Morphine Sulfate Hydromorphone Oxymorphone

Transcription

1 Federal Employee Program 1310 G Street, N.W. Washington, D.C Fax Subject: Morphine Drug Class Page: 1 of 12 Last Review Date: September 15, 2017 Morphine Sulfate Hydromorphone Oxymorphone Description Arymo ER Kadian, Morphabond, MS Contin (Morphine sulfate extended release), morphine sulfate immediate release, Exalgo (hydromorphone extended release), Dilaudid (hydromorphone), Opana (oxymorphone), Opana ER (oxymorphone extended release) Background Morphine sulfate IR and ER (Arymo ER, MS Contin, Kadian, Morphabond) and its derivatives hydromorphone (Exalgo, Dilaudid) and oxymorphone (Opana and Opana ER) are Schedule II narcotics prescribed to treat moderate to severe pain. Morphine produces both its therapeutic and adverse effects by interaction with one or more classes of specific opioid receptors located throughout the body. Morphine acts as a full agonist, binding with and activating opioid receptors at sites in brain and spinal cord. In addition to analgesia, the widely diverse effects of morphine include drowsiness, changes in mood, respiratory depression, decreased gastrointestinal motility, nausea, vomiting, and alterations of the endocrine and autonomic nervous system (1-9). Regulatory Status FDA-approved indications: Morphine sulfate, hydromorphone and oxymorphone are opioid agonists indicated for the relief of moderate to severe acute and chronic pain where an opioid is appropriate (1-9). Morphine sulfate extended-release (ER), hydromorphone (ER) and oxymorphone (ER) are opioid agonists indicated for the management of severe pain when a continuous, around-theclock opioid analgesic is needed for an extended period of time (1-9).

2 Subject: Morphine Drug Class Page: 2 of 12 Morphine sulfate IR and ER (Arymo ER, MS Contin, Kadian, Morphabond) and its derivatives hydromorphone (Exalgo, Dilaudid) and oxymorphone (Opana and Opana ER) have boxed warnings for the following (1-9): Respiratory depression is the chief hazard of opioid agonists, including morphine sulfate, which if not immediately recognized and treated, may lead to respiratory arrest and death. Risk is increased in patients receiving concurrent CNS depressants (including alcohol), patients with chronic obstructive pulmonary disease, orthostatic hypotension, increased intracranial pressure, biliary tract diseases, seizure disorders to reduce the risk of respiratory depression, proper dosing, titration, and monitoring are essential. All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Prolonged use of opioid agonists during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening. 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. Morphine sulfate and oxymorphone are contraindicated in patients with paralytic ileus (1-9). 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 (10) 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 (10). 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) (11).

3 Subject: Morphine Drug Class Page: 3 of 12 The safety and effectiveness of morphine sulfate in pediatric patients below the age of 18 have not been established (1-9). Related policies Abstral, Actiq, Butrans, Duragesic, Embeda, Fentanyl Powder, Fentora, Hysingla ER, Lazanda, Methadone, Meperidine, Nucynta, Onsolis, Oxycodone, Oxycodone Naloxone, 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. Morphine sulfate, hydromorphone and oxymorphone may be considered medically necessary in patients that are 18 years of age and older with moderate to severe pain and if the conditions below are met. Morphine sulfate (ER), hydromorphone (ER) and oxymorphone (ER) may be considered medically necessary in patient that are 18 years of age and older requiring management of 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 Morphine sulfate IR, hydromorphone IR, and oxymorphone IR may be 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 Diagnoses 18 years of age or older Morphine Sulfate IR, Hydromorphone IR and Oxymorphone IR Patient must have the following: 1. Moderate to severe pain AND ALL of the following: a. NO dual therapy with other immediate release opioid analgesic(s)

4 Subject: Morphine Drug Class Page: 4 of 12 b. Alternative treatment options have been ineffective, not tolerated or inadequate for controlling the pain i. These include: non-opioid analgesics 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) Morphine Sulfate ER, Hydromorphone ER and Oxymorphone ER Patient must have the following: 1. Pain, severe enough to require daily, around-the clock long term opioid treatment 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 analgesics and immediate release analgesics 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)

5 Subject: Morphine Drug Class Page: 5 of 12 vii. Clorazepate dipotassium (Tranxene) Prior Approval Renewal Requirements Age 18 years of age or older Diagnoses Morphine Sulfate IR, Hydromorphone IR and Oxymorphone IR Patient must have the following: 1. Moderate to severe pain AND ALL of the following: a. NO dual therapy with other immediate release 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) vii. Clorazepate dipotassium (Tranxene) Morphine Sulfate ER, Hydromorphone ER and Oxymorphone ER Patient must have the following: 1. Pain, severe enough to require daily, around-the clock long term 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

6 Subject: Morphine Drug Class Page: 6 of 12 Policy Guidelines Pre - PA Allowance Quantity 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) vii. Clorazepate dipotassium (Tranxene) Immediate-release Formulations Morphine sulfate (IR) Opana (oxymorphone) IR Dilaudid (hydromorphone) IR 360 tablets per 90 days Extended-release Formulations Arymo ER (morphine sulfate ER) Kadian (morphine sulfate ER) MS Contin (morphine sulfate ER) Morphabond Exalgo (hydromorphone ER) Opana (oxymorphone) ER 360 tablets per 90 days Prior - Approval Limits Quantity Immediate-release Formulations Morphine sulfate 15mg (IR) 900 tablets per 90 days OR Morphine sulfate 30mg (IR) 540 tablets per 90 days Maximum daily limit of any combination: 180mg

