Onzet

Ondansetron.

Tablet: Each film-coated tablet contains: Ondansetron Hydrochloride Dihydrate, USP eq. to Ondansetron 8 mg.
Injection: Each mL contains: Ondansetron (as Hydrochloride Dihydrate), USP 2 mg.

Pharmacology: Pharmacodynamics: Tablet: Mechanism of Action: Ondansetron is a potent, highly selective 5-HT3 receptor antagonist.
Its precise antiemetic and antinauseal mechanism of action is not known. Chemotherapeutic agents and radiotherapy may cause release of 5-HT3 in the small intestine initiating a vomiting reflex by activating vagal afferents via 5-HT3 receptors. Ondansetron blocks the initiation of this reflex. Activation of vagal afferents may also cause a release of 5-HT3 in the area postrema, located on the floor of the fourth ventricle, and this may also promote emesis through a central mechanism. Thus, the effect of Ondansetron in the management of the nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy is probably due to antagonism of receptors on neurons located both in the peripheral and central nervous system.
The mechanisms of action in post-operative nausea and vomiting are not known but there may be common pathways with cytotoxic induced nausea and vomiting.
Ondansetron does not alter plasma prolactin concentrations.
The role of Ondansetron in opiate-induced emesis is not yet established.
Injection: In normal volunteers, single intravenous doses of 0.15 mg/kg of ondansetron had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or a small intestinal transit time. In another study in six normal male volunteers, a 16 mg dose infused over 5 minutes showed no effect of the drug on cardiac output, heart rate, stroke volume, blood pressure, or electrocardiogram (ECG). However, no thorough QT study has been conducted with ondansetron. Multiday administration of ondansetron has been shown to slow colonic transit in normal volunteers. Ondansetron has no effect on plasma prolactin concentrations.
In a gender-balanced pharmacodynamic study (n = 50), ondansetron 4 mg administered intravenously or intramuscularly was dynamically similar in the prevention of nausea and vomiting using the ipecacuanha model of emesis.
Mechanism of Action: Ondansetron is a selective 5-HT₃ receptor antagonist. While ondansetron's mechanism of action has not been fully characterized, it is not a dopamine-receptor antagonist.
Pharmacokinetics: Tablet: Peak plasma concentrations of Ondansetron occur about 1.5 hours after an oral dose of 8 mg, and about 6 hours after a rectal dose. The absolute bioavailability may be somewhat higher (65%) and clearance lower, presumably due to reduced hepatic first-pass metabolism.
Ondansetron is extensively distributed in the body; about 70 to 75% of the drug is protein bound.
It is metabolized in the liver through multiple enzymatic pathways; Ondansetron is a substrate for cytochrome P450 isoenzymes, primarily CYP3A4, but also CYP1A2 and CYP2D6. Less than 5% of a dose is excreted unchanged in the urine.
Injection: In normal adult volunteers, the following mean pharmacokinetic data have been determined following a single 0.15 mg/kg intravenous dose. (See Table 1.)

