ondansetron

Brand: Zofran

Prototype Drug
Drug Class: antiemetic
Drug Family: antiemetic
Subclass: 5-HT3 serotonin receptor antagonist
Organ Systems: gastrointestinalcns

Mechanism of Action

Selective 5-HT3 antagonist blocking serotonin receptors in GI vagal afferents and centrally in area postrema; most effective for chemotherapy-induced nausea (high serotonin release).

5-HT3 serotonin receptor (peripheral vagal afferents and central CTZ)

Indications

  • chemotherapy-induced nausea/vomiting (CINV)
  • post-operative nausea/vomiting (PONV)
  • pregnancy nausea/vomiting (off-label but common)
  • radiation-induced nausea

Contraindications

  • congenital QT prolongation
  • electrolyte abnormalities (hypokalemia, hypomagnesemia)

Adverse Effects

Common

  • headache
  • constipation
  • dizziness
  • QT prolongation

Serious

  • QT prolongation/TdP (dose-dependent)
  • serotonin syndrome (with other serotonergic agents)

Pharmacokinetics (ADME)

Absorption ~60% oral bioavailability
Distribution moderate
Metabolism extensive hepatic CYP3A4 and CYP1A2
Excretion renal 5% unchanged
Half-life 3.5-5.9 hours
Onset 0.5-1 hours
Peak 1-2 hours
Duration 6-8 hours
Protein Binding 70-76%
Vd 1.9 L/kg

Drug Interactions

Drug / Agent Mechanism Severity
serotonergic drugs (SSRIs, MAOIs) serotonin syndrome risk major
QT-prolonging drugs additive QT prolongation major
apomorphine profound hypotension if given together — absolute contraindication major

Nursing Considerations

  1. QT prolongation: ECG before high-dose IV use; avoid with known QT prolongation
  2. Constipation is common side effect — manage with stool softeners
  3. IV single dose 32 mg is removed from US market due to QT risk; use 0.15 mg/kg per dose or 8 mg doses
  4. Serotonin syndrome risk with concomitant serotonergic agents

Clinical Pearls

  • 5-HT3 antagonism most effective for CINV because chemo releases serotonin from enterochromaffin cells
  • QT dose-dependency: 32 mg single IV dose removed from market; current max 16 mg IV dose
  • Pregnancy nausea: widely used off-label; no teratogenicity signal but avoid first-trimester if possible

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required