Nausea in Cancer

Aka: Nausea in Cancer, Vomiting in Cancer, Nausea in Terminally Ill Patients, Cancer Related Nausea, Chemotherapy-Induced Vomiting, Chemotherapy-Induced Nausea, Chemotherapy Induced Nausea and Vomiting

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II. Pathophysiology

  1. See Vomiting
  2. Images
    1. vomitingPathway.png

III. Causes: General

  1. Common Causes
    1. Small Bowel Obstruction
    2. Autonomic failure
    3. Hypercalcemia
    4. Narcotic bowel Syndrome
      1. Disappears 2-3 weeks after starting Narcotic
      2. Associated with Intracranial Pressure
  2. Mnemonic: 11 M's
    1. Metastases (Cerebral, Liver)
    2. Meninges irritated (Increased Intracranial Pressure)
    3. Movement (Vestibular stimulation)
    4. Mentation (Anxiety)
    5. Medications (Opioids, Chemotherapy, NSAIDs)
    6. Mucosal irritation (NSAIDs, GERD, Hyperacidity)
    7. Mechanical obstruction (Constipation, Tumor, Cancer Related Bowel Obstruction)
    8. Motility (Ileus, Opioids)
    9. Metabolic (HypercalcemiaHyponatremia, Uremia)
    10. Microbes (Local infection, Sepsis)
    11. Myocardial dysfunction (ischemia, CHF)

IV. Causes: Chemotherapy

  1. Severe Vomiting (Most Emetogenic Antineoplastic Drugs)
    1. Cisplatin
    2. Cyclophosphamide
    3. Cytarabine
    4. Dacarbazine
    5. Mechlorethamine
    6. Streptozocin
  2. Moderate Vomiting
    1. Carboplatin
    2. Carmustine
    3. Cyclophosphamide
    4. Dactinomycin
    5. Daunorubicin
    6. Doxorubicin
    7. Epirubicin
    8. Idarubicin
    9. Ifosfamide
    10. Lomustine
    11. Mitomycin
    12. Mitoxantrone
    13. Oxaliplatin
    14. Pentostatin
    15. Procarbazine
  3. Mild Vomiting
    1. Bleomycin
    2. Chlorambucil
    3. Cytarabine
    4. Etoposide
    5. Fluorouracil
    6. Hydroxyurea
    7. Melphalan
    8. Methotrexate
    9. Thioguanine
    10. Vinblastine

V. Approach: General Rules

  1. Attempt to identify a cause
  2. Consider combining Antiemetics if one not effective
    1. Use from different classes
  3. Avoid Nasogastric Tubes

VI. Management: General

  1. Always consider non-pharmacologic management first
    1. Small Frequent Meals
    2. Avoid bland foods (patient eats what they want)
  2. Starting Antiemetic agents
    1. Prochlorperazine (Compazine)
    2. Dimenhydrinate (Dramamine)
    3. Metoclopramide (Reglan)
  3. Consider specific agents
    1. Chemotherapy-Induced Vomiting (see below)
    2. Anxiety related Nausea: Benzodiazepines, Cannabinoids
    3. Bowel Obstruction: Octreotide
    4. Gastroparesis: Metoclopramide
    5. Increased Intracranial Pressure: Dexamethasone
    6. Opioid-related bowel dysfunction: Methylnaltrexone
  4. Refractory Nausea
    1. Combine 2-3 drugs from above
    2. Consider Haloperidol (Haldol)
      1. Start at 0.5 to 2 mg PO IV or SC q6 hours
      2. Titrate to 10 to 15 mg total daily dose
    3. Consider adding Prednisone or Dexamethasone
    4. Consider Cannabinoids
  5. Emesis continues
    1. Consider Rectal route (e.g. Compazine)
    2. Consider Subcutaneous Route (e.g. Haldol)
    3. Consider Transdermal route (e.g. Scopolamine)
  6. Other cause specific management
    1. See Cancer Related Bowel Obstruction
    2. Anxiety: Benzodiazepines or Cannabinoids
    3. Gastroparesis: Metoclopramide (Reglan)
    4. Increased Intracranial Pressure: Dexamethasone
    5. Medication related
      1. See Chemotherapy related Nausea treatment as above
      2. See Opioid Adverse Effect Management for Opioid-Induced Nausea
  7. Other medication selection precautions
    1. Comorbid Delirium
      1. Haloperidol
      2. Olanzapine
    2. Dry Mouth (Xerostomia)
      1. Avoid orally disintegrating tablets (requires Saliva to dissolve tablet)

