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Aetna Aetna
Clinical Policy Bulletin:
Antiemetic Injection Therapy
Number: 0724


Policy

This policy is based in part on antiemetic practice guidelines from the National Comprehensive Cancer Network (NCCN) (2008; updated 2012) and the American College of Obstetrics and Gynecology (ACOG) practice guidelines on nausea and vomiting of pregnancy (2004).

  1. Cancer Chemotherapy:

    Aetna considers palonosetron (Aloxi) or fosaprepitant dimeglumine (Emend) antiemetic intravenous therapy medically necessary for the following indications: (i) the prevention of acute nausea or vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy, including high-dose cisplatin; and (ii) for treatment of chemotherapy-induced nausea or vomiting from low or minimally emetogenic cancer chemotherapy in persons who have an inadequate response or contraindication to intravenous granisetron (Kytril) or ondansetron (Zofran) at the Food and Drug Administration (FDA) recommended dose (see table in Appendix).

    Aetna considers granisetron (Kytril) and ondansetron (Zofran) antiemetic intravenous therapy medically necessary for the following indications: (i) prevention of acute and delayed nausea and/or vomiting associated with initial and repeat courses of moderately and highly emetogenic cancer chemotherapy including high-dose displatin; and (ii) for treatment of chemotherapy-induced nausea and/or vomiting of low or minimally emetogenic cancer chemotherapy in persons who have an inadequate response or contraindication to oral granisetron (Kytril) or ondansetron (Zofran) at the FDA recommended dose (see table in Appendix).

    Aetna considers intravenous dolasetron (Anzemet) experimental and investigational for prevention of nausea or vomiting from cancer chemotherapy.

  2. Radiotherapy:

    Aetna considers dolasetron mesylate (Anzemet), medically necessary for the prevention of radiation-induced nausea or vomiting secondary to total body irradiation (TBI) when intravenous antiemetic therapy with granisetron (Kytril) or ondansetron (Zofran) at the FDA recommended dose has failed or is contraindicated.

    Aetna considers granisetron (Kytril) or ondansetron (Zofran) medically necessary for the prevention of radiation-induced nausea and/or vomiting secondary to TBI when oral granisetron (Kytril) or ondansetron (Zofran) at the FDA recommended dose has failed or is contraindicated.

    Aetna considers intravenous palonosetron (Aloxi) and fosaprepitant dimeglumine (Emend) experimental and investigational for the prevention of radiation-induced nausea and vomiting because there is insufficient evidence of their effectiveness for this indication.

  3. Post-operative:

    Aetna considers intravenous palonosetron (Aloxi), dolasetron mesylate (Anzemet) or fosaprepitant dimeglumine (Emend) medically necessary for the prevention or treatment of post-operative nausea or vomiting when intravenous granisetron (Kytril) or ondansetron (Zofran) at the FDA recommended dose has failed or is contraindicated.

    Aetna considers intravenous granisetron (Kytril) or ondansetron (Zofran) medically necessary for the prevention or treatment of post-operative nausea or vomiting when oral granisetron (Kytril) or ondansetron (Zofran) has failed or is contraindicated. 

    Note: As with other antiemetics, routine prophylaxis is not recommended for individuals in whom there is little expectation that nausea and/or vomiting will occur post-operatively.

  4. Pregnancy:

    Aetna considers intravenous granisetron (Kytril) or ondansetron (Zofran) antiemetic intravenous therapy medically necessary for severe, intractable, persistent nausea or vomiting during pregnancy when clinical signs of dehydration are present or nausea and vomiting have persisted for more than 3 weeks and all of the following conditions are met:

    1. Conservative treatment has failed (e.g., dietary changes, ginger, multi-vitamin, vitamin B6 (pyridoxine) with or without doxylamine (Unisom)); and
    2. Oral, sublingual, or rectal antiemetics have failed or are contraindicated including 2 or more of the following:

      1. Dimenhydrinate (Dramamine); and
      2. Ondansetron (Zofran) or granisetron (Kytril); and
      3.  Promethazine (Phenergan); and
      4. Trimethobenzamide (Tigan); and
    3. Other injectable/intravenous antiemetics have failed or are contraindicated including all of the following:

      1. Dimenhydrinate (Dramamine); and
      2. Promethazine (Phenergan).

        Aetna considers intravenous palonosetron (Aloxi), dolasetron mesylate (Anzemet) or fosaprepitant dimeglumine (Emend) medically necessary for severe, intractable, persistent nausea or vomiting during pregnancy when clinical signs of dehydration are present or nausea and vomiting have persisted for more than 3 weeks and intravenous granisetron (Kytril) or ondansetron (Zofran) at the FDA recommended dose has failed or is contraindicated.

  5. Motion Sickness:

    Aetna considers 5-HT3 receptor antagonist antiemetic intravenous therapy experimental and investigational for motion-induced nausea and vomiting (motion-sickness).

  6. Other Indications:

    Aetna considers granisetron (Kytril) or ondansetron (Zofran) antiemetic intravenous therapy medically necessary for refractory cases of nausea or vomiting for other indications (e.g., bulimia nervosa, cyclic vomiting syndrome, HIV) when oral granisetron (Kytril) or ondansetron (Zofran) has failed or is contraindicated.