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Absorption: A study was performed in normal volunteers (n = 56) to evaluate the pharmacokinetics of single 4 mg dose administered as a 5 minute infusion compared to a single intramuscular injection. Systemic exposure as measured by mean AUC were equivalent, with values of 156 (95% CI 136, 180) and 161 (95% CI 137, 190) ng/h/mL for intravenous and intramuscular groups, respectively. Mean peak plasma concentrations were 42.9 (95% CI 33.8, 54.4) ng/mL at 10 minutes after intravenous infusion and 31.9 (95% CI 26.3, 38.6) ng/mL at 41 minutes after intramuscular injection. In normal volunteers (19 to 39 years old, n = 23), the peak plasma concentration was 264 ng/mL following a single 32 mg dose administered as a 15 minute intravenous infusion.
Distribution: Plasma protein binding of ondansetron as measured in vitro was 70% to 76%, over the pharmacologic concentration range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.
Metabolism: Ondansetron is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation.
Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of ondansetron. The metabolites are observed in the urine.
In vitro metabolism studies have shown that ondansetron is a substance for multiple human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall ondansetron turnover, CYP3A4 plays a predominant role while formation of the major in vivo metabolites is apparently mediated by CYP1A2. The role of CYP2D6 in ondansetron in vivo metabolism is relatively minor. The pharmacokinetics of intravenous ondansetron did not differ between subjects who were poor metabolisers of CYP2D6 and those who were extensive metabolisers of CYP2D6, further supporting the limited role of CYP2D6 in ondansetron disposition in vivo.
Elimination: In normal volunteers (19 to 39 years old, n = 23), following a single 32 mg dose administered as a 15 minute intravenous infusion, the mean elimination half-life was 4.1 hours. Systemic exposure to 32 mg ondansetron was not proportional to dose as measured by comparing dose-normalized AUC values to an 8 mg dose. This is consistent with a small decrease in systemic clearance with increasing plasma concentrations.
In adult cancer patients, the mean elimination half-life was 4.0 hours, and there was no difference in the multidose pharmacokinetics over a 4 day period.
Geriatrics: A reduction in clearance and increase in elimination half-life are seen in patients over 75 years of age. In clinical trials with cancer patients, safety and efficacy were similar in patients over 65 years of age and those under 65 years of age; there was an insufficient number of patients over 75 years of age to permit conclusion in that age group. No dosage adjustment is recommended in the elderly.
Pediatrics: In general, surgical and cancer pediatric patients younger than 18 years tend to have a higher ondansetron clearance compared to adults leading to a shorter half-life in most pediatric patients. In patients 1 month to 4 months of age, a longer half-life was observed due to the higher volume of distribution in this age group.
In a study of 21 pediatric cancer patients (4 to 18 years of age) who received three intravenous doses of 0.15 mg/kg of ondansetron at 4 hour intervals, patients older than 15 years of age exhibited ondansetron pharmacokinetic parameters similar to those adults.
Renal Impairment: Due to the very small contribution (5%) of renal clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of ondansetron. However, ondansetron mean plasma clearance was reduced by about 41% in patients with severe renal impairment (creatinine clearance < 30 mL/min). This reduction in clearance is variable and was not consistent with an increase in half-life. No reduction in dose or dosing frequency in these patients is warranted.
Hepatic Impairment: In patients with mild to moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared to 5.7 hours in those without hepatic impairment. In patients with severe hepatic (Child-Pugh score of 10 or greater), clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours. In patients with severe hepatic impairment, a total daily dose of 8 mg should not be exceeded.
Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Carcinogenic effects were not seen in 2 year studies in rats and mice with oral ondansetron doses up to 10 and 30 mg/kg per day, respectively (approximately 2.5 and 3.8 times the recommended human intravenous dose of 32 mg/day, based on body surface area).
Ondansetron was not mutagenic in standard test for mutagenicity.
Oral administration of ondansetron up to 15 mg/kg per day (approximately 3.8 times the recommended human intravenous dose, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.

Tablet: Ondansetron is a 5-HT3 antagonist with antiemetic activity. It is used in the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. It is also used for the prevention and treatment of post-operative nausea and vomiting.
Injection: Prevention of Nausea and Vomiting Associated with Initial and Repeat Courses of Emetogenic cancer Chemotherapy: Ondansetron (Onzet) Injection is indicated for the prevention of nausea and vomiting associated with initial and repeat course of emetogenic cancer chemotherapy, including high-dose cisplatin.
Ondansetron (Onzet) Injection is approved for patients aged 6 months and older.
Prevention of Postoperative Nausea and/or Vomiting: Ondansetron (Onzet) Injection is indicated for the 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 in whom nausea and/or vomiting must be avoided postoperatively. Ondansetron (Onzet) Injection is recommended even when the incidence of postoperative nausea and/or vomiting is low. For patients who do not receive prophylactic Ondansetron (Onzet) Injection and experience nausea and/or vomiting postoperatively. Ondansetron (Onzet) Injection may be given to prevent further episodes.
Ondansetron (Onzet) Injection is approved for patients aged 1 month and older.

