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Asset Publisher
Antiemetic Step Therapy with Quantity Limit Program Summary
Policy Number: PH-1025
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
POLICY REVIEW CYCLE
Effective Date |
Date of Origin |
10/1/2022 |
|
FDA APPROVED INDICATIONS AND DOSAGE
Agent(s) |
FDA Indication(s) |
Notes |
Ref# |
Akynzeo® (netupitant/palonosetron) Capsule |
|
|
1 |
Anzemet® (dolasetron) Tablet |
|
|
2 |
Emend® (aprepitant) Capsule* Oral suspension |
Emend capsules
Emend oral suspension
Limitations of use:
|
* – generics available |
3 |
granisetron^ Tablet |
|
^ – available as generic only |
4 |
Sancuso® (ganisetron) Transdermal patch |
|
|
5 |
Varubi® (rolapitant) Tablet |
|
|
6 |
Zofran®/ Zofran ODT®/ondansetron* (ondansetron) Tablet Orally disintegrating tablet^ Oral solution |
|
* – generics available ^ – available as generic only |
7 |
Zuplenz® (ondansetron) Oral soluble film |
|
|
8 |
See package insert for FDA prescribing information: https://dailymed.nlm.nih.gov/dailymed/index.cfm
CLINICAL RATIONALE
Guidelines |
Multiple randomized clinical trials along with current guidelines in antiemesis demonstrate that granisetron (oral and injectable), ondansetron (oral and injectable), palonosetron (injectable), and dolasetron (oral) are largely therapeutically equivalent and considered first line treatment for chemotherapy induced nausea and vomiting (CINV), radiation induced nausea and vomiting (RINV) and postoperative nausea and vomiting (PONV) and are associated with relatively few mild adverse events.(9-11) |
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Chemotherapy and Radiation Therapy Induced Nausea and Vomiting |
Nausea and vomiting caused by anticancer agents and/or radiation therapy (RT) can have significant impact on a patient’s quality of life, leading to poor compliance with further anticancer agents and/or RT. In addition, nausea and/or vomiting can result in dehydration, metabolic imbalances, degeneration of self-care and functional ability, nutrient depletion, anorexia, decline of the patient’s performance status and mental status, wound dehiscence, esophageal tears, and withdrawal from potentially useful or curative anticancer treatment.(9)
The incidence and severity of nausea and/or vomiting in patients receiving anticancer agents and/or RT are affected by several factors including specific chemotherapy agents, dose, route of administration, schedule of administration, radiation target, and patient variability (age, sex, prior chemotherapy, history of alcohol use, etc.). In highly emetogenic regimens more than 90% of patients will experience episodes of vomiting but only about 30% will do so when given antiemetic prophylactic therapy.(10)
Vomiting is triggered by afferent impulses to the vomiting center from the chemoreceptor trigger zone, pharynx and gastrointestinal tract (GI), and cerebral cortex. The principal chemoreceptors involved in the emetic response are the serotonin and dopamine receptors. Additional neuroreceptors stimulated include acetylcholine, corticosteroid, histamine, cannabinoid, opioid, and neurokinin-1 receptors. Due to the variety of receptors involved and no final common pathway for emesis identified, multiple agents are used to block different pathways to provide a synergistic effect in an antiemesis prophylactic regimen.(10)
There are several identified classes of CINV including acute onset (typically occurs within the first few minutes to hours after chemotherapy administration), delayed onset (occurs more than 24 hours after chemotherapy dosing), anticipatory (occurs prior to chemotherapy administration and is considered a conditioned response), breakthrough (occurs despite prophylactic treatment and requires “rescue” antiemetic agents), and refractory (occurs during subsequent chemotherapy treatment cycles despite prophylactic and rescue therapy).(10)
National Comprehensive Cancer Network (NCCN) Guidelines recommend antiemetic therapy begins prior to chemotherapy and continues for the same length of time as the duration of the emetic activity of the drug given. The frequency of chemotherapy induced emesis depends mostly on the potential for the regimen to cause nausea and vomiting. Many chemotherapy regimens have been categorized by their potential to cause emesis. The classification (i.e., high, moderate, low, minimal) is based on the percentage of patients that experience acute emesis. High emetogenic risk is defined as 90% or more of patients, moderate risk has 30%-90% of patients, low risk is between 10% and 30% of patients, and minimal risk is less than 10% of patients experience acute emesis.(10)
