Ondansetron (Dosing, Interaction, Side Effect, Administration, Etc..)

DRUG CLASS:
Antiemetic
Serotonin Receptor Antagonist
5-HT3

DOSING:

Adult Dose

:
Important Note:
Ondansetron tablets are oral disintegrating tablets and solution is bioequivalent. The

doses

are interchangeable for tablets; oral disintegrating tablets; and

oral solution

Chemotherapy-induced nausea and vomiting; Highly emetogenic chemotherapy; Prophylaxis:
24 mg dissolved orally on tongue 30 minutes prior to the start of single-day chemotherapy

Chemotherapy-induced nausea and vomiting; Moderately emetogenic chemotherapy; Prophylaxis:
8 mg dissolved orally on tongue 30 minutes prior to chemotherapy and repeated in 8 hours; then 8 mg every 12 hours for 1 to 2 days post chemotherapy

Postoperative nausea and vomiting; Prophylaxis:
16 mg dissolved orally on the tongue 1 hour before anesthesia induction

Radiation-induced nausea and vomiting; Prophylaxis:
Daily fractionated radiotherapy to abdomen: 8 mg dissolved orally on tongue 1 to 2 hours prior to radiotherapy and every 8 hours after first

dose

for each day radiotherapy is given
Single high-

dose

fraction radiotherapy to abdomen: 8 mg dissolved orally on tongue 1 to 2 hours prior to radiotherapy and every 8 hours after first

dose

for 1 to 2 days after radiotherapy completion
Total body irradiation radiotherapy: 8 mg dissolved orally on tongue 3 times daily given 1 to 2 hours prior to each fraction of radiotherapy administered each day

Pediatric Dose

:
Important Note:
Ondansetron tablets are oral disintegrating tablets; and solution is bioequivalent. The

doses

are interchangeable for tablets; oral disintegrating tablets; and

oral solution

Chemotherapy-induced nausea and vomiting; moderately emetogenic chemotherapy; Prophylaxis:
(4 to 11 years)
4 mg dissolved orally on tongue 30 minutes prior to chemotherapy; repeated 4 and 8 hours after the first

dose

; then every 8 hours for 1 to 2 days post chemotherapy

(12 years or older)
8 mg dissolved orally on tongue 30 minutes prior to chemotherapy and repeated in 8 hours; then 8 mg every 12 hours for 1 to 2 days post chemotherapy

Gastroenteritis – Vomiting:
(Orally disintegrating tablet; 8 to 15 kg)
2 mg dissolved orally as a single

dose

(Orally disintegrating tablet; 15 to 30 kg)
4 mg dissolved orally as a single

dose

(Orally disintegrating tablet; greater than 30 kg)
8 mg dissolved orally as a single

dose

INDICATIONS:
FDA-LABELED INDICATIONS:
Chemotherapy-induced nausea and vomiting; Highly emetogenic chemotherapy; Prophylaxis
Chemotherapy-induced nausea and vomiting; Moderately emetogenic chemotherapy; Prophylaxis
Postoperative nausea and vomiting; Prophylaxis
Radiation-induced nausea and vomiting; Prophylaxis

NON-FDA LABELED INDICATIONS:
Gastroenteritis – Vomiting

MECHANISM OF ACTION:

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron’s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5-HT3 receptors and initiate the vomiting reflex.

ADVERSE EFFECT:
Common:
Gastrointestinal:
Constipation (6% to 9%)
Diarrhea (3% to 7%)

Neurologic:
Headache (9% to 27%)

Respiratory:
Hypoxia (9%)

Other:
Fatigue
Malaise
Serious

Cardiovascular:
Electrocardiogram abnormal (Less than 2%)
Prolonged QT interval
Torsades de pointes

Other:
Serotonin syndrome

CONTRAINDICATION:
Concomitant

use

of apomorphine
Hypersensitivity to ondansetron or any component of the product

DRUG INTERACTION:
Serotonergic:
Drugs Serotonin syndrome (including altered mental status; autonomic instability; and neuromuscular symptoms) has been described following the concomitant

use

of 5-HT3 receptor antagonists and other serotonergic drugs; including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs). Monitor for the emergence of serotonin syndrome. If symptoms occur; discontinue ondansetron and initiate supportive treatment

