Ondansetron Hcl (ondansetron HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Ondansetron hydrochloride, a selective, first-generation inhibitor of type 3 serotonin (5-HT3) receptors, is an antiemetic.
Ondansetron, a selective inhibitor of type 3 serotonin (5-HT3) receptors, is an antiemetic agent. Although the precise mechanism of action has not been fully elucidated, ondansetron does not function as a dopamine receptor antagonist. Serotonin type 3 (5-HT3) receptors are located both peripherally on vagal afferent nerve terminals and centrally within the chemoreceptor trigger zone of the area postrema.
It remains unclear whether the antiemetic effect of ondansetron is mediated through central mechanisms, peripheral mechanisms, or a combination of both. Evidence suggests that cytotoxic chemotherapy is associated with serotonin release from enterochromaffin cells in the small intestine. In humans, administration of cisplatin is accompanied by an increase in urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), which parallels the onset of emesis.
The released serotonin is thought to activate vagal afferent pathways via 5-HT3 receptors, thereby initiating the vomiting reflex.
Ondansetron is absorbed from the GI tract after oral administration and undergoes some first-pass metabolism. The mean bioavailability after administration of a single 8-mg tablet is approximately 56%. The systemic exposure of ondansetron does not increase proportionately to dose.
The AUC from a 16-mg tablet was 24% greater than predicted from an 8-mg tablet dose; this may reflect some reduction of first-pass metabolism at higher oral dosages. Food slightly increases ondansetron bioavailability. Peak plasma concentrations are attained approximately 1.6-2.2 hours after oral administration, approximately 10 minutes after IV infusion, or 41 minutes after IM injection.
Commercially available oral solution and orally disintegrating tablets are bioequivalent to corresponding doses of conventional tablets. The extent and rate of ondansetron absorption are increased in women compared with men; however, it is not known whether differences are clinically important.
Plasma protein binding of ondansetron is 70-76%. The circulating drug also distributes into erythrocytes. Ondansetron is extensively metabolized in the liver via hydroxylation followed by subsequent glucuronide or sulfate conjugation.
Ondansetron is a substrate of cytochrome P-450 (CYP) isoenzymes 1A2, 2D6, and 3A4 in vitro. CYP3A4 plays the predominant role in terms of overall ondansetron turnover; the formation of major in vivo metabolites is apparently mediated by CYP1A2. CYP2D6 has a limited role in ondansetron disposition in vivo.
Although some nonconjugated metabolites of ondansetron have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron. Less than 5% of a dose is excreted unchanged in urine; metabolites are observed in urine.
The half-life of ondansetron after a single 8-mg oral dose in healthy adults (age range, 18 to >=75 years of age) ranged from 3.1-6.2 hours. Following a single IV dose of ondansetron 0.15 mg/kg in normal adult volunteers, the mean elimination half-life of ondansetron was 3.5, 4.7, and 5.5 hours in adults 19-40 years of age, 61-74 years of age, and >=75 years of age, respectively. In adult patients with cancer, the mean elimination half-life of ondansetron was 4 hours after IV administration, and there was no difference in the multidose pharmacokinetics over a 4-day period.
Following a single IV dose of ondansetron 2 mg (3-7 years of age) or 4 mg (8-12 years of age) immediately prior to anesthesia induction in pediatric patients undergoing surgery, the mean terminal half-life was slightly reduced (range, 2.5-3 hours) in comparison with adults (range, 3-3.5 hours). Following a single IV dose of ondansetron 0.1 or 0.2 mg/kg in pediatric patients undergoing surgery and requiring general anesthesia, the half-life of ondansetron was 2.9 hours in infants 5-24 months of age and 6.7 hours in infants 1-4 months of age.
USES: This medication is used alone or with other medications to prevent nausea and vomiting caused by cancer drug treatment (chemotherapy) and radiation therapy. It is also used to prevent and treat nausea and vomiting after surgery. It works by blocking one of the body's natural substances (serotonin) that causes vomiting.
Generic name: ondansetron HCl
Pronunciation: (on-DAN-se-tron)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Ondansetron Hcl
Indications
The following indications are listed for Ondansetron Hcl:
- Prevention Of Cancer Chemotherapy-Induced Nausea And Vomiting
- Prevention Of Post-Operative Nausea And Vomiting
- Prevention Of Radiation-Induced Nausea And Vomiting
Also known as: Cancer Chemotherapy-Induced N & V Prophylaxis, Postop Nausea And Vomiting Prophylaxis, Postoperative Nausea And Vomiting Prophylaxis, Radiation-Induced Nausea And Vomiting Prophylaxis.
Dosing
Dosage of ondansetron, which is available for oral or IV/IM use as the hydrochloride dihydrate and also for oral use as ondansetron base (orally disintegrating tablets), is expressed in terms of ondansetron.
Corresponding doses of ondansetron conventional tablets, orally disintegrating tablets, and oral solution may be used interchangeably.