The American Society of Clinical Oncology (ASCO) Practice Guidelines for Antiemetics in Oncology recommends that for patients who receive high-risk radiation therapy, patients receive a 5-HT3 antagonist before each radiation fraction and at least 24 hours after completing radiation therapy. Patients should also be given a five-day course of dexamethasone during fractions one to five.(9)
NCCN recommends starting pretreatment for each day of radiation therapy treatment with either granisetron or ondansetron, with or without dexamethasone.(10)
NCCN suggests when a serotonin (5-HT3) antagonist is used as part of an antiemetic regimen that does not include an NK-1 antagonist, either palonosetron or granisetron extended-release injection is the preferred 5-HT3 antagonist compared to the other 5-HT3 antagonists [i.e., ondansetron, granisetron (tablets, intravenous injection), dolasetron], due to longer half-life and prolonged inhibition of the 5-HT3 receptor.(10)
NCCN and ASCO recommends the following for CINV and RINV:(9-10)
NK-1RA (aprepitant, fosaprepitant, netupitant, rolapitant) = neurokinin 1 antagonist; 5-HT3 = Serotonin 5-HT3 antagonist (dolasetron, granisetron, ondansetron, palonosetron IV); DEX = dexamethasone
In a comparative clinical trial, the granisetron transdermal patch was shown to be non-inferior to oral granisetron in the prevention of nausea and vomiting.(4) The granisetron transdermal patch must be applied 24-48 hours before the start of chemotherapy. Patients often have blood counts tested on the day of chemotherapy and if they do not qualify for chemotherapy that day, the patch may be wasted. The manufacturer of the granisetron patch does provide free replacement patches to patients that waste one.(5) |
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Postoperative Nausea and Vomiting |
Nausea and vomiting are two of the most common adverse events in the postoperative period with an estimated incidence of 30% in the general surgical population and as high as 80% in high risk patients. Unresolved postoperative nausea and vomiting (PONV) is a highly distressing experience and may result in prolonged post anesthesia care unit stay and unanticipated hospital admission that leads to a significant increase in overall health care costs. The goal of PONV prophylaxis is to decrease the incidence of PONV, patient-related distress, and health-care costs.(11)
Optimal management of PONV is a complex process. There are numerous antiemetics with varying pharmacokinetics, efficacy, and side-effect profiles, thus the choice of an antiemetic will depend on the clinical context. The benefit of PONV prophylaxis also needs to be balanced with the risk of adverse effects. At an institutional level, the management of PONV is also influenced by factors such as cost-effectiveness, drug availability, and drug formulary decisions.(11)
The Society for Ambulatory Anesthesiology has published Consensus Guidelines for the management of postoperative nausea and vomiting. The goals of these guidelines include:(12)
Risk for PONV in adults can be identified using an assessment called Apfel’s simplified risk score for identification of high-risk patients.(11,13) Patients are given 1 point for each of the following when met:
A score of 0, 1, 2, 3, and 4 correlates with an approximate risk of PONV of 10%, 20%, 40%, 60% and 80% respectively. Patients with a score of 0-1 are classified as low risk, a score of 2 is medium risk, and a score of 3-4 indicates high risk.(11,13)
Risk for PDNV in adults can also be assessed using an assessment also by Apfel et al. Patients are given 1 point for each of the following when met:(11,13)
A score of 0, 1, 2, 3, 4, or 5 correlates with an approximate risk of PDNV of 10%, 20%, 30%, 50%, 60%, and 80% respectively.(11,13)
The risk factors for POV/PONV in children are different from those in adults. Pediatric patients are evaluated using a Simplified Risk Score from Eberhart et al.(11,14) Similar to the adult risk factor assessments, patients are given 1 point for each risk factor met.
