TARGINIQ ER (Page 3 of 11)

3 DOSAGE FORMS AND STRENGTHS

Extended-release tablets: 10 mg/5 mg, 20 mg/10 mg, and 40 mg/20.

• 10 mg/5 mg film-coated extended-release tablets (capsule shaped, white film-coated tablets debossed with “ONX” on one side and “10” on the other)
• 20 mg/10 mg film-coated extended-release tablets (capsule shaped, pink film-coated tablets debossed with “ONX” on one side and “20” on the other)
• 40 mg/20 mg film-coated extended-release tablets (capsule shaped, yellow film-coated tablets debossed with “ONX” on one side and “40” on the other)

4 CONTRAINDICATIONS

​ TARGINIQ ER is contraindicated in patients with:

• ​ Significant respiratory depression [see Warnings and Precautions (5.2)]
• ​ Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.6)]
• ​ Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.10)]
• ​ Hypersensitivity (e.g., anaphylaxis) to oxycodone or naloxone [see Adverse Reactions (6.2)]
• ​ Moderate to severe hepatic impairment [see Clinical Pharmacology (12.2)]

5 WARNINGS AND PRECAUTIONS

5.1 Addiction, Abuse, and Misuse

​ TARGINIQ ER contains oxycodone, a Schedule II controlled substance. As an opioid, TARGINIQ ER exposes users to the risks of addiction, abuse, and misuse. Because extended-release products such as TARGINIQ ER deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxycodone present [see Drug Abuse and Dependence (9)].

​ Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed TARGINIQ ER. Addiction can occur at recommended doses and if the drug is misused or abused.

​ Assess each patient’s risk for opioid addiction, abuse or misuse, prior to prescribing TARGINIQ ER, and monitor all patients receiving TARGINIQ ER for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as TARGINIQ ER, but use in such patients necessitates intensive counseling about the risks and proper use of TARGINIQ ER along with intensive monitoring for signs of addiction, abuse, and misuse.

​ Abuse or misuse of TARGINIQ ER by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of oxycodone and can result in overdose and death [see Overdosage (10)].

​ Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing TARGINIQ ER. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

5.2 Life-Threatening Respiratory Depression

​ Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)]. Carbon dioxide (CO₂ ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

​ While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of TARGINIQ ER, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases of TARGINIQ ER.

​ To reduce the risk of respiratory depression, proper dosing and titration of TARGINIQ ER are essential [see Dosage and Administration (2)]. Overestimating the TARGINIQ ER dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

​ Accidental ingestion of even one dose of TARGINIQ ER, especially by children, can result in respiratory depression and death due to an overdose of oxycodone.

5.3 Neonatal Opioid Withdrawal Syndrome

​ Prolonged use of TARGINIQ ER during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1), Patient Counseling Information (17)].

5.4 Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers

​ Concomitant use of TARGINIQ ER with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions (5.2)] , particularly when an inhibitor is added after a stable dose of TARGINIQ ER is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in TARGINIQ ER-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions. When using TARGINIQ ER with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in TARGINIQ ER-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of TARGINIQ ER until stable drug effects are achieved [see Drug Interactions (7)].

​ Concomitant use of TARGINIQ ER with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using TARGINIQ ER with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see Drug Interactions (7)].