    Aetna considers intravenous palonosetron (Aloxi), dolasetron mesylate (Anzemet) or fosaprepitant dimeglumine (Emend) medically necessary for refractory cases of nausea or vomiting for other indications (e.g., bulimia nervosa, cyclic vomiting syndrome, HIV) when intravenous granisetron (Kytril) or ondansetron (Zofran) at the FDA recommended dose has failed or is contraindicated.

See also Pharmacy Clinical Policy Bulletin (PCPB): Antiemetics.

See also CPB 0020 - Injectable Medications and CPB 0676 - Electrical Stimulation for Nausea, Vomiting and Motion Sickness (PrimaBella and ReliefBand).

Note: This policy does not address the use of 5-HT3 receptor antagonists in the emergency room.  Serotonin 3 receptor antagonists have been used in the management of acute toxicities (e.g., acetaminophen, theophylline).



Background

Serotonin 3 (5-HT3) receptor antagonists [(i.e., palonosetron (Aloxi), dolasetron mesylate (Anzemet), granisetron (Kytril), and ondansetron (Zofran)] are used for the treatment and prevention of post-operative nausea and vomiting as well as nausea and vomiting caused by cancer chemotherapy, radiotherapy, and pregnancy.  5-HT3 receptor antagonists work by blocking serotonin binding at vagal afferents in the gut and in regions of the central nervous system (CNS) involved in emesis. 

Antiemetic practice guidelines from the National Comprehensive Cancer Network (NCCN, 2008) recommend antiemetic regimens based upon the emetogenic potential of the chemotherapy drug as well as individual risk factors.  The antiemetic regimen for highly emetogenic drugs includes aprepitant, dexamethasone, and a 5-HT3 antagonist with or without lorazepam.  The antiemetic regimen for moderately emetogenic drugs includes dexamethosone and a 5-HT3 antagonist (palonosetron is preferred) with or without lorazepam; consider adding aprepitant for select patients (those receiving carboplatin, cyclophosphamide, doxorubixin, epirubicin, ifosfamide, irinotecan, or methotrexate).  The antiemetic regimen for low emetogenic drugs includes the following non-5-HT3 anatgonists: dexamethasone with or without lorazepam, prochlorperazine, spansule, or metoclopramide with or without diphenhydramine.  For minimal risk chemotherapy, the NCCN guidelines recommend that no routine prophylactic treatment be given. 

According to NCCN, the basic strategy of any antiemetic regimen is to prevent nausea/vomiting from occurring, thus, prophylactic antiemetics should be administered before chemotherapy begins and for patients receiving high or moderate emetogenic chemotherapy, antiemetics should continue for at least 4 days.  Although oral and intravenous (I.V.) antiemetics have equivalent efficacy, patients who are unable to swallow or digest tablets because of emesis, should be given I.V. antiemetics (NCCN).  Breakthrough nausea/vomiting induced by high, moderate and low emetic risk chemotherapy can be very difficult to treat.  Adding an additional agent from a different drug class is the general management approach recommended by NCCN as well as adjusting either the intensity or frequency of dosing.  Dopamine antagonists, metoclopramide, thiethylperazine, butyrophenones (e.g., halpreridol), corticosteroids, and agents such as lorazepam may be required.  Routine around-the-clock administration should be considered, rather than as needed.  Also, while not likely to be effective, anecdotal evidence suggests that switching to a different 5-HT3 may be efficacious (NCCN). 

Studies have demonstrated that all of the 5-HT3 antagonists are effective and have mild, infrequent side effects, although optimal antiemetic therapy requires concomitant dexamethasone or methylprednisolone, unless the patient can not tolerate corticosteroids (NCCN).  According to the NCCN guidelines, dolasetron mesylate, granisetron, and ondansetron are effective in preventing acute emesis but are less effective for delayed emesis compared with palonosetron.  Palonosetron is effective for preventing both delayed and acute emesis and is the preferred medication for patients undergoing moderate emetic risk chemotherapy (NCCN).  In the trial data submitted to the Food and Drug Adminsitration (FDA) for licensure, palonosetron achieved equivalent or superior results compared to the control arms (ondansetron and dolasetron), especially with regard to delayed nausea.  The side effect and safety profile of palonosetron has been demonstrated to be the same as dolasetron mesylate and ondansetron but it has a slightly higher tissue binding affinity for the 5-HT3 receptor and a significantly longer serum half-life than other 5-HT3 antagonists.  Palonosetron is administered intravenously and is approved by the FDA as a single dose of 0.25 mg I.V. over 30 seconds on day 1, approximately 30 mins before chemotherapy.  Higher doses (e.g., 0.75 mg) were studied and were no more effective than the 0.25 mg dose.  Repeat dosing of palonosetron in the days following chemotherapy (e.g., day 2 to 3) or in the setting of multi-day chemotherapy regimens is not supported by the scientific literature.

In December 2010, the FDA released a special announcement that the injection form of dolasetron mesylate (Anzemet) should no longer be used to prevent nausea and vomiting associated with CINV in pediatric and adult patients.  New data demonstrated that intravenous dolasetron can increase the risk of developing an abnormal heart rhythm (torsade de pointes) which can be fatal.

