Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 Subject: Meperidine Page: 1 of 7 Last Review Date: September 15, 2017 Meperidine Description Demerol (meperidine oral tablet, oral solution), Meperitab (oral tablet) Background Meperidine is a Schedule II narcotic analgesic prescribed to treat acute episodes of moderate to severe pain. Meperidine has multiple actions qualitatively similar to those of morphine. Meperidine produces both its therapeutic and adverse effects by interaction with one or more classes of specific opioid receptors in the central nervous system to cause the therapeutic actions of analgesia and sedation. In addition to analgesia, the adverse effects of meperidine include lightheadedness, confusion, respiratory depression, nausea, vomiting, sweating, and mood changes. Meperidine should not be used for treatment of chronic pain due to the risk of toxicity (1-3). Meperidine is a Schedule II controlled substance and can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing meperidine in a situation where misuse, abuse, or diversion are a concern (1-3). Regulatory Status FDA-approved indications: Meperidine hydrochloride is indicated for the relief of moderate to severe pain (1-3). Meperidine oral tablets and syrups should only be used in the treatment of acute episodes of moderate to severe pain, not for treatment of chronic pain. Prolonged meperidine use may increase the risk of toxicity from the accumulation of the meperidine metabolite, normeperidine,
Subject: Meperidine Page: 2 of 7 which may cause CNS excitement and convulsions. If these events preclude adequate pain relief, another opioid agent should be substituted (1-3). 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. Patients should be assessed for the risk of developing abuse prior to the start of treatment and should be routinely monitored during therapy (1-3). Meperidine hydrochloride is contraindicated in patients who are receiving monoamine oxidase inhibitors or have recently received such agents, patients with respiratory depression, and those with hypersensitivity to meperidine or any of its ingredients. 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. To reduce the risk of respiratory depression, proper dosing, titration, treatment duration, and monitoring are essential (1-3). 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 (4) 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 (4). 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) (5). The safety and effectiveness of meperidine hydrochloride in pediatric patients below the age of 18 have not been established (1-3). Related policies Abstral, Actiq, Butrans, Duragesic, Embeda, Fentanyl Powder, Fentora, Hysingla ER, Lazanda, Methadone, Morphine, 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.
Subject: Meperidine Page: 3 of 7 Meperidine hydrochloride may be considered medically necessary in patients that are 18 years of age and older with moderate to severe acute pain and if the conditions below are met. Meperidine hydrochloride may be considered investigational in below 18 years of age and for all other indications. Prior-Approval Requirements Prior authorization is not required if prescribed by an oncologist Age Diagnosis 18 years of age or older Patient must have ALL of the following: Moderate to severe acute pain AND the following: a. NO dual therapy with other immediate release 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 patient for serotonin syndrome d. NO dual therapy with opioid addiction treatment or methadone e. NO dual therapy with any anti-anxiety benzodiazepines i. Alprazolam (Xanax) ii. Clonazepam (Klonopin) iii. Diazepam (Valium) iv. Lorazepam (Ativan) v. Oxazepam (Serax) vi. Chlordiazepoxide (Librium) vii. Clorazepate dipotassium (Tranxene) Prior Approval Renewal Requirements None Policy Guidelines
Subject: Meperidine Page: 4 of 7 Pre - PA Allowance Age Quantity 18 years of age or older Meperidine 50mg/ 5ml oral solution Meperidine 50mg tablets Meperidine 100mg tablets Prior - Approval Limits Quantity Meperidine 50mg/ 5ml oral solution Meperidine 50mg tablets Meperidine 100mg tablets Max combination 360 ml per 90 days, OR 90 tablets per 90 days OR 90 tablets per 90 days 3600 ml per 90 days, OR 720 tablets per 90 days OR 360 tablets per 90 days 400mg per day Duration 3 months Rationale Summary Meperidine is a Schedule II narcotic analgesic with multiple actions similar to those of morphine. Meperidine is prescribed to treat acute episodes of moderate to severe pain and should not be used to manage chronic pain. The principal therapeutic actions of meperidine are analgesia and sedation. 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. The safety and effectiveness of meperidine hydrochloride in pediatric patients below the age of 18 have not been established (1-3). Prior approval is required to ensure the safe, clinically appropriate and cost effective use of meperidine hydrochloride while maintaining optimal therapeutic outcomes. References 1. Demerol [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; July 2014. 2. Meperidine hydrochloride tablets Meperidine hydrochloride oral solution [package insert]. Columbus, OH: Roxane Laboratories, Inc.; March 2012. 3. Meperidine [package insert]. Deerfield, IL: Baxter Healthcare Corporation; 2011. 4. Dowell D, Haegerich T, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain. CDC Guidelines 2016.
Subject: Meperidine Page: 5 of 7 5. 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 May 2015 March 2016 September 2016 March 2017 June 2017 September 2017 Action Addition to PA Annual editorial review and reference update Policy number changed from 5.02.40 to 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 an antianxiety benzodiazepine(s): alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), oxazepam (Serax), chlordiazepoxide (Librium), clorazepate dipotassium (Tranxene) Annual editorial review Removal of Prescriber agrees to assess the benefits of pain control after 3 months of therapy from criteria Addition of no dual therapy with Methadone Annual review Keywords This policy was approved by the FEP Pharmacy and Medical Policy Committee on September 15, 2017 and is effective on October 1, 2017.
Subject: Meperidine Page: 6 of 7 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 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: Meperidine Page: 7 of 7 amoxapine maprotiline nefazodone trazodone buspirone vilazodone mirtazapine llthium Oleptro 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