Ondansetron; Uses, Dosage, Side Effects, Interactions, Pregnancy

Mechanism of Action of Ondansetron

Ondansetron is a selective serotonin 5-HT₃ receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT₃ receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT₃ receptors, in turn, inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. Ondansetron is a highly specific and selective serotonin 5-HT₃ receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors. The serontonin 5-HT₃ receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema. The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents, suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine? by causing degenerative changes in the GI tract. The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT₃ receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.

Indications of Ondansetron

For the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy, postoperation, and radiation. Also used for the treatment of postoperative nausea and vomiting.

• Nausea/Vomiting
• Gastroenteritis
• Nausea/Vomiting, Chemotherapy Induced
• Nausea/Vomiting, Radiation Induced
• Nausea/Vomiting, Postoperative
• Obsessive Compulsive Disorder
• Postanesthetic Shivering
• Pruritus?
• Cholestatic pruritus
• Prophylaxis against postoperative nausea and vomiting
• Uremic Pruritus
• Prophylaxis of acute chemotherapy induced nausea and vomiting
• Radiation induced nausea and vomiting
• Severe? Hyperemesis gravidarum
• Alcohol Dependence
• Cyclic vomiting syndrome.
• Functional dyspepsia

Therapeutic? Indications of Ondansetron

• Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin .
• Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
• Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen?, or daily fractions to the abdomen.
• Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.
• In patients where nausea and/or vomiting must be avoided postoperatively, and are recommended even where the incidence of postoperative nausea and/or vomiting is low.

• Low amount of magnesium in the blood
• Low amount of potassium in the blood
• Neuroleptic Malignant? Syndrome?
• Serotonin syndrome – adverse drug interaction
• Heart Muscle? Disease caused by the Medication Doxorubicin
• Complete Heart Block
• Very Rapid Heartbeat – Torsades de Pointes
• Slow Heartbeat
• Prolonged QT interval on EKG
• Chronic heart failure
• Abnormal EKG with QT changes from Birth
• kidney? disease with a reduction in kidney function
• Allergies to Serotonin 5HT-3 Antagonists

Dosage? of Ondansetron

Strengths: 4 mg, 8 mg, 16 mg ,32 mg,  4 mg/5 mL; 32 mg/50 mL-D5%; 2 mg/mL;

Chemotherapy Induced Nausea/Vomiting 

Highly Emetogenic Cancer Chemotherapy (HEC)

• Recommended dose: 24 mg orally 30 minutes before the start of single-day HEC (including cisplatin doses of 50 mg/m2 or greater)

Moderately Emetogenic Cancer Chemotherapy (MEC)

• Recommended dose: 8 mg orally twice a day, with the first dose administered 30 minutes before the start of chemotherapy and the subsequent dose 8 hours later; then 8 mg orally 2 times a day (every 12 hours) for 1 to 2 days after the completion of chemotherapy

Parenteral

• Recommended dose: 0.15 mg/kg IV, with the first dose (infused over 15 minutes) 30 minutes before the start of emetogenic chemotherapy and subsequent doses given 4 and 8 hours after the first dose.
• Maximum dose: 16 mg per dose

Nausea/Vomiting

Highly Emetogenic Cancer Chemotherapy (HEC)

• Recommended dose: 24 mg orally 30 minutes before the start of single-day HEC (including cisplatin doses of 50 mg/m2 or greater)

Moderately Emetogenic Cancer Chemotherapy (MEC)

• Recommended dose: 8 mg orally twice a day, with the first dose administered 30 minutes before the start of chemotherapy and the subsequent dose 8 hours later; then 8 mg orally 2 times a day (every 12 hours) for 1 to 2 days after the completion of chemotherapy

Parenteral

• Recommended dose: 0.15 mg/kg IV, with the first dose (infused over 15 minutes) 30 minutes before the start of emetogenic chemotherapy and subsequent doses given 4 and 8 hours after the first dose.
• Maximum dose: 16 mg per dose

Postoperative Nausea/Vomiting 

• Recommended dose: 16 mg orally 1 hour before the induction of anesthesia

Parenteral

• Recommended dose: 4 mg IV (undiluted) immediately before induction of anesthesia or postoperatively (nausea and/or vomiting within 2 hours after surgery)
• Alternative route: 4 mg IM (undiluted)

Radiation Induced Nausea/Vomiting

• Recommended dose: 8 mg orally 3 times a day
• Total Body Irradiation: 8 mg orally 1 to 2 hours before each fraction of radiotherapy administered each day
• Single High-dose Fraction Radiotherapy to the Abdomen: 8 mg orally 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after the completion of radiotherapy
• Daily Fractionated Radiotherapy to the Abdomen: 8 mg orally 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given

