Difference between revisions of "Antiemesis"

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NCCN and MASCC categories of emetic risk in the absence of prophylaxis:
 
NCCN and MASCC categories of emetic risk in the absence of prophylaxis:
−
*High: >90% frequency of emesis
+
*High: >90% frequency of emesis (HEC)
−
*Moderate: 30-90% frequency of emesis
+
*Moderate: 30-90% frequency of emesis (MEC)
 
*Low: 10-30% frequency of emesis
 
*Low: 10-30% frequency of emesis
 
*Minimal: <10% frequency of emesis
 
*Minimal: <10% frequency of emesis
Line 797: Line 797:
 
=Antiemetics for highly emetogenic IV chemotherapy=
 
=Antiemetics for highly emetogenic IV chemotherapy=
 
{| class="wikitable"
 
{| class="wikitable"
−
! colspan="4" |Acute CINV prophylaxis regiments for HEC
+
!
 +
! colspan="4" |Acute and Delayed CINV prophylaxis regiments for HEC
 +
!Reference
 
|-
 
|-
−
|DEX
+
|1
−
|5HT3
+
|DEX +
−
|NK1
+
|5HT3 +
−
|OLN
+
|NK1 +
 +
|OLN  
 +
|
 
|-
 
|-
−
|DEX
+
|2
−
|5HT3
+
|DEX +
 +
|5HT3 +
 
|NK1
 
|NK1
 +
|
 
|
 
|
 
|-
 
|-
−
|DEX
+
|3
−
|5HT3
+
|DEX +
 +
|5HT3 +
 
|OLN
 
|OLN
 +
|
 
|
 
|
 
|}
 
|}
  
 
==Neurokinin-1 (NK1) antagonist-containing regimen (except netupitant)==
 
==Neurokinin-1 (NK1) antagonist-containing regimen (except netupitant)==
−
===Neurokinin 1 antagonist (IV and PO formulation at recommended doses are equally effective)===
+
===Neurokinin 1 (NK1) antagonist (IV and PO formulation at recommended doses are equally effective)===
 
*[[Aprepitant (Emend)]] 125 mg PO once on day 1, then 80 mg PO once per day on days 2 & 3
 
*[[Aprepitant (Emend)]] 125 mg PO once on day 1, then 80 mg PO once per day on days 2 & 3
 
*[[Fosaprepitant (Emend for Injection)]] 150 mg IV once on day 1
 
*[[Fosaprepitant (Emend for Injection)]] 150 mg IV once on day 1
Line 834: Line 842:
 
*[[Tropisetron (Navoban)]] 5 mg IV or PO day 1
 
*[[Tropisetron (Navoban)]] 5 mg IV or PO day 1
  
−
===Steroid===
+
===Dexamethasone (DEX)===
 
''Steroids contraindicated for use with interleukin-2 and interferon.''
 
''Steroids contraindicated for use with interleukin-2 and interferon.''
 
*If [[Aprepitant (Emend)]] used:  
 
*If [[Aprepitant (Emend)]] used:  
Line 852: Line 860:
 
*[[Dexamethasone (Decadron)]] 12 mg IV or PO once on day 1, then 8 mg IV or PO once per day on days 2 to 4
 
*[[Dexamethasone (Decadron)]] 12 mg IV or PO once on day 1, then 8 mg IV or PO once per day on days 2 to 4
  
−
==Olanzapine-containing regimen==
+
==Olanzapine (OLN) containing regimen==
−
''Note: a 4-drug regimen based on [https://www.nejm.org/doi/full/10.1056/NEJMoa1515725 Navari et al. 2016]<ref>Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. [https://www.nejm.org/doi/full/10.1056/NEJMoa1515725 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27410922 PubMed]</ref> is likely to be recommended in the next release of the NCCN Guidelines.''
+
''Note: a 4-drug regimen based on [https://www.nejm.org/doi/full/10.1056/NEJMoa1515725 Navari et al. 2016]<ref>Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. [https://www.nejm.org/doi/full/10.1056/NEJMoa1515725 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27410922 PubMed]</ref>''
 
*[[Olanzapine (Zyprexa)]] 10 mg PO once per day on days 1 to 4
 
*[[Olanzapine (Zyprexa)]] 10 mg PO once per day on days 1 to 4
−
*[[Palonosetron (Aloxi)]] 0.25 mg IV once on day 1
+
*[[Aprepitant (Emend)]] 125 mg PO once on day 1, then 80 mg PO once per day on days 2 & 3, '''OR''' [[Fosaprepitant (Emend for Injection)]] 150 mg IV once on day 1
−
*[[Dexamethasone (Decadron)]] 20 mg IV once on day 1
+
*[[Palonosetron (Aloxi)]] 0.25 mg IV once on day 1, '''OR''' Granisetron 1mg IV or 2mg PO,  '''OR''' Ondansetron 8 mg PO or IV
 +
*[[Dexamethasone (Decadron)]] 12 mg PO on day 1, and 8 mg PO on days 2, 3, and 4
  
 
==Optional==
 
==Optional==

Revision as of 23:55, 31 March 2019

Adapted from the NCCN[1], ASCO[2] and MASCC/ESMO[3]

Emetic risk of chemotherapy, immunotherapy, TKIs and other agents

Hint: You can sort the table by clicking on the boxes containing arrows at the top of each column.
All drugs are IV route unless otherwise specified.

NCCN and MASCC categories of emetic risk in the absence of prophylaxis:

  • High: >90% frequency of emesis (HEC)
  • Moderate: 30-90% frequency of emesis (MEC)
  • Low: 10-30% frequency of emesis
  • Minimal: <10% frequency of emesis

ASCO guidelines say that in cases of combination chemotherapy regimens, patients should be given antiemetics that are recommended for the individual medication with the highest emetic risk. The exception is with anthracycline and Cyclophosphamide (Cytoxan) combinations as described below.

Drug NCCN emetogenic potential ASCO emetogenic potential MASCC/ESMO emetogenic potential (2016) Comment
Ado-trastuzumab emtansine (Kadcyla) Low
Anthracycline (see differences between NCCN & ASCO) & Cyclophosphamide (Cytoxan) combination chemotherapy High (Doxorubicin (Adriamycin) or Epirubicin (Ellence) with Cyclophosphamide (Cytoxan)) High (Daunorubicin (Cerubidine), Doxorubicin (Adriamycin), Epirubicin (Ellence), or Idarubicin (Idamycin) with Cyclophosphamide (Cytoxan)) High MASCC comment - in patients with breast cancer
Aldesleukin (Proleukin) Moderate: >12 to 15 million international units/m2
Low: ≤12 million international units/m2
Alemtuzumab (Campath) Minimal Moderate Moderate
Altretamine (Hexalen) (oral) High/Moderate NCCN did not further delineate between degrees of emetic potential
Amifostine (Ethyol) Moderate: >300 mg/m2
Low: ≤300 mg
Arsenic trioxide (Trisenox) Moderate
Asparaginase (Elspar) Minimal
Axitinib (Inlyta) (oral) Low/Minimal Low
Azacitidine (Vidaza) Moderate Moderate Moderate
Bendamustine Moderate Moderate Moderate
Bevacizumab (Avastin) Minimal Minimal Minimal
Bexarotene (Targretin) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Bleomycin (Blenoxane) Minimal Minimal Minimal
Bortezomib (Velcade) Minimal Low Low
Bosutinib (Bosulif) (oral) Low/Minimal Moderate
Brentuximab vedotin (Adcetris) Low Low
Busulfan (Myleran) High/Moderate: ≥4 mg/day
Low/Minimal: <4 mg/day 		Minimal Minimal
Busulfan (Myleran) (oral) High/Moderate: ≥4 mg/day
Low/Minimal: <4 mg/day 		NCCN did not further delineate between degrees of emetic potential
Cabazitaxel (Jevtana) Low Low Low
Cabozantinib (Cometriq) (oral) Low/Minimal
Capecitabine (Xeloda) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Carboplatin (Paraplatin) High: AUC ≥4

Moderate: AUC <4

Moderate (but recommended triplet combination of NK1, 5-HT3, and dexamethasone) Moderate (but recommended triplet combination of NK1, 5-HT3, and dexamethasone) ASCO and MASCC/ESMO did not subclassify based on dose
Carfilzomib (Kyprolis) Low Low
Carmustine (BCNU) High: >250 mg/m2
Moderate: ≤250 mg/m2 		High High ASCO and MASCC/ESMO did not subclassify based on dose
Catumaxomab (Removab) Low Low
Cetuximab (Erbitux) Minimal Minimal Low
Chlorambucil (Leukeran) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Cisplatin (Platinol) High High High Some only consider emetogenic potential high when receiving ≥70 mg/m2
Cladribine (Leustatin) Minimal Minimal Minimal
Clofarabine (Clolar) Moderate Moderate Moderate
Crizotinib (Xalkori) (oral) High/Moderate Moderate
Cyclophosphamide (Cytoxan) High: >1500 mg/m2 or when given with certain anthracyclines
Moderate: ≤1500 mg/m2 		High: ≥1500 mg/m2 or when given with anthracyclines
Moderate: <1500 mg/m2 		High: > 1500 mg/m2 or when combined with anthracyclines (in breast cancer patients)

