HemOncRx

CHEMOTHERAPY INDUCED NAUSEA AND VOMITING

13–20 minutes

Clinical Pearls

  • Prevention is the key
  • Emetogenicity Risk of chemotherapy
    • Highly emetic risk chemotherapy IV: NK1 RA, 5-HT3 RA, dexamethasone ± lorazepam
    • NK1 RA: Place in therapy is for prevention of CINV, not treatment of CINV. Largest benefit seen in delayed CINV setting.
    • Corticosteroid antiemetic premedication should be avoided for 3–5 days prior to and 90 days after CAR T-cell therapies.
  • Treat other underlying causes
  • Consider H2 blockers or proton pump inhibitors to prevent dyspepsia – drug interaction with some anticancer medications
  • Keep an eye on drug interactions with anticancer medications

Epidemiology

  • Overall incidence of emesis (83%) with anticancer. With antiemetics, incidence is reduced to nausea (~35%) and vomiting (13%)
  • Consequences of CINV: low QoL, dehydration, e- disturbance, anorexia/wt loss, low PS, low compliance

Clinical Presentation (Terminology)

NauseaRetching (dry heaves)Vomiting (emesis)Anticipatory vomitingBreakthrough emesisRefractory emesis
Awareness of discomfort that may or may not precede vomitingVomiting without the expulsion of vomitusEjection or expulsion of gastric contents through the mouthTriggered by sights, smells, or sounds and is a conditioned response(incidence 20%) Occurs despite prophylactic treatment or necessitates additional rescue medicationsEmesis that occurs during treatment cycles when antiemetic prophylaxis or rescue therapy has failed in previous cycles

Onset: Acute ≤24 hours and Delayed nausea >24h

Duration: at least 3 days for high-emetic risk and 2 days for moderate-emetic risk after the last dose of anticancer agents.

MOA:

  • Nausea is accompanied by decreased gastric tone and decreased peristalsis
  • Neurotransmitters: Serotonin, Substance P, Dopamine, Others (Neurokinin-1 (NK1), ACh, Corticosteroid, Histamine, Cannabinoid, Opioid)
  • Peripheral pathway (acute, serotonin, vomiting): Chemo triggers serotonin release in the GI tract, chemoreceptor trigger zone (CTZ), and pharynx, activating 5-HT3 and dopamine receptors on vagal afferents → signals the vomiting center (VC) in the medulla → vomiting + activation of salivation center, abdominal muscles, respiratory center, and cranial nerves.
  • Central pathway (delayed, substance P, nausea): Chemo activates NK1 receptors in the CNS, leading to NV via a different mechanism.
  • Anticipatory vomiting/nausea: triggered by sights, smells, or sounds, more common in patients with poor prior CINV control.

Risk factors

  • Patient-related (< 50 [less exposure], female, motion sickness hx, morning sickness or N/V during pregnancy hx, poor control of NV in previous chemo cycles, little or no history of alcohol use)
  • Emetogenicity (Hesketh model) – Choose highest risk in multi-cancer drugs
    • Parenteral chemotherapy: minimal, low, moderate, high emetogenic risk
    • Oral chemotherapy: prophylaxis recommended or as needed
  • Radiation-induced NV: mild (head, neck, extremities), moderate (upper abdomen, pelvis, craniospinal radiation), high (total body irradiation, total nodal irradiation, upper-half-body irradiation))

Nonpharmacological therapy

  • Lifestyle measures may help to alleviate nausea/vomiting, such as eating small frequent meals, choosing healthful foods, controlling the amount of food consumed, and eating food at room temperature.
  • Avoid Greasing, spices.
  • Aromatherapy (spearment)
  • Seaband (motion sickness)
  • BRAT (Bananas, rice, apple sauce, toast)