The Multinational Association of Supportive Care in Cancer (MASCC) International Consensus Conference (2005) classified the risk of radiotherapy-induced emesis as follows: (i) high - total body irradiation, (ii) moderate - upper abdomen, (iii) low - lower thorax, pelvis, cranium (radiosurgery) and craniospinal, (iv) minimal risk - head and neck, extremities, cranium and breast (Maranzano et al, 2005).  NCCN (2006) antiemesis guidelines for the use of antiemetics in radiotherapy are based on the site of radiation and whether radiotherapy is combined with chemotherapy; when radiotherapy is combined with chemotherapy, prophylaxis is dictated by the emetogenic potential of the chemotherapy regimen.  For total body irradiation, NCCN guidelines recommend pretreatment for each day of radiation treatment with either oral ondansetron or oral / I.V. granisetron.  For upper abdomen radiation, NCCN guidelines recommend pretreatment for each day of radiation treatment with either oral ondansetron or oral granisetron.  NCCN guidelines do not recommend primary treatment for patients receiving radiation to other sites.

Nausea and vomiting are common in pregnancy.  Approximately 70 to 85 % of pregnant women experience nausea and/or vomiting.  Hyperemesis gravidarum, a severe and intractable form of nausea and vomiting during pregnancy, may result in weight loss, nutritional deficiencies, and dehydration.  The peak incidence occurs at 8 to 12 weeks of pregnancy, and symptoms usually resolve by week 16.  The American College of Obstetrics and Gynecology (ACOG) (2004) recommend a step-wise approach to alleviating nausea and vomiting in pregnancy, beginning with prevention at the time of conception.  Two studies found that women who take a multi-vitamin at the time of conception were less likely to need medical attention for vomiting.  While there is little published evidence regarding the efficacy of dietary changes for prevention or treatment of nausea and vomiting of pregnancy, a small study showed that protein meals were more likely to relieve nausea and vomiting of pregnancy than carbohydrate and fatty meals.  Other conservative treatments recommended by ACOG included ginger capsules and electrical stimulation or acupressure at the P6 (or Neguian) point on the inside of the wrist.  Women with more complicated nausea and vomiting of pregnancy may need pharmacologic therapy.  While many conventional antiemetics have been used for nausea and vomiting of pregnancy, it is important to note that no drug has been approved by the FDA for the treatment of nausea and vomiting in pregnancy since Benedictine (an antiemetic no longer available in the U.S. but still widely used in Europe). 

According to ACOG guidelines, pharmacologic treatment of nausea and vomiting of pregnancy should begin with pyridoxine (vitamin B6).  If there is no improvement, doxylamine (Unisom) should be added with the pyridoxine.  A 70 % reduction in nausea and vomiting has been reported with this combination.  Doxylamine and pyridoxine are currently available separately without a prescription in the U.S.  Several studies involving more than 170,000 exposures have found this combination to be safe with regard to fetal exposure.  If this is unsuccessful, adding or switching to antiemetics and antihistamines may be necessary.  Medications for which there are some safety data but no conclusive evidence of efficacy include anticholinergics and metoclopramide (Reglan) (ACOG, 2004). 

Evidence is limited on the safety and efficacy of ondansetron injectable for treatment of pregnancy-related nausea and vomiting.  However, this medication is being prescribed as an off-label use for the treatment of nausea and vomiting of pregnancy due to its reported effectiveness in reducing chemotherapy-induced emesis (ACOG, 2004).  In a limited comparative study with other antiemetics, no increased risks of major malformations were reported (Einarson et al, 2004).  In a small trial of I.V. therapy in women with hyperemesis gravidarum, no increased benefit was demonstrated with ondansetron over promethazine (Sullivan et al, 1996).  However, according to ACOG’s step-wise approach to managing nausea and vomiting of pregnancy, ondansetron may be tried in refractory cases as a last resort.  When indicated, ACOG guidelines recommend 8 mg of ondansetron over 15 mins every 12 hrs I.V.

According to the peer-reviewed medical literature, selective 5-HT3 receptor antagonists have been proven safe and effective for the management of post-operative nausea and vomiting (Loewen et al, 2000; Kovac, 2000; Fuji, 2005).

Ondansetron for bulimia nervosa was reported to be effective in 3 small trials by one group of investigators, and may be an option after failure of traditional therapies (Fung and Ferrill, 2001).  Additionally, some studies on bulimia nervosa recommend short-term use of antiemetics at the onset of a patient's treatment.  Antiemetics are thought to reduce a patient's stimuli to vomit and help patients through the few weeks it takes for antidepressants to become fully effective (Moreno, 2005). 

A Prodigy Clinical Practice Recommendation (SCHIN, 2006) on palliative care - nausea/vomiting/malignant bowel obstruction.stated, “[o]ndansetron, tropisetron, granisetron, and dolasetron are rarely indicated in the palliative care setting.  Their use is limited to chemotherapy and radiotherapy induced nausea…[t]he role of somatostatin analogues in the relief of nausea and vomiting due to malignant bowel obstruction is not clear.”

In a single-blind, randomized controlleds tudy, Yonemura et al (2009) evaluated the non-inferiority of 1-mg to 3-mg granisetron (GRN) injection for the treatment of acute chemotherapy-induced nausea and vomiting (CINV) and assessed the tolerability of GRN given at 1-mg in Japanese cancer patients.  Patients with cancer receiving highly emetogenic chemotherapy were enrolled in this study.  Patients were randomly assigned to receive GRN at a single dose of 1-mg or 3-mg.  The primary endpoint was the rate of complete protection from emetic events (no vomiting, no retching and no need for rescue medication) during the first 24 hrs following the initiation of chemotherapy.  There were 89 patients in the 1-mg group and 90 patients in the 3-mg group.  Complete protection was achieved in 70 patients (78.7 %) in the 1-mg group and 73 (81.1 %) patients in the 3-mg group.  The 1-sided test did not reveal non-inferiority of either dose of GRN to the other at a 5 % significance level.  The authors concluded that these findings failed to show the non-inferiority of 1-mg of GRN to 3-mg of GRN administered as a single dose.  However, the rate of complete protection from nausea and vomiting was similar in the 2 groups.  They stated that given the recommended dosage in the guidelines and the economic need for reduction of medical care expenses in Japan, prophylactic administration of GRN at 1-mg may be an appropriate, alternative treatment for acute CINV in cancer patients.

Results of clinical trials indicated that 5-HT3 receptor antagonists for the reduction of motion sickness have not been proven effective (Levine et al, 2000; Reid et al, 2000).

 

Appendix

Table: Emetogenic Potential of Intravenous and Oral Antineoplastic Agents

Emetic Risk Without Prophylaxis

Agent

 

High-risk (greater than 90 % frequency of emesis)*

AC combination defined as either doxorubicin or epirubicin with cyclophosphamide
Altretamine (oral)
Carmustine > 250 mg/m2
Cisplatin ≥ 50 mg/m2
Cyclophosphamide > 1,500 mg/m2

Dacarbazine
Doxorubicin > 60 mg/m2
Epirubicin > 90 mg/m2
Estramustine (oral)Etoposide (oral)
Ifosfamide ≥ 10 mg/m2
Lomustine (single day) (oral)
Mechlorethamine
Procarbazine (oral)
Streptozocin
Temozolamide (> 75 mg/m2/day) (oral)

Moderate-risk (30 - 90 % frequency of emesis)*

Aldesleukin > 12 - 15 million IU/m2
Amifostine > 300 mg/m2
Arsenic trioxide
Azacytidine
Bendamustine
Busulfan ≥ 4 mg/day (oral)
Carboplatin
Carmustine ≤ 250 mg/m2
Cisplatin < 50 mg/m2
Cyclophosphamide ≤ 1,500 mg/m2
Cyclosphosphamide ≥ 100 mg/m2/day (oral)
Cytarabine > 200 mg/m2
Dactinomycin
Daunorubicin
Doxorubicin ≤ 60 mg/m2
Epirubicin ≤ 90 mg/m2 

Etoposide (oral)
Idarubicin
Ifosfamide < 10 g/m2
Interferon alfa ≥ 10 million IU/m2
Irinotecan
Lomustine (single day) (oral)
Melphalan 
Methotrexate ≥ 250 mg/m2
Oxaliplatin
Temozolomide  
Temozolomide > 75 mg/m2/day (oral)

Low-risk (10 - 30 % frequency of emesis)

Amisfostine ≤ 300 mg
Aldesleukin ≤ 12 million IU/m2
Bexarotene (oral) 
Capecitabine (oral)
Cytarabine (low-dose) 100 - 200 mg/m2
Docetaxel
Doxorubicin (liposomal)
Eribulin
Etoposide
5-Fluorouracil 

Fludarabine (oral and intravenous)
Gemcitabine
Interferon alfa >5  <10 million IU/m2
Ixabepilone
Methotrexate > 50 mg/m2 < 250 mg/m2
Mitomycin
Mitoxantrone
Paclitaxel
Paclitaxel-albumin
Pemetrexed
Pentostatin
Pralatrexate
Romidepsin
Thiotepa
Topotecan
Vorinostat

Minimal-risk (less than 10 % frequency of emesis)*

Alemtuzumab
Asparaginase
Bevacizumab
Bleomycin
Bortezomib
Busulfan < 4 mg/day (oral)
Cetuximab
Chlorabmucil (oral)
Cladribine (2-chlorodeoxyadenosine)
Cyclophosphamide < 100 mg/m2/day (oral)
Cytarabine < 100 mg/m2
Decitabine
Denileukin diftitox
Dexrazoxane
Erlotinib (oral)
Fludarabine
Gefitnib (oral)

Hydroxyurea (oral)
Imatinib (oral)
Interferon alfa ≤ 5 million IU/m2
Ipilimumab
Lapatinib (oral)
Lenalidomide (oral)
Melphalan (oral)
Mercaptopurine (oral)
Methotrexate (oral)
Methotrexate ≤  50 mg/m2
Nelarabine
Nilotinib (oral)
Ofatumumab
Pazopanib (oral)
Panitumumab
Pegaspargase
Peginterferon
Pertuzumab
Rituximab
Sorafenib (oral)
Sunitinib (oral)
Temozolamide ≤ 75 mg/m2/day (oral)
Temsirolimus
Thalidomide (oral)
Thioguanine (oral)
Topotecan (oral)
Trastuzumab
Tretinoin (oral)
Valrubicin
Vandetanib (oral)
Vinblastine
Vincristine
Vinorelbine
Vorinostat (oral)

*Proportion of patients who experience emesis in the absence of effective antiemetic prophylaxis

Note: National Comprehensive Cancer Network guidelines on antiemesis lists the emetogenic potential of additional cancer drugs; these guidelines are available at the following web address (free registration required): http://www.nccn.org/clinical.asp.

