Short-Acting Fentanyl

Transcription

1 Short-Acting Fentanyl Policy Number: Last Review: 08/2018 Origination: 9/2007 Next Review: 08/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for oral short-acting fentanyl products when the criteria outlined below have been met. The following medications must be prior authorized through pharmacy services: Abstral (fentanyl sublingual tablet Novartis/ProStrakan) Actiq (oral transmucosal fentanyl citrate Cephalon, generics) Fentora (fentanyl buccal tablet Cephalon, authorized generic) Lazanda (fentanyl nasal spray Depomed) Onsolis (fentanyl buccal soluble film Meda Pharmaceuticals [discontinued]) Subsys (fentanyl sublingual spray Insys) When Policy Topic is covered Prior authorization is recommended for prescription benefit coverage of fentanyl transmucosal drugs. All approvals are provided for the duration noted below. Automation: If the patient has a prescription for a cancer medication (see Appendix A) within a 180- day period, the claim will adjudicate. When available, the ICD-9/ICD-10 codes for cancer will be used as part of automation to allow approval of the requested medication (see Appendix B). Food and Drug Administration (FDA)-Approved Indications 1. Breakthrough Pain in Patients with Cancer: Approve for 1 year if the patient meets the following criteria (A and B): A) Patient meets ONE of the following conditions (i or ii): i. Patient is unable to swallow, has dysphagia, esophagitis, mucositis, 8 or uncontrollable nausea/vomiting (In the professional opinion of specialist physicians reviewing the data, we have adopted this criterion); OR ii. Patient is unable to take two other short-acting narcotics (e.g., oxycodone, morphine sulfate, hydromorphone, etc.) secondary to allergy or severe adverse events (In the professional opinion of specialist physicians reviewing the data, we have adopted this criterion); AND B) Patient is on or will be on an oral or transdermal long-acting narcotic (e.g., Duragesic, OxyContin, morphine extended-release), or the patient is on intravenous, subcutaneous, or spinal (intrathecal, epidural) narcotics (e.g., morphine sulfate, hydromorphone, fentanyl citrate). Actiq (generics), Abstral, Fentora, Lazanda, Onsolis, and Subsys are indicated for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. 1-7

2 When Policy Topic is not covered Oral short-acting fentanyl products are considered investigational when used for any condition other than breakthrough cancer pain, including, but not limited to, the treatment of pain associated with migraine headaches. Other Conditions Not Recommended for Approval Fentanyl transmucosal drugs have not been shown to be effective, or there are limited or preliminary data or potential safety concerns that are not supportive of general approval for the following conditions. Rationale for non-coverage for these specific conditions is provided below. (Note: This is not an exhaustive list of Conditions Not Recommended for Approval.) 1. Acute and/or Postoperative Pain including surgery/post-surgery, trauma/post-trauma, acute medical illness (acute abdominal pain, pelvic pain, muscle spasm): Actiq (generics), Abstral, Fentora, Lazanda, Onsolis, and Subsys are contraindicated for use in the management of acute or postoperative pain. 1-7 A case series reported the efficacious outpatient use (75% reduction in pain intensity at 2 hours; n = 18) of Actiq for the management of treating an acute, refractory migraine headache in 20 patients. 9 Actiq was used as a rescue medication for management of a moderate to severe migraine after ineffective treatment with the patients usual antimigraine therapy. All of these patients were managed by a headache clinic and had undergone a full evaluation of their medical history, vital signs, and physical and neurological examinations. In addition, all 20 patients had been previously treated with multiple other therapies (e.g., 5-hydroxytryptamine [5-HT] 1 receptor agonists, ergots, antiemetics, prescription and over-the-counter analgesics, and antiinflammatory drugs) and all had previously received outpatient opioid therapies in an attempt to manage their migraine pain. All patients were also known responders to use of parenteral opioid therapy. Side effects reported included nausea (n = 3), vomiting (n = 1), somnolence (n = 2), itching (n = 1), and dry mouth (n = 1). Controlled research is needed to fully determine the role of Actiq for the management of acute, refractory migraine. 2. Pre-Anesthesia (Preoperative Anxiolysis and Sedation and/or Supplement to Anesthesia): Another similar product, Fentanyl Oralet, was previously available (but was discontinued in 2001). This product, Fentanyl Oralet was approved for the preoperative anxiolysis and sedation and as a supplement to anesthesia. 10 Fentanyl Oralet was only to be used when the patient would be monitored by trained personnel supported by appropriate, readily available equipment and only for use as a premedicant prior to anesthesia or for inducing conscious sedation prior to diagnostic or therapeutic procedures in a monitored anesthesia care setting. Fentanyl Oralet was contraindicated for use in a home setting or any setting other than a hospital setting such as an operating room, emergency department, intensive-care unit, or other monitored anesthesia care setting in which adequate facilities, equipment, and drugs for monitoring and treating potential complications of therapy are immediately accessible. Because of the excessive frequency of clinically important hypoventilation associated with high doses, buccal doses were not > 15 mcg/kg (maximum dose is 400 mcg) for children and were not > 5 mcg/kg (maximum dose is 400 mcg) for adults. This use is typically a one-time dose administered in the monitored setting, and there is a multitude of other narcotic options for use as a pre-anesthetic for adults and children. Considerations This Blue Cross and Blue Shield of Kansas City policy statement was developed using available resources such as, but not limited to: Food and Drug Administration (FDA) approvals, Facts and Comparisons, National specialty guidelines, Local medical policies of other health plans, Medicare (CMS), Local providers. Description of Procedure or Service Overview Actiq (generics), Abstral, Fentora, Onsolis (discontinued), and Subsys are immediate-release oral transmucosal formulations of fentanyl citrate. 1-6 Lazanda is a nasal spray intended for intranasal transmucosal administration. 7 The transmucosal fentanyl products are indicated only for the