Moderate: < 1500 mg/m2

Cyclophosphamide (Cytoxan) (oral) High/Moderate: ≥100 mg/m2/day
Low/Minimal: <100 mg/m2/day 		Moderate NCCN did not further delineate between degrees of emetic potential
Cytarabine (Ara-C) Moderate: >200 mg/m2
Low: 100 to 200 mg/m2
Minimal: <100 mg/m2 		Moderate: >1000 mg/m2
Low: ≤1000 mg/m2 		Moderate: > 1000 mg/m2 

Low: < 1000 mg/m2

Dabrafenib (Tafinlar) (oral) Low/Minimal Low
Dacarbazine (DTIC) High High High
Dactinomycin (Cosmegen) Moderate High
Dasatinib (Sprycel) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Daunorubicin (Cerubidine) Moderate High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone 		High: when given with combined with cyclophosphamide (in breast cancer patients)

Moderate: when used alone

Decitabine (Dacogen) Minimal
Denileukin diftitox (Ontak) Minimal
Dexrazoxane (Zinecard) Minimal
Docetaxel (Taxotere) Low Low Low
Doxorubicin (Adriamycin) High: ≥60 mg/m2 or when given at any dose with Cyclophosphamide (Cytoxan)
Moderate: <60 mg/m2 		High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone 		High: when given with combined with cyclophosphamide (in breast cancer patients)

Moderate: when used alone

Pegylated liposomal doxorubicin (Doxil) Low Low Low
Epirubicin (Ellence) High: >90 mg/m2 or when given at any dose with Cyclophosphamide (Cytoxan)
Moderate: ≤90 mg/m2 		High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone 		High: when combined with cyclophosphamide (in breast cancer patients)

Moderate: when used alone

Eribulin (Halaven) Low Low
Erlotinib (Tarceva) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Estramustine (Emcyt) (oral) High/Moderate NCCN did not further delineate between degrees of emetic potential
Etoposide (Vepesid) Low Low Low
Etoposide (Vepesid) (oral) High/Moderate Low NCCN did not further delineate between degrees of emetic potential
Everolimus (Afinitor) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Floxuridine (FUDR) Low
Fludarabine (Fludara) Minimal Minimal Minimal
Fludarabine (Fludara) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Fluorouracil (5-FU) Low Low Low
Gefitinib (Iressa) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Gemcitabine (Gemzar) Low Low Low
Hydroxyurea (Hydrea) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Idarubicin (Idamycin) Moderate High when given with Cyclophosphamide (Cytoxan)
Moderate when used alone 		High: when combined with cyclophosphamide (in breast cancer patients) Moderate: when used alone
Ifosfamide (Ifex) High: ≥2 g/m2 per dose
Moderate: <2 g/m2 per dose 		Moderate Moderate ASCO and MASCC did not subclassify based on dose
Imatinib (Gleevec) (oral) Low/Minimal Moderate NCCN did not further delineate between degrees of emetic potential
Interferon alfa-2a (Roferon-A) Moderate: ≥10 million international units/m2
Low: >5, <10 million international units/m2
Minimal: ≤5 million international units/m2 		NCCN did not specify interferon alfa-2a vs. 2b
Interferon alfa-2b (Intron-A) Moderate: ≥10 million international units/m2
Low: >5, <10 million international units/m2
Minimal: ≤5 million international units/m2 		NCCN did not specify interferon alfa-2a vs. 2b
Ipilimumab (Yervoy) Minimal Low
Irinotecan (Camptosar) Moderate Moderate Moderate
Ixabepilone (Ixempra) Low Low Low
Lapatinib (Tykerb) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Lenalidomide (Revlimid) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Lomustine (CCNU) (oral) High/Moderate (single day) single day; NCCN did not further delineate between degrees of emetic potential
Mechlorethamine (Mustargen) High High High
Melphalan (Alkeran) Moderate
Melphalan (Alkeran) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Mercaptopurine (6-MP) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Methotrexate (MTX) Moderate: ≥250 mg/m2
Low: >50, <250 mg/m2
Minimal: ≤50 mg/m2 		Low Low ASCO and MASCC did not subclassify based on dose
Methotrexate (MTX) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Mitomycin (Mutamycin) Low Low Low
Mitotane (Lysodren) (oral) High/Moderate
Mitoxantrone (Novantrone) Low Low Low
Nelarabine (Arranon) Minimal
Nilotinib (Tasigna) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Ofatumumab (Arzzera) Minimal Minimal
Omacetaxine (Synribo) Low
Oxaliplatin (Eloxatin) Moderate Moderate Moderate
Paclitaxel (Taxol) Low Low Low
Paclitaxel, nanoparticle albumin-bound (Abraxane) Low Low
Panitumumab (Vectibix) Minimal
Pazopanib (Votrient) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Peg-asparginase (Oncaspar) Minimal
Peginterferon alfa-2a (Pegasys) Minimal NCCN did not specify interferon alfa-2a vs. 2b
Peginterferon alfa-2b (PegIntron) Minimal NCCN did not specify interferon alfa-2a vs. 2b
Pemetrexed (Alimta) Low Low Low
Pentostatin (Nipent) Low
Pertuzumab (Perjeta) Minimal Low
Pomalidomide (Pomalyst) (oral) Low/Minimal Minimal
Ponatinib (Iclusig) (oral) Low/Minimal Low
Pralatrexate (Folotyn) Low Minimal Minimal
Procarbazine (Matulane) (oral) High/Moderate High NCCN did not further delineate between degrees of emetic potential
Regorafenib (Stivarga) (oral) Low/Minimal Low
Rituximab (Rituxan) Minimal Minimal Minimal
Romidepsin (Istodax) Low Moderate
Ruxolitinib (Jakafi) (oral) Low/Minimal Minimal
Sorafenib (Nexavar) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Streptozocin (Zanosar) High High High
Sunitinib (Sutent) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Temozolmide (Temodar) Moderate Moderate MASCC remark: No direct evidence found for temozolomide IV. Classification is based on oral temozolomide, since all sources indicate a