VII. Management: Chemotherapy-Induced Vomiting

  1. Background
    1. Regimens are started before Chemotherapy and continued for 3 days after
    2. Typical dosing 30 minutes before Chemotherapy
      1. Ondansetron 16 to 32 mg IV or 24 mg orally (or other 5-HT3 Antagonist) AND
      2. Dexamethasone 4 mg (often 20 mg orally daily given)
    3. 5-HT3 Antagonists used in Chemotherapy induced Vomiting
      1. Ondansetron (Zofran)
      2. Dolasetron (Anzemet)
      3. Granisetron (Kytril)
  2. Chemotherapy with the strongest emetic effects (e.g. Cisplatin)
    1. Ondansetron (or other 5-HT3 Antagonist) AND
    2. Dexamethasone AND
    3. Aprepitant (or Zyprexa)
      1. Akynzeo (Palonosetron and Netupitant) may be used as a single dose prior to Chemotherapy
      2. Akynzeo lasts for 3 days and can be used in place of Aprepitant and Ondansetron
  3. Chemotherapy with the moderate emetic effects (e.g. Oxaliplatin)
    1. Ondansetron (or other 5-HT3 Antagonist) AND
    2. Dexamethasone
    3. Consider adding Aprepitant (or Zyprexa) if needed
  4. Chemotherapy with the lower emetic effects (e.g. Paclitaxel)
    1. Dexamethasone (e.g. 20 mg orally) for a single dose prior to Chemotherapy
    2. Alternatives to Dexamethasone
      1. Ondansetron OR
      2. Prochlorperazine OR
      3. Metoclopramide
  5. Delayed Chemotherapy-Induced Nausea
    1. Metoclopramide (Reglan) 1-2 mg IV or orally every 2-4 hours AND
    2. Dexamethasone 4 mg
  6. References
    1. (2014) Presc Lett 21(12): 71

VIII. Preparations: Antiemetics

  1. Anticholinergics
    1. Consider in excess oral secretions
    2. Scopolamine (Transdermal 1.5 mg patch) 1-2 patches replaced every 48 to 72 hours
  2. Phenothiazines
    1. Prochlorperazine (Compazine) 5-10 mg PO or IV every 6-8 hours or 25 mg rectally every 12 hours
    2. Promethazine (Phenergan) 25-50 mg orally, rectally or IV every 6 hours
      1. Overused, sedating and relatively ineffective in Palliative Care
    3. Chlorpromazine (Thorazine) 12.5 to 25 mg IV every 6-8 hours or 25-50 mg orally every 8 hours
  3. Butyrophenones
    1. Haloperidol (Haldol) 0.5 to 2 mg orally or IV every 4-8 hours
    2. Droperidol (Inapsine) 1.25 to 2.5 mg IV
      1. Strong black box warning in U.S. due to risk of QT Prolongation, but appears safe
      2. Calver (2015) Ann Emerg Med 66(3): 230-8 +PMID:25890395 [PubMed]
  4. Thienobenzodiazepine
    1. Olanzapine (Zyprexa)
      1. Often dosed prophylactically at night (e.g. 2.5 mg ODT before bedtime)
  5. Antihistamines
    1. Meclizine (Antivert)
      1. Indicated for vestibular associated Emesis
    2. Diphenhydramine (Benadryl) 12.5 to 50 mg orally, rectally, or IV every 4-12 hours
    3. Hydroxyzine (Atarax, Vistaril)
  6. Gastrokinetic agents
    1. Consider in Gastroparesis, but avoid in suspected malignant Small Bowel Obstruction
    2. Metoclopramide (Reglan) 5-20 mg orally or IV every 6 hours
  7. 5-HT3 Receptor Antagonists
    1. Ondansetron (Zofran) 4-8 mg orally (esp. ODT dissolvable) or IV every 4-8 hours
    2. Granisetron (Kytril) 1 mg orally or IV twice daily
    3. Dolasetron (Anzemet)
  8. Cannabinoids
    1. Consider in anticipatory Nausea
    2. Nabilone (Cesamet) 1-2 mg orally every 12 hours
    3. Dronabinol (Marinol) 5-10 mg orally, rectally or sublingual every 6-8 hours
  9. Corticosteroids
    1. Consider in malignant Small Bowel Obstruction or Increased Intracranial Pressure
    2. Dexamethasone (Decadron) 2-8 mg orally or IV every 4-8 hours
  10. Benzodiazepines
    1. Consider in anticipatory Nausea
    2. Lorazepam (Ativan) 0.5 to 2 mg orally or IV every 6 hours

IX. References

  1. (2003) Med Lett Drugs Ther 45(W1162B): 62-4 [PubMed]
  2. Albert (2017) Am Fam Physician 95(6): 356-61 [PubMed]
  3. Ross (2001) Am Fam Physician 64(5):807-14 [PubMed]

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