Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.70.44 Subject: Oxycodone Naloxone Page: 1 of 9 Last Review Date: December 2, 2016 Oxycodone Naloxone Description Targiniq ER (oxycodone/naloxone extended-release), Troxyca ER (oxycodone /naltrexone extended-release) Background Targiniq ER (oxycodone/naloxone) and Troxyca ER (oxycodone/naltrexone) are combination opioid agonist/opioid antagonist products designed to deliver analgesia over 12 hours. Oxycodone is a Schedule II opioid agonist used to treat pain, while naloxone and naltrexone are opioid antagonists used to treat opioid overdose. Oxycodone exposes users to the risks of addiction, abuse, and misuse. Abuse or misuse of these medications by cutting, breaking, chewing, crushing, or dissolving and then swallowing, snorting or injecting will result in the uncontrolled delivery of the oxycodone and can result in overdose and death. Misuse or abuse by these methods may also release sufficient naloxone or naltrexone to precipitate withdrawal in opioid-dependent individuals. Targiniq ER and Troxyca ER should be individually dosed for each patient based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse (1-2). Regulatory Status FDA-approved indication: Targiniq ER and Troxyca ER are combination opioid agonist/opioid antagonist products 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 (1-2).
Subject: Oxycodone Naloxone Page: 2 of 9 Limitations of Use: Targiniq ER and Troxyca ER carry several boxed warnings regarding addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; and cytochrome P450 3A4 interactions (1-2): Each patient treated with opioids should be assessed for their risk of addiction, abuse, and misuse prior to prescribing Targiniq ER or Troxyca ER. All patients should be monitored regularly for the development of these behaviors or conditions. Prescribers should monitor for respiratory depression, especially during initiation or following a dose increase. Accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to an overdose of oxycodone. Prolonged use of opioid agonists during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening. Monitor patients receiving a concomitant CYP3A4 inhibitor or inducer, as this may result in varying oxycodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. Targiniq ER and Troxyca ER are contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, or known or suspected paralytic ileus and gastrointestinal obstruction. Targiniq ER is contraindicated in moderate to severe hepatic impairment (1-2). CDC guidelines find that concurrent use of benzodiazepines and opioids might put patients at greater risk for potentially fatal overdose. Three studies of fatal overdose deaths found evidence of concurrent benzodiazepine use in 31% 61% of decedents (3). CDC guidelines finds that given uncertain benefits and substantial risks that opioids should not be considered first-line or routine therapy for chronic pain (i.e., pain continuing or expected to continue longer than 3 months or past the time of normal tissue healing) outside of active cancer, palliative, and end-of-life care (3). FDA warns that opioids can interact with antidepressants and migraine medicines to cause a serious central nervous system reaction called serotonin syndrome, in which high levels of the chemical serotonin build up in the brain and cause toxicity (see Appendix 1 for list of drugs) (4) Safety and effectiveness of Targiniq ER and Troxyca ER in patients less than 18 years of age have not been established (1-2).
Subject: Oxycodone Naloxone Page: 3 of 9 Related policies Abstral, Actiq, Duragesic, Embeda, Fentanyl Powder, Fentora, Hysingla ER, Lazanda, Morphine drug class, Nucynta, Onsolis, Oxycodone, Subsys, Tramadol, Xartemis ER, Zohydro ER Policy This policy statement applies to clinical review performed for pre-service (Prior Approval, Precertification, Advanced Benefit Determination, etc.) and/or post-service claims. Targiniq ER and Troxyca ER may be considered medically necessary in patients that are 18 years of age and older with pain severe enough to require daily, around-the-clock, long-term opioid; no dual therapy with other extended release opioid analgesic(s); alternative therapies are ineffective, not