Pharmacological Therapy

Emetic Risk – Parenteral Emetic Risk Management

Emetic RiskDaysOption A (preferred)Option BOption C
HighDay1Olanzapine 2.5-10mg/day PO + NK1 RA (-pitant) + 5-HT3 RA (-setron) + Dexamethasone 12mg PO/IVOlanzapine 2.5-10mg/day PO + Palonosetron 0.25mg IV + Dexamethasone 12mg PO/IVNK1 RA (-pitant) + 5-HT3 RA (-setron) + Dexamethasone 12mg PO/IV
Day 2-4Olanzapine 2.5-10mg/day PO OR Aprepitant (if used on D1) 80mg/day PO D2-3 ± Dexamethasone 8mg/daily PO/IVOlanzapine 2.5-10mg/day POAprepitant (if used on D1) 80mg/day PO D2-3 OR Dexamethasone 8mg/daily PO/IV
ModerateDay15-HT3 RA (-setron) + Dexamethasone 12mg PO/IVOlanzapine 2.5-10mg/day PO + Palonosetron 0.25mg IV + Dexamethasone 12mg PO/IVNK1 RA (-pitant) + 5-HT3 RA (-setron) + Dexamethasone 12mg PO/IV
Day 2-3Dexamethasone 8mg/daily PO/IV OR 5-HT3 RA (-setron PO)Olanzapine 2.5-10mg/day POAprepitant (if used on D1) 80mg/day PO D2-3 ± Dexamethasone 8mg/daily PO/IV

Low Emetic Risk: Dexamethasone, Metoclopramide, Prochlorperazine, or 5-HT3 RA

Minimal Emetic Risk: No routine prophylaxis

Dosing:

  • Olanzapine 2.5-10mg/day PO
  • NK1 RA
    • Aprepitant 125 mg PO, Aprepitant 130 mg IV
    • Fosaprepitant 150 mg IV
    • Netupitant/palonosetron 300mg/0.5mg PO
    • Fosnetupitant/palonosetron 235mg/0.25mg IV
    • Rolapitant 180 mg PO
  • 5-HT3 RA
    • Dolasetron 100 mg PO
    • Granisetron 10 mg SC or 2 mg PO or 0.01 mg/kg (max 1 mg) IV or 3.1 mg transdermal patch applied 24–48 h prior to first dose of anticancer therapy
    • Ondansetron 16–24 mg PO or 8–16 mg IV once
    • Palonosetron 0.25 mg IV
  • Dexamethasone 12mg PO/IV (on D2-4: 8mg/day PO/IV)

Oral Emetic Risk Management

Moderate-High Emetic Risk (prophylaxis required): 5-HT3 RA or Olanzapine

Minimal-low Emetic Risk (PRN recommended): Metoclopramide, Prochlorperazine, or 5-HT3 RA

Serotonin receptor antagonist (5-HT3 RA; -setron)

  • MOA: selective 5-HT3 receptor antagonist, blocking serotonin, both on vagal nerve terminals in the periphery and centrally in the chemoreceptor trigger zone
  • Indication: acute, scheduled
  • Administered prior to mod/severe emetogenic chemotherapy
  • Side effects: headache and constipation
 Dose/RoutePearls
PalonosetronIV: 0.25 mg once   • High efficacy for a 3-day chemo • Repeat doses is safe (0.25mg IV at 48-72h) but limited data on efficacy • Preferred in MEC without NK1 RA/olanzapine regimen • Substance P
GranisetronER SQ: 10 mg once weekly Oral: 2mg daily or 1 mg bid IV: 10 mcg/kg once Transdermal patch: 1 patch prior to and upto 24h after chemo – needs prior auth• ER SQ once weekly (polymer-based drug delivery system) – administered in the clinic • ER SQ; preferred in MEC without NK1 RA/olanzapine regimen • Less headache than ondansetron due to more selective 5-HT • Patch: at home, a day before • Mostly paeds
OndansetronIV: 8 mg or 0.15 mg/kg (max 16 mg/day to avoid QT prolong (3-4 msec) Oral/ODT: 8 mg bid or 24 mg once IV:PO conversion 1:2• QT prolongation • Monitor LFT
DolasetronOral: 100 mg within 1h prior• Headache • QT prolongation (less but dose dependent)
  • Granisetron ER SQ:
    • Single SQ 10 mg is non-inferior to single palonosetron 0.25mg IV for prevention of acute/delayed CINV post MEC/HEC; + dexamethasone.
    • Single SQ 10 mg is superior to single ondansetron IV for prevention of delayed CINV post HEC; + fosaprepitant and dexamethasone.
  • Clinical pearls:
    • After receiving palonosetron, granisetron patch/ER SQ, breakthrough 5-HT3 RAs play a limited role in the delayed infusion period and breakthrough antiemetic should focus on a different MOA.
    • Non-sedating; most common side effects are headache and constipation. Optimal effects seen with scheduled administration, not PRN use. Educate patients regarding constipation and its management.
  • No further 5-HT3 therapy is required if palonosetron or granisetron ER SQ/patch is administered on day 1.

