2 DOSAGE AND ADMINISTRATION To be prescribed only by healthcare providers knowledgeable in use of potent opioids for management of chronic pain. (2.1) TROXYCA ER 60 mg/7.2 mg and 80 mg/9.6 mg capsules, single doses of TROXYCA ER greater than 40 mg/4.8 mg, or a total daily dose greater than 80 mg/9.6 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. (2.1) 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. (2.1) Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals. (2.1) Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. (2.1) Instruct patients to swallow TROXYCA ER capsules intact, or to sprinkle the capsule contents on applesauce and immediately swallow without chewing. (2.1, 2.5) Instruct patients not to crush, chew, or dissolve the pellets in the capsule to avoid the risk of release and absorption of a potentially fatal dose of oxycodone and to avoid release of sequestered naltrexone that could precipitate opioid withdrawal. (2.1, 2.5, 5.1) For opioid-naïve and opioid non-tolerant patients, initiate with the 10 mg/1.2 mg capsule every 12 hours. (2.1, 2.2) Do not abruptly discontinue TROXYCA ER. (2.4, 5.12) 2.1 Important Dosage and Administration Instructions TROXYCA ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. TROXYCA ER 60 mg/7.2 mg and 80 mg/9.6 mg capsules, single doses of TROXYCA ER greater than 40 mg/4.8 mg, or a total daily dose greater than 80 mg/9.6 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. 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 consistent with individual patient treatment goals [see Warnings and Precautions (5)]. Initiate the dosing regimen for each patient individually; taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24–72 hours of initiating therapy and following dosage increases with TROXYCA ER and adjust the dosage accordingly [see Warnings and Precautions (5.2)]. Instruct patients to swallow TROXYCA ER capsules whole [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving the pellets in TROXYCA ER capsules will result in uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and Precautions (5.1)]. Instruct patients who are unable to swallow TROXYCA ER capsules to sprinkle the capsule contents on applesauce and immediately swallow without chewing [see Dosage and Administration (2.5)]. Administer TROXYCA ER orally every 12 hours. 2.2 Initial Dosing Use of TROXYCA ER as the First Opioid Analgesic (opioid-naïve patients) Initiate treatment with TROXYCA ER with 10 mg/1.2 mg capsule orally every 12 hours. Use of TROXYCA ER in Patients who are not Opioid-Tolerant (opioid-non-tolerant patients) The starting dose for patients who are not opioid-tolerant is TROXYCA ER 10 mg/1.2 mg capsule orally, every 12 hours. Use of higher starting doses in patients who are not opioid-tolerant may cause fatal respiratory depression [see Warnings and Precautions (5.2)]. Conversion from Other Oral Oxycodone HCl Formulations to TROXYCA ER Patients receiving other oral oxycodone HCl formulations may be converted to TROXYCA ER by administering one half of the patient's total daily oral oxycodone HCl dose as TROXYCA ER every 12 hours. Conversion from Other Opioids to TROXYCA ER Discontinue all other around-the-clock opioid drugs when TROXYCA ER therapy is initiated. There is inter-patient variability in the relative potency of opioid drugs and formulations. Therefore, a conservative approach is advised when determining the total daily dosage of TROXYCA ER. It is safer to underestimate a patient's 24-hour TROXYCA ER dosage and provide rescue medication (e.g., immediate-release oxycodone) than to overestimate the 24-hour oxycodone dosage and manage an adverse reaction due to overdose. In a TROXYCA ER clinical trial with an open-label titration period, patients were converted from their prior opioid to TROXYCA ER using Table 1. 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 TROXYCA ER. The table cannot be used to convert from TROXYCA ER to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose. To calculate the estimated TROXYCA ER dose using Table 1: Calculate the approximate total daily oral oxycodone dose For patients on a single opioid, multiply the current total daily dose of the opioid by the appropriate conversion factor listed in Table 1. For patients on a regimen of more than one opioid, use Table 1 to calculate the total daily oral oxycodone dose for each opioid and sum the totals. For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products for calculating the approximate total daily oral oxycodone dose. Reduce the estimated total daily oxycodone dose by 50% to obtain the daily dose of TROXYCA ER. Divide the daily dose in half to obtain the every 12-hour dose of TROXYCA