tolerated or provided inadequate pain control, these include non-opioid analgesic and immediate release opioids; prescriber is knowledgeable in the use of potent opioids for the management of chronic pain; prescriber agrees to assess the benefits of pain control (i.e. Care Plan signs of abuse, severity of pain) after 3 months of therapy; prescriber agrees to assess patient for serotonin syndrome; no dual therapy with opioid addiction treatment; no dual therapy with an anti-anxiety benzodiazepine(s): alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), oxazepam (Serax), chlordiazepoxide (Librium), clorazepate dipotassium (Tranxene); opioid naïve patient or opioid non-tolerant patient: Targiniq ER: initiation therapy must start at 10 mg/5 mg twice daily for no less than 7 days before changing to a higher dose or Troxyca ER: initiation therapy must start at 10 mg/1.2 mg twice daily for no less than 7 days before changing to a higher dose; opioid tolerant patient patients are considered opioid tolerant if they have been receiving at least one of the listed opioids, for one week or longer. Targiniq ER and Troxyca ER are considered investigational in patients less than 18 years of age and for all other indications. Prior-Approval Requirements Prior authorization is not required if prescribed by an oncologist. Age 18 years of age or older Diagnosis Patient must have the following:
Subject: Oxycodone Naloxone Page: 4 of 9 Pain severe enough to require daily, around-the clock, long-term opioid treatment AND ALL of the following: a. NO dual therapy with other extended release opioid analgesic(s) b. Alternative treatment options have been ineffective, not tolerated or inadequate for controlling the pain a. These include non-opioid analgesic and immediate release opioids c. The prescriber is knowledgeable in the use of potent opioids for the management of chronic pain d. Prescriber agrees to assess the benefits of pain control (i.e. Care Plan signs of abuse, severity of pain) after 3 months of therapy e. Prescriber agrees to assess patient for serotonin syndrome f. NO dual therapy with opioid addiction treatment g. NO dual therapy with an anti-anxiety benzodiazepine(s) i. Alprazolam (Xanax) ii. Clonazepam (Klonopin) iii. Diazepam (Valium) iv. Lorazepam (Ativan) v. Oxazepam (Serax) vi. Chlordiazepoxide (Librium) vii. Clorazepate dipotassium (Tranxene AND ONE of the following: 1. Opioid naïve patient or opioid non-tolerant patient with ONE of the following: a. Targiniq ER: initiation therapy MUST start at 10 mg/5 mg twice daily for no less than 7 days before changing to a higher dose b. Troxyca ER: initiation therapy MUST start at 10 mg/1.2 mg twice daily for no less than 7 days before changing to a higher dose 2. Opioid tolerant patient patients are considered opioid tolerant if they have been receiving, for one week or longer, at least ONE of the following: a. 60 mg oral morphine per day b. 25 mcg transdermal fentanyl per hour c. 30 mg oral oxycodone per day d. 8 mg oral hydromorphone per day e. 25 mg oral oxymorphone per day f. 60 mg oral hydrocodone per day
Subject: Oxycodone Naloxone Page: 5 of 9 g. Or an equianalgesic dose of another opioid Prior Approval Renewal Requirements Age 18 years of age or older Diagnosis Patient must have the following: Pain severe enough to require daily, around-the clock, long-term opioid treatment AND the following: 1. NO dual therapy with other extended release opioid analgesic(s) 2. Prescriber agrees to assess the benefits of pain control (i.e. Care Plan signs of abuse, severity of pain) 3. Prescriber agrees to assess patient for serotonin syndrome 4. NO dual therapy with opioid addiction treatment 5. NO dual therapy with an anti-anxiety benzodiazepine(s) a. Alprazolam (Xanax) b. Clonazepam (Klonopin) c. Diazepam (Valium) d. Lorazepam (Ativan) e. Oxazepam (Serax) f. Chlordiazepoxide (Librium) g. Clorazepate dipotassium (Tranxene) Policy Guidelines Pre - PA Allowance None Prior - Approval Limits Opioid-Naïve / Opioid Non-Tolerant Quantity Targiniq ER 10 mg/5 mg 180 tablets per 90 days OR Troxyca ER 10 mg/1.2 mg 180 capsules per 90 days
