Prior Authorization Protocol ALOXI (palonosetron), ANZEMET (dolasetron), SANCUSO , GRANISOL ™ (granisetron) NATL Coverage of drugs is first determined by the member’s pharmacy or medical benefit. Please consult with or refer to the Evidence of Coverage document. I. FDA Approved Indications: Granisetron Anzemet Anzemet Granisetron Sancuso Aloxi injection tablet & injection tablet injection patch Granisol Moderately emetogenic X cancer X Patient is chemotherapy X In adults receiving (MEC)- Also approved and chemotherapy prevention of for delayed X X children 2 regimens up acute nausea & nausea and years and to 5 vomiting vomiting older consecutive associated with days duration initial and repeat courses X Also indicated in pediatric patients aged 1 month to Highly less than 17 years emetogenic for prevention of X cancer acute nausea and Patient is chemotherapy vomiting receiving (HEC)- associated with chemotherapy prevention of initial and repeat X X regimens up acute nausea & courses of to 5 vomiting emetogenic consecutive associated with cancer days duration initial and chemotherapy, repeat courses. including highly emetogenic cancer chemotherapy Prevention of nausea & vomiting X associated with radiation (RINV), Draft Prepared: December 17, 2002 1 Approved by Health Net Pharmacy and Therapeutics Committee: 4.11.06, 5.16.07, 05.21.08, 11.18.09, 11.17.10, 11.9.11, 11.14.12, 11.20.13, 11.19.14, 11.18.15 Updated: 10.17.03, 1.24.05, 12.07.05 RJL, 01.02.06 JP, 02.06.06 RJL, 02.27.06 RJL, 08.18.06 RO, 04.03.07 RO, 9.20.07 RO, 1.04.08 RO, 08.08.08 RO, 08.01.09 R Olegario, 10.26.10 R Olegario, 06.07.11 A Giordano, 7.12.12 R. Gedey, 07.11.13 MJMcClusky,07.07.14 S Mirando, 06.19.15 T You02.10S Ahantab, 12.15.16 M Del Nero Prior Authorization Protocol ALOXI (palonosetron), ANZEMET (dolasetron), SANCUSO , GRANISOL ™ (granisetron) NATL Granisetron Anzemet Anzemet Granisetron Sancuso Aloxi injection tablet & injection tablet injection patch Granisol including total body irradiation and fractionated abdominal radiation X Used for up to X Prevention of 24 hours In adults postoperative following and nausea and surgery. X children 2 vomiting Efficacy beyond years and (PONV). 24 hours has older not been demonstrated X Treatment of In adults postoperative and nausea and X children 2 vomiting years and (PONV) older II. Health Net Approved Indications and Usage Guidelines: Prevention of nausea and vomiting associated with cancer chemotherapy for Anzemet tablet, Granisetron injection and tablet, Granisol and Sancuso patch: • Patient has received, or will receive, highly or moderately emetogenic chemotherapy AND • Failure or clinically significant adverse events to ondansetron or Aloxi Prevention of nausea and vomiting associated with radiation therapy (RINV) for Granisetron tablet and Granisol: • Patient will receive radiation therapy AND • Failure or clinically significant adverse events to ondansetron Prevention of postoperative nausea and vomiting (PONV) for Aloxi, Anzemet injection and Granisetron injection: • Patient is undergoing surgery AND Draft Prepared: December 17, 2002 2 Approved by Health Net Pharmacy and Therapeutics Committee: 4.11.06, 5.16.07, 05.21.08, 11.18.09, 11.17.10, 11.9.11, 11.14.12, 11.20.13, 11.19.14, 11.18.15 Updated: 10.17.03, 1.24.05, 12.07.05 RJL, 01.02.06 JP, 02.06.06 RJL, 02.27.06 RJL, 08.18.06 RO, 04.03.07 RO, 9.20.07 RO, 1.04.08 RO, 08.08.08 RO, 08.01.09 R Olegario, 10.26.10 R Olegario, 06.07.11 A Giordano, 7.12.12 R. Gedey, 07.11.13 MJMcClusky,07.07.14 S Mirando, 06.19.15 T You02.10S Ahantab, 12.15.16 M Del Nero Prior Authorization Protocol ALOXI (palonosetron), ANZEMET (dolasetron), SANCUSO , GRANISOL ™ (granisetron) NATL • Failure or clinically significant adverse events to ondansetron Treatment of PONV for Anzemet injection and Granisetron injection: • Patient underwent surgery AND • 5-HT 3 antagonist was not used for prevention of PONV III. Coverage is Not Authorized For: • Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section unless there is sufficient documentation of efficacy and safety in the published literature. • Anzemet injection solution is contraindicated in adult and pediatric patients for the prevention of nausea and vomiting associated with the initial and repeat courses of emetogenic cancer chemotherapy IV. General Information: • The NCCN Antiemesis guidelines Version 1.2012 added Aloxi as the preferred 5HT-3 antagonist for highly or moderately emetogenic chemotherapy • Anzemet injection solution prolongs the QT interval in a dose dependent fashion. Torsades de Pointes has been reported during post-marketing experience. Avoid