7 Subject: Morphine Drug Class Page: 7 of 12 Opana 5mg (Oxymorphone) (IR) 900 tablets per 90 days OR Opana 10mg (Oxymorphone) (IR) 720 tablets per 90 days Maximum daily limit of any combination: 80mg Dilaudid 2mg (Hydromorphone) (IR) 900 tablets per 90 days OR Dilaudid 4mg (Hydromorphone) (IR) 900 tablets per 90 days OR Dilaudid 8mg (Hydromorphone) (IR) 810 tablets per 90 days Maximum daily limit of any combination: 72mg OR Extended-release Formulations Arymo ER 15 mg (Morphine sulfate) 540 tablets per 90 days OR Arymo ER 30 mg (Morphine sulfate) 540 tablets per 90 days OR Arymo ER 60 mg (Morphine sulfate) 540 tablets per 90 days Maximum daily limit of any combination: 360mg Exalgo 8mg (Hydromorphone) 900 tablets per 90 days OR Exalgo 12mg (Hydromorphone) 900 tablets per 90 days OR Exalgo 16mg (Hydromorphone) 720 tablets per 90 days OR Exalgo 32mg (Hydromorphone) 360 tablets per 90 days Maximum daily limit of any combination: 128mg Kadian 10mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 20mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 30mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 40mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 50mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 60mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 80mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 100mg (Morphine sulfate) 900 capsules per 90 days OR Kadian 200mg (Morphine sulfate) 540 capsules per 90 days Maximum daily limit of any combination: 1200mg MS Contin 15mg (Morphine sulfate) MS Contin 30mg (Morphine sulfate) MS Contin 60mg (Morphine sulfate) MS Contin 100mg (Morphine sulfate) 900 tablets per 90 days OR 900 tablets per 90 days OR 900 tablets per 90 days OR 900 tablets per 90 days OR

8 Subject: Morphine Drug Class Page: 8 of 12 MS Contin 200mg (Morphine sulfate) 540 tablets per 90 days Maximum daily limit of any combination: 1200mg Morphabond 15mg (Morphine sulfate) 540 tablets per 90 days OR Morphabond 30mg (Morphine sulfate) 540 tablets per 90 days OR Morphabond 60mg (Morphine sulfate) 540 tablets per 90 days OR Morphabond 100mg (Morphine sulfate) 540 tablets per 90 days Maximum daily limit of any combination: 600mg - Opana ER 5mg (Oxymorphone) 900 tablets per 90 days OR Opana ER 7.5mg (Oxymorphone) 900 tablets per 90 days OR Opana ER 10mg (Oxymorphone) 900 tablets per 90 days OR Opana ER 15mg (Oxymorphone) 900 tablets per 90 days OR Opana ER 20mg (Oxymorphone) 900 tablets per 90 days OR Opana ER 30mg (Oxymorphone) 540 tablets per 90 days OR Opana ER 40mg (Oxymorphone) 450 tablets per 90 days Maximum daily limit of any combination: 200mg Duration 6 months Prior Approval Renewal Limits Same as above Rationale Summary Morphine sulfate IR and ER (Arymo ER, MS Contin, Kadian, Morphabond) and its derivatives hydromorphone (Exalgo, Dilaudid) and oxymorphone (Opana and Opana ER) are Schedule II narcotics prescribed to treat moderate to severe pain. In addition to analgesia, the widely diverse effects of morphine include drowsiness, changes in mood, respiratory depression, decreased gastrointestinal motility, nausea, vomiting, and alterations of the endocrine and autonomic nervous system. All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use (1-9). Prior approval is required to ensure the safe, clinically appropriate and cost effective use of morphine sulfate IR/ER, hydromorphone IR/ER and oxymorphone IR/ER while maintaining optimal therapeutic outcomes.

9 Subject: Morphine Drug Class Page: 9 of 12 References 1. Armyo ER [package insert]. Wayne, PA: Egalet US Inc; January Dilaudid [package insert]. Whippany, NJ: Halo Pharmaceutical, Inc.; September Exalgo [package insert]. Hazelwood, MO: Mallinckrodt Brand Pharmaceuticals, Inc.; June MS Contin [package insert]. Stamford, CT: Purdue Pharma L.P.; September Kadian [package insert]. Morristown, NJ: Actavis Elizabeth LLC; April Opana [package insert]. Malvern, PA: Endo Pharmaceuticals; September Opana ER [package insert]. Chadds Ford, PA: Endo Pharmaceuticals; April Morphine sulfate [package insert]. Columbus, OH: Roxane Laboratories, Inc.; February Morphabond [package insert]. Valley Cottage, NY: Inspirion Delivery Technologies LLC; October Dowell D, Haegerich T, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain. CDC Guidelines FDA Safety Release. FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. March 22, Policy History Date September 2014 June 2015 November 2015 March2016 September 2016 Action Addition to PA Annual review Addition of Morphabond Annual editorial review and reference update Addition of not used in combination with any other long acting opioids to renewal section Policy code changed from to Annual review Addition of no dual therapy with other immediate release opioid analgesic(s); 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). Change of the Standard Allowance limits to 360 tabs per 90 days

10 Subject: Morphine Drug Class Page: 10 of 12 March 2017 June 2017 June 2017 September 2017 Keywords Annual review and reference update Removal of Avinza and addition of Arymo ER Change in Morphabond maximum daily limit from 1200mg to 600mg Annual 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.

11 Subject: Morphine Drug Class Page: 11 of 12 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

12 Subject: Morphine Drug Class Page: 12 of 12 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 Bromfed-DM, Delsym, Mucinex DM, Nuedexta linezolid Zyvox cyclobenzaprine Amrix methylene blue St. John s wort tryptophan