Download MD WISE PRIOR AUTHORIZATION PROTOCOL FOR INJECTABLE 5-

MD WISE PRIOR AUTHORIZATION PROTOCOL FOR INJECTABLE 5HYDROXYTRYPTAMINE-3 (5HT3) SEROTONIN RECEPTOR ANTAGONISTS
FORMULARY STATUS: Generic Ondansetron or Granisetron Preferred
Aloxi® palonosetron hydrochloride: 0.25 mg in 5 ml, is supplied as a single-use vials ready for
ntravenous injection
Anzemet® dolasetron mesylate: 20mg/ml supplied as 12 .5mg/0.625ml single-use vial, 12.5mg/0.625ml fill
in single-use 2ml cartridge, 100mg/5ml single-use vial, 500mg/25ml multi-dose vial
Kytril® granisetron hydrochloride: 1 mg/1 ml, is supplied in 1 ml single-use vials and 4 ml multi-use vials
and 0.1 mg/1 ml, is supplied in 1 ml single-use vials
Zofran® ondansetron: 2 mg/ml is supplied as follows: 2 ml single-dose vials and 20 ml multidose vials
(singles)
Initial Approval:

The request for the medication is for an Food and Drug Administration (FDA) approved indication,
and/or is used for a medical condition that is supported by the medical compendium (Micromedex,
American Hospital Formulary Service (AHFS), Drug Points , Drug Package Insert) as defined in the
Social Security Act 1927 and/or per the National Comprehensive Cancer Network (NCCN), the
American Society of Clinical Oncology (ASCO), National Cancer Institute {NCI} (a Division of the U.S.
National Institutes of Health) and the Multinational Association of Supportive Care in Cancer (MASCC)
standard of care guidelines for antiemetic therapy.

Patients receiving an antineoplastic agent classified as Level 4 or greater per the Hesketh classification
(see appendix1) can receive Aloxi® (palonosetron hydrochloride) as a first line antiemetic agent.

For all other patients, if the medication request is for any other 5-hydroxytryptamine-3 (5HT3) serotonin
receptor antagonist other than generic Ondansetron or generic Granisetron, the patient has a
documented (consistent with pharmacy claims data, OR for new members to the health plan consistent
with medical chart history) treatment failure after receiving an adequate trial of generic Ondansetron or
generic Granisetron and/or has another documented medical reason ( intolerance, hypersensitivity,
contraindication, etc) for not utilizing these medications to treat their medical condition.

Prescribed dosing of the 5HT3 serotonin receptor antagonist is within FDA approved indications and/or
is supported by the medical compendium as defined by the Social Security Act and/or per the NCCN,
ASCO, NCI or MASCC standard of care guidelines.

The medication is recommended and prescribed by a specialist in the field to treat the patient’s
respective medical condition.
If all of the above conditions are met, the request will be approved for up to 3 months or as recommended
per FDA approved indications and/or as defined by the medical compendium as defined above and/or per
the NCCN, ASCO, NCI or MASCC standard of care guidelines; if all of the above criteria are not met, the
request is referred to a Medical Director for medical necessity review.
Reauthorization of Medication:

The prescribing physician has provided documentation as to the clinical benefits of the medication
supporting continued treatment, OR the medication is being continued in accordance with the
recommended time as defined by FD drug package insert, and/or per recommendations of the medical
compendium as described above, and/or per the NCCN, ASCO, NCI or MASCC standard of care
guidelines.
If all of the above conditions are met, the request will be approved for up to 3 months or as recommended
per FDA approved indications and/or as defined by the medical compendium as defined above and/or per
the NCCN, ASCO, NCI or MASCC standard of care guidelines; if all of the above criteria are not met, the
request is referred to a Medical Director for medical necessity review.
FDA Approved Indications, Dosing and Administration:
Palonosetron (Aloxi®)
Highly or moderately emetogenic chemotherapy-induced [acute or delayed] nausea and vomiting
prophylaxis:

18 y/o and older: single dose of 0.25 mg administered IV over 30 seconds given approximately 30
minutes before the start of chemotherapy. No safety or efficacy established for repeat doses, therefore,
administration of an additional dose within a 7-day period is not recommended.
Postoperative Nausea and Vomiting

18 y/o and older: single dose of 0.25 mg administered IV over 10 seconds given immediately before the
induction of anesthesia.
Dolasetron (Anzemet®)
Highly or moderately emetogenic chemotherapy-induced nausea and vomiting prophylaxis in adults
or children:

For patients 2-16 y/o:1.8 mg/kg IV given over a period of up to 15 minutes, beginning approximately 30
minutes before administration of emetogenic chemotherapy drug. (Maximum pediatric dose is 100 mg).

For patients 17 y/o and older: 1.8mg/kg given as a single dose approximately 30 minutes before
chemotherapy. Alternatively, for most patients, a fixed dose of 100mg can be administered over 30
seconds.
Post-Operative nausea and vomiting:

17 y/o and older (prophylaxis): 12.5 mg IV as a single dose approximately 15 minutes before cessation
of anesthesia.

17 y/o and older (treatment): 12.5 mg IV as a single dose as soon as nausea and/or vomiting presents.

