Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.70.39 Subject: Embeda Page: 1 of 8 Last Review Date: September 15, 2017 Embeda Description Embeda (morphine sulfate and naltrexone hydrochloride) Background Embeda is an extended-release capsule consisting of morphine sulfate and naltrexone hydrochloride. Embeda is indicated for the management of moderate to severe pain when a continuous around-the-clock long term opioid analgesic is needed and for which alternative treatment options are inadequate. It is not approved for as-needed pain relief. Embeda capsules contain pellets of morphine sulfate, an opioid receptor agonist with a sequestered core of naltrexone hydrochloride, an opioid receptor antagonist (1). Regulatory Status FDA-approved indication: Embeda is indicated for the management of moderate to severe pain that requires daily, around the clock, long-term opioid treatment and for which alternative treatment options are inadequate (1). Limitations of use: 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, reserve Embeda 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. Embeda is not indicated as an as-needed (prn) analgesic (1).
Subject: Embeda Page: 2 of 8 Embeda carries several boxed warnings regarding addiction, abuse, and misuse; lifethreatening respiratory depression; accidental exposure; neonatal opioid withdrawal syndrome; and interaction with alcohol (1). Embeda is contraindicated in patients who have significant respiratory depression, acute or severe bronchial asthma, and in patients who have or are suspected of having paralytic ileus and gastrointestinal obstruction (1). Care should be taken to use low initial doses of Embeda in patients who are not already opioidtolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS active medications. Embeda 100 mg/4mg capsules are for use in opioid tolerant patients only (1). 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 (2) 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 (2). 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) (3). The safety and effectiveness of Embeda in pediatric patients below the age of 18 years have not been established (1). Related policies Belbuca, Butrans, Duragesic, Hysingla ER, Methadone, Meperidine, Morphine Drug Class, Nucynta, Oxycodone, 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.
Subject: Embeda Page: 3 of 8 Embeda may be considered medically necessary in patients that are 18 years of age and older with moderate to severe pain when a continuous, around the-clock opioid analgesic is needed for an extended period of time and if the conditions below are met. Embeda is considered investigational in patients below 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: Moderate to severe pain when a continuous, around the-clock long acting opioid analgesic is needed AND ALL of the following: a. NO dual therapy with other long acting opioid analgesic(s) b. Alternative treatment options have been ineffective, not tolerated or inadequate for controlling the pain i. These include non-opioid analgesic and immediate release opioids c. Prescriber agrees to assess the benefits of pain control (i.e. Care Plan signs of abuse, severity of pain) after 3 months of therapy d. Prescriber agrees to assess patient for serotonin syndrome e. NO dual therapy with opioid addiction treatment or methadone f. 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)
Subject: Embeda Page: 4 of 8 AND ONE of the following: 1. Opioid naïve patient and opioid non-tolerant patient initiation therapy MUST start at 20/0.8 mg once or twice daily AND for no less than 7 days before changing to a higher dose. OR 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. Or an equianalgesic dose of another opioid Prior Approval Renewal Requirements Age 18 years of age or older Diagnosis Patient must have the following: 1. Pain moderate to severe enough to require continuous around-the clock long acting opioid treatment AND ALL of the following: a. NO dual therapy with other long acting opioid analgesic(s) b. Prescriber agrees to assess the benefits of pain control (i.e. Care Plan signs of abuse, severity of pain) after 3 months of therapy c. Prescriber agrees to assess patient for serotonin syndrome d. NO dual therapy with opioid addiction treatment or methadone e. 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)
Subject: Embeda Page: 5 of 8 Policy Guidelines Pre - PA Allowance Quantity 180 capsules per 90 days Prior - Approval Limits vii. Clorazepate dipotassium (Tranxene) Quantity Duration 6 months 20/0.8 mg 900 capsules per 90 days OR 30/1.2 mg 900 capsules per 90 days OR 50/2 mg 900 capsules per 90 days OR 60/2.4 mg 900 capsules per 90 days OR 80/3.2 mg 900 capsules per 90 days OR 100/4 mg 900 capsules per 90 days Maximum daily limit of any combination: 1200mg Prior Approval Renewal Limits Quantity Duration Rationale 6 months 20/0.8 mg 900 capsules per 90 days OR 30/1.2 mg 900 capsules per 90 days OR 50/2 mg 900 capsules per 90 days OR 60/2.4 mg 900 capsules per 90 days OR 80/3.2 mg 900 capsules per 90 days OR 100/4 mg 900 capsules per 90 days Maximum daily limit of any combination: 1200mg Summary Embeda is an extended release oral formulation used in the treatment moderate to severe pain. It should not be used for as needed pain relief. The potential for developing substance abuse and addiction is extreme. Patients should be thoroughly assessed for their risk of developing
Subject: Embeda Page: 6 of 8 severe respiratory depression, as well as substance abuse prior to being prescribed Embeda and should be routinely monitored for signs of misuse, abuse and addiction during therapy (1). Prior approval is required to ensure the safe, clinically appropriate and cost effective use of Embeda while maintaining optimal therapeutic outcomes. References 1. Embeda [package insert]. Elizabeth, NJ: Actavis Elizabeth LLC; October, 2014. 2. Dowell D, Haegerich T, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain. CDC Guidelines 2016 3. 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 March 2015 June 2015 March 2016 September 2016 March 2017 June 2017 September 2017 Keywords Action New addition to PA Annual review Annual editorial review and reference update Addition of no dual therapy with other long acting opioid analgesic(s) in renewal section Policy number changed from 5.02.39 to 5.70.39 Annual review Addition of 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 any antianxiety benzodiazepines: alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), oxazepam (Serax), chlordiazepoxide (Librium), clorazepate dipotassium (Tranxene) Annual editorial review Addition of no dual therapy with Methadone Annual review This policy was approved by the FEP Pharmacy and Medical Policy Committee on September 15, 2017 and is effective on October 1, 2017.
Subject: Embeda Page: 7 of 8 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 Other Psychiatric Medicines
Subject: Embeda Page: 8 of 8 amoxapine maprotiline nefazodone trazodone buspirone vilazodone mirtazapine llthium No brand name currently marketed No brand name currently marketed No brand name currently marketed Oleptro No brand name currently marketed Viibryd Remeron, Remeron Soltab 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 Bromfed-DM, Delsym, Mucinex DM, Nuedexta linezolid Zyvox cyclobenzaprine Amrix methylene blue St. John s wort tryptophan