Clinical Policy: Nabilone (Cesamet), Dronabinol (Marinol, Syndros) Reference Number: CP.CPA.242 Effective Date: 11.16.16 Last Review Date: 11.17 Line of Business: Commercial Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description The following are synthetic cannabinoids requiring prior authorization: dronabinol (Marinol, Syndros ), nabilone (Cesamet ) FDA approved indication Marinol Cesamet Syndros Controlled Substance Schedule Category CIII CII CII Treatment of nausea and vomiting associated with X X X cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments Treatment of Anorexia associated with weight loss in patients with acquired immune deficiency syndrome (AIDS) X X Policy/Criteria Provider must submit documentation (which may include office chart notes and lab results) supporting that member has met all approval criteria It is the policy of health plans affiliated with Centene Corporation that Cesamet, Marinol, and Syndros are medically necessary when the following criteria are met: I. Initial Approval Criteria A. Nausea and Vomiting Associated with Cancer Chemotherapy (must meet all): 1. Diagnosis of nausea and vomiting associated with cancer chemotherapy; 2. Patient has received highly or moderately emetogenic chemotherapy; 3. Failure of a trial of a 5-HT3 serotonin antagonist (e.g. ondansetron), in combination with Emend and dexamethasone unless contraindicated or clinically significant adverse effects are experienced; 4. Failure of TWO of the following unless contraindicated or clinically significant adverse effects are experienced: metoclopramide, prochlorperazine, lorazepam; 5. Dose does not exceed 15 mg/m 2 per dose (6 doses per day) (Marinol), 6 mg/day (Cesamet), 12.6 mg/m 2 per dose (6 doses per day) (Syndros). Approval duration: Length of benefit B. Anorexia (Marinol and Syndros requests only) (must meet all): 1. Diagnosis of anorexia with weight loss in patients with AIDS or cancer; Page 1 of 9
2. Prescribed for appetite stimulation; 3. Request is for Marinol or Syndros; 4. Failure of a trial of megestrol at maximally indicated doses unless contraindicated or clinically significant adverse effects are experienced; 5. Dose does not exceed 20 mg/day (Marinol), 16.8 mg/day (Syndros). Approval duration: Length of benefit C. Other diagnoses/indications 1. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) II. Continued Therapy A. All indications in Section I (must meet all): 1. Currently receiving medication via a health plan affiliated with Centene Corporation or member has previously met initial approval criteria; 2. Member is responding positively to therapy; 3. If request is for a dose increase, new dose does not exceed the FDA approved maximum recommended dose for the relevant indication. Approval duration: Length of benefit B. Other diagnoses/indications (must meet 1 or 2): 1. Currently receiving medication via a health plan affiliated with Centene Corporation and documentation supports positive response to therapy. Approval duration: Duration of request or 12 months (whichever is less); or 2. Refer to CP.CPA.09 if diagnosis is NOT specifically listed under section (Diagnoses/Indications for which coverage is NOT authorized) III. Diagnoses/Indications for which coverage is NOT authorized: A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy CP.CPA.09 or evidence of coverage documents IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AIDS: acquired immune deficiency syndrome Appendix B: General Information Cesamet may be administered for 48 hours after the last dose of each cycle of chemotherapy. Cesamet is not intended for use on an as-needed basis. Because of its potential to alter the mental state, Cesamet is intended for use under circumstances that permit close supervision of the patient by a responsible individual particularly during initial use of Cesamet and during dose adjustments. Marinol capsules contain cannabinoid and sesame oil and should never be used by patients allergic to these substances. Page 2 of 9
The following table is the National Comprehensive Cancer Network s classification for emetogenic potential of significant chemotherapy and other agents. Agents AC combination defined as either doxorubicin or epirubicin with cyclophosphamide, carmustine > 250 mg/m 2, cisplatin, cyclophosphamide > 1,500 mg/m 2, dacarbazine, doxorubicin 60 mg/m² epirubicin >90 mg/m², ifosamide > 2 g/m² per dose, mechlorethamine, streptozocin aldesleukin > 12-15 million IU/m 2, amifostine > 300 mg/m 2, arsenic trioxide, azacitidine, bendamustine, busulfan, carboplatin, carmustine 250 mg/m 2, clofarabine, cyclophosphamide 1500 mg/m2, cytarabine > 200 mg/m 2, dactinomycin, daunorubicin, doxorubicin <60 mg/ m², epirubicin 90 mg/m², idarubicin, ifosfamide <2 g/m² per dose, interferon alfa 10 million IU/m 2, irinotecan, melphalan, methotrexate (MTX) 250 mg/m 2, oxaliplatin, temozolomide ado-trastuzumab emtansine, amifostine 300 mg/m 2, aldesleukin 12 million IU/m 2, belinostatm, blinatumomab, brentuximab vedotin, cabazitaxol, carfilzomib, cytarabine (low dose) 100-200 mg/m 2, docetaxel, doxorubicin (liposomal), eribulin, etoposide, 5-fluorouracil, floxuridine, gemcitabine, interferon alfa > 5 <10 million IU/m 2, ixabepilone, MTX > 50 mg/m 2 < 250 mg/m2, mitomcyin, mitoxantrone, omacetaxine, paclitaxel, paclitaxel-albumin, pemetrexed, pentostatin, pralatrexate, romidepsin,thiotepa, topotecan, ziv-aflibercept alemtuzumab, asparaginase, bevacizumab, bleomycin, bortezomib, cetuximab, 2-chlorodeoxyadenosine (cladribine), cytarabine < 100 mg/m 2, decitabine, denileukin diftitox, dexrazoxane, fludarabine, interferon alfa 5 million IU/m 2, ipilimumab, MTX 50 mg/m 2, nelarabine, nivolumab, obinutuzumab, ofatumumab, panitumumab, pegaspargase,peginterferon, pembrolizumab, pertuzumab, rituximab, temsirolimus, trastuzumab, valrubicin, vinblastine, vincristine, vincristine (liposomal), vinorelbine altretamine, busulfan ( 4 mg/d), crizotinib, cyclophosphamide ( 100 mg/m 2 /d), estramustine, etoposide, lomustin (single day), mitotane, procarbazine, temozolomide (> 75 mg/m 2 /d), vismodegib Afatinib, axitinib, bexarotene,bosutinib, busulfan (< 4 mg/d), cabozantinib, capecitabine, chlorambucil, cyclophosphamide (< 100 mg/m 2 /d), dasatinib,dabrafenib, erlotinib, everolimus, fludarabine, gefitinib, hydroxyurea, imatinib, lapatinib, lenalidomide, melphalan, mercaptopurine, methotrexate, nilotinib, pazopanib, pomalidomide, ponatinib, regorafenib, ruxolitinib, sorafenib, sunitinib, temozolomide ( 75 mg/m2/d), Frequency of Emesis High Emetic Risk >90% Moderate Emetic Risk 30-90% Low Emetic Risk 10-30% Minimal Emetic Risk <10% Emetogenic potential of oral antineoplastic agents: Moderate to High Emetogenic potential or oral antineoplastic agents: Minimal to low Page 3 of 9
thalidomide, thioguanine, topotecan, trametinib, tretinoin, vandetanib, vemurafenib, vorinostat Appendix C: Therapeutic Alternatives Drug Dosing Regimen Dose Limit/Maximum Dose 5-HT3 Antagonists Ondansetron (Zofran )* Moderately emetogenic chemotherapy (MEC): 12 years or older: 8 mg PO beginning 30 minutes before chemotherapy; repeat dose 8 hours after initial dose, then 8 mg PO BID for 1 to 2 days after chemotherapy completed Adults: 0.15 mg/kg IV for 3 doses up to a maximum of 16 mg per dose. The first dose is infused over 15 minutes beginning 30 minutes before the start of chemotherapy. Subsequent doses may be repeated twice, administered 4 and 8 hours after the first dose. Highly emetogenic chemotherapy (HEC): Adults: 24 mg PO (given as three 8 mg tablets) 30 minutes prior to start of single day chemotherapy As specified by length 5-HT3 Antagonists Anzemet (dolasetron)* 5-HT3 Antagonists Granisetron* Adults: 0.15 mg/kg IV for 3 doses up to a maximum of 16 mg per dose. The first dose is infused over 15 minutes beginning 30 minutes before the start. Subsequent doses may be repeated twice, administered 4 and 8 hours after the first dose. Moderately emetogenic chemotherapy: Adults: 100 mg PO within 1 hour prior to chemotherapy Moderately and highly emetogenic chemotherapy: As specified by length As specified by length 2 mg PO QD 1 hour prior to chemotherapy OR 1 mg BID 1 hour prior to chemotherapy and then 12 hours later 5-HT3 Antagonists MEC and HEC: As specified by length Page 4 of 9
Drug Dosing Regimen Dose Limit/Maximum Dose Sancuso (granisetron)* Adults: Apply a single patch to the upper outer arm from 24 to 48 hours before chemotherapy. Remove the patch a minimum of 24 hours after completion of chemotherapy. 5-HT3 Antagonists Aloxi (palonosetron)* NK1 Receptor Antagonist Emend (aprepitant)* Oral corticosteroids Dexamethasone Phenothiazines Promethazine (Phenergan) Dopamine Receptor Antagonist Metoclopramide (Reglan, Metozolv) Benzodiazepines Lorazepam (Ativan) Miscellaneous Oxandrolone (Oxandrin ) The patch can be worn for up to 7 days depending on the duration regimen. Highly or Moderately emetogenic chemotherapy: 0.25 mg IV infused over 30 seconds beginning 30 minutes prior to chemotherapy Moderately and highly emetogenic chemotherapy: 125 mg PO 1 hour prior to chemotherapy and 80 mg on days 2, 3 20 mg (12 mg with Emend) PO (prechemotherapy) and 8 mg PO daily on Days 2, 3 Various chemotherapy dosage regimens Oral: 5-10 mg PO q 6-8 hours. Rectal: 25 mg PR q 12 hours Intramuscular/Intravenous: 5-10 mg IM or IV q3-4 hours PRN 1-2mg/kg dose IV 30 minutes before chemotherapy. May repeat every 2 hours for 2 doses then repeat every 3 hours for 3 doses. Oral: 2.5 mg PO the evening prior to and after initiation Intramuscular/Intravenous: 0.025-0.05 mg/kg (maximum 4 mg) IM or IV given slowly (2 mg/min) 30 to 35 minutes prior to chemotherapy. May supplement with 1-2 mg PO every hour PRN Various chemotherapy dosage regimens Weight loss due to AIDS wasting 2.5 20 mg PO QD in 2 to 4 divided doses for 2 to 4 weeks As specified by length 1 x 125 mg and 2 x 80 mg capsules per cycle 40 mg/day PO/IM 40 mg/day PR: 50 mg/day 10 mg/day 20 mg/day Page 5 of 9
Drug Dosing Regimen Dose Limit/Maximum Dose Weight loss due to anorexia 800 mg/day 400-800 mg PO QD Miscellaneous Megestrol suspension (Megace ) Therapeutic alternatives are listed as Brand name (generic) when the drug is available by brand name only and generic (Brand name ) when the drug is available by both brand and generic *Requires Prior Authorization V. Dosage and Administration Drug Indication Dosing Regimen Maximum Dose Nabilone (Cesamet) Nausea & Vomiting 1 or 2 mg PO BID. 1st dose is given 1-3 hours before chemotherapy. A dose the night before chemotherapy may be useful. Start with the lower dose and increase as necessary. Max dose 6 mg/day in divided doses TID. Dosing may continue during entire course of each cycle and, if needed, for 48 hours after the last dose of each cycle. Safety and effectiveness have not been established in patients younger than 18 6 mg/day Dronabinol (Marinol) Nausea & Vomiting Initially given as 5 mg/m 2 PO per dose. 1st dose is given 1-3 hours before chemotherapy, then every 2-4 hours after chemotherapy for total of 4-6 doses/day. This dose may be increased by 2.5 mg/m² increments to a maximum 15 mg/m 2 per dose. 15 mg/m 2 per dose (6 doses per day) Dronabinol (Syndros) Appetite Stimulant Nausea & Vomiting Initially, 2.5 mg PO BID before lunch and dinner. The dose may be increased to a maximum dose 20 mg/day administered in divided oral doses Initially given as 4.2 mg/m 2 PO per dose. 1st dose is given 1-3 hours before chemotherapy, then every 2-4 hours after chemotherapy for total of 4-6 doses/day. This dose may be increased by 2.1 mg/m² increments to a maximum 12.6 mg/m 2 per dose. 20 mg/day 12.6 mg/m 2 per dose (6 doses per day) Appetite Stimulant Initially, 2.1 mg PO BID before lunch and dinner. The dose may be increased 16.8 mg/day Page 6 of 9
VI. Product Availability Drug Availability Dronabinol 2.5 mg, 5 mg, 10 mg capsules (Marinol) Nabilone 1 mg capsules (Cesamet) Dronabinol 5 mg/ml oral solution (Syndros) to a maximum dose 16.8 mg/day administered in divided oral doses VII. References 1. Marinol [Prescribing Information] North Chicago, IL: AbbVie, Inc; February 2013. 2. Cesamet [Prescribing Information] Somerset, NJ: MEDA Pharmaceuticals Inc.; September 2013. 3. Syndros [Prescribing Information] Lakewood, NJ: Insys Therapeutics, Inc.; May 2017. 4. Basch E, Prestrud AA, Hesketh, PJ, et al. Antiemetics: American Society of Clinical Oncology (ASCO) Clinical Practice Guideline Update 2011 J Clin Oncol 29:4189-4198. 5. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology - Antiemesis V.1.2012. NCCN Web site. Available at http://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf. Accessed June 10, 2017 6. Clinical Pharmacology Web site, Available at http://clinicalpharmacologyip.com/default.aspx. Accessed June 10, 2017. 7. Micromedex Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed June 10, 2017. 8. Cesamet. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 10, 2017. 