2-16 y/o (prophylaxis and treatment): 0.35 mg/kg as a single dose approximately 15 minutes before
cessation of anesthesia or as soon as nausea and/or vomiting develops to a maximum dose of 12.5 mg
per dose.
Granisetron (Kytril®)
Highly or moderately emetogenic chemotherapy-induced nausea and vomiting prophylaxis in adults
or children:

10 mcg/kg IV administered within 30 minutes before initiation of emetogenic chemotherapy. The dose
may be administered undiluted over 30 seconds, or diluted in 5% dextrose or NSS and infused over 5
minutes. Pediatric patients under 2 years of age have not been studied.
Post-Operative nausea and vomiting:

4 y/o and older (prophylaxis): single IV dose of 1 mg is given undiluted over 30 seconds before
induction of anesthesia or immediately before reversal of anesthesia.

4 y/o and older (treatment): 1 mg undiluted IV is given over 30 seconds.
Ondansetron (Zofran®)
Highly or moderately emetogenic chemotherapy-induced nausea and vomiting prophylaxis: {several
regimens exist}
18 y/o and older

single-dose of 32mg given as a 15 minute infusion IV 30 minutes before administration of single day
chemotherapy agent. Do not repeat. This dosing is typically reserved for highly emetogenic
chemotherapy.

0.15mg/kg as 15 minute infusion begin 30 minutes before administration of chemotherapy and
subsequent doses given at 4 and 8 hours after first dose.

8 mg IV over 15 minutes begin 30 minutes prior to chemotherapy followed immediately by a continuous
infusion of 1mg/hr for up to 24 hrs.
6 mos to 18 y/o:

0.15mg/kg as 15 minute infusion begin 30 minutes before administration of chemotherapy and
subsequent doses given at 4 and 8 hours after first dose.

3-5mg/m2 given over 15 minutes begin immediately prior to chemotherapy followed after chemotherapy
by oral ondansetron 4 mg Q8hrs for up to 5 days.
Post-Operative nausea and vomiting:

12 y/o and older (prophylaxis): single IV dose of 4 mg preferably over 2-5 minutes beginning
immediately prior to induction of anesthesia OR 4mg as a single undiluted IM injection given
immediately prior to induction of anesthesia.

12 y/o and older (treatment): if patient experiences nausea and/or vomiting shortly after surgery can
give single IV dose of 4 mg.

1month -12y/o (prophylaxis and treatment): single IV dose of 0.1 mg/kg for patient weight of 40kg or
less OR if weight is between 40-80 kg give single IV dose of 4mg IV. Administer over 2-5 minutes
immediately prior to or following anesthesia induction or shortly after surgery if nausea and/or vomiting
occurs.

