Abuse-Deterrentdosage

OXYCONTIN should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. OXYCONTIN 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of OXYCONTIN for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OXYCONTIN. Consider this risk when selecting an initial dose and when making dose adjustments. OXYCONTIN is administered orally every 12 hours. Instruct patients to swallow tablets intact and not to cut, break, chew, crush, or dissolve tablets (risk of potentially fatal dose). Instruct patients to take tablets one at a time, with enough water to ensure complete swallowing immediately after placing in mouth. Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with OXYCONTIN, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. Periodically reassess patients receiving OXYCONTIN to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. Do not rapidly reduce or abruptly discontinue OXYCONTIN in a physically-dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

Adults: For patients who are not opioid tolerant, initiate with 10 mg tablets orally every 12 hours. See full prescribing information for instructions on conversion from other opioids to OXYCONTIN, titration and maintenance of therapy. Pediatric Patients 11 Years of Age and Older: For use only in pediatric patients 11 years and older already receiving and tolerating opioids for at least 5 consecutive days with a minimum of 20 mg per day of oxycodone or its equivalent for at least two days immediately preceding dosing with OXYCONTIN. See full prescribing information for instructions on conversion from other opioids to OXYCONTIN, titration and maintenance of therapy.

Geriatric Patients: In debilitated, opioid non-tolerant geriatric patients, initiate dosing at one third to one half the recommended starting dosage and titrate carefully.

Patients with Hepatic Impairment: Initiate dosing at one third to one half the recommended starting dosage and titrate carefully.

2.1 Important

Dosage and Administration Instructions OXYCONTIN should be prescribed only by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. OXYCONTIN 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Adult patients who are opioid- tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of OXYCONTIN for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with OXYCONTIN. Consider this risk when selecting an initial dose and when making dose adjustments. OXYCONTIN is administered orally every 12 hours. Instruct patients to swallow OXYCONTIN tablets whole, one tablet at a time, with enough water to ensure complete swallowing immediately after placing in the mouth. Instruct patients not to pre-soak, lick, or otherwise wet the tablet prior to placing in the mouth. Cutting, breaking, crushing, chewing, or dissolving OXYCONTIN tablets will result in uncontrolled delivery of oxycodone and can lead to overdose or death.

2.2 Patient

Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient. Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent.

2.3 Initial

Dosage in Adults It is safer to underestimate a patient's 24-hour oral oxycodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone dosage and manage an adverse reaction due to an overdose. While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioids. Frequently reevaluate patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to OXYCONTIN. Use of OXYCONTIN in Adults who are not Opioid Tolerant The starting dosage for adults who are not opioid tolerant is OXYCONTIN 10 mg orally every 12 hours. Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression. Conversion from Other Oral Oxycodone Formulations to OXYCONTIN If switching from other oral oxycodone formulations to OXYCONTIN, administer one half of the patient's total daily oral oxycodone dose as OXYCONTIN every 12 hours. Conversion from Methadone to OXYCONTIN Regular evaluation is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma. Conversion from Fentanyl Transdermal System to OXYCONTIN Treatment with OXYCONTIN can be initiated after the fentanyl transdermal system has been removed for at least 18 hours. Although there has been no systematic assessment of such conversion, start with a conservative conversion: substitute 10 mg of OXYCONTIN every 12 hours for each 25 mcg per hour fentanyl transdermal system. Follow the patient closely during conversion from fentanyl transdermal system to OXYCONTIN, as there is limited documented experience with this conversion. Conversion from Other Opioid Analgesics to OXYCONTIN When OXYCONTIN therapy is initiated, discontinue all other opioid analgesics other than those used on an as needed basis for breakthrough pain when appropriate. There are no established conversion ratios for conversion from other opioids to OXYCONTIN defined by clinical trials. Initiate dosing using OXYCONTIN 10 mg orally every 12 hours.

2.4 Initial

Dosage in Pediatric Patients 11 Years and Older The following dosing information is for use only in pediatric patients 11 years and older already receiving and tolerating opioids for at least five consecutive days. For the two days immediately preceding dosing with OXYCONTIN, patients must be taking a minimum of 20 mg per day of oxycodone or its equivalent. OXYCONTIN is not appropriate for use in pediatric patients requiring less than a 20 mg total daily dose. Table 1, based on clinical trial experience, displays the conversion factor when switching pediatric patients 11 years and older (under the conditions described above) from opioids to OXYCONTIN. When OXYCONTIN therapy is initiated, discontinue all opioid analgesics other than those used on an as needed basis for breakthrough pain when appropriate. There is substantial inter-patient variability in the relative potency of different opioid drugs and formulations. Therefore, a conservative approach is advised when determining the total daily dosage of OXYCONTIN. It is safer to underestimate a patient's 24-hour oral oxycodone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral oxycodone requirements and manage an adverse reaction due to an overdose. Consider the following when using the information in Table 1. This is not a table of equianalgesic doses. The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to OXYCONTIN. The table cannot be used to convert from OXYCONTIN to another opioid. Doing so will result in an over-estimation of the dose of the new opioid and may result in a fatal overdose. The formula for conversion from prior opioids, including oral oxycodone, to the daily dose of OXYCONTIN is mg per day of prior opioid x factor = mg per day of OXYCONTIN. Divide the calculated total daily dose by 2 to get the every-12-hour OXYCONTIN dose. If rounding is necessary, always round the dose down to the nearest OXYCONTIN tablet strength available.