Drugs Affecting Cytochrome P-450 Enzymes:
Ondansetron does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver
Because ondansetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4; CYP2D6; CYP1A2); inducers or inhibitors of these enzymes may change the clearance and; hence; the half-life of ondansetron. In patients treated with potent inducers of CYP3A4 (i.e.; phenytoin; carbamazepine; and rifampin); the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However; on the basis of available data; no dosage adjustment for ondansetron is recommended for patients on these drugs

Tramadol:
Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed; data from 2 small trials indicate that when used together; ondansetron may increase patient-controlled administration of tramadol. Monitor patients to ensure adequate pain control when ondansetron is administered with tramadol

Chemotherapy:
Carmustine; etoposide; and cisplatin do not affect the pharmacokinetics of ondansetron. In a crossover trial in 76 pediatric patients; intravenous ondansetron did not increase systemic concentrations of high-

dose

methotrexate

Alfentanil and Atracurium:
ondansetron does not alter the respiratory depressant effects produced by alfentanil or the degree of neuromuscular blockade produced by atracurium. Interactions with general or local anesthetics have not been studied

Major:
Acecainide (theoretical)
Alfentanil (probable)
Alfuzosin (theoretical)
Amiodarone (theoretical)
Amitriptyline (theoretical)
Amoxapine (theoretical)
Amphetamine (theoretical)
Anagrelide (theoretical)
Aripiprazole (theoretical)
Aripiprazole Lauroxil (theoretical)
Arsenic Trioxide (theoretical)
Asenapine (theoretical)
Astemizole (theoretical)
Atazanavir (theoretical)
Azimilide (theoretical)
Azithromycin (theoretical)
Bedaquiline (theoretical)
Benzhydrocodone (theoretical)
Benzphetamine (theoretical)
Bretylium (theoretical)
Buprenorphine (theoretical)
Bupropion (theoretical)
Buserelin (theoretical)
Butorphanol (theoretical)
Ceritinib (theoretical)
Chloroquine (theoretical)
Chlorpromazine (theoretical)
Ciprofloxacin (theoretical)
Citalopram (theoretical)
Clarithromycin (theoretical)
Clomipramine (theoretical)
Clozapine (theoretical)
Codeine (theoretical)
Conivaptan (theoretical)
Crizotinib (theoretical)
Cyclobenzaprine (theoretical)
Dabrafenib (theoretical)
Darunavir (theoretical)
Dasatinib (theoretical)
Degarelix (theoretical)
Delamanid (theoretical)
Desipramine (theoretical)
Deslorelin (theoretical)
Deutetrabenazine (theoretical)
Dextroamphetamine (theoretical)
Dihydrocodeine (theoretical)
Disopyramide (theoretical)
Dofetilide (theoretical)
Dolasetron (theoretical)
Domperidone (theoretical)
Donepezil (probable)
Doxepin (theoretical)
Droperidol (theoretical)
Ebastine (theoretical)
Efavirenz (theoretical)
Encorafenib (theoretical)
Enflurane (theoretical)
Eribulin (theoretical)
Erythromycin (theoretical)
Escitalopram (theoretical)
Famotidine (theoretical)
Felbamate (theoretical)
Fentanyl (theoretical)
Fingolimod (theoretical)
Flecainide (theoretical)
Fluoxetine (theoretical)
Foscarnet (theoretical)
Fosnetupitant (theoretical)
Fosphenytoin (theoretical)
Galantamine (theoretical)
Gatifloxacin (theoretical)
Gemifloxacin (theoretical)
Gonadorelin (theoretical)
Goserelin (theoretical)
Granisetron (theoretical)
Halofantrine (theoretical)
Haloperidol (theoretical)
Halothane (theoretical)
Histrelin (theoretical)