Subject: Oxycodone Naloxone Page: 6 of 9 Duration 6 months Opioid Tolerant Quantity OR Targiniq ER 10 mg/5 mg 180 tablets per 90 days OR Targiniq ER 20 mg/10 mg 180 tablets per 90 days OR Targiniq ER 40 mg/20 mg 180 tablets per 90 days Combination of strengths not to exceed 80 mg/40 mg per day Troxyca ER 10 mg/1.2 mg 180 capsules per 90 days OR Troxyca ER 20 mg/2.4 mg 180 capsules per 90 days OR Troxyca ER 30 mg/3.6 mg 180 capsules per 90 days OR Troxyca ER 40 mg/4.8 mg 180 capsules per 90 days OR Troxyca ER 60 mg/7.2 mg 180 capsules per 90 days OR Troxyca ER 80 mg/9.6 mg 180 capsules per 90 days Combination of strengths not to exceed 160 mg/19.2 mg per day Duration 6 months Prior Approval Renewal Limits Quantity OR Targiniq ER 10 mg/5 mg 180 tablets per 90 days OR Targiniq ER 20 mg/10 mg 180 tablets per 90 days OR Targiniq ER 40 mg/20 mg 180 tablets per 90 days Combination of strengths not to exceed 80 mg/40 mg per day Troxyca ER 10 mg/1.2 mg 180 capsules per 90 days OR Troxyca ER 20 mg/2.4 mg 180 capsules per 90 days OR Troxyca ER 30 mg/3.6 mg 180 capsules per 90 days OR Troxyca ER 40 mg/4.8 mg 180 capsules per 90 days OR Troxyca ER 60 mg/7.2 mg 180 capsules per 90 days OR Troxyca ER 80 mg/9.6 mg 180 capsules per 90 days Combination of strengths not to exceed 160 mg/19.2 mg per day
Subject: Oxycodone Naloxone Page: 7 of 9 Duration 6 months Rationale Summary Targiniq ER (oxycodone/naloxone) and Troxyca ER (oxycodone/naltrexone) are combination opioid agonist/antagonist products 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. Targiniq ER and Troxyca ER carry several boxed warnings regarding addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; and cytochrome P450 3A4 interactions. Safety and effectiveness of these medications in pediatric patients less than 18 years of age have not been established (1-2). Prior approval is required to ensure the safe, clinically appropriate and cost effective use of Targiniq ER and Troxyca ER while maintaining optimal therapeutic outcomes. References 1. Targiniq ER [package insert]. Purdue Pharma L.P. Stamford, CT. July 2014. 2. Troxyca ER [package insert]. Pfizer, Inc. New York, NY. August 2016. 3. Dowell D, Haegerich T, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain. CDC Guidelines 2016 4. FDA Safety Release. FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. March 22, 2016. Policy History Date October 2016 December 2016 Keywords Action Addition to PA Annual editorial review and reference update This policy was approved by the FEP Pharmacy and Medical Policy Committee on December 2, 2016 and is effective on January 1, 2017. Deborah M. Smith, MD, MPH
Subject: Oxycodone Naloxone Page: 8 of 9 Appendix 1 - List of Serotonergic Medications Selective Serotonin Reuptake Inhibitors (SSRIs) paroxetine Paxil, Paxil CR, Pexeva, Brisdelle fluvoxamine Luvox, Luvox CR fluoxetine Prozac, Prozac Weekly, Sarafem, Selfemra, Symbyax sertraline Zoloft citalopram Celexa escitalopram Lexapro Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) venlafaxine Effexor XR desvenlafaxine Pristiq, Khedezla duloxetine Cymbalta milnacipran Savella Tricyclic Antidepressants (TCAs) amitriptyline No brand name currently marketed desipramine Norpramin clomipramine Anafranil imipramine Tofranil, Tofranil PM nortriptyline Pamelor, Aventyl protriptyline Vivactil doxepin Zonalon, Silenor trimipramine Surmontil Monoamine Oxidase Inhibitors (MAOIs) isocarboxazid Marplan phenelzine Nardil selegiline Emsam, Eldepryl, Zelapar tranylcypromine Parnate
Subject: Oxycodone Naloxone Page: 9 of 9 Other Psychiatric Medicines amoxapine No brand name currently marketed maprotiline No brand name currently marketed nefazodone No brand name currently marketed trazodone Oleptro buspirone No brand name currently marketed vilazodone Viibryd mirtazapine Remeron, Remeron Soltab llthium Lithobid Migraine Medicines almotriptan Axert frovatriptan Frova naratriptan Amerge rizatriptan Maxalt, Maxalt-MLT sumatriptan Imitrex, Imitrex Statdose, Alsuma, Sumavel Dosepro, Zecuity, Treximet zolmitriptan Zomig, Zomig-ZMT Antiemetics ondansetron granisetron dolasetron palonosetron Zofran, Zofran ODT, Zuplenz Kytril, Sancuso Anzemet Aloxi Other Serotonergic Medicines dextromethorphan linezolid cyclobenzaprine methylene blue St. John s wort tryptophan Bromfed-DM, Delsym, Mucinex DM, Nuedexta Zyvox Amrix