Neurokinin-1 receptor antagonists (NK1 RA; -pitant)

  • MOA: inhibiting the substance P/neurokinin 1 (NK1) receptor; augments the antiemetic activity of 5-HT3 receptor antagonists and corticosteroids to inhibit acute and delayed phases of chemotherapy-induced emesis.
  • Indication: Prevention (NOT ttt), delayed CINV; multiday admin
  • DDI:
    • All (except Rolapitant) inhibits metabolism of dexamethasone, thus increasing dexamethasone serum levels when administered concomitantly.
    • Aprepitant/Fosaprepitant also inhibits/induce metabolism of Ifosfamide leading to increased neurotoxicity and decreased efficacy.
 Dose/RoutePearls
AprepitantIV: 130 mg 0.5h prior Oral: 125 mg 1h prior followed by 80 mg once daily• Monitor LFT, INR, PT • Germline cancer on 5-day cisplatin regimen: aprepitant (125 mg D3, 80 mg D4–7) + 5-HT3 RA (D1–5) + dexamethasone (20 mg days 1, 2) • Limited data for PO on days 4-5
FosaprepitantIV: 150 mg 0.5h prior (prodrug)• Generic better/cheaper • Infusion-site reaction (Polysorbate 80)
Netupitant/ palonosetronOral: 1 capsule regimen• Monitor LFT, RF • No need for 5-HT3 RA
Fosnetupitant/ palonosetronIV: 235 mg/0.25 mg 0.5h prior• Monitor LFT, RF • No need for 5-HT3 RA
RolapitantIV: 166.5 mg 2h prior Oral: 180 mg 2h prior Every 2 weeks• DDI: CYP2D6 inhibitor (warfarin , OCP) • Extended t½ (q2w) – can be used in ifosfamide • Doesn’t inhibit dexamethasone metabolism (others do) • Infusion reaction
  • Aprepitant IV emulsion is a unique formulation of aprepitant and is NOT interchangeable with the IV formulation of fosaprepitant.
  • NO available studies investigating repeat dosing of aprepitant IV emulsion, fosaprepitant, netupitant, fosnetupitant, and rolapitant.

Corticosteroids – Dexamethasone

  • MOA of antiemesis is unknown – long-acting corticosteroids
  • Dose (IV:PO):
    • Day 1: 12 mg (with NK1 RA) or 20 mg (without NK1 RA)
    • Day 2+: 8 mg once daily (with NK1 RA) or BID (without NK1 RA) in significant delayed emesis.
      • IV >8mg: perianal itching – so give it as IV drip
  • Administered in the morning (to minimize insomnia) and is given on chemo days
  • Side effects: hyperglycemia (caution in DM), dyspepsia (H2RA for short duration, PPI for long duration), hiccups
    • If intolerant to dexamethasone: consider olanzapine
  • Dexamethasone-sparing strategies: For patients receiving MEC or non-cisplatin HEC, especially those patients with few identifiable (CINV) risk factors or who are intolerant to corticosteroids, limiting the administration of dexamethasone to day 1 only is an option that may not be associated with a significant reduction in antiemetic control.
  • Clinical pearl: Extended delayed CINV: consider extending the course of delayed dexamethasone as clinically appropriate.
  • Avoid corticosteroids for 3–5 days prior to and 90 days after CAR T-cell therapies. Upon disease progression, corticosteroids may be resumed if needed.
    • CAR T cells’ ability to proliferate and work properly (Liu S et al. Blood Cancer J. 2020 Feb 6;10(2):15)
    • Steroids may inhibit CAR T-cell persistence and their antimalignancy efficacy (Liu S et al. Blood Cancer J. 2020 Feb 6;10(2):15)
  • Lower doses, given for shorter durations, or even elimination of dexamethasone on subsequent days (for delayed nausea and emesis prevention) may be acceptable based on patient characteristics.