ER. After conversion, if the total daily opioid requirement is ≤20 mg per day of oral oxycodone, initiate therapy with TROXYCA ER 10 mg/1.2 mg every 12 hours (i.e., TROXYCA ER 20 mg per day). Always round the dose down, if necessary, to the appropriate TROXYCA ER strength(s) available. Provide rescue medication as needed (e.g., immediate-release oxycodone). Table 1. Conversion Factors to TROXYCA ERUse this formula to calculate total daily dose of TROXYCA ER: mg/day prior opioid × conversion factor = mg/day TROXYCA ER Prior Oral Opioid Approximate Oral Conversion Factor Codeine (including combination drugs) 0.1 Hydrocodone (including combination drugs) 0.67 Hydromorphone 2.67 Methadone See note on conversion below Morphine 0.67 Oxycodone (including combination drugs) 1 Tramadol See note on conversion below Transdermal fentanyl See note on conversion below Example conversion from a single opioid to TROXYCA ER: Step 1: Sum the total daily dose of the prior opioid. For example, extended-release hydrocodone 30 mg twice daily = 60 mg total daily dose of hydrocodone. Step 2: Calculate the equivalent dose of oral oxycodone based on the total daily dose of the current opioid using Table 1. In this example, 60 mg total daily dose of hydrocodone × 0.67 (conversion factor) = 40.2 mg of oral oxycodone daily. Step 3: Reduce the dose by 50% and divide in half to obtain the every 12-hour dose of TROXYCA ER. In this example, the total daily dose would be 20 mg, and the final dosing regimen would be TROXYCA ER 10 mg/1.2 mg every 12 hours. Close observation and frequent titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to TROXYCA ER. Conversion from Transdermal Fentanyl to TROXYCA ER Treatment with TROXYCA ER can be initiated after the transdermal fentanyl patch 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/1.2 mg of TROXYCA ER every 12 hours for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to TROXYCA ER, as there is limited documented experience with this conversion. Conversion from Transdermal Buprenorphine to TROXYCA ER There has been no systematic assessment of this conversion. The recommended starting dose of TROXYCA ER in patients receiving transdermal buprenorphine is 10 mg/1.2 mg every 12 hours. Conversion from Tramadol to TROXYCA ER Tramadol has both serotonergic and opioid activity, and there has been no systematic assessment of this conversion. The recommended starting dose of TROXYCA ER in patients receiving tramadol is 10 mg/1.2 mg every 12 hours. Conversion from Methadone to TROXYCA ER Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma. 2.3 Titration and Maintenance of Therapy Individually titrate TROXYCA ER to a dosage that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving TROXYCA ER to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics. Patients who experience breakthrough pain may require a dosage increase of TROXYCA ER, 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 TROXYCA ER dosage. Because steady-state plasma concentrations are achieved within 48 hours, the total daily dose of TROXYCA ER may be adjusted by 20 mg/2.4 mg every 2 to 3 days as needed based on efficacy, safety, and tolerability. If unacceptable opioid-related adverse reactions are observed, 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. 2.4 Discontinuation of TROXYCA ER When a patient no longer requires therapy with TROXYCA ER, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue TROXYCA ER [see Warnings and Precautions (5.12), Drug Abuse and Dependence (9.3)]. 2.5 Administration of TROXYCA ER Instruct patients to swallow TROXYCA ER capsules intact. The capsules contain pellets that consist of oxycodone HCl and sequestered naltrexone HCl. The pellets in the capsules are not to be manipulated, i.e., 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)]. Consuming TROXYCA ER capsules that have been altered by crushing, dissolving, or chewing the pellets can release sufficient naltrexone to precipitate withdrawal in opioid-dependent individuals [see Warnings and Precautions (5.12)]. Alternatively, the contents of the TROXYCA ER capsules (pellets) may be sprinkled over applesauce and then swallowed. This method is appropriate only for patients able to reliably swallow the applesauce without chewing. Other foods have not been tested and should not be substituted for applesauce. Instruct the patient to: Open the capsule. Sprinkle the pellets onto a small amount of applesauce and swallow immediately without chewing. Rinse the mouth to ensure all pellets have been swallowed. Discard the empty capsule shell after the contents have been sprinkled on applesauce. Do not administer TROXYCA ER pellets through a nasogastric or gastric tube.