Ondansetron hydrochloride is commercially available as tablets (4 mg and 8 mg), oral solution (4 mg/5 mL), and injection for IV or IM use (4 mg/2 mL single-dose vial). Ondansetron is also available as orally disintegrating tablets (4 mg and 8 mg).
Administer ondansetron orally, by IV infusion, or by IV or IM injection.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Ondansetron is a substrate of cytochrome P-450 (CYP) isoenzymes 1A2, 2D6, and 3A4 in vitro; ondansetron does not appear to induce or inhibit CYP isoenzymes.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Known hypersensitivity (e.g., anaphylaxis) to ondansetron or any ingredient in the formulation.
*Concomitant use with apomorphine due to reports of profound hypotension and loss of consciousness when ondansetron was administered concomitantly with apomorphine.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
The most common adverse effects with oral ondansetron (incidence >=5%) when used for the prevention of chemotherapy-induced nausea and vomiting in adults were headache, malaise/fatigue, constipation, and diarrhea.
The most common adverse effects with oral ondansetron (incidence >=2%) when used for the prevention of radiation-induced nausea and vomiting in adults were headache, constipation, and diarrhea.
The most common adverse effects with oral ondansetron (incidence >=9%) when used for the prevention of PONV in adults were headache and hypoxia.
The most common adverse effects with IV ondansetron (incidence >=7%) when used for the prevention of chemotherapy-induced nausea and vomiting in adults were diarrhea, headache, and fever.
The most common adverse effect with IV ondansetron (incidence >=10% and occurring at a higher frequency compared to placebo) when used for the prevention of PONV in adults was headache.
The most common adverse effect with IV ondansetron (incidence >=2% and occurring at a higher frequency compared to placebo) when used for the prevention of PONV in pediatric patients 1-24 months of age was diarrhea.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
The safety and effectiveness of oral ondansetron have been established in pediatric patients >=4 years of age for the prevention of nausea and vomiting associated with moderately emetogenic chemotherapy. Efficacy of oral ondansetron for the prevention of nausea and vomiting induced by highly emetogenic chemotherapy in pediatric patients has not been established. Efficacy of oral ondansetron for prevention of radiation-induced or postoperative nausea and vomiting (PONV) in pediatric patients has also not been established.
The manufacturer states that little information is available on IV use of ondansetron for the prevention of PONV in pediatric patients younger than 1 month of age, or for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients younger than 6 months of age.
In infants 1-4 months of age, clearance of ondansetron is reduced and half-life is prolonged (by approximately 2.5-fold relative to values in infants older than 4 months up to 24 months of age); thus, the manufacturer recommends that infants younger than 4 months of age receiving IV ondansetron therapy be closely monitored.
Published epidemiological studies evaluating the association between ondansetron use and major birth defects have reported inconsistent findings and have important methodological limitations that preclude definitive conclusions regarding the safety of the drug during pregnancy. Methodological limitations include uncertainty regarding actual medication intake among women who filled prescriptions, concomitant use of other medications or therapies, recall bias, and other unadjusted confounding factors.
Available postmarketing surveillance data have not identified a drug-related risk of miscarriage or adverse maternal outcomes. In reproductive studies conducted in rats and rabbits, IV administration of ondansetron during the period of organogenesis did not result in evidence of fetal harm at exposure levels approximately 3.6- and 2.9-fold, respectively, above the maximum recommended human IV dosage of 0.15 mg/kg administered 3 times daily, based on body surface area (BSA) comparisons. Similarly, reproductive studies in rats and rabbits demonstrated no evidence of fetal harm when ondansetron was administered during organogenesis at exposure levels approximately 6- and 24-fold, respectively, above the maximum recommended human oral dosage of 24 mg/day, based on BSA.
Ondansetron administered IV at doses up to 4 mg/day in lactating women is not expected to result in clinically important exposure in breast-fed infants. Data from a lactation study that included pharmacokinetic sampling from 80 lactating women and 20 infants demonstrate that ondansetron is present at low concentrations in human milk and in the plasma of breast-fed infants. The estimated daily infant dose (0.002 mg/kg per day) and the relative infant dose (3.7%) were both minimal. No adverse effects attributable to ondansetron were observed in infants exposed via breast milk. There are no available data regarding the effects of ondansetron on human milk production.
No dosage adjustment of ondansetron is necessary in geriatric patients.
In clinical studies with ondansetron that included patients 65 years of age and older, no overall differences in efficacy or safety were observed between patients in this age group and younger patients. Plasma clearance of ondansetron may be decreased and elimination half-life increased in patients older than 75 years of age. There were an insufficient number of patients 75 years of age and older in clinical trials of ondansetron to permit safety or efficacy conclusions in this age group. Other reported clinical experience has not identified differences in responses between geriatric and younger patients. However, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.
ICD codes
No ICD codes are available for this drug.
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Last reviewed · Source: First Databank (FDB) drug data
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