Olanzapine (DA antagonist)

  • MOA: second generation thienobenzodiazepine antipsychotic, antagonism of D2, 5-HT2C, and 5-HT3 receptors. Some cholinergic effect
  • Indication: severe nausea, significant delayed emesis, intolerant to dexa – (AC Bca instead of dexa; antifungal DDI dexa)
  • Side effects: sedation, dystonic reaction, QT prolongation; postural hypotension, anticholinergic side effects, fatigue
  • DDI with Metoclopramide (category X)
  • Dose is dependent on sedation: 10 mg > 5 mg > 2.5 mg – 5 mg is efficacious at bedtime (sedative)
    • Suggest lower dose in high fall-risk patient, debilitated, frail, risk for orthostatic hypotension
    • Give higher dose if ineffective, give lower dose if ADE
    • Most notable on day 2 and improves over time
  • Olanzapine may stimulate appetite, may consider 2.5 mg of olanzapine for patients experiencing concurrent chemotherapy-related anorexia [new addition to NCCN 2024, Sandhya 2023]

Benzodiazepines

  • MOA: Binds to stereospecific BDZ R on the postsynaptic GABA neuron at several sites within the CNS (limbic system, reticular formation); shifts in Cl-, results in hyperpolarization (a less excitable state) and stabilization.
    • Pancreatic cancer with other meds in BDZ
  • Side effects: CNS depression (use caution in elderly, frail and those at high risk of fall)
  • Indication: anticipatory CINV or when breakthrough CINV has an anxiety component
 Lorazepam
Dose/RoutePO/IV/SL: 0.5–2 mg every 6 hours on days 1–4
Pearls• Anticipatory /anxiety • Caution with opioid (resp depression) • Caution with high fall risk/old/frail/dependence (CNS depression)

Phenothiazine (DA antagonist)

  • MOA: muscarinic-blocking effect may be responsible for antiemetic activity
  • Side effects: CNS depression (use caution in elderly, frail and those at high risk of fall), dystonic reaction (give diphenhydramine 25–50 mg PO/IV q4-6h
 PromethazineProchlorperazine (COMPAZINE)
Dose/RouteSuppository (rectum): 25 mg every 6 h Oral: 12.5–25 mg every 4–6 hSuppository (rectum): 25 mg every 12 h Oral/IV: 10 mg every 6 h
Pearls• More histamine blockage ~ more sedating • IV: severe tissue injuryGives 2 weeks to give real effect

Metoclopramide (DA antagonist): PO/IV: 10–20 mg every 4-6h PRN

  • MOA: blocks DA R and (when given in higher doses) also blocks serotonin R in CTZ of the CNS
  • Indication: gastroparesis (increases gut motility), parenteral/oral LEC, breakthrough
  • Side effects:
    • CNS depression (use caution in elderly, frail and those at high risk of fall)
    • Dystonic reaction: give diphenhydramine 25–50 mg PO/IV either every 4 or every 6 h
    • QT prolongation
    • Tardive dyskinesia: risk increases with increasing cumulative doses and duration of treatment  FDA recommends <12 weeks therapy

Haloperidol (DA antagonist): PO/IV: 0.5-2 mg every 4-6h

  • MOA: butyrophenone antipsychotic that nonselectively blocks postsynaptic D2 R in the brain
  • Indication: breakthrough, refractory
  • Lower doses to produce antiemetic compared to antipsychotic doses
  • Side effects:
    • CNS depression (use caution in elderly, frail and those at high risk of fall)
    • Dystonic reaction: give diphenhydramine 25–50 mg PO/IV either every 4 or every 6 h
    • QT prolongation (some data: lower doses don’t prolong QT)