Source: NCCN Clinical Practice Guidelines in Oncology. Guidelines for Supportive Care. Antiemesis. Version 3.2008. Jenkintown, PA; NCCN; 2008.  (Updated version: 1.2012; Fort Washington, PA: NCCN) 

 
CPT Codes / HCPCS Codes / ICD-9 Codes
Other CPT codes related to this CPB:
77371 - 77425
96401 - 96549
HCPCS codes covered if selection criteria are met:
J1260 Injection, dolasetron mesylate, 10 mg
J1453 Injection, fosaprepitant, 1 mg
J1626 Injection, granisetron HCl, 100 mcg
J2405 Injection, ondansetron HCl, per 1 mg
J2469 Injection, palonosetron HCl, 25 mcg
HCPCS codes related to High Emetic Risk Without Prophylaxis (greater than 90% frequency of emesis):
J8530 Cyclophosphamide, oral, 25 mg
J8700 Temozolomide, oral, 1 mg
J9000 Injection, doxorubicin HCl, 10 mg
J9050 Injection, carmustine, 100 mg [> 250mg/m2]
J9070 Cyclophosphamide, 100 mg [> 1,500 mg/m2]
J9130 Dacarbazine, 100 mg
J9178 Injection, epirubicin HCl, 2 mg
J9230 Injection, mechlorethamine HCl, (nitrogen mustard), 10 mg
J9320 Injection, streptozocin, 1 g
Q2050 Injection, doxorubicin hydrochloride, liposomal, not otherwise specified, 10 mg
S0182 Procarbazine HCl, oral, 50 mg
HCPCS codes related to Moderate Emetic Risk Without Prophylaxis (30-90% frequency of emesis):
J0207 Injection, amifostine, 500 mg [> 300]
J0594 Injection, busulfan, 1 mg [> 4 mg/d]
J8510 Busulfan; oral, 2 mg [> 4 mg/d]
J8560 Etoposide, oral, 50 mg
J8600 Melphalan, oral, 2 mg [> 50 mg/m2]
J8610 Methotrexate, oral, 2.5 mg [250 - > 1,000 mg/m2]
J8700 Temozolomide, oral, 5 mg
J9000 Injection, doxorubicin HCl, 10 mg
J9015 Injection, aldesleukin, per single use vial [Interleukin-2] [> 12-15 million units/m2]
J9017 Injection, arsenic trioxide, 1 mg
J9025 Injection, azactidine, 1 mg
J9045 Injection, carboplatin, 50 mg
J9050 Injection, carmustine, 100 mg [< 250mg/m2]
J9060 Injection, cisplatin, powder or solution, per 10 mg [< 50 mg/m2]
J9070 Cyclophosphamide, 100 mg [< 1,500 mg/m2]
J9098 Injection, cytarabine liposome, 10 mg [> 1 g/m2]
J9100 Injection, cytarabine, 100 mg [> 1 g/m2]
J9120 Injection, dactinomycin, 0.5 mg
J9150 Injection, daunorubicin, 10 mg
J9151 Injection, daunorubicin citrate, liposomal formulation, 10 mg
J9178 Injection, epirubicin HCl, 2 mg
J9206 Injection, irinotecan, 20 mg
J9208 Injection, ifosfamide, 1 g
J9211 Injection, idarubicin HCl, 5 mg
J9245 Injection, melphalan HCI, 50 mg [> 50 mg/m2]
J9250 Methotrexate sodium, 5 mg [250 - > 1,000 mg/m2]
J9260 Methotrexate sodium, 50 mg [250 - > 1,000 mg/m2]
J9263 Injection, oxaliplatin, 0.5 mg [> 75 mg/m2]
S0178 Lomustine, oral, 10 mg
Q2050 Injection, doxorubicin hydrochloride, liposomal, not otherwise specified, 10 mg
HCPCS codes related to Low Emetic Risk Without Prophylaxis (10-30% frequency of emesis):
J0207 Injection, amifostine, 500 mg [< 300 mg]
J8520 Capecitabine, oral, 150 mg
J8521 Capecitabine, oral, 500 mg
J8560 Etoposide, oral, 50 mg
J8610 Methotrexate, oral, 2.5 mg [> 50 mg/m2 < 250 mg/m2]
J8700 Temozolomide, oral, 5 mg
J8705 Topotecan, oral, 0.25 mg
J9000 Injection, doxorubicin HCl, 10 mg [liposomal]
J9041 Injection, bortezomib, 0.1 mg
J9055 Injection, cetuximab, 10 mg
J9098 Injection, cytarabine liposome, 10 mg [low dose] [100-200 mg/m2]
J9100 Injection, cytarabine, 100 mg [low dose] [100-200 mg/m2]
J9171 Injection, docetaxel, 1 mg
J9181 Injection, etoposide, 10 mg
J9185 Injection, fludarabine phosphate, 50 mg [oral]
J9190 Injection, fluorouracil, 500 mg
J9201 Injection, gemcitabine HCl, 200 mg
J9250 Methotrexate sodium, 5 mg [> 50 mg/m2 < 250 mg/m2]
J9260 Methotrexate sodium, 50 mg [> 50 mg/m2 < 250 mg/m2]
J9264 Injection, paclitaxel protein-bound particles, 1 mg
J9265 Injection, paclitaxel, 30 mg
J9268 Injection, pentostatin, 10 mg
J9280 Injection, mitomycin, 5 mg
J9291 Mitomycin, 40 mg
J9293 Injection, mitoxantrone HCI, per 5 mg
J9305 Injection, pemetrexed, 10 mg
J9307 Injection, pralatrexate, 1 mg
J9315 Injection, romidepsin, 1 mg
J9328 Injection, Temozolomide, 1 mg [Temodar]
J9340 Injection, thiotepa, 15 mg
J9351 Injection, topotecan, 0.1 mg
J9355 Injection, trastuzumab, 10 mg
Q2050 Injection, doxorubicin hydrochloride, liposomal, not otherwise specified, 10 mg
HCPCS codes related to Minimal Emetic Risk Without Prophylaxis (< 10% frequency of emesis):
J0594 Injection, busulfan, 1 mg
J1190 Injection, dexrazoxane HCl, per 250 mg
J8510 Busulfan, oral, 2mg
J8565 Gefitinib, oral, 250 mg
J8600 Melphalan, oral, 2 mg [low-dose]
J8610 Methotrexate, oral, 2.5 mg [< 50 mg/m2]
J9010 Injection, alemtuzumab, 10 mg
J9020 Injection, asparaginase, 10,000 units
J9035 Injection, bevacizumab, 10 mg
J9040 Injection, bleomycin sulfate, 15 units
J9065 Injection, cladribine, per 1 mg
J9185 Injection, fludarabine phosphate, 50 mg
J9212 Injection, interferon alfacon-1, recombinant, 1 mcg
J9213 Injection, interferon alfa-2A, recombinant, 3 million units
J9214 Injection, interferon alfa-2B, recombinant, 1 million units
J9215 Injection, interferon alfa-N3, (human leukocyte derived), 250,000 IU
J9228 Injection, ipilimumab, 1 mg
J9245 Injection, melphalan HCI, 50 mg [oral low-dose]
J9250 Methotrexate sodium, 5 mg [< 50 mg/m2]
J9260 Methotrexate sodium, 50 mg [< 50 mg/m2]
J9300 Injection, gemtuzumab ozogamicin, 5 mg
J9302 Injection, ofatumumab, 10 mg
J9306 Injection, pertuzumab, 1 mg
J9310 Injection, rituximab, 100 mg
J9357 Injection, valrubicin, intravesical, 200 mg
J9360 Injection, vinblastine sulfate, 1 mg
J9370 Vincristine sulfate, 1 mg
J9390 Injection, vinorelbine tartrate, per 10 mg
S0088 Imatinib, 100 mg
S0172 Chlorambucil, oral, 2 mg
S0176 Hydroxyurea, oral, 500 mg
Other HCPCS codes related to this CPB:
A9153 Multiple vitamins, with or without minerals and trace elements, oral, per dose, not otherwise specified
C8957 Intravenous infusion for therapy/diagnosis; initiation of prolonged infusion (more than 8 hours), requiring use of portable or implantable pump
J1240 Injection, dimenhydrinate, up to 50 mg
J2550 Injection, promethazine HCl, up to 50 mg
J3250 Injection, trimethobenzamide HCl, up to 200 mg
J3415 Injection, pyridoxine HCl, 100 mg
Q0083 - Q0085 Chemotherapy administration
Q0162 Ondansetron 1 mg, oral, FDA-approved prescription anti-emetic, for use as a complete therapeutic substitute for an IV anti-emetic at a time of chemotherapy treatment, not to exceed a 48 hour dosage regimen
Q0166 Ganisetron HCl, 1 mg, oral, FDA approved prescription anti-emetic, for use as a complete therapeutic substitute for an IV anti-emetic at the time of chemotherapy treatment, not to exceed a 24-hour dosage regimen
Q0169 Promethazine HCl, 12.5 mg, oral, FDA approved prescription anti-emetic, for use as a complete therapeutic substitute for an IV anti-emetic at the time of chemotherapy treatment, not to exceed a 48-hour dosage regimen
Q0180 Dolasetron mesylate, 100 mg, oral, FDA approved prescription anti-emetic, for use as a complete therapeutic substitute for an IV anti-emetic at the time of chemotherapy treatment, not to exceed a 24-hour dosage regimen
S0091 Ganisetron HCl, 1 mg (for circumstances falling under the Medicare statute, use Q0166)
S0119 Ondansetron, oral 4 mg (or circumstances falling under the medicare statute, use Q0162)
S0174 Dolasetron mesylate, oral, 50 mg (for circumstances falling under the Medicare statute, use Q0180)
S9351 Home infusion therapy, continuous or intermittent anti-emetic infusion therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and visits coded separately), per diem
S9370 Home therapy, intermittent antiemetic injection therapy; administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem [covered for high or moderate emetic risk only]
ICD-9 codes covered if selection criteria are met:
042 Human immunodeficiency virus [HIV] disease
307.51 Bulimia nervosa
536.2 Persistent vomiting [cyclical]
643.00 - 643.93 Excessive vomiting in pregnancy [when clinical signs of dehydration are present or nausea and vomiting have persisted more than 3 weeks and criteria A,B, and C are met]
990 Effects of radiation, unspecified [secondary to total body irradiation]
E933.1 Adverse effect of antineoplastic and immunosuppressive drugs [not covered for Anzemet]
V58.0 Encounter for radiotherapy [for total body radiation when oral antiemetic therapy has failed or is contraindicated]
V58.11 - V58.12 Encounter for antineoplastic chemotherapy and immunotherapy [with initial and repeat courses of moderately highly emetogenic cancer chemotherapy and for breakthrough chemotherapy induced nausea and vomiting of low emetogenic cancer chemotherapy]
ICD-9 codes not covered for indications listed in the CPB:
994.6 Motion sickness
Other ICD-9 codes related to this CPB:
140.0 - 208.91 Malignant neoplasm
230.0 - 234.9 Carcinoma in situ
276.0 Hyperosmolality and/or hypernatremia
276.1 Hyposmolality and/or hyponatremia
276.51 Dehydration
564.2 Postgastric surgery syndromes
787.01 - 787.03 Nausea and vomiting
997.4 Digestive system complications
V45.89 Other postprocedural status


