Subject: Antiemetics

Status	Drug	PR	PR-QL	PR-AL	ST	M EX‡
P	dronabinol	X
P	granisetron		X
P	metoclopramide
P	prochlorperazine
P	ondansetron		X
P	promethazine			X
P	promethegan			X
P	trimethobenzamide
P	Emend®  (aprepitant)		X
NP	Compazine®  (prochlorperazine)
NP	Marinol®  (dronabinol)	X
NP	Phenergan®  (promethazine)			X
NP	Reglan®  (metoclopramide)
NP	Tigan®  (trimethobenzamide)
FE	Akynzeo®  (netupitant-palonosetron®)	X			X	X
FE	Anzemet®  (dolasetron)		X			X
FE	Cesamet®  (nabilone)		X			X
FE	Diclegis®  (doxylamine/ pyridoxine delayed release)	X	X		X	X
FE	Granisol ®  (granisetron)		X			X
FE	Sancuso pad®  (granisetron TD patch)		X			X
FE	Transderm Scop®  (scopalamine)					X
FE	Zofran®  (ondansetron)		X			X
FE	Zofran ODT®  (ondansetron)		X			X
FE	Zuplenz ®  (ondansetron)		X			X
Non-prescription (OTC) products (NOT covered under standard benefit plans)
OTC	doxylamine
OTC	pyridoxine
OTC	Dramamine

Policy:

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary, Akynzeo, Anzemet, Cesamet, Diclegis, dronabinol, Emend,  granisetron, Granisol, Marinol, ondansetron, ondansetron ODT, Phenergan, promethazine, promethegan, Sancuso pad, Zofran, Zofran ODT and Zuplenz are subject to precertification.  If precertification requirements apply, Aetna considers these drugs to be medically necessary for those members who meet the following precertification criteria:

For Akynzeo

• A documented diagnosis of nausea and vomiting associated with cancer chemotherapy.

For Phenergan, promethazine, and promethegan

• Member is < 2 years of age and prescriber provides documentation (controlled clinical trial) from the peer reviewed medical literature that supports use in specified indication for this age group
           
       Note:   Per FDA alert: Use of Phenergan/promethazine is contraindicated in infants and children < 2 years of age due to risks for fatal respiratory depression.                    

For dronabinol and Marinol

• A documented diagnosis of one of the following:
  • Nausea and vomiting associated with cancer chemotherapy following previous failure of ondansetron or granisetron OR
  • Anorexia associated with weight loss in patients with AIDS following failure (one month trial) of megestrol or oxandrolone 

For Diclegis

• A documented diagnosis of nausea and vomiting in pregnant women who do not respond to conservative management (i.e. trigger avoidance, small frequent meals, etc) AND 
• A documented contraindication or intolerance or allergy or failure of an adequate trial of one week of any of the following: otc doxylamine, or otc pyridoxine (vit B6), or metoclopramide, or promethazine, or ondansetron

According to the manufacturers, the antiemetics Akynzeo, Anzemet, Cesamet, Diclegis, Emend, granisetron, ondansetron, ondansetron odt, Sancuso pad, Zofran, Zofran, and Zuplenz can be dosed up to a maximum daily dose as indicated in the table below.  A quantity of each drug will be considered medically necessary as indicated in the table below:
  

Drug	Maximum Daily Dose	Dosage Strength	Quantity Limits
Akynzeo	300mg-0.5mg	300mg-0.5mg	Up to 2 capsules in 30 days
Anzemet	100 mg	50 mg, 100 mg	Up to 5 tablets in 30 days
Cesamet	6mg	1 mg	Up to 20 capsules in 30 days
Diclegis	40 mg/ 40 mg	10 mg/ 10 mg	Up to 120 tablets in 30 days
Emend	3-day regimen, 125 mg on day 1 and 80 mg on days 2 and 3 of the chemotherapy regimen	40 mg, 80 mg, 125 mg	Up to 5 capsules in 30 days
Emend	3-day regimen, 125 mg on day 1 and 80 mg on days 2 and 3 of the chemotherapy regimen	80 mg, 125 mg (tri-fold pack)	Up to 2 packs (6 capsules)/30 days
granisetron	2 mg	1 mg	Up to 10 tablets per 30 days
granisetron	2 mg	2 mg/10ml	Up to 5 (10ml) doses per 30 days
Granisol	2 mg	2 mg/10ml	Up to 6 (10ml) doses per 30 days
Sancuso pad	1 patch once weekly	3.1 mg	Up to 1 patch per 21 days
ondansetron Zofran, ODT	24mg	4 mg, 8 mg	Up to 12 tablets per 30 days
ondansetron Zofran	24mg	24 mg	Up to 5 tablets per 30 days
ondansetron Zofran	24mg	4 mg/5ml	Up to 10 (5ml) doses per 30 days
Zuplenz	24mg	4 mg, 8 mg	Up to 12 films per 30 days





