Contents

Search

ondansetron (Zofran)

Tradename: Zofran. Indications: 1) refractory or severe reactions to standard anti-emetic therapy 2) young patients (< 45 years of age) who are more likely to develop extrapyramidal reactions to high-dose metoclopramide 3) post-operative nausea & vomiting 4) chemotherapy-induced nausea/vomiting [11] 5) vomiting in children [5,14] 6) refractory nausea/vomiting of pregnancy [10] 7) bulimia nervosa [6] Contraindications: - NOT for use with chemotherapeutic agents with low emetic potential: bleomycin, busulfan, cyclophosphamide (< 1000 mg), etoposide, 5-fluorouracil, vinblastine, vincristine - congenital long QT syndrome [8] - hypokalemia or hypomagnesemia [8] Benefit/risk: - pediatric & adolescent gastroenteritis - number needed to treat (NNT) - 5 to stop vomiting [13] - 6 to prevent dehydration - no benefit in preventing hospitalization [13] - no harm noted [13] Dosage: 1) prescribe on a scheduled basis, not on a PRN basis 2) 0.15 mg/kg or 12 mg IV over 15 min every 4-8 hours - avoid use of a single 32 mg IV dose [8,9] - no single IV dose should exceed 16 mg [8] 3) decreased effectiveness after 3 doses 4) maximum daily dose of 8 mg in patients with cirrhosis 5) 8 mg PO TID if > 11 yo 6) 4 mg PO TID 4-11 yo When given with cyclophosphamide (Cytoxan) infusion: - 8 mg PO at start of infusion, then 8 mg PO in 24 hours Tabs: 4 & 8 mg. Injection: 2 mg/mL (20 mL). Adverse effects: 1) common (> 10%) - constipation, diarrhea, headache, fever 2) less common (1-10%) - abdominal cramps, dizziness, dry mouth, rash, weakness 3) uncommon (< 1%) - shortness of breath, wheezing, tachycardia, lightheadedness, seizures, rash, hypokalemia, transient elevations of serum transaminases & bilirubin - arrhythmias - QT prolongation including Torsade de Pointes [8] 4) other - use during the 1st trimester of pregnancy doubles the risk of congenital heart disease & cleft palate [12] Drug interactions: - other drugs that prolong QT interval - fluoxetine Mechanism of action: 1) acts to prevent nausea, not in the rescue of nausea 2) 5-hydroxytryptamine-3 (5HT-3) receptor antagonist [3]

Interactions

drug interactions

General

anti-emetic serotonin antagonist

Properties

INHIBITS: serotonin [5HT]-3 receptor MISC-INFO: elimination route LIVER pregnancy-category B safety in lactation ?

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Bruera & Neumann Canadian Medical Assoc. J (CAMJ):158:1717, 1998
  4. Department of Veterans Affairs, VA National Formulary - resticted to oncology, anesthesiology
  5. Prescriber's Letter 14(8): 2007 Ondansetron (Zofran) in Children with Viral Gastroenteritis Detail-Document#: 230804 (subscription needed) http://www.prescribersletter.com
  6. Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
  7. Prescriber's Letter 17(1): 2010 "Off-Label" Uses of Ondansetron COMMENTARY: "Off-Label" Uses of Ondansetron GUIDELINES: CDC Recommendations for Managing Acute Gastroenteritis Among Children GUIDELINES: ACOG Practice Bulletin on Nausea and Vomiting of Pregnancy GUIDELINES: AGA Position Statement on the Use of Gastrointestinal Medications in Pregnancy Detail-Document#: 260108 (subscription needed) http://www.prescribersletter.com
  8. FDA MedWatch Zofran (ondansetron): Drug Safety Communication - Risk of Abnormal Heart Rhythms http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm272041.htm - Ondansetron (Zofran) IV: Drug Safety Communication - QT prolongation http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm310219.htm
  9. FDA MedWatch: 12/4/2012 Ondansetron (Zofran) 32 mg, Single Intravenous (IV) Dose: Updated Safety Communication - Product Removal due to Potential For Serious Cardiac Risks http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm330772.htm
  10. Pasternak B et al. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med 2013 Feb 28; 368:814 PMID: 23445092 http://www.nejm.org/doi/full/10.1056/NEJMoa1211035
  11. Deprecated Reference
  12. Prescriber's Letter 21(1): 2014 Ondansetron in Pregnancy-Is it Safe? Detail-Document#: 300109 (subscription needed) http://www.prescribersletter.com
  13. The NNT: Ondansetron (Zofran) for Pediatric and Adolescent Gastroenteritis http://www.thennt.com/nnt/ondansetron-for-pediatric-gastroenteritis/ - Fedorowicz Z, Jagannath VA, Carter B. Antiemetics for reducing vomiting related to acute gastroenteritis in children and adolescents. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD005506 PMID: 21901699 - Carter B, Fedorowicz Z Antiemetic treatment for acute gastroenteritis in children: an updated Cochrane systematic review with meta-analysis and mixed treatment comparison in a Bayesian framework. BMJ Open 2012;2:e000622 http://bmjopen.bmj.com/content/2/4/e000622.long
  14. Bonvanie IJ, Weghorst AA, Holtman GA et al. Oral ondansetron for paediatric gastroenteritis in primary care: A randomised controlled trial. Br J Gen Pract 2021 Oct; 71:e728. PMID: 34426397 PMCID: PMC8407859 Free PMC article https://bjgp.org/content/71/711/e728