Table 1: Conversion Factors When Switching Pediatric Patients 11 Years and Older to OXYCONTIN Prior Opioid Conversion Factor Oral Parenteral 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. Oxycodone 1 -- Hydrocodone 0.9 -- Hydromorphone 4 20 Morphine 0.5 3 Tramadol 0.17

0.2 Step #1:

To calculate the estimated total OXYCONTIN daily dosage using Table 1: For pediatric patients taking a single opioid, sum the current total daily dosage of the opioid and then multiply the total daily dosage by the approximate conversion factor to calculate the approximate OXYCONTIN daily dosage. For pediatric patients on a regimen of more than one opioid, calculate the approximate oxycodone dose for each opioid and sum the totals to obtain the approximate OXYCONTIN daily dosage. For pediatric patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion. Step #2: If rounding is necessary, always round the dosage down to the nearest OXYCONTIN tablet strength available and initiate OXYCONTIN therapy with that dose. If the calculated OXYCONTIN total daily dosage is less than 20 mg, there is no safe strength for conversion and do not initiate OXYCONTIN. Example conversion from a single opioid (e.g., hydrocodone) to OXYCONTIN: Using the conversion factor of 0.9 for oral hydrocodone in Table 1, a total daily hydrocodone dosage of 50 mg is converted to 45 mg of oxycodone per day or 22.5 mg of OXYCONTIN every 12 hours. After rounding down to the nearest strength available, the recommended OXYCONTIN starting dosage is 20 mg every 12 hours. Step #3: Close observation and titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-sedation/toxicity after converting patients to OXYCONTIN for important instructions on titration and maintenance of therapy. There is limited experience with conversion from transdermal fentanyl to OXYCONTIN in pediatric patients 11 years and older. If switching from transdermal fentanyl patch to OXYCONTIN, ensure that the patch has been removed for at least 18 hours prior to starting OXYCONTIN. Although there has been no systematic assessment of such conversion, start with a conservative conversion: substitute 10 mg of OXYCONTIN every 12 hours for each 25 mcg per hour fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to OXYCONTIN. If using asymmetric dosing, instruct patients to take the higher dose in the morning and the lower dose in the evening.

2.5 Titration and

Maintenance of Therapy in Adults and Pediatric Patients 11 Years and Older Individually titrate OXYCONTIN to a dosage that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving OXYCONTIN to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for the development of addiction, abuse and misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During use of opioid therapy for an extended period of time, periodically reassess the continued need for the use of opioid analgesics. Patients who experience breakthrough pain may require a dosage adjustment of OXYCONTIN or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the OXYCONTIN dosage. Because steady-state plasma concentrations are approximated in 1 day, OXYCONTIN dosage may be adjusted every 1 to 2 days. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after a dosage increase), consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. There are no well-controlled clinical studies evaluating the safety and efficacy with dosing more frequently than every 12 hours. As a guideline for pediatric patients 11 years and older, the total daily oxycodone dosage usually can be increased by 25% of the current total daily dosage. As a guideline for adults, the total daily oxycodone dosage usually can be increased by 25% to 50% of the current total daily dosage, each time an increase is clinically indicated.

2.6 Dosage Modifications with

Concomitant Use of Central Nervous System Depressants If the patient is currently taking a central nervous system (CNS) depressant and the decision is made to begin OXYCONTIN, start with one-third to one-half the recommended starting dosage of OXYCONTIN, consider using a lower dosage of the concomitant CNS depressant, and regularly evaluate patients for signs of respiratory depression, sedation, and hypotension.

2.7 Dosage Modifications in

Geriatric Patients who are Debilitated and not Opioid-Tolerant For geriatric patients who are debilitated and not opioid-tolerant, start dosing patients at one-third to one-half the recommended starting dosage and titrate the dosage cautiously. Regularly evaluate for signs of respiratory depression, sedation, and hypotension.

2.8 Dosage Modifications in

Patients with Hepatic Impairment For patients with hepatic impairment, start dosing patients at one-third to one-half the recommended starting dosage and titrate the dosage carefully. Regularly evaluate for signs of respiratory depression, sedation, and hypotension.

2.9 Safe Reduction or

Discontinuation of OXYCONTIN Do not rapidly reduce or abruptly discontinue OXYCONTIN in patients who may be physically dependent on opioids. Rapid reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid reduction or abrupt discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking OXYCONTIN, there are a variety of factors that should be considered, including the total daily dose of opioid (including OXYCONTIN) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on OXYCONTIN who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic.