Important Dosing and Administration Instructions

​TARGINIQ ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

​A single dose of TARGINIQ ER greater than 40 mg/20 mg or a total daily dose greater than 80 mg/40 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 (5.1)].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 with TARGINIQ ER and following dosage increases with TARGINIQ and adjust the dosage accordingly [see Warnings and Precautions (5.2)].

​Instruct patients to swallow TARGINIQ ER tablets whole [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving TARGINIQ ER tablets will result in uncontrolled delivery of oxycodone and can lead to overdose or death [see Warnings and Precautions (5.1)].

​TARGINIQ ER is administered orally every 12 hours.

Initial Dosage

​Use of TARGINIQ ER as the First Opioid Analgesic (opioid-naïve patients)
Initiate treatment with TARGINIQ ER with one 10 mg/5 mg tablet orally every 12 hours.

​Use of TARGINIQ ER in Patients who are not Opioid Tolerant (opioid non-tolerant patients)
The starting dosage for patients who are not opioid tolerant is TARGINIQ ER 10 mg/5 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 TARGINIQ ER
Patients receiving other oral oxycodone formulations may be converted to TARGINIQ ER by administering one-half of the patient's total daily oral oxycodone dose as TARGINIQ ER every 12 hours.

​Conversion from Other Opioids to TARGINIQ ER
Discontinue all other around-the-clock opioid drugs when TARGINIQ ER therapy is initiated.

​There is inter-patient variability in the relative potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of TARGINIQ ER. 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.

​In a TARGINIQ ER clinical trial with an open-label titration period, patients were converted from their prior opioid to TARGINIQ ER using both Table 1 and Table 2 below.

​Consider the following when using the information in Table 1 and Table 2:

• ​These are not tables of equianalgesic doses. The conversion factors in Table 1 are only for the conversion from one of the listed oral opioid analgesics to the Equivalent Daily Oral Morphine Dose.
• ​The conversion factors in Table 2 are only for conversion from the calculated Equivalent Daily Oral Morphine Dose to TARGINIQ ER.
• ​The tables cannot be used to convert from TARGINIQ ER to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in a fatal overdose.

​Convert patients from their previous opioid to TARGINIQ ER as follows:

1. ​Using Table 1, calculate the Equivalent Daily Oral Morphine Dose by multiplying the current total daily dose of each opioid by the appropriate Conversion Factor.
2. ​Using Table 2, determine the starting dose of TARGINIQ ER by reading across from the appropriate Equivalent Daily Dose of Oral Morphine range, rounding down, if necessary.

​Example conversion from a single opioid to TARGINIQ ER:

​Step 1: A patient receiving oxymorphone at a total daily dose of 10 mg would equate to an Equivalent Daily Oral Morphine Dose of 40 mg (10 mg x 4; Table 1).

​Step 2: Based on Table 2, the starting dose is TARGINIQ ER 10 mg/5 mg every 12 hours.

• ​For patients on a regimen of more than one opioid, use Table 1 to calculate the Equivalent Daily Oral Morphine dose for each opioid and sum the totals, then use Table 2 to obtain the starting dose of TARGINIQ ER.
• ​Round down, if necessary, to the appropriate TARGINIQ ER tablet strengths available.
• ​Monitor patients for signs and symptoms of opioid withdrawal or for signs of over-sedation/toxicity after converting patients to TARGINIQ ER.
• ​Titrate appropriately to a stable and tolerated dose.

​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 TARGINIQ ER.

​Conversion from Methadone to TARGINIQ 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.

​Conversion from Transdermal Fentanyl to TARGINIQ ER
Treatment with, TARGINIQ 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/5 mg of TARGINIQ ER every 12 hours for each 25 mcg/hr fentanyl transdermal patch. Follow the patient closely during conversion from transdermal fentanyl to TARGINIQ ER, as there is limited documented experience with this conversion.

​Conversion from Transdermal Buprenorphine to TARGINIQ ER
For patients receiving transdermal buprenorphine (<20 mcg/hr), the recommended starting dose is TARGINIQ ER 10 mg/5 mg every 12 hours. Follow the patient closely during conversion from transdermal buprenorphine to TARGINIQ ER, as there is limited experience with this conversion.

Titration and Maintenance of Therapy

​Individually titrate TARGINIQ ER to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving TARGINIQ 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, and 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 the use of opioid analgesics.

​Patients who experience breakthrough pain may require a dosage adjustment of TARGINIQ 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 TARGINIQ ER dose.

​As a guideline, the dose of TARGINIQ ER can be up-titrated from the current dose by increasing the dose 10 mg/5 mg q12h every 1 to 2 days as needed based on efficacy, safety, and tolerability. The total daily dose of TARGINIQ ER should not exceed 80 mg/40 mg (40 mg/20 mg q12h).

​The highest total daily dose of TARGINIQ ER studied in the main clinical program is 80 mg/40 mg (40 mg/20 mg twice daily). Total daily doses above 80 mg/40 mg have not been studied sufficiently to ensure patient safety and may be associated with symptoms of opioid withdrawal or decreased analgesia.

​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.

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 TARGINIQ ER, start with one-third to one-half the recommended starting dosage of TARGINIQ ER, consider using a lower dosage of the concomitant CNS depressant, and monitor patients for signs of respiratory depression, sedation, and hypotension [see Warnings and Precautions (5.4), Drug Interactions (7)].

Dosage Modifications in Patients with Mild Hepatic Impairment

​TARGINIQ ER is contraindicated in patients with moderate and severe hepatic impairment. When administering TARGINIQ ER to patients with mild hepatic impairment, reduce the dose to one-third to one-half the usual starting dose followed by careful dose titration. Monitor for signs of respiratory depression, sedation, and hypotension [see Use in Specific Populations (8.7), Clinical Pharmacology (12.3)].

Dosage Modifications in Patients with Renal Impairment

​When administering TARGINIQ ER to patients with renal impairment, reduce the initial dose to one-half the usual starting dose followed by careful dose titration. Monitor for signs of respiratory depression, sedation, and hypotension [see Use in Specific Populations (8.8), Clinical Pharmacology (12.3)].

Discontinuation of TARGINIQ ER

​When the patient no longer requires therapy with TARGINIQ 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 TARGINIQ ER [see Warnings and Precautions (5.12), Drug Abuse and Dependence (9.3)].

​Table 3 presents a suggested taper schedule that was used in a clinical trial to discontinue patients from TARGINIQ ER: