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5-HT3 Receptor Antagonist

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5-HT3 Receptor Antagonist, 5-HT3 Antagonist, Serotonin 5-HT3 Receptor Antagonist, Ondansetron, Zofran, Granisetron, Kytril, Dolasetron, Anzemet, Palonosetron, Aloxi

  • See Also
  1. Nausea in Cancer
  • Indications
  1. Chemotherapy associated Nausea
  2. Radiation Therapy associated Nausea
  3. Vomiting refractory to first-line Antiemetics
  4. Theophylline Overdose
    1. Used instead of phenothiazines due to Seizure risk
  • Mechanism
  1. Blocks peripheral and central 5HT3 receptors
    1. Peripheral 5HT3 receptors at vagal nerve terminals
    2. Central 5HT3 receptors at chemoreceptor Trigger Zone in Medulla (area postrema controls Vomiting)
  • Contraindications
  1. First trimester pregnancy (relative contraindication based on preliminary data)
    1. Previously thought to be safe in pregnancy
    2. FDA cautions use in Gestational age <10 weeks
    3. As of 2013, Ondansetron may be associated with 2 fold increased risk of congenital malformations
      1. Congenital Heart Defects
      2. Cleft Palate
    4. References
      1. (2014) Presc Lett 21(1): 5
      2. Anderka (2012) Birth Defects Res A Clin Mol Teratol 94(1):22-30 +PMID:22102545 [PubMed]
      3. Danielsson (2014) Reprod Toxicol 50:134-7 +PMID:25450422 [PubMed]
  • Adverse Effects
  1. Mild Headache
  2. Dizziness
  3. Malaise or Fatigue
  4. Constipation
  5. QT Prolongation
    1. More common with single doses >16 mg IV
    2. If QTc is already prolonged, Metoclopramide (Reglan) is a safe alternative without risk of QTc Prolongation
    3. Unlikely to cause harm (even at highest dose, Ondansetron prolongs QTc only 20 ms)
      1. Freedman (2014) Ann Emerg Med 64(1): 19-25 +PMID:24314899 [PubMed]
      2. Moffett (2016) Acad Emerg Med 23(1): 102-5 +PMID: 26720490 [PubMed]
  6. Serotonin Syndrome
    1. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/AdverseDrugEffects/ucm351864.htm
  • Dosing
  • Ondansetron (Zofran)
  1. Gastroenteritis using Ondansetron 4 mg ODT tabs
    1. Weight 8-15 kg: Ondansetron 2mg (half tab)
    2. Weight 15-30 kg: Ondansetron 4 mg (one tab)
    3. Weight >30 kg: Ondansetron 8 mg (two tabs)
    4. Freedman (2006) N Engl J Med 354:1698-705 [PubMed]
  2. Nausea with Chemotherapy
    1. Intravenous dosing
      1. Timing
        1. First dose: 30 minutes before Chemotherapy
        2. Subsequent dosing: 4 and 8 hours after first dose
      2. Adult: 32 mg IV over 15 min
      3. Child: 0.15 mg/kg IV over 15 min (maximum: 8 mg/dose)
    2. Oral dosing (ODT)
      1. Over age 12 years: 8 mg orally twice daily
      2. Age 4 to 11 years: 4 mg orally three times daily
      3. Age under 4 years: 0.15 mg/kg/dose (up to 4 mg)
  3. Nausea with Radiation Therapy (adult)
    1. Dose: 8 mg orally four times daily
  4. Surgery related Nausea (adult)
    1. Prevention: 8-16 mg orally 1 hour before surgery
    2. Treatment: 4 mg IV or IM over 2-5 minutes
    3. Efficacy
      1. Meta-analysis of 7 randomized trials, n=1043
      2. Works in only 25% of patients
      3. No more effective than less expensive drugs
      4. Tramer (1997) BMJ 314:1088-93 [PubMed]
  • Dosing
  • Dolasetron (Anzemet)
  1. Nausea with Chemotherapy
    1. Dose: 1.8 mg/kg IV or PO for single dose to 100 mg
  2. Prevention of Surgery related Nausea
    1. Adult: 100 mg PO 2 hours before surgery
    2. Child: 1.2 mg/kg PO 2 hours before surgery
  3. Surgery related Nausea
    1. Adult: 12.5 mg IV for single dose
    2. Child: 0.35 mg/kg IV for single dose
  • Dosing
  • Granisetron (Kytril)
  1. Nausea with Chemotherapy (administer 30 minutes before)
    1. Intravenous: 10 ug/kg IV over 5 minutes
    2. Oral: 1 mg PO bid for 1 day
  2. Nausea with Radiation Therapy (adult)
    1. Dose: 2 mg PO 1 hour before each irradiation
  • Preparations
  • Palonosetron (Aloxi)
  1. Indications: Preventing Chemotherapy indiuced Nausea
    1. Not effective in treating Nausea after it occurs
    2. Most effective in preventing delayed Emesis
      1. Longer half-life and higher 5-HT affinity
  2. Dosing: 25 mg IV 30 minutes before Chemotherapy
    1. Do not repeat dose more than once weekly
  • References
  1. Johnson (1993) Harriet Lane, Mosby, p. 521
  2. (2002) Tarascon Pocket Pharmacopoeia, p. 67
  3. (1998) Med Lett Drugs Ther 40(1026): 53-4 [PubMed]
  4. (1991) Med Lett Drugs Ther 33(847): 63-4 [PubMed]
  5. Bell and Lovecchio (2016) Crit Dec Emerg Med 30(8): 28