A score of 0, 1, 2, 3, or 4 correlates with an approximate risk of POV of 10%, 10%, 30%, 50%, and 70% respectively.(11,14)
The guidelines recommend the use of multimodal prophylaxis in patients with one or more risk factors for PONV. Patients with 1-2 risk factors for PONV should receive 2 agents for prophylaxis of PONV and patients with greater than 2 risk factors should receive 3-4 agents for prophylaxis. Ondansetron is the most commonly used and studied 5-HT3 receptor antagonist and is considered the gold standard in PONV management.(11)
There is not sufficient evidence for the guidelines to guide the clinician to select the most effective individual antiemetic over other combination therapies with the exception of using agents from a different pharmacologic class. Recommended agents for adults and children (listed in alphabetical order) are: Note not all products are available in the United States and not all products are FDA labeled for PONV(11)
Adults
Pediatrics
|
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Nausea and Vomiting of Pregnancy(12) |
American College of Obstetricians and Gynecologists (ACOG, 2015) recommends the following for nausea and vomiting during pregnancy:
|
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Safety(1-8) |
|
REFERENCES
Number |
Reference |
1 |
Akynzeo prescribing information. Helsinn Therapeutics, Inc. June 2021. |
2 |
Anzemet prescribing information. Sanofi Aventis. September 2014. |
3 |
Emend prescribing information. Merck & Co., Inc. November 2019. |
4 |
Granisetron (tablets) prescribing information. Natco Pharma Limited. October 2019. |
5 |
Sancuso prescribing information. ProStrakan. April 2020. |
6 |
Varubi prescribing information. Tesaro, Inc. August 2020. |
7 |
Zofran prescribing information. Novartis Pharmaceuticals Corporation. October 2021. |
8 |
Zuplenz prescribing information. Praelia Pharmaceuticals, Inc. August 2021. |
9 |
Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO Guideline Update. J Clin Oncol 2020 38:24/,2782-2797 |
10 |
National Comprehensive Cancer Network (NCCN). Antiemesis Guidelines. Version 1.2022. |
11 |
Gan TJ, Belani KG, Bergese S, et al. Fourth Consensus Guidelines for the Management of Postoperative Nausea and Vomiting. International Anesthesia Research Society. August 2020. Volume 131. Number 2. |
12 |
American College of Obstetrician and Gynecologists (ACOG). ACOG Practice Bulletin: Nausea and Vomiting of Pregnancy. Obstet Gynecol. 2015;106(3):e12-e24. |
13 |
Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N. A simplified risk score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology. 1999;91:693–700. |
14 |
Eberhart LH, Geldner G, Kranke P, et al. The development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients. Anesth Analg. 2004;99:1630–1637. |
POLICY AGENT SUMMARY STEP THERAPY
Agent Names |
Strength |
Targeted MSC |
Available MSC |
Effective Date |
|
||||
SANCUSO*granisetron td patch |
3.1 MG/24HR |
M ; N ; O |
N |
|
ZUPLENZ*ondansetron oral soluble film |
4 MG ; 8 MG |
M ; N ; O |
N |
|
POLICY AGENT SUMMARY QUANTITY LIMIT
Target Agent GPI |
Agent Names |
Strength |
QL Amount |
Dose Form |
Days Supply |
Duration |
Addtl QL Info |
Allowed Exceptions |
Targeted NDCs When Exclusions Exist |
Effective Date |
|
||||||||||
50309902290120 |
AKYNZEO*Netupitant-Palonosetron Cap 300-0.5 MG |
0 ; 300 MG |
2.0 |
CAPS |
30 |
Days |
|
|
|
|
502500252003 |
ANZEMET*dolasetron mesylate tab |
100 MG ; 50 MG |
7.0 |
TABS |
30 |
Days |
|
|
|
|
50280020000130 |
APREPITANT*Aprepitant Capsule 125 MG |
125 MG |
2.0 |
CAPS |
30 |
Days |
|
|
|
|
50280020000120 |
APREPITANT*Aprepitant Capsule 80 MG |
80 MG |
4.0 |
CAPS |
30 |
Days |
|
|
|
|
50280020006320 |
APREPITANT*Aprepitant Capsule Therapy Pack 80 & 125 MG |
80 MG |
2.0 |
PACKS |
30 |
Days |
|
|
|
|
50280020001930 |
EMEND*Aprepitant For Oral Susp 125 MG (125 MG/5ML) |
125 MG/5ML |
6.0 |
PACKS |
30 |
Days |
|
|
|
|
502500351003 |
GRANISETRON*granisetron hcl tab |
1 MG |
14.0 |
TABS |
30 |
Days |
|
|
|
|
50250065050340 |
ONDANSETRON HCL*Ondansetron HCl Tab 24 MG |
24 MG |
1.0 |
TAB |
30 |
Days |
|
|
|
|
50250065052070 |
ONDANSETRON HYDROCHLORIDE*Ondansetron HCl Oral Soln 4 MG/5ML |
4 MG/5ML |
100.0 |
MLS |
30 |
Days |
|
|
|
|
50250065050310 |