For coverage of additional quantities, a member's treating physician must request prior authorization through the Pharmacy Management Precertification Unit. Additional quantities of the antiemetics Akynzeo, Anzemet, Cesamet, Emend, granisetron, Granisol, ondansetron, ondansetron odt, Zofran, Zofran ODT, and Zuplenz will be considered medically necessary for those members who meet the criteria specified below:

For Akynzeo

• A documented chemotherapy regimen that requires more than two cycles of antiemetic per 30 days

For Anzemet, Cesamet, Emend, granisetron, and Granisol

• A documented chemotherapy regimen that doses on more than 5 days per 30 days or doses more frequently than 2 times per 30 days that requires more than one cycle of antiemetic per 30 days

Quantities for Approval:
Anzemet Tablets:  (maximum of one tablet per day X number of days per month the patient has treatment) + 4 tablets for one year
Granisol and granisetron Tablets:  (maximum of two tablets per day X number of days per month the patient has treatment) + 8 tablets for one year
Granisol Oral Solution: (maximum 10 mL per day X number of days per month the patient has treatment) + 40 mL for one year
Cesamet capsules: Up to 60 caps for one year
Emend: Maximum of 1 capsule of the 125 mg strength X the number of chemotherapy cycles per month, AND Maximum of 2 capsules or 1 Bi-pack of the 80 mg strength X the number of chemotherapy cycles per month for one year, OR
Maximum of 2 capsules or Bi-pack of the 80 mg strength X the number of chemotherapy cycles per month for one year, OR
Maximum of 1 Tri-pack (contains one 125 mg capsule and two 80mg capsules) X the number of chemotherapy cycles per month for one year

For ondansetron, ondansetron odt, Zofran, Zofran ODT, and Zuplenz

• A documented diagnosis of cancer and chemotherapy or radiation therapy requires greater antiemetic quantity

OR

• A documented diagnosis of hyperemesis gravidarum, AND 
• Parenteral hydration would otherwise be necessary or has already been tried, AND
• Vomiting despite adequate treatment with at least two of the following antiemetics: 
  • dimenhydrinate (Dramamine) 
  • diphenydramine (Benadryl) 
  • doxylamine 
  • promethazine (Phenergan), promethegan - oral or per rectum 
  • prochlorperazine (Compazine) - oral or per rectum 
  • hydroxyzine (Vistaril) 
  • meclizine (Antivert) 
  • metoclopromide (Reglan) 
  • trimethobenzamide (Tigan) 

OR 

• A documented diagnosis of hyperemesis gravidarum, AND 
  • Patient is being released from the hospital and is being transitioned to oral ondansetron/ odt/ Zofran from i.v. ondansetron/ Zofran or ondansetron/ Zofran pump, OR
  • Patient has received i.v. ondansetron/ Zofran or ondansetron/ Zofran pump previously to treat hyperemesis gravidarum during the current pregnancy

Quantities for Approval (chemotherapy):
Zofran (ondansetron) 4 mg and 8 mg Tablets/ODT:  (maximum of three tablets/ODT per day x number of days per month the patient has treatment) + 12 tablets/ODT for one year
Zofran (ondansetron) Solution:  (maximum of 30 mL per day x number of days per month the patient has treatment) + 120 mL for one year
ondansetron 24 mg Tablets:  (maximum of one tablet per day x number of days per month the patient has treatment) for one year
Zuplenz 4 mg and 8 mg oral soluble film: (maximum of three films per day x number of days per month the patient has treatment) + 12 oral soluble films for one year
Quantities for Approval (hyperemesis gravidarum):
ondansetron products only: 90 tablets/films (900 ml) for a 30-day supply for 3 months.  Approval is renewable if criteria continue to be met.

 




2. Step Therapy Criteria

Under some plans, including plans that use an open or closed formulary, Diclegis is subject to step-therapy.  Aetna considers this drug to be medically necessary for those members who meet the following step-therapy criteria:

For Akynzeo

• A documented trial of 1 generic 5-HT3 receptor antagonist (granisetron or ondansetron) AND Emend.