3 management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. 1-7 Patients considered opioid tolerant are those who are taking at least 60 mg of oral morphine daily, at least 25 mcg of transdermal fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg oral hydromorphone daily, at least 25 mg oral oxymorphone daily, or an equianalgesic dose of another opioid for a week or longer. The appropriate dosing and safety of Actiq (generics) in opioid tolerant children with breakthrough cancer pain have not been established in those below 16 years of age. 1,3 The safety and efficacy of Abstral, Fentora, Onsolis, Subsys, and Lazanda have not been established in pediatric patients below 18 years of age. 2,4-7 The transmucosal fentanyl products are contraindicated in the management of acute or postoperative pain and in patients with known intolerance or hypersensitivity to any of its components or the drug fentanyl. 1-7 In addition, these products must not be used in opioid non-tolerant patients (contraindicated). The transmucosal fentanyl products are approved for use only in the care of cancer patients and only by healthcare professionals 1-6 (oncologists and pain specialists) 2-3,6 who are knowledgeable of and skilled in the use of Schedule II opioids to treat cancer pain. Because of the risk of misuse, abuse, addition, and overdose, these products are available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Transmucosal Immediate- Release Fentanyl (TIRF) REMS ACCESS program. Under the TIFR REMS ACCESS program, outpatients, prescribers who prescribe to outpatients, pharmacies, and distributors must enroll in the program. Rationale Actiq (generics), Abstral, Fentora, Lazanda, Onsolis, and Subsys are indicated for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Actiq (generics), Abstral, Fentora, Lazanda, Onsolis, and Subsys are indicated for use in conjunction with a long-acting narcotic agent in treating patients with cancer pain. In addition, in clinical studies, long-acting narcotics were used concomitantly with oral transmucosal fentanyl citrate for chronic (noncancer) pain. Limited data are available on the use of oral transmucosal fentanyl citrate (OTFC) in the management of non-cancer chronic pain A nonrandomized, open-label, prospective, single-center study assessed the efficacy of transdermal fentanyl plus OTFC for breakthrough pain in 215 opioid-naïve adults with severe noncancer pain (defined as visual analog scale score [VAS] of at least 8 of 10) for at least 6 months. 9 The types of noncancer chronic pain were arthrosis (24%), ischemic vascular disease (20%), postlaminectomy syndrome (16%), vertebral compression fracture (10%), trigeminal neuralgia (10%), disk herniation (8%), rheumatoid arthritis (4%), diabetic polyneuropathy (4%), scoliosis (2%), and central pain (2%). Use of transdermal and transmucosal fentanyl lead to a reduction in the VAS score from 9.86 at baseline to 2.05 at Month 6 (P < 0.001). Another change seen was a drop in the poor sleep quality from 99% at baseline to 2.8% at Month 6 (P < 0.001). The average daily consumption of OTFC units was 4.64 at Month 1, 3.21 at Month 3, and 2.62 at Month 6. Another study involving 90 patients with chronic pain (most [58%] had degenerative spine disease) who were also receiving a long-acting opioid were allowed to use Actiq for self-treatment of emergency pain flares. 10 Nearly 96% of these patients found Actiq effective for self-treatment. In addition, case reports have noted that use of Actiq for treating breakthrough pain in patients with sickle cell disease (SCD), in conjunction with a long-acting opioid, was efficacious for pain relief and decreased hospital admissions for these SCD patients. 11 Two patient-reported surveys on OTFC (Actiq) use for breakthrough pain management in chronic non-cancer pain patients also receiving other opioid therapy for persistent pain have also been published In the first patient survey (n = 29), over 95% of patients stated that OTFC provided good, very good, or excellent reduction in breakthrough pain, and over 80% stated that