Scopolamine: Transdermal patch: 1 patch (1.5 mg) every 72 h

  • MOA: Blocks the action of ACh at parasympathetic sites in smooth muscle, secretory glands and the CNS; increases CO, dries secretions, antagonizes histamine and serotonin
  • Indication: breakthrough, motion issues (positional changes, movement, or excessive secretions are triggering episodes of N/V)
  • Positional changes, movement, or excessive secretion
  • Side effects:
    • CNS depression (use caution in elderly, frail and those at high risk of fall)

Cannabinoid

  • MOA: activates cannabinoid receptors CB1 and CB2.
    • Central cannabinoid receptors (CB1): analgesia, appetite enhancement, muscle relaxation, hormonal actions
  • Indication: refractory N/V with no response to other regiments; stimulate appetite
  • Side effects:
    • CNS depression (use caution in elderly, frail and those at high risk of fall)
    • To minimize ADE, start lower doses (especially in older or marijuana-naïve) and titrate to effect.
    • Excessive cannabinoid use can lead to cannabinoid hyperemesis.
    • Dronabinol PO solution (Marinol as Rx) has greater PO bioavailability than dronabinol capsules; 2.1 mg PO solution = 2.5 mg capsules.
  • Prefer edible preparation
    • Smoking can cause aspergillosis, heavy metal toxins
    • Vaping: popcorn lungs
    • Vaporing (tincture): gives faster effect but not for a long time and less ADE compared to other routes (vaping/smoking)
      • Different shops provides different tincture %
      • Non-prescription, provider certification, taxed less
 Dronabinol
Dose/RouteOral (capsule): 5–10 mg/m2  3–4 times daily Oral solution (5mg/mL): 2.1–4.2 mg/m2 3–4 times daily
PearlsOral solution BA > oral capsules; 2.1 mg solution = 2.5 mg capsules.

Anticipatory, Anxiety-related, or Breakthrough nausea

  • Consider adding lorazepam 0.5–1 mg PO/IV/SL every 6 hours PRN on days 1-4.
    • Use the lowest effective dose and interval.
    • May be administered with or without H2 blocker or PPI if patient exhibits reflux symptoms

Anticipatory Emesis (PREVENTION IS THE KEY)

  • Use optimal antiemetic therapy during every cycle
  • Avoid strong smells that may trigger emesis; cognitive distraction
  • Consider anxiolytic therapy:
    • lorazepam 0.5–2 mg PO beginning on the night before treatment and then repeat next day 1–2h before chemotherapy begins
  • Complementary/alternative therapy (Category 2A)
    • Behavioral therapy: Relaxation/systematic desensitization, hypnosis, relaxation exercises (guided imagery, progressive muscle relaxation, biofeedback, music therapy)
    • Yoga (if proven by physician)
    • Acupuncture/acupressure

Breakthrough Emesis

  • Add one agent from a different class to the current regimen
    • Routine/scheduled/around-the-clock admin should be considered
    • Oral route is not feasible if patient is vomiting; consider IV/rectal – neutropenic (ANC<500) avoid rectal meds
    • Dopamine antagonists (phenothiazines, olanzapine, metoclopramide, haloperidol), corticosteroids, and agents such as lorazepam may be required.
  • Treat any underlying cause and correct any electrolyte imbalance
    • Adequate hydration or fluid repletion
  • Reassess patients for breakthrough N/V reasons prior to next cycle:
    • Brain metastases
    • Electrolyte abnormalities
    • Tumor infiltration of the bowel or other GI abnormality
    • Other comorbidities
  • Managements:
    • Add an NK1 RA if not previously included.
    • Consider changing from NK1-RA–containing regimens to an olanzapine-containing regimen, or vice versa.
    • Consider combining an NK1 RA regimen with olanzapine
    • Consider changing to a different NK1 RA with different PK/PD profile (No head-to-head clinical trial but anecdotal evidence suggests it may be helpful)
    • Add other concomitant antiemetics (metoclopramide or haloperidol), if applicable.
    • Possibly adjust dose(s), either intensity or frequency, of the 5-HT3 RA (maybe anticancer therapy regimen is more emetogenic than generally classified)
    • Possibly switch to a different 5-HT3 RA (anecdotal and limited investigational trial suggest it may be efficacious)
      • 5-HT3 RAs have different PK/PD and different routes of metabolism that may account for different efficacy in certain populations.
    • If goal of anticancer therapy is non-curative, consider other appropriate regimens, if any, that might be less emetogenic.
    • It may be beneficial to add an anxiolytic agent in combination with the antiemetic agents.
  • Consider antacid if dyspepsia (H2RA or PPI)

Drug-drug interactions between antiemetics used in cancer patients Article

Parenteral Emetic Risks

NCCN Guideline. Antiemesis. Version 2.2025. May 12, 2025.

