`
`
`
`
`Page 12 of 37
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`REMS APPENDIX 2 – OXYCONTIN® DEAR HEALTHCARE PROFESSIONAL LETTER
`
`
`
`
`
`
`
`[Date]
`
`
`
`
`
`[prescriber name]
`
`
`
`[street address]
`
`
`
`[city, state zip code]
`
`
`
`
`
`Dear Prescriber:
`
`
`Purdue Pharma, L.P. is introducing a Risk Evaluation and Mitigation Strategy (REMS) for OxyContin® (oxycodone
`
`
`
`
`
`
`
`
`
`HCl controlled-release) Tablets to educate prescribers about the potential abuse, misuse, overdose and addiction
`
`
`
`
`
`
`
`
`
` from exposure to OxyContin® (oxycodone HCl controlled-release) Tablets.
`
`
`
`
`
`
`
` The goals of the OxyContin® REMS program are:
`
`
`
`
`
`
`
`
`
`
`
`
`
`Goal 1: To inform patients and healthcare professionals about the potential for abuse, misuse, overdose,
`
`
`
`
`
`
`
`
`
`
`
`and addiction of OxyContin®
`
`
`
`
`
`Goal 2: To inform patients and healthcare professionals about the safe use of OxyContin®.
`
`
`
`
`
`
`
`
`
`OxyContin® Tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the
`
`
`
`
`
`management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an
`
`
`
`
`
`
`
`
`extended period of time. OxyContin® Tablets are not intended for use on an as needed (prn) basis.
`
`
`
`
`
`
`
`
`
`
`OxyContin® is not intended 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.
`
`
`
`
`OxyContin® contains oxycodone which is an opioid agonist and a Schedule II controlled substance with an abuse
`
`
`
`
`
`liability similar to morphine. Oxycodone 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, overdose, and addiction.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Page 13 of 37
`CONFIDENTIAL
`
`
`
`
`
`1 April 2010
`
`

