Pharmacology of Ondansetron (Zofran)

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 b inding of these antagonists to 5-HT3 inhibits serotonin from eliciting its effects

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

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

8. Chemotherapy-Induced Nausea and Vomiting 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

9. Chemotherapy Induced Nausea and Vomiting 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

10. 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

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

12. 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

13. 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%

14. Pharmacokinetics Metabolism Extensively metabolized Liver Excretion Kidneys

15. 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

16. 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%

17. 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

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

19. 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

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

21. 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

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

23. Contraindications When should Ondansetron not be administered? C hildren younger than 4 years old Hypersensitivity to Ondansetron or any of its components Patient is also taking Apomorphine

24. 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

25. 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