4 OTFC was better than other breakthrough pain medications that they had used, except for morphine, in which only 41% rated OTFC better. 12 Another patient-reported survey (n = 43) found that OTFC was effective in controlling breakthrough pain and improved various quality of life measures (e.g., enjoyment of life, mood, general activity level, ability to work with others, work, ability to sleep at night, etc.). 13 There are two published, randomized, double-blind, placebo-controlled studies which assessed the use of Fentora in opioid-tolerant patients receiving long-acting or around-the-clock (ATC) opioid therapy for the management of breakthrough pain episodes due to chronic neuropathic pain (associated with diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, or complex regional pain syndrome) 14 or chronic low back pain. 15 In both of these studies, Fentora was statistically significantly better than placebo at reducing the pain intensity scores and providing pain relief, and Fentora patients were four times less likely to require supplemental rescue (opioid) medication use than placebo patients In an 18-month, open-label safety study 16 that accepted patients naïve to Fentora, as well as patients from one of the previously detailed controlled studies involving adults with chronic noncancer pain, secondary efficacy assessments showed that average pain ratings (assessed by Brief Pain Inventory [BPI]) remained relatively stable throughout the study. 16 In a 12-week study with three within-patient, randomized, double-blind, placebo-controlled, multi-crossover segments at monthly intervals in patients with chronic non-cancer pain (not including headache or migraine), Fentora demonstrated continued efficacy vs. placebo (P < ) as assessed by the summed pain intensity differences 5 to 60 minutes post-dose (SPID 60 ) [mean 7.7 vs. 4.6, respectively, during the final randomized, controlled segment]. 17 References 1. Actiq oral transmucosal [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; December Fentora buccal tablet [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; December Oral Transmucosal Fentanyl Citrate (OTFC) [prescribing information]. Chestnut Ridge, NY: Par Pharmaceuticals; March Onsolis buccal soluble film [prescribing information]. Somerset, NJ: Meda Pharmaceuticals, Inc.; December Abstral sublingual tablets [prescribing information]. Solana Beach, CA: Sentynl Therapeutics, Inc.; December Subsys sublingual spray [prescribing information]. Chandler, AZ: Insys Therapeutics, Inc.; December Lazanda nasal spray [prescribing information]. Newark, CA: Depomed, Inc.; March Shaiova L, Lapin J, Manco LS, et al. Tolerability and effects of two formulations of oral transmucosal fentanyl citrate (OTFC; ACTIQ) in patients with radiation-induced oral mucositis. Support Care Cancer. 2004;12: Landy SH. Oral transmucosal fentanyl citrate for the treatment of migraine headache pain in outpatients: a case series. Headache. 2004;44(8): McEvoy GE, ed. AHFS drug information Bethesda, MD: American Society of Health- System Pharmacists; 2001: Billing Coding/Physician Documentation Information NA Pharmacy benefit Additional Policy Key Words Policy Implementation/Update Information 9/2007 New policy titled Short Acting Fentanyl 9/2008 No policy statement changes. 9/2009 Removed criteria for breakthrough chronic non-cancer pain. Added statement: formulary short-acting strong narcotic analgesic alternatives (other than fentanyl) have been

