TARGINIQ ER- oxycodone hydrochloride and naloxone hydrochloride tablet, film coated, extended release
Purdue Pharma LP
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Addiction, Abuse, and Misuse
TARGINIQTM ER exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing TARGINIQ ER and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions (5.1)].
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of TARGINIQ ER. Monitor for respiratory depression, especially during initiation of TARGINIQ ER or following a dose increase. Instruct patients to swallow TARGINIQ ER tablets whole; crushing, chewing, or dissolving TARGINIQ ER tablets can cause rapid release and absorption of a potentially fatal dose of oxycodone [see Warnings and Precautions (5.2)].
Accidental ingestion of even one dose of TARGINIQ ER, especially by children, can result in a fatal overdose of oxycodone [see Warnings and Precautions (5.2)].
Neonatal Opioid Withdrawal Syndrome
Prolonged use of TARGINIQ ER during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.3)].
Cytochrome P450 3A4 Interaction
The concomitant use of TARGINIQ ER with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving TARGINIQ ER and any CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.4), Drug Interactions (7), Clinical Pharmacology (12.3)].
Risks From Concomitant Use With Benzodiazepines
Or Other CNS Depressants
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions (5.5), Drug Interactions (7)].
- Reserve concomitant prescribing of TARGINIQ ER Injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
- Limit dosages and durations to
the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation.
1 INDICATIONS AND USAGE
TARGINIQ ER is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
- Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see Warnings and Precautions (5.1)] , reserve TARGINIQ ER for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
- TARGINIQ ER is not indicated as an as-needed (prn) analgesic.
- The maximum total daily dose of TARGINIQ ER should not exceed 80 mg/40 mg (40 mg/20 mg q12h) because higher doses may be associated with symptoms of opioid withdrawal or decreased analgesia [see Warnings and Precautions 5.12].
2 DOSAGE AND ADMINISTRATION
2.1 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.
2.2 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 ERDiscontinue 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:
- 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.
- 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.
| Current Oral Opioid|| Conversion Factor|
| Morphine|| 1|
| Codeine|| 0.3|
| Hydrocodone|| 1.8|
| Hydromorphone|| 8|
| Methadone†|| 3|
| Oxycodone|| 2|
| Oxymorphone|| 4|
| Tramadol*|| –|
| Tapentadol|| 0.3|
| † See note on conversion of methadone to TARGINIQ ER below* patients on tramadol should be initiated on the lowest available TARGINIQ ER dose, 10 mg/5 mg every 12 hours|
| Equivalent Daily Oral Morphine Dose|| Recommended TARGINIQ ER Starting Dose|
| 20 to <70 mg|| 10 mg/5 mg every 12 hours (ie. 20 mg oxycodone daily)|
| 70 to <110 mg|| 20 mg/10 mg every 12 hours (ie. 40 mg oxycodone daily)|
| 110 to <150 mg|| 30 mg/15 mg every 12 hours (ie. 60 mg oxycodone daily)|
| 150 to 160 mg|| 40 mg/20 mg every 12 hours (ie. 80 mg oxycodone daily)|
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 ERFor 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.
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