High emetic risk (>90%)
• Any AC regimens
• Carboplatin AUC ≥4
• Carmustine >250 mg/m2
• Cisplatin
• Cyclophosphamide >1500 mg/m2
• Dacarbazine		• Datopotamab deruxtecan-dlnk
• Doxorubicin ≥60 mg/m2
• Epirubicin >90 mg/m2
• Fam-trastuzumab deruxtecan-nxki
• Ifosfamide ≥2 g/m2/dose		• Mechlorethamine
• Melphalan ≥140 mg/m2
• Sacituzumab govitecan-hziy
• Streptozocin
• Zolbetuximab-clzb
Moderate emetic risk (>30%–90%)
• Aldesleukin >12–15 million IU/m2 or 600,000 IU/kg
• Amifostine >300 mg/m2
• Bendamustine
• Busulfan
• Carboplatin AUC <4
• Carmustine ≤250 mg/m2
• Clofarabine
• Cyclophosphamide ≤1500 mg/m2
• Cytarabine >200 mg/m2		• Dactinomycin
• Daunorubicin
• Dinutuximab
• Doxorubicin <60 mg/m2
• Dual-drug liposomal encapsulation of cytarabine and daunorubicin (Vyxeos; CPX-351)
• Epirubicin ≤90 mg/m2
• Idarubicin
• Ifosfamide <2 g/m2/dose
• Irinotecan		• Irinotecan (liposomal)
• Lurbinectedin
• Melphalan <140 mg/m2
• Methotrexate ≥250 mg/m2
• Mirvetuximab soravtansine-gynx
• Naxitamab-gqgk
• Oxaliplatin
• Romidepsin
• Temozolomide
• Trabectedin
Low emetic risk (10%–30%)
• Ado-trastuzumab emtansine
• Aldesleukin ≤12 million IU/m2
• Amifostine ≤300 mg/m2
• Amivantamab-vmjw
• Arsenic trioxide
• Axicabtagene ciloleucel (Yescarta)
• Azacitidine
• Belinostat
• Brentuximab vedotin
• Brexucabtagene autoleucel (Tecartus)
• Cabazitaxel
• Carfilzomib
• Ciltacabtagene autoleucel (Carvykti)
• Copanlisib
• Cytarabine (low dose) 100–200 mg/m2
• Docetaxel
• Doxorubicin (liposomal)
• Elranatamab-bcmm
• Enfortumab vedotin-ejfv		• Epcoritamab-bysp
• Eribulin
• Etoposide
• Floxuridine
• 5-Fluorouracil (5-FU)
• Gemcitabine
• Gemtuzumab ozogamicin
• Idecabtagene vicleucel
• Inotuzumab ozogamicin
• Isatuximab-irfc
• Ixabepilone
• Lifileucel
• Lisocabtagene maraleucel (Breyanzi)
• Loncastuximab tesirine-lpyl
• Methotrexate >50 – <250 mg/m2
• Mitomycin
• Mitomycin pyelocalyceal solution
• Mitoxantrone
• Mogamulizumab-kpkc		• Mosunetuzumab-axgb
• Moxetumomab pasudotox-tdfk (Lumoxiti)
• Necitumumab
• Omacetaxine
• Paclitaxel
• Paclitaxel-albumin
• Pemetrexed
• Pentostatin
• Polatuzumab vedotin-piig
• Pralatrexate
• Tafasitamab-cxix
• Tagraxofusp-erzs
• Talimogene laherparepvec
• Tebentafusp-tebn
• Thiotepa
• Tisagenlecleucel (Kymriah)
• Tisotumab vedotin-tftv (Tivdak)
• Topotecan
• Ziv-aflibercept
Minimal emetic risk (<10%)
• Alemtuzumab
• Asparaginase
• Atezolizumab
• Atezolizumab and hyaluronidase-tqjs
• Avelumab
• Betibeglogene autotemcel
• Belantamab mafodotin-blmf (Blenrep)
• Bevacizumab
• Bleomycin
• Blinatumomab (Blincyto)
• Bortezomib (Velcade)
• Cemiplimab-rwlc
• Cetuximab
• Cladribine
• Cytarabine <100 mg/m2
• Daratumumab
• Daratumumab and hyaluronidase-fihj
• Decitabine
• Degarelix
• Dexrazoxane
• Dostarlimab-gxly
• Durvalumab		• Elotuzumab
• Fludarabine
• Fulvestrant
• Glofitamab-gxbm
• Goserelin
• Histrelin
• Imetelstat
• Ipilimumab
• Lanreotide
• Leuprolide
• Lovotibeglogene autotemcel (Lyfgenia)
• Luspatercept-aamt
• Margetuximab-cmkb
• Methotrexate ≤50 mg/m2
• Nelarabine
• Nivolumab
• Nivolumab and hyaluronidase-nvhy
• Nivolumab/relatlimab-rmbw
• Obinutuzumab
• Octreotide
• Ofatumumab
• Panitumumab
• Pembrolizumab
• Pertuzumab		• Pertuzumab/trastuzumab and hyaluronidase-zzxf
• Ramucirumab
• Retifanlimab-dlwr
• Rituximab
• Rituximab and hyaluronidase
• Siltuximab
• Sirolimus-albumin
• Talquetamab-tgvs
• Tarlatamab-dlle
• Teclistamab-cqyv
• Temsirolimus
• Tislelizumab-jsgr
• Toripalimab-tpzi
• Trastuzumab
• Trastuzumab and hyaluronidase-oysk
• Tremelimumab-actl
• Triptorelin
• Valrubicin
• Vinblastine
• Vincristine
• Vincristine (liposomal)
• Vinorelbine