For Diclegis

• A documented trial of one week of any of the following: otc doxylamine, or otc pyridoxine (vit B6), or metoclopramide, or promethazine, or ondansetron

If it is medically necessary for a member to be treated initially with a medication subject to step-therapy, the member, a person appointed to manage the member’s care, or the member's treating physician may contact the Aetna Pharmacy Management Precertification Unit to request coverage as a medical exception at 1-800-414-2386. (See Medical Exceptions Criteria below.)

3. Medical Exception Criteria

Diclegis is currently listed on the Aetna Formulary Exclusions and Step-Therapy lists.*  Therefore, it is excluded from coverage for members enrolled in prescription drug benefit plans that use a closed formulary or that require step-therapy criteria, unless a medical exception is granted.  Aetna considers this drug to be medically necessary for those members who meet the criteria specified below:

Akynzeo, Anzemet, Cesamet, Granisol, Sancuso pad, Transderm Scop, Zofran/ODT, and Zuplenz are currently listed on the Aetna Formulary Exclusions List.*  Therefore these medications are excluded from coverage for members enrolled in prescription drug benefits plans that use a closed formulary, unless a medical exception is granted.  Aetna considers these drugs to be medically necessary for those members who meet any of the following criteria:

For Akynzeo

• A documented diagnosis of nausea and vomiting associated with cancer chemotherapy.
  AND
• The member has a documented contraindication to, intolerance to, allergy to, or failure to eneric  5-HT3 receptor antagonist (granisetron or ondansetron) AND Emend.

For Anzemet, Cesamet, Granisol, Sancuso pad, Transderm Scop, Zofran/ODT, and Zuplenz

• A documented contraindication or intolerance or allergy or failure of an adequate trial of one day or one course of one preferred alternative antiemetic agent indicated for the member's condition OR
• Member is being treated as  terminal care and requires transdermal Transderm Scop

For Diclegis

• A documented diagnosis of nausea and vomiting in pregnant women who do not respond to conservative management (i.e. trigger avoidance, small frequent meals, etc) AND 
• A documented contraindication or intolerance or allergy or failure of an adequate trial of one week of any of the following: otc doxylamine, or otc pyridoxine (vit B6), or metoclopramide, or promethazine, or ondansetron

 

Place of Service:

Outpatient

The above policy is based on the following references:

1. AHFS Drug Information® with AHFSfirstReleases®. ( www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. Updated periodically.
2. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
3. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. Updated periodically.
4. PDR® Electronic Library™ [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
5. Clinical Pharmacology [Internet database]. Gold Standard Inc. Tampa, FL. Updated periodically.
6. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, et al. Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer. 2003;97(12):3090-8.
7. Navari RM. Pharmacological management of chemotherapy-induced nausea and vomiting: a focus on recent developments. Drugs 2009;69:515-33.
8. Grunberg SM, Rolski J, Strausz J et al. Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK-1) receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin based highly emetogenic chemotherapy: a randomized, double-blind, placebo-control trial. Lancet Oncology 2009;10:549-58.
9. Wender RH. Do current antiemetic practice results in positive patient outcomes? Results of a new study. AJHP 2009;2009;66:(1 Suppl): S3-S10.
10. Hesketh PJ. Chemotherapy induced nausea and vomiting. N Engl J Medicine 2008;358:2482-94.
11. Naeim A, Dy SM, Lorenz KA et al. Evidence-based recommendations for cancer nausea and vomiting. J Clin Oncology 2008;10:3903-10.
12. Ettinger DS, Armstrong DK, Barbour S et al. Antiemesis. Clinical practice guidelines in oncology. 2009;7:572-95.
13. Diclegis® [package insert]. Bryn Mawr, PA: Duchesnay USA, Inc.; April 2013
14. American College of Obstetricians and Gynecology. Nausea and vomiting of pregnancy. ACOG Practice Bulletin No. 52. Obstet Gynecol 2004;103:803-1415051578.
15. Arsenault MY, Lane CA, MacKinnon CJ. The management of nausea and vomiting of pregnancy. (SOGC clinical practice guidelines). J Obstet Gynaecol Can 2002;24:817-23.
16. Niebyl JR. Nausea and vomiting in pregnancy. N Engl J Med 2010;363:1544-50. Erratum 2010;363:21:2078.
17. Committee on Drugs. American Academy of Pediatrics. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776-89.

Copyright Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

January 12, 2015