9. Marinol. American Hospital Formulary Service Drug Information. Available at: http://www.medicinescomplete.com/mc/ahfs/current/. Accessed June 10, 2017. Reviews, Revisions, and Approvals Date P&T Approval Date Converted to new template. Minor changes to verbiage and 06.10.17 11.17 grammar. References updated. Added Syndros to criteria. 09.21.17 Important Reminder This clinical policy has been developed by appropriately experienced and licensed health care professionals based on a review and consideration of currently available generally accepted standards of medical practice; peer-reviewed medical literature; government agency/program approval status; evidence-based guidelines and positions of leading national health professional organizations; views of physicians practicing in relevant clinical areas affected by this clinical policy; and other available clinical information. The Health Plan makes no representations and Page 7 of 9
accepts no liability with respect to the content of any external information used or relied upon in developing this clinical policy. This clinical policy is consistent with standards of medical practice current at the time that this clinical policy was approved. Health Plan means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan s affiliates, as applicable. The purpose of this clinical policy is to provide a guide to medical necessity, which is a component of the guidelines used to assist in making coverage decisions and administering benefits. It does not constitute a contract or guarantee regarding payment or results. Coverage decisions and the administration of benefits are subject to all terms, conditions, exclusions and limitations of the coverage documents (e.g., evidence of coverage, certificate of coverage, policy, contract of insurance, etc.), as well as to state and federal requirements and applicable Health Plan-level administrative policies and procedures. This clinical policy is effective as of the date determined by the Health Plan. The date of posting may not be the effective date of this clinical policy. This clinical policy may be subject to applicable legal and regulatory requirements relating to provider notification. If there is a discrepancy between the effective date of this clinical policy and any applicable legal or regulatory requirement, the requirements of law and regulation shall govern. The Health Plan retains the right to change, amend or withdraw this clinical policy, and additional clinical policies may be developed and adopted as needed, at any time. This clinical policy does not constitute medical advice, medical treatment or medical care. It is not intended to dictate to providers how to practice medicine. Providers are expected to exercise professional medical judgment in providing the most appropriate care, and are solely responsible for the medical advice and treatment of members. This clinical policy is not intended to recommend treatment for members. Members should consult with their treating physician in connection with diagnosis and treatment decisions. Providers referred to in this clinical policy are independent contractors who exercise independent judgment and over whom the Health Plan has no control or right of control. Providers are not agents or employees of the Health Plan. This clinical policy is the property of the Health Plan. Unauthorized copying, use, and distribution of this clinical policy or any information contained herein are strictly prohibited. Providers, members and their representatives are bound to the terms and conditions expressed herein through the terms of their contracts. Where no such contract exists, providers, members and their representatives agree to be bound by such terms and conditions by providing services to members and/or submitting claims for payment for such services. 2016 Centene Corporation. All rights reserved. All materials are exclusively owned by Centene Corporation and are protected by United States copyright law and international copyright law. No part of this publication may be reproduced, copied, modified, distributed, displayed, stored in a retrieval system, transmitted in any form or by any means, or otherwise published without the prior written permission of Centene Corporation. You may not alter or remove any trademark, copyright Page 8 of 9
or other notice contained herein. Centene and Centene Corporation are registered trademarks exclusively owned by Centene Corporation. Page 9 of 9