High emetic Risk

Chemo DayOption 1Option 2Option 3
Day 1Olanzapine PO 2.5-10mg + NK1 RA (-pitant) + 5-HT3 RA (-setron) + Dexamethasone PO/IV 12mgOlanzapine PO 2.5-10mg + Palonosetron IV 0.25mg + Dexamethasone PO/IV 12mgNK1 RA (-pitant) + 5-HT3 RA (-setron) + Dexamethasone PO/IV 12mg
Day 2-4Olanzapine PO 2.5-10mg OR Aprepitant PO (if on D1) 80mg D2-3 ± Dexamethasone PO/IV 8mgOlanzapine PO 2.5-10mgAprepitant PO (if on D1) 80mg D2-3 OR Dexamethasone PO/IV 8mg¨

Moderate Emetic Risk

Chemo DayOption 1Option 2Option 3
Day 15-HT3 RA (-setron) + Dexamethasone PO/IV 12mgOlanzapine PO 2.5-10mg + Palonosetron IV 0.25mg + Dexamethasone PO/IV 12mgNK1 RA (-pitant) + 5-HT3 RA (-setron) + Dexamethasone PO/IV 12mg
Day 2-3Dexamethasone PO/IV 8mg OR 5-HT3 RA (-setron PO)Olanzapine PO 2.5-10mgAprepitant PO (if on D1) 80mg D2-3 ± Dexamethasone PO/IV 8mg/day

Low Emetic Risk

Dexamethasone, Metoclopramide, Prochlorperazine, or 5-HT3 RA

Minimal Emetic Risk

No routine prophylaxis

Oral Emetic Risks

NCCN Guideline. Antiemesis. Version 2.2025. May 12, 2025.