5 ineffective, not tolerated, or contraindicated. Added statement: Patient is opioid tolerant and taking at least the equivalent of 60 mg of oral morphine daily. Added table. Added statement: Fentanyl citrate oral transmucosal lozenge is considered investigational when used for any condition other than breakthrough cancer pain, including, but not limited to, the treatment of pain associated with migraine headaches. 7/2010 Removed references to Actiq and Fentora, replaced with oral short-acting fentanyl. 9/2010 No policy statement changes 9/2011 No policy statement changes 09/2012 Reviewed no changes made 09/2013 Reviewed no changes made 09/2014 Reviewed no changes made 09/2015 Reviewed- updated references. No changes to policy statement 09/2016 No changes to policy statement 03/2017 Added step therapy requirement 09/2017 Reviewed no changes made to policy statement 12/2017 Changed step therapy requirement to fentanyl citrate lozenges as preferred 08/2018 Reviewed no changes made to policy statement, formatting changes only State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC. APPENDIX A STC * STC Description 0475 ANTINEOPLASTICS, MISCELLANEOUS ANTINEOPLASTICS /-DRUG 7235 COMPLEXES 0471 ANTINEOPLASTIC - ANTIMETABOLITES C232 ANTINEOPLASTIC - MTOR KINASE INHIBITORS 9150 ANTINEOPLASTIC SYSTEMIC ENZYME INHIBITORS 0470 ANTINEOPLASTIC - ALKYLATING AGENTS C593 ANTINEOPLASTIC - AROMATASE INHIBITORS ANTINEOPLAST HUM VEGF INHIBITOR RECOMB MC 8585 ANTINEOPLAST, HISTONE DEACETYLASE (HDAC) B759 INHIBITORS 6323 ANTINEOPLASTIC - ANTIANDROGENIC AGENTS C532 ANTINEOPLASTIC - TOPOISOMERASE I INHIBITORS G575 ANTINEOPLASTIC - MEK1 AND MEK2 KINASE INHIBITORS F501 ANTINEOPLASTIC - VEGFR ANTAGONIST G590 ANTINEOPLASTIC - ANTI-CD38 MONOCLONAL ANTINEOPLASTIC LHRH(GNRH) AGONIST, PITUITARY 8254 SUPPR. ANTINEOPLASTIC - ANTI-SLAMF7 MONOCLONAL G607 ANTINEOPLASTIC EGF RECEPTOR BLOCKER MCLON 8569 E150 ANTINEOPLASTIC - HEDGEHOG PATHWAY INHIBITOR ANTINEOPLASTIC LHRH(GNRH) 8460 ANTAGONIST,PITUIT.SUPPRS D560 ANTINEOPLASTIC - HALICHONDRIN B ANALOGS ANTINEOPLASTIC - IMMUNOTHERAPY, VIRUS-BASED G545 AGENTS

6 C370 ANTINEOPLASTIC - EPOTHILONES AND ANALOGS E039 ANTINEOPLASTIC - JANUS KINASE (JAK) INHIBITORS ANTINEOPLASTIC, ANTI-PROGRAMMED DEATH-1 (PD-1) F665 MAB ANTINEOPLASTIC, PDGFR-ALPHA BLOCKER MC H ANTINEOPLASTIC - VINCA ALKALOIDS 7977 ANTINEOPLASTIC IMMUNOMODULATOR AGENTS ANTINEOPLASTIC - IMMUNOTHERAPY, THERAPEUTIC D426 VAC F495 ANTINEOPLASTIC - INTERLEUKIN-6(IL-6)INHIB, ANTINEOPLASTIC- B CELL LYMPHOMA-2(BCL-2) G802 INHIBITORS E600 ANTINEOPLASTIC - VEGF-A,B AND PLGF INHIBITORS 0473 ANTIBIOTIC ANTINEOPLASTICS CYTOTOXIC T-LYMPHOCYTE ANTIGEN (CTLA-4) RMC D687 G857 ANTI-PROGRAMMED CELL DEATH-LIGAND 1 (PD-L1) MAB ANTINEOPLASTIC COMB-KINASE AND AROMATASE H214 INHIBIT ANTINEOPLASTIC-ISOCITRATE DEHYDROGENASE H289 INHIBITORS H309 ANTINEOPLASTIC ANTIBIOTIC AND ANTIMETABOLITE ANTINEOPLASTIC CD22 -CYTOTOXIC H317 ANTIBIOTIC ANTINEOPLASTIC- CD19 DIR. CAR-T CELL H324 IMMUNOTHERAPY ANTINEOPLASTIC CD33 -CYTOTOXIC H329 ANTIBIOTIC * Excluding topical products APPENDIX B ICD-9 Codes ICD-10 Codes Cancer-related codes 140.* to 209 C00.* to D09.* 230.* to 234 D3A.* to D48.* 235.* to 239 E34.0* Q85.0*