The above policy is based on the following references:
  1. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Guidelines for Supportive Care. Antiemesis. Version 1.2006. Jenkintown, PA: NCCN; January 10, 2006: 1-32. Available at: http://www.nccn.org/. Accessed March 10, 2006.
  2. Roila F, Hesketh PJ, Herrstedt J; Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer. Prevention of chemotherapy- and radiotherapy-induced emesis: Results of the 2004 Perugia International Antiemetic Consensus Conference. Ann Oncol. 2006;17(1):20-28.
  3. Maranzano E, Feyer PCh, Molassiotis A, et al; Participants in the Perugia Consensus Conference 2004. Evidence-based recommendations for the use of antiemetics in radiotherapy. Radiother Oncol. 2005;76(3):227-233.
  4. Kris MG, Hesketh PJ, Herrstedt J, et al. Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer. 2005;13(2):85-96.
  5. Aguilar AE, Figueiras CM, Cortes-Funes H, et al. Clinical practice guidelines on antiemetics in oncology. Expert Rev Anticancer Ther. 2005;5(6):963-972.
  6. U.S. Food and Drug Administration (FDA). Zofran (ondansetron hydrochloride) injection prescribing information. Rockville, MD: FDA; May 13, 2005. Available at: www.fda.gov/medwatch/SAFETY/2005/Mar_PI/Zofran_PI.pdf. Accessed March 10, 2006.
  7. U.S. Food and Drug Administration (FDA). Anzemet (dolasetron mesylate) injection prescribing information. Rockville, MD: FDA; August 24, 2005. Available at: www.fda.gov/medwatch/SAFETY/2005/Jun_PI/Anzemet_PI.pdf. Accessed March 10, 2006.
  8. U.S. Food and Drug Administration (FDA). Kytril (granisetron hydrochloride) injection prescribing information. Rockville, MD: FDA; 2005. Available at: www.fda.gov/medwatch/safety/2005/Nov_PI/Kytril_Inj_PI.pdf. Accessed March 10, 2006.
  9. U.S. Food and Drug Administration (FDA). Aloxi (palonosetron hydrochloride) injection prescribing information. Rockville, MD: FDA; 2005. Available at: http://www.fda.gov/cder/foi/nda/2003/21-372_Alox_Prntlbl.pdf. Accessed March 10, 2006.
  10. Feyer P, Seegenschmiedt MH, Steingraeber M. Granisetron in the control of radiotherapy-induced nausea and vomiting: A comparison with other antiemetic therapies. Support Care Cancer. 2005;13(9):671-678.
  11. Goldsmith B. First choice for radiation-induced nausea and vomiting--the efficacy and safety of granisetron. Acta Oncol. 2004;43 Suppl 15:19-22.
  12. Abbott B, Ippoliti C, Bruton J, et al. Antiemetic efficacy of granisetron plus dexamethasone in bone marrow transplant patients receiving chemotherapy and total body irradiation. Bone Marrow Transplant. 1999;23(3):265-269.
  13. American College of Obstetrics and Gynecology (ACOG). Nausea and vomiting of pregnancy. ACOG Practice Bulletin No.52. Washington, DC: ACOG; April 2004.
  14. Bashiri A, Neumann L, Maymon E. Hyperemesis gravidarum: Epidemiologic features, complications and outcome. Eur J Obstet Gynecol Reprod Biol 1995;63(2):135-138.
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  20. Sullivan CA, Johnson CA, Roach H, et al. A pilot study of intravenous ondansetron for hyperemesis gravidarum. Am J Obstet Gynecol. 1996;174(5):1565-1568.
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  22. Gan TJ. Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: Are they all the same? CNS Drugs. 2005;19(3):225-238.
  23. Fujii Y. The utility of antiemetics in the prevention and treatment of postoperative nausea and vomiting in patients scheduled for laparoscopic cholecystectomy. Curr Pharm Des. 2005;11(24):3173-3183.
  24. Goldfaden A, Birkmeyer JD. Evidence-based practice in laparoscopic surgery: Perioperative care. Surg Innov. 2005;12(1):51-61.
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  29. Loewen PS, Marra CA, Zed PJ. 5-HT3 receptor antagonists vs traditional agents for the prophylaxis of postoperative nausea and vomiting. Can J Anaesth. 2000;47(10):1008-1018.
  30. Levine ME, Chillas JC, Stern RM, et al. The effects of serotonin (5-HT3) receptor antagonists on gastric tachyarrhythmia and the symptoms of motion sickness. Aviat Space Environ Med. 2000;71(11):1111-1114.
  31. Reid K, Palmer JL, Wright RJ, et al. Comparison of the neurokinin-1 antagonist GR205171, alone and in combination with the 5-HT3 antagonist ondansetron, hyoscine and placebo in the prevention of motion-induced nausea in man. Br J Clin Pharmacol. 2000;50(1):61-64.
  32. Benline TA, French J, Poole E. Anti-emetic drug effects on pilot performance: Granisetron vs. ondansetron. Aviat Space Environ Med. 1997;68(11):998-1005.
  33. Public Health Agency of Canada. An Advisory Committee Statement (ACS): Statement on motion sickness. Canada Communicable Dis Rep CCDR. 2003;15(29):1-12. Available at: http://www.phac-spc.gc.ca/publicat/ccdr-rmtc/03pdf/acs-dcc-29-11.pdf. Accessed March 29, 2006.
