Pharmacological Classification, Mechanism of Action, Clinical Uses, Administration Routes, Dosing for Adults and Pediatrics, Pharmacokinetics, Dose Adjustments, Patient Counseling, Adverse Effects, Drug Interactions, Contraindications, Personal Experience with Ondansetron, Future Clinical Uses of Ondansetron

1. ONDANSETRON
(ZOFRAN)
GI PHARMACOLOGY
Dana Luery

2. About Ondansetron
■ Generic Name
– Ondansetron
– Ondansetron Hydrochloride
■ Brand Name
– Zofran
■ Different Formulations of Drug Available
– Oral tablets
– IV infusion
– Rectal Suppository
– Injections

3. Classification
■ Ondansetron is classified as an antiemetic
– Antiemetic drugs help to control nausea and
vomiting induced by various causes

4. Pharmacological Class of
Ondansetron
■ Selective Serotonin 5-HT3 Receptor
Antagonist
– Serotonin is a neurotransmitter that may cause nausea
when present in the stomach

5. Mechanism of Action
■ Blocks the action of serotonin 5-HT3 receptor sites
– Serotonin 5-HT3 receptor sites are present on vagal nerve
terminals and certain areas of the brain
– Serotonin 5-HT3 antagonists bind to the 5-HT3 receptors sites to
suppress vomiting and nausea
– The binding of these antagonists to 5-HT3 inhibits serotonin from
eliciting its effects

7. Uses
■ Ondansetron is used to treat nausea and vomiting
in the following cases:
– Side Effects from Cytotoxic Chemotherapy Drugs
– Post-Surgery
– Gastroenteritis

8. Methods of Administration
■ Dose and route depends on the reason for taking
the medication
■ Routes for administering Ondansetron
– Oral
– Intravenous
– Intramuscular

9. Chemotherapy-Induced
Nausea andVomiting
■ Intravenous
– 0.15 mg/kg IV infusion 30 minutes before chemotherapy
– Administer again at 4 hours and 8 hours after the first
dose
– Maximum single dose for IV administration is 16mg

10. Chemotherapy Induced
Nausea andVomiting
■ Oral
– 8 mg oral 30 minutes before chemotherapy
– Administer again 8 hours after the first dose
– 8 mg every 12 hours for 1-2 days post-chemotherapy
– For those experiencing repeated courses of intensive
chemotherapy, administer 24 mg orally prior to
chemotherapy

11. Postoperative Nausea and
Vomiting■ Intravenous and Intramuscular
– 4 mg IV or IM immediately prior to anesthesia
induction
– 4 mg IV or IM postoperatively
■ Oral
– 16 mg oral tablet 1 hour before anesthesia is
administered

12. Gastroenteritis
■ Oral
– 4 mg oral tablet once daily
– May go up to 8 mg orally 3 times per day as
needed

13. Pediatric Dosing
■ Give orally dissolving tablets
■ Dosages depend on weight
■ 8 kg to 15 kg = 2 mg
■ 15 to 30 kg = 4 mg
■ >30 kg = 8 mg

14. Pharmacokinetics
■ Absorption depends on the method of
administration
– Intramuscular, 40 minutes
– Intravenous, 10 minutes
– Oral, 1.6 hours to 2.2 hours
■ Distribution
– Not fully understood
– Estimated protein binding of 75%

15. Pharmacokinetics
■Metabolism
– Extensively metabolized
– Liver
■Excretion
– Kidneys

16. Pharmacokinetics
■ Half-Life
– Adults: 3 hours to 6 hours
– Pediatrics: 6.7 hours for infants 1 to 4
months old; 2.8 hours for 5 months to 18
years
– Hepatic Impairment: 12 hours to 20 hours

17. Pharmacokinetics
■ First-Pass Metabolism
– Definition: concentration of drug is greatly
reduced before reaching systemic circulation
– Ondansetron is well absorbed from the GI tract
and undergoes some first-pass metabolism
– Average Bioavailability ~56%

18. Dose Adjustments for Hepatic Disease
■ No dosage adjustment is needed in patients with
mild or moderate hepatic disease
■ Severe hepatic disease may affect the clearance of
Ondansetron because the drug is excreted by
hepatic metabolism

19. Does having renal disease affect
dosing of medication?
■ No dosage adjustment is needed for patients with
any degree of renal impairment

20. Patient Counseling
■ Medication Administration
– Administer medication as prescribed
■ Stopping Medication
– As needed medication
– Should not be used long term
– Follow instructions on prescription
■ Increasing dosage
– Do not exceed 16 mg dosage

21. Adverse Effects
■ Most common side effects:
– Headache
– Constipation
■ Can cause an arrhythmia in the QT interval of
an electrocardiogram

22. Adverse Effects
■ Serotonin Syndrome
– Symptoms include: mental status changes,
autonomic instability (i.e. tachycardia,
fluctuating blood pressure) and neuromuscular
symptoms (i.e. tremors).
– Most reports associated with combined use of
Zofran and other serotonergic drugs like anti-
depressants
– Also reported in overdose of Zofran

23. Interactions
■ Drug-Drug Interactions
– Apopmorphine and Ondansetron together
cause low blood pressure and loss of
consciousness
– Serotonergic Drugs increase likelihood of
developing serotonin syndrome

24. Contraindications
■ When should Ondansetron not be administered?
– Children younger than 4 years old
– Hypersensitivity to Ondansetron or any of its
components
– Patient is also taking Apomorphine

25. My Personal Experience with
Ondansetron■ Chronic Idiopathic Nausea
– Prescribed 4 mg of Ondansetron every 4 to 6 hours as
needed
– 2012
■ Laparoscopic Surgery for Endometriosis
– Prescribed 4 mg of Ondansetron every 4 to 6 hours as
needed for nausea
– Nausea was a side effect of pain killers
– 2017

26. Using Ondansetron in Practice
■ BS/MS in Health Science at Colorado State University
■ Medical School
■ Possible Professions
General Practitioner
• Use Ondansetron to
treat cases of
Gastroenteritis
Medical Oncologist
• Use Ondansetron to
treat chemotherapy-
induced N/V
Gynecologic Oncologist
• Use Ondansetron to
treat chemotherapy-
induced N/V