Moderate to high emetic risk (≥30%): Prophylaxis required on days of oral anticancer
• Azacitidine
• Busulfan ≥4 mg/day
• Ceritinib
• Cyclophosphamide
   ≥100 mg/m2/day		• Fedratinib
• Lomustine (single day)
• Midostaurin
• Mitotane
• Mobocertinib		• Selinexor
• Temozolomide >75 mg/m2/day
• Temozolomide ≤75 mg/m/day with concurrent RT
Moderate to high emetic risk (≥30%): PRN dosing is initially appropriate on days of oral anticancer
• Abemaciclib
• Adagrasib
• Avapritinib
• Binimetinib
• Bosutinib >400 mg/day
• Cabozantinib
• Crizotinib		• Dabrafenib
• Elacestrant
• Enasidenib
• Encorafenib
• Estramustine
• Etoposide
• Imatinib >400 mg/day		• Lenvatinib >12 mg/day
• Niraparib
• Olaparib
• Procarbazine
• Rucaparib
• Tovorafenib
• Trifluridine/tipiracil
Minimal to low emetic risk (<30%)
• Abiraterone
• Acalabrutinib
• Afatinib
• Alectinib
• Alpelisib
• Anastrozole
• Apalutamide
• Asciminib
• Axitinib
• Belzutifan
• Bexarotene
• Bicalutamide
• Bosutinib ≤400 mg/day
• Brigatinib
• Busulfan <4 mg/day
• Capecitabine
• Capivasertib
• Capmatinib
• Chlorambucil
• Cobimetinib
• Cyclophosphamide <100 mg/m2/day
• Dacomitinib
• Darolutamide
• Dasatinib
• Decitabine and Cedazuridine
• Duvelisib
• Eflornithine
• Entrectinib
• Enzalutamide
• Erdafitinib
• Erlotinib
• Everolimus
• Exemestane
• Fludarabine		• Flutamide
• Fruquintinib
• Futibatinib
• Gefitinib
• Gilteritinib
• Glasdegib
• Hydroxyurea
• Ibrutinib
• Idelalisib
• Imatinib ≤400 mg/day
• Ivosidenib
• Ixazomib
• Lapatinib
• Larotrectinib
• Lenalidomide
• Lenvatinib ≤12 mg/day
• Letrozole
• Lorlatinib
• Megestrol
• Melphalan
• Mercaptopurine
• Methotrexate
• Momelotinib
• Neratinib
• Nilotinib
• Nilutamide
• Nirogacestat
• Olutasidenib
• Osimertinib
• Pacritinib
• Palbociclib
• Pazopanib
• Pemigatinib
• Pexidartinib
• Pirtobrutinib		• Pomalidomide
• Ponatinib
• Pralsetinib
• Quizartinib
• Regorafenib
• Relugolix
• Repotrectinib
• Ribociclib
• Ripretinib
• Ruxolitinib
• Selpercatinib
• Sonidegib
• Sorafenib
• Sotorasib
• Sunitinib
• Talazoparib tosylate
• Tamoxifen
• Tazemetostat
• Temozolomide ≤75 mg/m2/day
• Tepotinib
• Thalidomide
• Thioguanine
• Tivozanib
• Topotecan
• Toremifene
• Trametinib
• Tretinoin
• Tucatinib
• Vandetanib
• Vemurafenib
• Venetoclax
• Vismodegib
• Vorinostat
• Zanubrutinib

Moderate-High Emetic Risk (prophylaxis required): 5-HT3 RA or Olanzapine

Minimal-low Emetic Risk (PRN recommended): Metoclopramide, Prochlorperazine, or 5-HT3 RA

Dosing:

  • Olanzapine 2.5-10mg/day PO
  • NK1 RA
    • Aprepitant 125 mg PO, Aprepitant 130 mg IV
    • Fosaprepitant 150 mg IV
    • Netupitant/palonosetron 300mg/0.5mg PO
    • Fosnetupitant/palonosetron 235mg/0.25mg IV
    • Rolapitant 180 mg PO
  • 5-HT3 RA
    • Dolasetron 100 mg PO
    • Granisetron 10 mg SC or 2 mg PO or 0.01 mg/kg (max 1 mg) IV or 3.1 mg transdermal patch applied 24–48 h prior to first dose of anticancer therapy
    • Ondansetron 16–24 mg PO or 8–16 mg IV once
    • Palonosetron 0.25 mg IV
  • Dexamethasone 12mg PO/IV (on D2-4: 8mg/day PO/IV)