  34. Wilde MI, Markham A. Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. Drugs. 1996;52(5):773-794.
  35. Ljutic D, Perkovic D, Rumboldt Z, et al. Comparison of ondansetron with metoclopramide in the symptomatic relief of uremia-induced nausea and vomiting. Kidney Blood Press Res. 2002;25(1):61-64.
  36. Sowerby Centre for Health Informatics at Newcastle (SCHIN). Palliative care - nausea/vomiting/malignant bowel obstruction. PRODIGY Guidance. PRODIGY: Practical Support for Clinical Governance. Newcastle upon Tyne, UK: SCHIN; January 2006. Available at: http://www.prodigy.nhs.uk/ProdigyKnowledge/Guidance/WholeGuidanceView.aspx?GuidanceId=37443. Accessed March 29, 2006.
  37. Hartman BK, Faris PL, Kim SW, et al. Treatment of bulimia nervosa with ondansetron. Arch Gen Psychiatry 1997;54(10):969-970.
  38. Moreno MA. Eating disorder: Bulimia. eMedicine Pediatrics Topic 298. Omaha, NE: eMedicine.com; updated December 19, 2005. Available at: http://www.emedicine.com/ped/topic298.htm. Accessed March 29, 2006.
  39. Faris PL, Eckert ED, Kim SW, et al. Evidence for a vagal pathophysiology for bulimia nervosa and the accompanying depressive symptoms. J Affect Disord. 2006;92(1):79-90.
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  41. Kaplan AS. Academy for Eating Disorders International Conference on Eating Disorders. Denver, CO, USA, May 29-31, 2003. Expert Opin Investig Drugs. 2003;12(8):1441-1443.
  42. Fung SM, Ferrill MJ. Treatment of bulimia nervosa with ondansetron. Ann Pharmacother. 2001;35(10):1270-1273.
  43. Hasler WL. 5-HT(3) antagonist therapy of bulimia nervosa: A peripherally active agent for a central nervous system eating disorder? Gastroenterology. 2000;119(1):271-272.
  44. Faris PL, Kim SW, Meller WH, et al. Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: A randomised, double-blind trial. Lancet. 2000;355(9206):792-797.
  45. Scharman EJ. Use of ondansetron and other antiemetics in the management of toxic acetaminophen ingestions. J Toxicol Clin Toxicol. 1998;36(1-2):19-25.
  46. Wilde MI, Markham A. Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. Drugs. 1996;52(5):773-794.
  47. Cancer Care Ontario, Systemic Treatment Disease Site Group. Use of 5-HT3 receptor-antagonists in patients receiving moderately or highly emetogenic chemotherapy. Practice Guidelines Report #12-3. Cancer Care Ontario Practice Guidelines Initiative. Toronto, ON: Cancer Care Ontario; updated January 2003. Available at: http://www.cancercare.on.ca/pdf/pebc12_3f.pdf. Accessed October 12, 2007.
  48. Aubin CD. Toxicity, theophylline. eMedicine Pediatrics Topic 2725. Omaha, NE: eMedicine.com; updated August 2, 2004. Available at: http://www.emedicine.com/ped/topic2725.htm. Accessed March 29, 2006.
  49. Tucker J. Toxicity, acetaminophen. eMedicine Pediatrics Topic 7. Omaha, NE: eMedicine.com; updated December 12, 2003. Available at: http://www.emedicine.com/ped/topic7.htm. Accessed March 29, 2006.
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  54. Carlisle JB, Stevenson CA. Drugs for preventing postoperative nausea and vomiting. Cochrane Database Syst Rev. 2006;(3):CD004125. 
  55. Fujii Y, Tanaka H. Efficacy of granisetron for the treatment of postoperative nausea and vomiting in women undergoing breast surgery: A randomised, double-blind, placebo-controlled trial. Clin Drug Investig. 2006;26(4):203-208.
  56. Lee Y, Wang JJ, Yang YL, et al. Midazolam vs ondansetron for preventing postoperative nausea and vomiting: A randomised controlled trial. Anaesthesia. 2007;62(1):18-22.
  57. Aouad MT, Siddik-Sayyid SM, Taha SK, et al. Haloperidol vs. ondansetron for the prevention of postoperative nausea and vomiting following gynaecological surgery. Eur J Anaesthesiol. 2007;24(2):171-178.
  58. Subramaniam K, Pandia MP, Dash M, et al. Scheduled prophylactic ondansetron administration did not improve its antiemetic efficacy after intracranial tumour resection surgery in children. Eur J Anaesthesiol. 2007;24(7):615-619.
  59. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Guidelines for Supportive Care. Antiemesis. Version 3.2008. Jenkintown, PA: NCCN; February 5, 2008: 1-31. Available at: http://www.nccn.org/. Accessed July 18, 2008.
  60. U.S. Food and Drug Administration (FDA). Emend (fosaprepitant dimeglumine) injection prescribing information. Rockville, MD: FDA. January 25, 2008. Available at: http://www.fda.gov/cder/foi/label/2008/022023lbl.pdf. Accessed July 18, 2008.
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Copyright Aetna Inc. All rights reserved. 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.
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