Per the manufacturer of ondansetron, if the patient does not achieve adequate control of postoperative
nausea and vomiting with a single 4 mg IV dose given prior to induction of anesthesia they will not
nd
benefit from a 2 4mg dose given postop.
References:
1. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology: Antiemesis.
Version 3.2009.
2. American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update 2006. Journal of
Clinical Oncology.2006; 24(18):2932-2947. Erratum pages 5341-5342.
3. Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer
(MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at
www.mascc.org.
4. US National Institutes of Health. National Cancer Institute. Nausea and vomiting PDQ. Health
Professional Version. Treatment of acute/delayed emesis. Available at
www.cancer.gov/cancertopics/pdq/supportivecare/nausea/HealthProfessional. Last modified
10/19/2006.
5. Roila F. Warr D. Clark-Snow RA. Et al . Delayed emesis: moderately emetogenic chemotherapy.
Supportive Cancer Care. 2005;13:104-108.
6. Prescribing information Kyril®. Roche Pharmaceuticals. 11/2005.
7. Prescribing information Anzemet ® Sanofi-aventis. 10/2009.
8. Prescribing information Aloxi®. Helsinn. 02/2008.
9. Prescribing information Zofran®. GlaxoSmithKline. 10/2009.
10. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for Classifying the Acute Emetogenicity of Cancer
Chemotherapy. Journal of Clinical Oncology.1997;15(1): 103-09.
Revision/Review Date: MAC 10/12/2011
Associated Policy: Prior Authorization of Medications 236.200
NOTE: Physician reviewer must override criteria when, in his/her professional judgment, the
requested item is medically necessary.
APPENDIX
1
Emetogenic Potential of Single Chemotherapy Agents
Frequency of Emesis
Agent
2
2
>90
Carmustine > 250mg/m , Cisplatin > 50mg/m , Cyclophosphamide
2
>1,500 mg/m , Dacarbazine, Mechlorethamine, Streptozocin
2
2
4
60-90
Carboplatin, Carmustine < 250mg/m , Cisplatin <50mg/m ,
2
2
Cyclophosphamide > 750mg/m < 1,500 mg/m , Cytarabine > 1g/
2
2
2
m , Doxorubicin > 60 mg/m , Methotrexate > 1,000 mg/m ,
Procarbazine (oral)
2
3
30-60
Cyclophosphamide < 750mg/m , Cyclophosphamide (oral),
2
2
Doxorubicin 20 - 60 mg/m , Epirubicin < 90 mg/m ,
Hexamethylmelmine (oral), Idarubicin, Methotrexate 250-1,000 g/
2
2
m , Mitoxantrone < 15 mg/m
2
2
10-30
Docetaxel, Etoposide, 5-FU <1,000 mg/ m , Gemcitabine,
2
Methotrexate > 50 < 250 mg/ m , Mitomycin, Paclitaxel
1
<10
Bleomycin, Busulfan, Chlorambucil (oral), 2-Chlorodeoxyadenosine,
2
Fludarabine, Hydroxyurea, Methotrexate < 50 mg/ m , Lphenylalanine mustard (oral), Thioguanine (oral), Vinblastine,
Vincristine, Vinorelbine
Hesketh PJ, Kris MG, Grunberg SM, et al.. Proposal for Classifying the Acute Emetogenicity of Cancer
Chemotherapy. Journal of Clinical Oncology.199715(1): 103-09
Level
5
APPENDIX2
EMETIC RISK GROUPS
High
Risk in nearly all patients (>90%)
Moderate
Risk in 30% to 90% of patients
Low
Risk in 10% to 30% of patients
Minimal
Risk in fewer than 10% of patients
Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer
(MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at
www.mascc.org.
EMETIC RISK OF INTRAVENEOUSLY ADMINISTERED ANTINEOPLASTIC AGENTS
Emetic Risk (incidence of
emesis w/o antiemetics)
Agent
2
High (>90%)
Cisplatin ≥ 50 mg/m , Mechlorethamine, Streptozocin, Cyclophosphamide
2
≥ 1500mg/m , Carmustine, Dacarbazine, Dactinomycin, Altretamine, AC
combination defined as either Doxorubicin or Epirubicin with
Cyclophosphamide
2
Moderate (30%-90%)
Ifosfamide, Cyclophosphamide <1500mg/m , Doxorubicin, Daunorubicin,
2
Epirubicin, Idarubicin, Irinotecan, Aldesleukin >12-15 milllion units/m ,
2
Amifostine >300 mg/m , Arsenic Trioxide, Azacitidine, Bisulfan >4mg/day,
2
Dactinomycin, Lomustine, Melphalan >50mg/m , Methotrexate 250->1000
2
mg/m ,
2
Low (10%-30%)
Amifostine <300 mg/m , Bexarotene,Paclitaxel, Paclitaxel-albumin,
Docetaxel, Mitoxantrone, Topotecan, Etoposide, Pemetrexed,
2
2
Methotrexate >50mg/m <250mg/m , Mitomycin, Doxorubicin Liposomal,
2
Gemcitabine, Cytarabine ≤ 1000mg/m , 5-Fluorouracil, Bortezomib,
Cetuximab, Trastuzumab
Minimal (<10%)
Alemtuzumab, Alpha Interferon, Asparaginase, Bevacizumab, Bleomycin,
Bortezomib, Busulfan, 2-Chlorodeoxyadenosine (Cladribine), Decitabine,
Denileukin difititox, Dexrazoxane, Fludarabine, Gemtuzumab ozogamicin,
2
Methotrexate ≤ 50mg/m , Nelarabine, Pentostatin, Rituximab,
Trastuzumab, Vinblastine, Vincristine, Vinorelbine
American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update 2006. Journal of
Clinical Oncology.2006;24(18):2932-2947. Erratum pages 5341-5342.; National Comprehensive Cancer
Network. Clinical Practice Guidelines in Oncology: Antiemesis. Version 1.2007.
EMETIC RISK OF ORALLY ADMINISTERED ANTINEOPLASTIC AGENTS
Emetic Risk (incidence of
emesis w/o antiemetics)
Agent
High (>90%)
Hexamethylmelamine, Procarbazine
Moderate (30%-90%)
Cyclophosphamide, Etoposide, Temozolomide, Vinorelbine, Imatinib
Low (10%-30%)
Capecitabine, Fludarabine
Minimal (<10%)
Chlorambucil, Hydroxyurea, L-Phenylalanine mustard, 6-Thioguanine,
Methotrexate, Gefitinib, Dasatinib, Erlotinib, Lenalidomide, Melphalan,
Sorafenib, Sunitinub, Thalidomide, Thioguanine,
Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer
(MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at
www.mascc.org.
EMETIC RISK WITH RADIATION THERAPY
Emetic Risk (incidence of
emesis w/o antiemetics)
Agent
High (>90%)
Total Body Irradiation
Moderate (30%-90%)
Upper Abdomen
Low (10%-30%)
Lower thorax region, Pelvis, Cranium (radiosurgery), Craniospinal
Minimal (<10%)
Head and Neck, Extremities, Cranium, Breast,
Perugia International Cancer Conference VII. Multinational Association of Supportive Care in Cancer
(MASCC). Consensus Conference on Antiemetic Therapy. Last Updated 9/1/2005. Available at
www.mascc.org; American Society of Clinical Oncology Guidelines for Antiemetics in Oncology: Update
2006. Journal of Clinical Oncology.2006;24(18):2932-2947. Erratum pages 5341-5342.