Therapeutic Indication
● Chemotherapy-Induced Nausea and Vomiting (CINV)
● Post-operative Nausea and Vomiting (PONV)
● Radiation therapy induced nausea and vomiting
● Severe Hyperemesis gravidarum
Pharmacology
Mechanism of Action:
Ondansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist present in the CTZ, with low affinity for dopamine receptors. This reduces the communication to the vomiting center in the brain and decreases the nausea and vomiting the patient experiences. Cytotoxic chemotherapy and radiotherapy are associated with the release of serotonin (5-HT) from enterochromaffin cells of the small intestine, presumably initiating a vomiting reflex through stimulation of 5-HT3 receptors located on vagal afferents. It is thought that ondansetron's antiemetic action is mediated mostly via antagonism of vagal afferents with a minor contribution from antagonism of central receptors.
Pharmacokinetics:
Absorption:
It is completely and rapidly absorbed from the gastrointestinal tract
Because of first pass metabolism, its bioavailability is only about 60%
Absorptions is increased by 17% when taken with food
Distribution:
About 73% of the drug absorbed is bound to plasma protein
Volume of distribution is 160L
Metabolism:
Shows first pass metabolism
Metabolism is carried out by family of CYP enzymes
Excretion:
10% of the original dose of ondansetron is excreted unchanged in the urine
34-43% excreted in the urine as metabolites within 24 hours of administration
Half-life observed for 8mg dose was 3-4 hours
Side Effects
Common side effects of drug include:
● Headache
● Fatigue
● Constipation
● Diarrhea
● Dizziness
● Rash
● Hiccups
● Flushing
● Decrease in the frequency of urination decrease in the urine volume
● Painful urination
● Immediately discontinue the use if severe side effects are observed and consult your physician.
Contraindication
● Hypersensitivity to Ondansetron or any of the components of the formulation
● Avoid Ondansetron in patients with congenital long QT syndrome
● Serotonin Syndrome
Interaction
Drugs that are known to interact with ondansetron and may cause problems include:
● Apomorphine
● Other serotonin 5-HT3 antagonists liks alosetron, dolasetron, palonosetron and granisetron.
● Some antibiotics, such as clarithromycin and erythromycin
● Medications to treat irregular heartbeat, such as amiodarone, disopyramide, dofetilide and others
● Beta blockers, or drugs used to slow the heart rate, such as acebutolol, atenolol, bisoprolol and others
● Tramadol
● Some antiseizure medications, such as phenytoin
● Some antipsychotic medications, including thioridazine, haloperidol, and mesoridazine
● Some drugs used to treat depression, including venlafaxine and amitriptyline