Pediatric

Chemotherapy Induced Nausea/Vomiting 

4 to 11 years

• Recommended dose: 4 mg orally 3 times a day, with the first dose administered 30 minutes before the start of chemotherapy, and subsequent doses 4 and 8 hours after the first dose; then 4 mg orally 3 times a day (every 8 hours) for 1 to 2 days after the completion of chemotherapy

12 years and older

• Recommended dose: 8 mg orally twice a day, with the first dose administered 30 minutes before the start of chemotherapy and the subsequent dose 8 hours later; then 8 mg orally 2 times a day (every 12 hours) for 1 to 2 days after the completion of chemotherapy

Parenteral, 6 months to 18 years

• Recommended dose: 0.15 mg/kg IV, with the first dose (infused over 15 minutes) 30 minutes before the start of emetogenic chemotherapy, and subsequent doses given 4 and 8 hours after the first dose
• Maximum dose: 16 mg (per dose)

Chemotherapy Induced Nausea/Vomiting 

4 to 11 years

• Recommended dose: 4 mg orally 3 times a day, with the first dose administered 30 minutes before the start of chemotherapy, and subsequent doses 4 and 8 hours after the first dose; then 4 mg orally 3 times a day (every 8 hours) for 1 to 2 days after the completion of chemotherapy

12 years and older

• Recommended dose: 8 mg orally twice a day, with the first dose administered 30 minutes before the start of chemotherapy and the subsequent dose 8 hours later; then 8 mg orally 2 times a day (every 12 hours) for 1 to 2 days after the completion of chemotherapy

Parenteral, 6 months to 18 years

• Recommended dose: 0.15 mg/kg IV, with the first dose (infused over 15 minutes) 30 minutes before the start of emetogenic chemotherapy, and subsequent doses given 4 and 8 hours after the first dose
• Maximum dose: 16 mg (per dose)

Or

Side Effects of Ondansetron

The most common

• Diarrhea
• muscle twitching
• weakness
• Any signs of infection, or a skin rash.
• Stomach pain, especially if it comes along with fever and diarrhea or constipation
• Yellowing of the skin or eyes
• Loss of appetite
• Constipation
• Chest pain or discomfort
• lightheadedness, dizziness, or fainting?
• unusual tiredness or weakness
• a decrease in the amount of urine
• fast, pounding, or irregular heartbeat or pulse
• false sense of well-being
• increased watering of mouth
• lightheadedness
• constipation;
• vision changes;
• breast swelling (in men or women); or
• decreased sex drive, impotence, or difficulty having an orgasm.
• blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• restless muscle movements in your eyes, tongue, jaw, or neck;

Common

• Drowsiness and lightheadedness the day after taking the medicine.
• Confusion.
• Numbed emotions.
• Visual disturbances such as blurred vision or double vision.
• Shaky movements and unsteady walk (ataxia).
• Muscle weakness.
• Dizziness.
• A headache.
• Skin rashes.
• Disturbances of the gut such as diarrhea, constipation, nausea, vomiting or abdominal pain.
• Changes in sex drive.
• Low blood pressure (hypotension).
• Blood disorders.
• Unexpected aggression, restlessness or irritability.
• Nightmares or hallucinations 

Rare

• agitation
• anxiety
• behavioral changes, including aggressiveness, angry outbursts,
• confusion
• increased trouble sleeping
• muscle spasms
• shortness of breath
• difficult or labored breathing
• difficulty with swallowing
• dizziness, faintness, or lightheadedness 
• frequent urination
• hallucinations
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• hives or welts, itching, or skin rash
• the increased volume of pale, dilute urine

Drug Interactions of Ondansetron

Ondansetron may interact with following drugs, supplyments, & may change the efficacy of drugs

• alpha blockers (e.g., alfuzosin, tamsulosin)
• anti-psychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzepine, quetiapine, risperidone)
• atorvastatin
• aripiprazole
• antipsychotics (e.g. haloperidol, ziprasidone)
• “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
• beta-agonists (e.g., formoterol, salmeterol)
• cimetidine
• corticosteroids (e.g., hydrocortisone, methylprednisolone, prednisone)
• diuretics (water pills; e.g., furosemide, hydrochlorothiazide, indapamide)
• domperidone
• famotidine
• macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
• other serotonin receptor antagonists (e.g., granisetron,  dolasetron)
• quinolone antibiotics (e.g., ciprofloxacin, levofloxacin)
• selective serotonin re-uptake inhibitors (SSRIs; e.g., citalopram, fluoxetine)
• sotalol
• tapentadol
• tramadol
• tricyclic antidepressants (e.g., amitriptyline, imipramine, nortriptyline)
• trimethoprim
• tyrosine kinase inhibitors (e.g., nilotinib, sunitinib)

Pregnancy & Lactation Ondansetron

FDA Pregnancy Category B