Pharm

Ondansetron

search

Ondansetron, Zofran

  • See Also
  1. 5-HT3 Receptor Antagonist
  • 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
  • Contraindications
  1. QTc Prolongation (see adverse effects below)
  • Mechanism
  1. See 5-HT3 Receptor Antagonist
  2. Blocks peripheral and central 5HT3 receptors
    1. Peripheral 5HT3 receptors at vagal nerve terminals
    2. Central 5HT3 receptors at ChemoreceptorTrigger Zone in Medulla (area postrema controls Vomiting)
  • Dosing
  1. Dose Adjustments
    1. Severe Liver Disease: Max dose 8 mg orally, 16 mg IV
  2. Gastroenteritis
    1. Adults
      1. Take 4 mg ODT tabs (typical acute care dosing)
    2. Children
      1. Exercise caution in age <6 months
      2. Weight 8-15 kg: Ondansetron 2 mg (half tab)
      3. Weight 15-30 kg: Ondansetron 4 mg (one tab)
      4. Weight >30 kg: Ondansetron 4 to 8 mg (one to two tabs)
      5. Freedman (2006) N Engl J Med 354:1698-705 [PubMed]
  3. Nausea with Chemotherapy
    1. Timing
      1. First dose: 30 minutes before Chemotherapy
      2. Subsequent dosing: 4 and 8 hours after first dose
      3. Thereafter, may repeat every 12 hours for 1-2 days after Chemotherapy
    2. Intravenous dosing
      1. Adult: 8 to 16 mg IV over 15 min
      2. Child (over age 6 months): 0.15 mg/kg up to 8 to 16 mg IV over 15 min
    3. Oral dosing (ODT)
      1. Over age 12 years: 8 mg orally twice to three times daily
      2. Age 4 to 11 years: 4 mg orally twice to three times daily
      3. Age under 4 years: 0.15 mg/kg/dose (up to 4 mg) orally twice to three times daily
  4. Nausea with Radiation Therapy (adult)
    1. Dose: 8 mg orally three times daily
  5. Surgery Related Nausea (Prevention and Treatment of Post-Operative Nausea and Vomiting)
    1. Adult
      1. Prevention: 8 to 16 mg orally 1 hour before surgery
      2. Treatment: 4 mg IM or IV over 2-5 minutes
    2. Child
      1. Age 1 month to 12 years (weight <40 kg): 0.1 mg/kg up to 4 mg IV over 2 to 5 min given 30 min before surgery
      2. Age >12 years (weight >40 kg): 4 mg IV over 2 to 5 min given 30 min before surgery
    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]
  • Adverse Effects
  1. Mild Headache
  2. Dizziness
  3. Malaise or Fatigue
  4. Constipation
  5. QT Prolongation
    1. Risk Factors
      1. Single doses >16 mg IV
      2. Preexisting QTc Prolongation (avoid)
        1. If QTc is already prolonged, Metoclopramide (Reglan) is a safe alternative without risk of QTc Prolongation
      3. Congestive Heart Failure
      4. Bradycardia
      5. Hypomagnesemia
      6. Hypokalemia
    2. 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
  • Safety
  1. Unknown safety in Lactation
  2. First trimester pregnancy
    1. Ondansetron has a relative contraindication based on preliminary data
      1. Previously thought to be safe in pregnancy
      2. However it is also frequently used in Hyperemesis Gravidarum
      3. FDA cautions use in Gestational age <10 weeks
    2. As of 2013, Ondansetron may be associated with 2 fold increased risk of congenital malformations
      1. Congenital Heart Defects
      2. Cleft Palate
    3. 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]
  • Drug Interactions
  1. Apomorphine
    1. Drug Interaction with risk of hyoptension, Altered Level of Consciousness
  • Resources
  1. Ondansetron (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52dc6871-47d3-11dc-99cc-f742b487c00e
  • References
  1. Johnson (1993) Harriet Lane, Mosby, p. 521
  2. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  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