similar safety profile

Temozolmide (Temodar) (oral) High/Moderate: >75 mg/m2/day
Low/Minimal: ≤75 mg/m2/day 		Moderate NCCN did not further delineate between degrees of emetic potential
Temsirolimus (Torisel) Minimal Low
Thalidomide (Thalomid) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Thioguanine (Tabloid) (oral) Low/Minimal Minimal NCCN did not further delineate between degrees of emetic potential
Thiotepa (Thioplex) Low Moderate
Topotecan (Hycamtin) Low Low Low
Topotecan (Hycamtin) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Trametinib (Mekinist) (oral) Low/Minimal
Trastuzumab (Herceptin) Minimal Low Minimal
All-trans retinoic acid (ATRA) (oral) Low/Minimal NCCN did not further delineate between degrees of emetic potential
Valrubicin (Valstar) Minimal
Vandetanib (Caprelsa) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Vemurafenib (Zelboraf) (oral) Low/Minimal
Vinblastine (Velban) Minimal Minimal Minimal
Vincristine (Oncovin) Minimal Minimal Minimal
Vincristine liposomal (Marqibo) Minimal
Vinorelbine (Navelbine) Minimal Minimal Minimal
Vismodegib (Erivedge) (oral) High/Moderate Minimal
Vorinostat (Zolinza) (oral) Low/Minimal Low NCCN did not further delineate between degrees of emetic potential
Ziv-aflibercept (Zaltrap) Low

Antiemetics for highly emetogenic IV chemotherapy

Acute and Delayed CINV prophylaxis regiments for HEC Reference
1 DEX + 5HT3 + NK1 + OLN
2 DEX + 5HT3 + NK1
3 DEX + 5HT3 + OLN

Neurokinin-1 (NK1) antagonist-containing regimen (except netupitant)

Neurokinin 1 (NK1) antagonist (IV and PO formulation at recommended doses are equally effective)

Serotonin (5-HT3) antagonist

  • Dolasetron (Anzemet) 100 mg PO once on day 1
  • Granisetron (choose one of the options below):
    • 2 mg PO once on day 1
    • 0.01 mg/kg (maximum dose 1 mg) IV once on day 1
    • transdermal patch as 3.1 mg/24H patch (containing 34.3 mg granisetron total dose) placed ~24 to 48 hours before the first dose of chemotherapy. May use patch up to 7 days.
  • Ondansetron (Zofran) (choose one of the options below):
    • 16 to 24 mg PO once on day 1
    • 8 to 16 mg IV[4] IV once on day 1
  • Palonosetron (Aloxi) 0.25 mg IV once on day 1
  • Ramosetron (Iribo) 0.3mg IV day 1
  • Tropisetron (Navoban) 5 mg IV or PO day 1

Dexamethasone (DEX)

Steroids contraindicated for use with interleukin-2 and interferon.