`

`
`
`OxyContin® Tablets are contraindicated in:
`
`
`
`
` patients who have significant respiratory depression
`
`
`
`
`
` patients who have or are suspected of having paralytic ileus
`
`
`
`
`
`
` patients who have severe bronchial asthma
`
`
`
`
` patients who have known hypersensitivity to any of its components or the active ingredient, oxycodone
`
`
`
`
`
`
`
`
`
`
`
`
`Serious adverse reactions which may be associated with OxyContin® tablet therapy in clinical use are those
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, circulatory
`
`
`
`
`
`
`
`
`
`
`
`depression, hypotension, or shock. The most common adverse events (>5%) reported by patients at least once
`
`
`
`
`
`
`
`
`
`
`during therapy include constipation, nausea, somnolence, dizziness, pruritus, vomiting, headache, dry mouth,
`
`
`
`asthenia, and sweating.
`
`
`
`Prescribing and Dispensing
`
`
`
`
`
`
`
`
`
`
`
`Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, proper
`
`
`
`
`
`
`
`dispensing, and correct storage, handling and disposal are appropriate measures that help to limit the diversion
`
`
`
`
`
`
`
`and abuse of opioid drugs. Careful record-keeping of prescribing information, including quantity, frequency, and
`
`
`
`
`
`renewal requests is strongly advised.
`
`Prescribing OxyContin® 60 mg or 80 mg Tablets, or a single dose greater than 40 mg, should be reserved only
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`for those patients who have developed tolerance to the sedating and respiratory-depressant effects of opioids. A
`
`
`
`
`
`
`
`
`
`
`
`single dose greater than 40 mg, or total daily doses greater than 80 mg, may cause fatal respiratory depression
`
`
`
`
`
`
`
`
`when administered to patients who are not tolerant to the sedating and respiratory depressant effects of opioids.
`
`
`
`
`
`
`
`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.
`
`
`
`The concomitant use of OxyContin® with all cytochrome P450 3A4 inhibitors such as macrolide antibiotics (eg,
`
`
`
`
`
`
`
`
`
`
`erythromycin), azole-antifungal agents (eg, ketoconazole), and protease inhibitors (eg, 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 OxyContin® and a CYP3A4 inhibitor should be carefully
`
`
`
`
`
`
`
`
`monitored for an extended period of time and dosage adjustments should be made if warranted.
`
`
`
`
`
`
`When the patient no longer requires therapy with OxyContin® Tablets, doses should be tapered gradually to
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`prevent signs and symptoms of withdrawal in the physically dependent patient.
`
`
`
`Safe Use, Storage and Disposal
`
`As described in the boxed warning, OxyContin® Tablets are to be swallowed whole and are not to 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.
`
`Compromising the controlled-release delivery system of OxyContin® will result in the uncontrolled delivery of
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`oxycodone and poses a significant risk that could result in overdose and death.
`
`
`Misuse and Abuse
`
`
`
`
`
`
`
`
`
`
`Abuse may occur by taking intact tablets without legitimate purpose, by crushing and chewing or snorting the
`
`
`
`
`
`
`
`
`
`
`crushed formulation, or by injecting a solution made from the crushed formulation. The risk of fatal overdose is
`
`
`
`
`
`
`Page 14 of 37
`CONFIDENTIAL
`
`
`
`
`
`1 April 2010
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`further increased when oxycodone is abused concurrently with alcohol or other CNS depressants, including other
`
`opioids.
`
`
`
`Patient Counseling
`
`Patients should be counseled about the importance of storing opioid analgesics, including OxyContin®, safely and
`
`
`
`
`
`
`
`
`out of the reach of children, other household members, visitors and pets.
`
`
`
`
`
`
`
`
`
`
`Patients should be instructed against use by individuals other than the patient for whom it was prescribed, as
`
`
`
`
`
`
`
`
`
`
`
`such inappropriate use may have severe medical consequences, including death.
`
`
`
`
`
`You are strongly advised to discuss the risks associated with OxyContin® with your patients and/or their
`
`
`
`
`
`
`
`
`
`caregivers and encourage them to read the Mediation Guide. This Medication Guide contains important
`
`
`
`
`
`
`information on the safe and effective use of OxyContin®. In addition to the OxyContin® Full Prescribing
`
`
`
`
`Information, we have enclosed a copy of the OxyContin® Medication Guide, which should be provided to patients
`
`
`
`
`
`
`every time OxyContin® is dispensed.
`
`
`
`
`We are providing you with a packet which contains important information regarding the prescribing of OxyContin®,
`
`
`
`
`
`which we encourage you to review. In addition, the packet contains educational materials that discuss the risk of
`
`
`
`
`
`
`
`
`
`
`
`abuse, misuse, overdose and addiction from exposure to opioids, how to identify patients who are at risk for
`
`
`
`
`
`
`
`
`
`
`
`addiction, and information to counsel patients on proper safe storage of medications. Please complete the
`
`
`
`
`
`
`OxyContin® Education Confirmation Form and return once you have read the materials. A pre-addressed return
`
`
`
`
`
`
`
`
`envelope is included for your convenience.
`
`
`
`
`
`
`The following items are included in this packet:
`
`
`- OxyContin® Full Prescribing Information
`
`
`
`
`- OxyContin® Medication Guide
`
`
`
`Prescribing OxyContin® Tablets CII: A Training Guide for Healthcare Providers
`
`
`
`
`
`
`
`
`-
`- OxyContin® Education Confirmation Form
`
`
`
`
`
`
`
`
`
`
`Please see the attached Full Prescribing Information, including the boxed warning, and the sections specifically
`addressing overdose with and addiction to OxyContin®.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`For more information or to request additional copies of any of these materials, please contact your Purdue Sales
`
`
`
`
`Representative or visit us online at www.oxycontinrems.com. In addition, healthcare professionals and patients
`
`
`
`
`who have questions about prescribing, dispensing, or taking OxyContin® Tablets should contact the Purdue
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Medical Services department at (888)726-7535, prompt #1.
`
`Please report any adverse event information associated with the use of OxyContin® Tablets to Purdue Pharma
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`L.P., at (888)726-7535 (prompt #2), or to the FDA MedWatch system by phone at (800)FDA-1088, by fax at
`
`
`
`
`(800)FDA-0178, or via the Internet at www.FDA.gov/medwatch.
`
`
`
`Sincerely,
`
`
`
`
`Craig J. Landau, MD
`
`
`
`Chief Medical Officer
`
`
`
`
`
`
`
`Page 15 of 37
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`REMS APPENDIX 3 – HEALTHCARE PROVIDER TRAINING GUIDE
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Purdue
`
`
`OXYCONTIN
`
`
`REMS HCP Training Guide
`
`
`
`
`March 24, 2010
`
`
`
`
`
`Cover
`
`
`
`(HEADLINE)
`
`PRESCRIBING OXYCONTIN® TABLETS CII
`
`
`
`
`
`
`
`
`(Subhead)
`
`
`
`A Training Guide for Healthcare Providers
`
`
`
`
`
`
`(Copy)
`
`
`Please see Important Safety Information on Page 2 and accompanying full Prescribing
`
`
`
`
`Information, including the boxed warning and Medication Guide.
`
`
`
`
`
`
`Page 16 of 37
`
`
`CONFIDENTIAL
`
`
`1 April 2010
`
`
`
`
`

`

`
`
`
`
` Page 2
`
`
`
` (HEADLINE)
`
`
`
`
`(Box
`
`Warning)
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` IMPORTANT SAFETY INFORMATION
`
`
`
`
`
`
`
`
`
`
`
`
`
`WAR