Anzemet in patients with congenital long QT syndrome, hypokalemia or hypomagnesemia. • Anzemet injection solution administered intravenously is contraindicated in adult and pediatric patients for the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy due to dose dependent QT prolongation. • When prophylaxis has failed using Anezemt injection, a repeat dose should not be initiated as rescue therapy. • Serotonin subtype 3 (5-HT3) receptor antagonist may cause serotonin syndrome alone but particularly with concomitant use of serotonergic drugs. • According to the 2011 American Society of Clinical Oncology (ASCO) Guideline for Antiemetics in Oncology, the Update Committee recommends the following: • For chemotherapy of high emetic risk - three-drug combination of 5-hydroxytryptamine-3 (5-HT3) serotonin receptor antagonist, dexamethasone, and aprepitant. The oral combination of netupitant and palonosetron plus dexamethasone is an additional treatment option in this setting. For chemotherapy of moderate emetic risk - two-drug combination of a 5-HT3 serotonin receptor antagonist and dexamethasone • Per practice guidelines from the National Comprehensive Cancer Network (NCCN), selection of emetogenic agents used should be based on the emetic risk of the therapy, prior experience with antiemetics, as well as patient risk factors. • The following table is NCCN’s classification for emetogenic potential of significant chemotherapy and other agents. Draft Prepared: December 17, 2002 3 Approved by Health Net Pharmacy and Therapeutics Committee: 4.11.06, 5.16.07, 05.21.08, 11.18.09, 11.17.10, 11.9.11, 11.14.12, 11.20.13, 11.19.14, 11.18.15 Updated: 10.17.03, 1.24.05, 12.07.05 RJL, 01.02.06 JP, 02.06.06 RJL, 02.27.06 RJL, 08.18.06 RO, 04.03.07 RO, 9.20.07 RO, 1.04.08 RO, 08.08.08 RO, 08.01.09 R Olegario, 10.26.10 R Olegario, 06.07.11 A Giordano, 7.12.12 R. Gedey, 07.11.13 MJMcClusky,07.07.14 S Mirando, 06.19.15 T You02.10S Ahantab, 12.15.16 M Del Nero Prior Authorization Protocol ALOXI (palonosetron), ANZEMET (dolasetron), SANCUSO , GRANISOL ™ (granisetron) NATL Agents Frequency of Emesis AC combination defined as either doxorubicin or epirubicin with cyclophosphamide, carmustine > 250 mg/m 2, cisplatin, 2 High Emetic Risk cyclophosphamide > 1,500 mg/m , doxorubicin ≥ 60mg/m², epirubicin >90% >90mg/m², ifosfamide ≥ 2gm/m² per dose, dacarbazine, 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/m 2, cytarabine Moderate Emetic Risk > 200mg/m 2, dactinomycin, daunorubicin, doxorubicin < 60 mg/m2, 30-90% epirubicin ≤ 90mg/m², idarubicin, ifosfamide < 2gm/m² per dose, interferon alpha ≥ 10 million IU/m 2, irinotecan, melphalan, MTX ≥ 250 mg/m 2, oxaliplatin, temozolomide ado-trastuzumab emtansine, amifostine ≤ 300 mg, aldesleukin ≤ 12 million IU/m 2, brentuximab vedotin,cabazitaxel, carfilzomib, cytarabine (low dose) 100 - 200 mg/m 2, docetaxel, doxorubicin (liposomal), eribulin,etoposide, 5-fluorouracil, floxuridine, gemcitabine, interferon Low Emetic Risk alpha > 5 <10 million IU/m 2, ixabepilone, MTX > 50 mg/m 2 < 250 10-30% mg/m 2, mitomcyin, mitoxantrone, omacetaxine,paclitaxel, paclitaxel- albumin, pemetrexed, pentostatin,pralatrexate, romidepsin, thiotepa, topotecan, ziv-aflibercept alemtuzumab, asparaginase, bevacizumab, bleomycin, bortezomib, cetuximab, 2-chlorodeoxyadenosine (cladribine), cytarabine < 100mg/m 2, decitabine, denileukin diftitox, dexrazoxane, fludarabine, , Minimal Emetic Risk interferon alpha ≤ 5 million IU/m 2, ipilimumab, MTX ≤ 50 mg/m 2, <10% nelarabine, ofatumumab, panitumumab, pegaspargase,peginterferon, pertuzumab, rituximab, temsirolimus, trastuzumab, valrubicin, vinblastine, vincristine, vincristine (liposomal), vinorelbine altretamine, busulfan ( ≥ 4 mg/d), crizotinib, cyclophosphamide ( ≥ 100 Emetogenic potential of mg/m 2/d), estramustine, etoposide, lomustine (single day), mitotane, oral antineoplastic procarbazine, temozolomide (> 75 mg/m 2/d), vismodegib agents: Moderate to High axitinib,bexarotene, bosutinib, busulfan (< 4 mg/d), cabozantinib, capecitabine, chlorambucil, cyclophosphamide (< 100 mg/m 2/d), dasatinib,dabrafenib, erlotinib, everolimus, fludarabine, gefitinib, Emetogenic potential of hydroxyurea, imatinib, lapatinib, lenalidomide, melphalan, oral antineoplastic mercaptopurine, methotrexate, nilotinib, pazopanib, pomalidomide, agents: Minimal to low ponatinib, regorafenib, ruxolitinib,sorafenib, sunitinib, temozolomide ( ≤ 75 mg/m 2/d), thalidomide, thioguanine, topotecan,trametinib, tretinoin, vandetanib, vemurafenib, vorinostat V. Therapeutic Alternatives: Draft Prepared: December 17, 2002 4 Approved by Health Net Pharmacy