HIGHLIGHTS OF PRESCRIBING INFORMATION mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an These highlights do not include all the information needed to use equianalgesic dose of another opioid. (2.1) TM TARGINIQ ER safely and effectively. See full prescribing information • Use the lowest effective dosage for the shortest duration consistent with for TARGINIQ ER. individual patient treatment goals. (2.1) • Individualize dosing based on the severity of pain, patient response, prior TARGINIQ ER (oxycodone hydrochloride and naloxone hydrochloride analgesic experience, and risk factors for addiction, abuse, and misuse. extended-release tablets), for oral use, CII (2.1) Initial U.S. Approval: 2014 • Instruct patients to swallow tablets intact and not to cut, break, chew, crush, or dissolve tablets (risk of potentially fatal overdose). (2.1, 5.1) WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE­ • For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg/5 mg THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL tablets orally every 12 hours. (2.1) INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; • Mild Hepatic Impairment: Reduce the starting dose of TARGINIQ ER to CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM 1/3 to 1/2 the usual starting dose in patients with mild hepatic impairment. CONCOMITANT USE WITH BENZODIAZEPINES AND OTHER (8.7) CNS DEPRESSANTS • Renal Impairment: Reduce the initial dose to 1/2 the usual dose when See full prescribing information for complete boxed warning. administering TARGINIQ ER to patients with renal impairment. (8.8) • TARGINIQ ER exposes users to risks of addiction, abuse and misuse, • Do not abruptly discontinue TARGINIQ ER in a physically dependent which can lead to overdose and death. Assess patient’s risk before patient. (2.5) prescribing and monitor regularly for these behaviors and conditions. ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ (5.1) • Extended-release tablets: 10 mg/5 mg, 20 mg/10 mg, and 40 mg/20 mg (3) • Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. -------------------------------CONTRAINDICATIONS-----------------------------­ Instruct patients to swallow TARGINIQ ER tablets whole to avoid • Significant respiratory depression (4) exposure to a potentially fatal dose of oxycodone. (5.2) • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (4) • Accidental ingestion of TARGINIQ ER, especially by children, can • Known or suspected gastrointestinal obstruction, including paralytic ileus result in a fatal overdose of oxycodone. (5.2) (4) • Prolonged use of TARGINIQ ER during pregnancy can result in • Hypersensitivity to oxycodone or naloxone (4) neonatal opioid withdrawal syndrome, which may be life-threatening if • Moderate to severe hepatic impairment (4) not recognized and treated. If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid -----------------------WARNINGS AND PRECAUTIONS-----------------------­ withdrawal syndrome and ensure that appropriate treatment will be • Life-Threatening Respiratory Depression in Patients with Chronic available. (5.3) Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: • Concomitant use with CYP3A4 inhibitors (or discontinuation of Monitor closely, particularly during initiation and titration. (5.6) CYP3A4 inducers) can result in a fatal overdose of oxycodone. (5.4) • Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of • Concomitant use of opioids with benzodiazepines or other central corticosteroids, and wean patient off of the opioid. (5.7) nervous system (CNS) depressants, including alcohol, may result in • Severe Hypotension: Monitor during dose initiation and titration. Avoid profound sedation, respiratory depression, coma, and death. Reserve use in patients with circulatory shock. (5.8) concomitant prescribing for use in patients for whom alternative • Risks of Use in Patients with Increased Intracranial Pressure, Head Injury, treatment options are inadequate; limit dosages and durations to the Brain Tumors, or Impaired Consciousness: Monitor for sedation and minimum required; and follow patients for signs and symptoms of respiratory depression. Avoid use of TARGINIQ ER in patients with respiratory depression and sedation. (5.X, 7) impaired consciousness or coma. (5.9) • Withdrawal: Symptoms consistent with opioid withdrawal occurred in ----------------------------RECENT MAJOR CHANGES-------------------------­ some patients in the clinical trials. Monitor patients for symptoms of Box Warning 12/2016 withdrawal during treatment with TARGINIQ ER. (5.12) Warning and Precautions (5) 12/2016 ------------------------------ADVERSE REACTIONS------------------------------­ Most common adverse reactions (incidence ≥ 5%) were nausea and vomiting. ----------------------------INDICATIONS AND USAGE--------------------------­ (6.1) TARGINIQ ER is a combination product consisting of oxycodone, an opioid agonist, and naloxone, an opioid antagonist, indicated for the management of To report SUSPECTED ADVERSE REACTION, contact Purdue pain severe enough to require daily, around-the-clock, long-term opioid Pharma L.P. at 1-888-726-7535 or FDA at 1-800-FDA-1088 or treatment and for which alternative treatment options are inadequate. (1) www.fda.gov/medwatch. Limitations of Use ------------------------------DRUG INTERACTIONS------------------------------­ • Because of the risks of addiction, abuse, and misuse with opioids, even • CNS Depressants: Concomitant use may cause hypotension, profound at recommended doses, and because of the greater risks of overdose and sedation, respiratory depression, coma, and death. If co-administration is death with extended-release opioid formulations, reserve TARGINIQ required, decision to begin TARGINIQ ER is made, start with 1/3 to ½ the ER for use in patients for whom alternative treatment options (e.g., non- recommended starting dosage, consider a dosage of the concomitant CNS opioid analgesics or immediate-release opioids) are ineffective, not depressant, and monitor closely. (2.3, 5.5, 7) tolerated, or would be otherwise inadequate to provide sufficient • Serotonergic Drugs: Concomitant use may result in serotonin syndrome. management of pain. (1) Discontinue TARGINIQ ER if serotonin syndrome is suspected. (7) • TARGINIQ ER is not indicated as an as-needed (prn) analgesic. (1) • Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid • Total daily dose should not exceed 80 mg/40 mg (40 mg/20 mg q12h) use with TARGINIQ ER because they may reduce analgesic effect of because higher doses may be associated with symptoms of opioid TARGINIQ ER or precipitate withdrawal symptoms. (5.12, 7) withdrawal. (1) • Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects of morphine. Avoid concomitant use in patients receiving MAOIs or within ----------------------DOSAGE AND ADMINISTRATION----------------------­ 14 days of stopping treatment with an MAOI. (7) • To be prescribed only by healthcare providers knowledgeable in use of potent opioids for management of chronic pain. (2.1) -----------------------USE IN SPECIFIC POPULATIONS-----------------------­ • A single dose of TARGINIQ ER greater than 40 mg/20 mg or a total daily • Pregnancy: May cause fetal harm. (8.1) dose greater than 80 mg/40 mg are only for use in patients in whom • Lactation: Not recommended. (8.2) tolerance to an opioid of comparable potency has been established. • Patients considered opioid tolerant are those taking, for one week or longer, See 17 for PATIENT COUNSELING INFORMATION and Medication at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per Guide. hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 Revised: 12/2016 Reference ID: 4028822 FULL PRESCRIBING INFORMATION: CONTENTS* 5.10 Risk of Use in Patients with Gastrointestinal Conditions 5.11 Increased Risk of Seizures in Patients with Seizure Disorders WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE­ 5.12 Withdrawal THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL 5.13 Risks of Driving and Operating Machinery INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; 5.14 Laboratory Monitoring CYTOCHROME P450 3A4 INTERACTION; and RISKS FORM 6 ADVERSE REACTIONS CONCOMITANT USE WITH BENZODIAZEPINES AND OTHER 6.1 Clinical Trial Experience CNS DEPRESSANTS 6.2 Postmarketing Experience 7 DRUG INTERACTIONS 1 INDICATIONS AND USAGE 8 USE IN SPECIFIC POPULATIONS 2 DOSAGE AND ADMINISTRATION 8.1 Pregnancy 2.1 Important Dosage and Administration Instructions 8.2 Lactation 2.2 Initial Dosage 8.3 Females and Males of Reproductive Potential 2.3 Titration and Maintenance of Therapy 8.4 Pediatric Use 2.4 Dosage Modifications with Concomitant Use of Central Nervous 8.5 Geriatric Use System Depressants 8.6 Hepatic Impairment 2.5 Dosage Modifications in Patients with Mild Hepatic Impairment 8.7 Renal Impairment 2.6 Dosage Modifications in Patients with Renal Impairment 9 DRUG ABUSE AND DEPENDENCE 2.7 Discontinuation of TARGINIQ ER 9.1 Controlled Substance 3 DOSAGE FORMS AND STRENGTHS 9.2 Abuse 4 CONTRAINDICATIONS 9.3 Dependence 5 WARNINGS AND PRECAUTIONS 10 OVERDOSAGE 5.1 Addiction, Abuse, and Misuse 11 DESCRIPTION 5.2 Life-Threatening Respiratory Depression 12 CLINICAL PHARMACOLOGY 5.3 Neonatal Opioid Withdrawal Syndrome 12.1 Mechanism of Action 5.4 Risks of Concomitant Use or Discontinuation of Cytochrome