References

  1. Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE. J Clin Oncol. 2011 Apr 10;29(11):1495-501. Epub 2011 Mar 7. link to original article PubMed

Netupitant-containing regimen

Olanzapine (OLN) containing regimen

Note: a 4-drug regimen based on Navari et al. 2016[5]

Optional

Antiemetics for moderately emetogenic IV chemotherapy

Day 1

Select one option from each class on day 1:

Serotonin (5-HT3) antagonist

Note: NCCN lists all of the below as potential options, whereas ASCO only lists Palonosetron (Aloxi). Palonosetron (Aloxi) is preferred by the NCCN.

  • Dolasetron (Anzemet) 100 mg PO day 1
  • Granisetron (choose one of the options below):
    • 2 mg PO day 1
    • 1 mg PO twice per day day 1
    • 0.01 mg/kg (max 1mg) IV day 1
    • transdermal patch as 3.1 mg/24H patch (containing 34.3 mg Granisetron total dose) placed ~24 to 48 hours before the first dose of chemotherapy. May use patch up to 7 days.
  • Ondansetron (Zofran) (choose one of the options below):
    • 16 to 24 mg PO day 1
    • 8 to 16 mg IV day 1[4] IV day 1
  • Palonosetron (Aloxi) (choose one of the options below):
    • 0.25 mg IV day 1
    • 0.5 mg PO day 1

Steroid

Steroids contraindicated for use with interleukin-2 and interferon.

Optional

Day 2 and 3

ASCO only recommends Dexamethasone (Decadron), whereas NCCN allows you to choose any one class of medication to use: either a serotonin (5-HT3) antagonist, or steroid, or neurokinin 1 antagonist +/- steroid.

Serotonin (5-HT3) antagonist

  • Dolasetron (Anzemet) 100 mg PO daily
  • Granisetron (choose one of the options below):
    • 1 to 2 mg PO once per day on days 2 & 3
    • 1 mg PO twice per day on days 2 & 3
    • 0.01 mg/kg (max 1mg) IV on days 2 & 3
    • continued use of 3.1 mg/24H transdermal patch
  • Ondansetron (Zofran) (choose one of the options below):
    • 8 mg PO twice per day on days 2 & 3
    • 16 mg PO once per day on days 2 & 3
    • 8 to 16 mg IV [4] days 2 to 3

Steroid

Steroids contraindicated for use with interleukin-2 and interferon.

Neurokinin 1 antagonist +/- steroid if NK-1 used on day 1

Optional

Antiemetics for highly to moderately emetogenic PO chemotherapy

These are NCCN recommendations only. ASCO did not provide separate recommendations for PO vs. IV chemotherapy.
Start before chemotherapy and continue once per day:

Serotonin (5-HT3) antagonist

Optional

Antiemetics for low emetic risk IV chemotherapy

Repeat once per day for chemotherapy regimens that last more than one day. ASCO only recommends Dexamethasone (Decadron), whereas NCCN allows you to choose any one medication to use: either Dexamethasone (Decadron), metoclopramide, or prochlorperazine.

Optional

Minimal emetic risk chemotherapy

  • No routine prophylaxis

Antiemetics for low to minimal emetic risk PO chemotherapy

  • use antiemetics prn first

If nausea/vomiting

Choose one of the medications below to start before chemotherapy and continue once per day:

Optional

If continued nausea/vomiting

Use serotonin (5-HT3) antagonist:

Breakthrough antinausea treatment

Use a medication from a different drug class from the current regimen as a prn medication.

Benzodiazepine

Cannabinoid

Miscellaneous

Phenothiazine

Serotonin 5-HT3 antagonist

Steroid

Steroids contraindicated for use with interleukin-2 and interferon.

Anticipatory nausea/vomiting

  • Prevent anticipation by optimizing antiemetic therapy for every cycle of chemotherapy
  • Behavioral therapy
    • Relaxation/systemic desensitization
    • Hypnosis/guided imagery
    • Music therapy
  • Acupuncture/acupressure
  • Alprazolam (Xanax) 0.5 to 2 mg PO three times per day starting the night before treatment
  • Lorazepam (Ativan) 0.5 to 2 mg PO the night before and the morning of treatment

Reference

  1. ↑ NCCN antiemesis guidelines
  2. ↑ Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update
  3. ↑ MASCC antiemetic guidlines https://www.mascc.org/antiemetic-guidelines
  4. ↑ 4.0 4.1 4.2 As of 6/28/2012, the once daily dose of ondansetron (Zofran) 32 mg is no longer recommended due to dose-dependent QTc prolongation. The Ondansetron (Zofran) package insert recommends only a maximum of 16 mg per dose, which can be given as often as every 4 hours x up to 3 doses, as detailed in the 6/29/2012 FDA Drug Safety Communication.
  5. ↑ Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL. Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting. N Engl J Med. 2016 Jul 14;375(2):134-42. link to original article PubMed
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