Hydrocodone (theoretical)
Hydromorphone (theoretical)
Hydroquinidine (theoretical)
Hydroxychloroquine (probable)
Hydroxyzine (theoretical)
Ibutilide (theoretical)
Idelalisib (theoretical)
Iloperidone (theoretical)
Imipramine (theoretical)
Inotuzumab Ozogamicin (theoretical)
Isoflurane (theoretical)
Isradipine (theoretical)
Itraconazole (theoretical)
Ivabradine (theoretical)
Lapatinib (theoretical)
Leuprolide (theoretical)
Levofloxacin (theoretical)
Levorphanol (theoretical)
Lisdexamfetamine (theoretical)
Lithium (probable)
Lofexidine (probable)
Lopinavir (theoretical)
Lumefantrine (theoretical)
Macimorelin (theoretical)
Mefloquine (theoretical)
Meperidine (theoretical)
Metaxalone (theoretical)
Methadone (theoretical)
Methamphetamine (theoretical)
Methylene Blue (theoretical)
Metronidazole (theoretical)
Mifepristone (theoretical)
Mirtazapine (theoretical)
Mizolastine (theoretical)
Morphine (theoretical)
Morphine Sulfate Liposome (theoretical)
Moxifloxacin (theoretical)
Nafarelin (theoretical)
Nalbuphine (theoretical)
Netupitant (theoretical)
Nilotinib (theoretical)
Norfloxacin (theoretical)
Nortriptyline (theoretical)
Octreotide (theoretical)
Ofloxacin (theoretical)
Olanzapine (theoretical)
Osimertinib (theoretical)
Oxycodone (theoretical)
Oxymorphone (theoretical)
Paliperidone (theoretical)
Palonosetron (theoretical)
Panobinostat (theoretical)
Paroxetine (theoretical)
Pasireotide (theoretical)
Pazopanib (theoretical)
Pentamidine (theoretical)
Pentazocine (theoretical)
Perphenazine (theoretical)
Pimavanserin (theoretical)
Pitolisant (theoretical)
Pixantrone (theoretical)
Probucol (theoretical)
Procainamide (theoretical)
Prochlorperazine (theoretical)
Promethazine (theoretical)
Propafenone (theoretical)
Protriptyline (theoretical)
Quetiapine (theoretical)
Quinidine (theoretical)
Quinine (theoretical)
Ranolazine (theoretical)
Remifentanil (theoretical)
Ribociclib (theoretical)
Rilpivirine (theoretical)
Risperidone (theoretical)
Ritonavir (theoretical)
Salmeterol (theoretical)
Sematilide (theoretical)
Sertindole (theoretical)
Sertraline (theoretical)
Sevoflurane (theoretical)
Sodium Phosphate (theoretical)
Sodium Phosphate; Dibasic (theoretical)
Sodium Phosphate; Monobasic (theoretical)
Solifenacin (theoretical)
Sorafenib (theoretical)
Sotalol (theoretical)
Sufentanil (theoretical)
Sulpiride (theoretical)
Sunitinib (theoretical)
Tacrolimus (theoretical)
Tamoxifen (theoretical)
Tapentadol (theoretical)
Tedisamil (theoretical)
Telavancin (theoretical)
Telithromycin (theoretical)
Tetrabenazine (theoretical)
Tizanidine (theoretical)
Tolterodine (theoretical)
Toremifene (theoretical)
Tramadol (theoretical)
Trazodone (theoretical)
Trifluoperazine (theoretical)
Trimipramine (theoretical)
Triptorelin (theoretical)
Vandetanib (theoretical)
Vardenafil (theoretical)
Vemurafenib (theoretical)
Venlafaxine (theoretical)
Vinflunine (theoretical)
Voriconazole (theoretical
Vorinostat (theoretical)
Zuclopenthixol (theoretical)

Moderate:
Cyclophosphamide(Probable)

PHARMACOKINETICS:
Absorption:
Oral, Maximum Plasma Concentration (Tmax):
Soluble film: 1.3 hours
Disintegrating tablets: 1.17 hours

Bioavailability:
Oral soluble film: Well absorbed

Effect of food:
Maximum Plasma Concentration (Tmax) delayed by 1 to 1.5 hours when administered with a high fat meal

Distribution:
Plasma Protein binding:
70% to 76%

Metabolism:
Hepatic: extensive

Excretion:
Renal:
5% (unchanged)

Total body clearance:
Hepatic impairment (severe): reduced 2- to 3-fold
Renal impairment (severe): reduced by about 50%

Elimination:
Oral:
Soluble film: 4.6 hours
Disintegrating tablets: 4.79 hours

Hepatic impairment: 11.6 to 20 hours

PRECAUTION:
Cardiovascular:
QT prolongation and potentially fatal torsade de pointes; have been reported; monitoring recommended in patients with electrolyte abnormalities (eg; hypokalemia; hypomagnesemia); bradyarrhythmias; congestive heart failure; and with concomitant

use

of medications that prolong QT interval
Congenital long QT syndrome; avoid use

Endocrine and Metabolic:

use

caution in phenylketonurics; contains phenylalanine

Gastrointestinal:

Use

caution following abdominal surgery or chemotherapy-induced nausea and vomiting as it may mask a progressive ileus; gastric distention; or both; monitoring recommended
Do not

use

instead of nasogastric suction; does not stimulate gastric or intestinal peristalsis

Immunologic:
Hypersensitivity reactions; including anaphylaxis and bronchospasm; have been reported in patients that have shown hypersensitivity to selective 5-hydroxytryptamine-3 receptor antagonists; discontinue at first sign of hypersensitivity

Serotonin syndrome:
Serotonin syndrome; sometimes fatal; has been reported; particularly with the concomitant

use

of serotonergic medications and occurred in a post-anesthesia care unit or an infusion center; monitoring required and discontinue

use

if suspected

PREGNANCY CATEGORY:
Fetal Risk cannot be ruled out. (TH)

BREAST FEEDING:
Infant Risk Cannot Be Ruled Out

MONITORING:
Reduction in nausea and vomiting is indicative of clinical efficacy
ECG; in patients with electrolyte abnormalities (eg; hypokalemia; hypomagnesemia); congestive heart failure; bradyarrhythmias; or with concomitant

use

of QT-prolonging medications
Decreased bowel activity; especially in patients at risk for gastrointestinal obstruction
Signs and symptoms of serotonin syndrome; particularly when used concomitantly with drugs that affect serotonin

HOW TO TAKE OR ADMINISTRATION:
Oral:
Disintegrating tablets:
with dry hands, peel back foil backing and gently remove tablet; do not push oral disintegrating tablet through foil backing; administer immediately on tongue and oral disintegrating tablet dissolves in sec; swallow with saliva; liquid not required

Soluble film:
with dry hands, fold the pouch and tear along the edge of the dotted line; remove film and place immediately on tongue; film dissolves in 4 to 20 sec; swallow with saliva; liquid not required; when more than one film is needed to make the total

dose

(16-mg or 24-mg

dose

), allow each oral soluble film to completely dissolve prior to taking the next film

DOSAGE FORM:
Oral Tablet; Disintegrating:4mg;8mg

TOXICOLOGY:
MANAGEMENT OF MILD TO MODERATE TOXICITY:
Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids.

MANAGEMENT OF SEVERE TOXICITY:
Treatment is symptomatic and supportive. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur. Treat severe hypotension IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Therapeutic

doses

of ondansetron may cause prolongation of the QT interval. Concomitant

use

of ondansetron and other drugs that prolong the QT interval may increase the risk of torsades de pointes. Treat torsades de pointes with IV magnesium sulfate, and correct electrolyte abnormalities; overdrive pacing may be necessary.

PATIENT COUNSELING OR CLINICAL TEACHING:
Instruct patient to avoid the concomitant

use

of apomorphine due to the risk of significant hypotension and loss of consciousness

Side effects

may include constipation; diarrhea; headache; fatigue; or malaise
Instruct patient to report signs or symptoms of serious cardiac arrhythmias; including QT prolongation (eg; change in heart rate; lightheadedness; syncope)
Advise patient to report hypersensitivity reactions; including anaphylaxis and bronchospasm
Instruct patient on how to take the oral soluble films
Patient should not to chew or swallow the oral film but should wash their hands after taking it



Disclaimer:
For the Registered Medical Practitioner Only. We are not recommended for self medication. self medication is may harmful for health. We are only information about medicine.