Ondansetron Hcl (ondansetron HCl)

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.

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.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Selected 5-Ht3 Antagonists/Apomorphine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The mechanism for risk of profound hypotension or loss of consciousness is not known.

CLINICAL EFFECTS: Concurrent use of apomorphine with a 5-HT3 antagonist may result in profound hypotension and loss of consciousness.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of apomorphine states that concurrent use with 5-HT3 antagonists is contraindicated. Alternative agents, such as trimethobenzamide, are recommended for prevention of nausea and vomiting caused by apomorphine.(3)

DISCUSSION: Profound hypotension and loss of consciousness have been reported with the concurrent use of apomorphine and ondansetron.(1,2) Selected 5-HT3 Antagonists linked to this monograph include: alosetron, azasetron, and ramosetron.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

5-Ht3 Antagonists/Tramadol

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The interaction may involve a reduction in the binding involving 5-HT3 receptors.(1)

CLINICAL EFFECTS: Concurrent use of 5-HT3 antagonists may decrease the effectiveness of tramadol, resulting in increased use of tramadol.(1-3) 5-HT3 antagonists may not be effective in reducing tramadol-induced nausea.(4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Consider the use of alternative anti-emetics in patients receiving tramadol, or the use of other opioids in patients receiving 5-HT3 antagonists.

DISCUSSION: In a randomized study in 59 post-surgical patients in recovery, compared to tramadol alone, patients receiving concurrent ondansetron required significantly larger doses of tramadol at four hours (223 mg versus 71 mg), at 8 hours (285 mg versus 128 mg), and at 12 hours (406 mg versus 190 mg). Vomiting rates at 4 hours and 8 hours were significantly higher with tramadol and concurrent ondansetron compared to tramadol alone.(1) In a randomized, double-blind study in 40 surgical patients undergoing lumbar laminectomy, compared to tramadol alone, cumulative tramadol consumption with concurrent ondansetron during the first 24 hours was significantly increased (between 26% and 35%) as well as thereafter (22% to 25%).(2) In another randomized study in 120 post-surgical patients, it was discovered that tramadol consumption was increased in those patients receiving concurrent ondansetron compared to tramadol alone.(3) In a prospective, randomized, double-blinded study in dental patients, patients received one of four treatments: fentanyl and metoclopramide, tramadol and metoclopramide, fentanyl and ondansetron, or tramadol and ondansetron. The patients who received tramadol and ondansetron had the highest nausea scores among the treatment groups. There were no significant differences in the incidences of pain or nausea in the 24 hours following the procedure.(4) In a randomized, controlled trial in 40 surgical patients undergoing hernioplasty or thyroidectomy, compared to tramadol alone, cumulative tramadol consumption was higher at the 2-hour time point with concurrent ondansetron (0.24 +/- 0.1 vs. 0.17 +/- 0.16; p = 0.01).(5) A systematic review and meta-analysis of randomized controlled trials in the postoperative setting comparing tramadol alone and in combination with ondansetron were included. At 4-hours, 8-hours, 12-hours, and 24-hours post-procedure, patients had increased tramadol requirements when administered with concurrent ondansetron compared to tramadol alone.(6) 5-HT3 antagonists linked to this monograph include: alosetron, azasetron, dolasetron, granisetron, ondansetron, palonosetron, ramosetron, and tropisetron.

*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.

• Congenital long QT syndrome
• Prolonged QT interval
• Torsades de pointes

• Bradycardia
• Chronic heart failure
• Hypokalemia
• Hypomagnesemia
• Neuroleptic malignant syndrome
• Serotonin syndrome
• Severe hepatic disease

• Extrapyramidal disease
• Myocardial ischemia

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.

Rare or Very Rare

• Abnormal ECG
• Abnormal hepatic function tests
• Acute hepatic failure
• Anaphylaxis
• Angioedema
• Atrial fibrillation
• Bradycardia
• Bronchospastic pulmonary disease
• Dyspnea
• Extrapyramidal disease
• Heart block
• Hypotension
• Hypoxia
• Laryngeal edema
• Myocardial ischemia
• Oculogyric crisis
• Prolonged QT interval
• Shock
• Stevens-johnson syndrome
• Supraventricular tachycardia
• Tachycardia
• Torsades de pointes
• Toxic epidermal necrolysis
• Transient blindness
• Ventricular premature beats

More Frequent

• Constipation
• Diarrhea
• Drowsy
• Fever
• Headache disorder
• Malaise

Less Frequent

• Dizziness
• Fatigue
• General weakness
• Pruritus of skin
• Skin rash
• Symptoms of anxiety
• Urinary retention

Rare or Very Rare

• Agitation
• Angina
• Blurred vision
• Hiccups
• Palpitations
• Paresthesia
• Urticaria
• Ventricular tachycardia
• Xerostomia

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.