ONDANSETRON HYDROCHLORIDE*Ondansetron HCl Tab 4 MG |
4 MG |
21.0 |
TABS |
30 |
Days |
|
|
|
|
50250065050320 |
ONDANSETRON HYDROCHLORIDE*Ondansetron HCl Tab 8 MG |
8 MG |
21.0 |
TABS |
30 |
Days |
|
|
|
|
502500650072 |
ONDANSETRON*ondansetron orally disintegrating tab ; ZOFRAN*ondansetron orally disintegrating tab |
4 MG ; 8 MG |
21.0 |
TABS |
30 |
Days |
|
|
|
|
50250035005920 |
SANCUSO*Granisetron TD Patch 3.1 MG/24HR (Contains 34.3 MG) |
3.1 MG/24HR |
2.0 |
PATCHS |
30 |
Days |
|
|
|
|
5028005020B720 |
VARUBI*Rolapitant HCl Tab Therapy Pack 2 x 90 MG (Base Equiv) |
90 MG |
4.0 |
TABS |
30 |
Days |
|
|
|
|
50250065008220 |
ZUPLENZ*Ondansetron Oral Soluble Film 4 MG |
4 MG |
20.0 |
FILMS |
30 |
Days |
|
|
|
|
50250065008240 |
ZUPLENZ*Ondansetron Oral Soluble Film 8 MG |
8 MG |
20.0 |
FILMS |
30 |
Days |
|
|
|
|
CLIENT SUMMARY – STEP THERAPY
Agent Names |
Strength |
Client Formulary |
SANCUSO*granisetron td patch |
3.1 MG/24HR |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ZUPLENZ*ondansetron oral soluble film |
4 MG ; 8 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
CLIENT SUMMARY – QUANTITY LIMITS
Agent Names |
Strength |
Client Formulary |
AKYNZEO*Netupitant-Palonosetron Cap 300-0.5 MG |
0 ; 300 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ANZEMET*dolasetron mesylate tab |
100 MG ; 50 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
APREPITANT*Aprepitant Capsule 125 MG |
125 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
APREPITANT*Aprepitant Capsule 80 MG |
80 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
APREPITANT*Aprepitant Capsule Therapy Pack 80 & 125 MG |
80 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
EMEND*Aprepitant For Oral Susp 125 MG (125 MG/5ML) |
125 MG/5ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
GRANISETRON*granisetron hcl tab |
1 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ONDANSETRON HCL*Ondansetron HCl Tab 24 MG |
24 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ONDANSETRON HYDROCHLORIDE*Ondansetron HCl Oral Soln 4 MG/5ML |
4 MG/5ML |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ONDANSETRON HYDROCHLORIDE*Ondansetron HCl Tab 4 MG |
4 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ONDANSETRON HYDROCHLORIDE*Ondansetron HCl Tab 8 MG |
8 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ONDANSETRON*ondansetron orally disintegrating tab ; ZOFRAN*ondansetron orally disintegrating tab |
4 MG ; 8 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
SANCUSO*Granisetron TD Patch 3.1 MG/24HR (Contains 34.3 MG) |
3.1 MG/24HR |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
VARUBI*Rolapitant HCl Tab Therapy Pack 2 x 90 MG (Base Equiv) |
90 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ZUPLENZ*Ondansetron Oral Soluble Film 4 MG |
4 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
ZUPLENZ*Ondansetron Oral Soluble Film 8 MG |
8 MG |
Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx |
STEP THERAPY CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
||
|
PRIOR AUTHORIZATION CRITERIA FOR APPROVALTarget Agent(s) will be approved when ONE of the following is met:
Length of Approval: 12 months
NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. |
QUANTITY LIMIT CLINICAL CRITERIA FOR APPROVAL
Module |
Clinical Criteria for Approval |
AkynzeoEmendVarubi |
Quantities above the program set limit for Akynzeo, Emend, or Varubi will be approved when ONE of the following is met:
Length of Approval: 12 months
|
AnzametGranisetronOndansetron&ODTZuplenz |
Quantities above the program set limit for Anzemet, granisetron, ondansetron/ondansetron ODT, or Zuplenz will be approved when ONE of the following is met:
Length of Approval: 12 months |
Sancuso |
Quantities above the program set limit for Sancuso will be approved when ONE of the following is met:
Length of Approval: 12 months |
This program applies to Blue Partner, Commercial, GenPlus, NetResults A series, SourceRx and Health Insurance Marketplace formularies.
This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
The purpose of Blue Cross and Blue Shield of Alabama’s pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment.
BCBSAL _ PS _ Antiemetic Step Therapy with Quantity Limit _ProgSum_ 10/1/2022 _