Tablet: ADULTS: 8 mg can be given by mouth up to 2 hours before treatment followed by 8 mg to 12 hours later.
To protect against delayed emesis, these regimens are followed by Ondansetron 8 mg by mouth twice daily for up to 5 days after the end of a course of chemotherapy.
Or as prescribed by the physician.
PEDIATRIC USE: For children aged 4 to 11 years a dose of 4 mg can be given 30 minutes before start of chemotherapy, with subsequent 4 mg doses given 4 and 8 hours thereafter. A dose of 4 mg three times daily by mouth may be given for 1 to 2 days after the end of chemotherapy.
PREVENTION AND TREATMENT OF POST-OPERATIVE NAUSEA AND VOMITING: Adults: 16 mg orally an hour before anaesthesia or 8 mg orally an hour before anaesthesia followed by 2 further doses of 8 mg at 8-hour intervals.
PATIENTS WITH RENAL/HEPATIC IMPAIRMENT Patients with renal impairment: A total dose should not exceed 8 mg.
Injection: Prevention of Nausea and Vomiting Associated with Initial and Repeat Courses of Emetogenic Chemotherapy: Ondansetron (Onzet) Injection should be diluted in 50 mL of 5% Dextrose Injection or 0.9% Sodium Chloride Injection before administration.
Adults: The recommended adult intravenous dosage of Ondansetron (Onzet) Injection is a single 32-mg dose or three 0.15-mg/kg doses. A single 32-mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Efficacy of the 32-mg single dose beyond 24 hours has not been established. The recommended infusion rate should not be exceeded. With the three-dose (0.15-mg/kg) regimen, the first dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Ondansetron Injection.
Pediatrics: For pediatric patients 6 months through 18 years of age, the intravenous dosage of Ondansetron (Onzet) Injection is three 0.15-mg/kg doses. The first dose is to be administered 30 minutes before the start of moderately to highly emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Ondansetron (Onzet) Injection. The drug should be infused intravenously over 15 minutes.
Prevention of Postoperative Nausea and Vomiting: Ondansetron (Onzet) Injection should not be mixed with solutions for which physical and chemical compatibility have not been established. In particular, this applies to alkaline solutions as a precipitate may form.
Adults: The recommended adult intravenous dosage of Ondansetron (Onzet) Injection is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient did not receive prophylactic antiemetics and experiences nausea and/or vomiting occurring within 2 hours after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. While recommended as a fixed dose for patients weighing more than 40 kg, few patients above 80 kg have been studied. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, intravenous dose of ondansetron (Onzet) 4 mg, administration of a second intravenous dose of 4 mg ondansetron (Onzet) postoperatively does not provide additional control of nausea and vomiting.
Pediatrics: For pediatric patients 1 month through 12 years of age, the dosage is a single 0.1-mg/kg dose for patients weighing 40 kg or less, or a single 4-mg dose for patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes immediately prior to or following anesthesia induction, or postoperatively if the patient did not receive prophylactic antiemetics and experiences nausea and/or vomiting occurring shortly after surgery. Prevention of further nausea and vomiting was only studied in patients who had not received prophylactic Ondansetron (Onzet) Injection or as prescribed by the physician.
Stability and Handling: After dilution, do not use beyond 24 hours. Although Ondansetron (Onzet) Injection is chemically and physically stable when diluted as recommended, sterile precautions should be observed because diluents generally do not contain a preservative.
Note: Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.
Precaution: Occasionally, ondansetron (Onzet) precipitates at the stopper/vial interface in vials stored upright. Potency and safety are not affected. If a precipitate is observed, resolubilize by shaking the vial vigorously.
Dosage Adjustment for Patients with Impaired Hepatic Function: In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), a single maximal daily dose of 8 mg infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended. There is no experience beyond first-day administration of ondansetron in these patients.

Tablet: Manifestations that have been reported include severe constipation, visual disturbances, hypotension and a vasovagal episode with transient second degree AV block. In case of suspected overdose, symptomatic and supportive therapy should be given as appropriate, as there is no specific antidote for Ondansetron.
Injection: There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy individual intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered without significant adverse events. These doses are more than 10 times the recommended daily dose.
In addition to the adverse reactions listed as follows, the following events have been described in the setting of ondansetron overdose: "Sudden blindness" (amaurosis) of 2 to 3 minutes' duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose. Hypotension (and faintness) occurred in another patient that took 48 mg of ondansetron hydrochloride tablets. Following infusion of 32 mg over only a 4 minute period, a vasovagal episode with transient second degree heart block was observed. In all instances, the events resolved completely.

Tablet: The concomitant use of apomorphine with Ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with Ondansetron.
Injection: Ondansetron Injection is contraindicated for patients known to have hypersensitivity (e.g., anaphylaxis) to this product or any of its components. Anaphylaxis reactions have been reported in patients taking ondansetron.
The concomitant use of apomorphine with ondansetron is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron.

Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists.
Electrocardiographic Changes: Rarely and predominantly with intravenous ondansetron, transient electrocardiogram (ECG) changes including QT/QTc interval prolongation have been reported.
Masking of Progressive Ileus and Gastric Distension: The use of Ondansetron Injection in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and gastric distention.
Effect on Peristalsis: Ondansetron Injection is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction.
Keep away from children.
Drug Abuse and Dependence: Animal studies have shown that ondansetron is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.
Hepatic Impairment: In patients with severe hepatic impairment (Child-Pugh score of 10 or greater), clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life. In such patients, a total daily dose of 8 mg should not be exceeded.
Renal Impairment: Although plasma clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 mL/min), no dosage adjustment is recommended.
Use in Children: Little information is available about the use of ondansetron in pediatric surgical patients younger than 1 month of age. Little information is available about the use of ondansetron in pediatric cancer patients younger than 6 months of age.
The clearance of ondansetron in pediatric patients 1 month to 4 months of age is slower and the half-life is ~2.5 fold longer than patients who are > 4 to 24 months of age. As a precaution, it is recommended that patients less than 4 months of age receiving this drug be closely monitored.
Use in Elderly: Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US and foreign controlled clinical trials, 862 were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experiences has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Dosage adjustment is not needed in patients over age of 65.

Pregnancy: Tablet: The safety of Ondansetron for use in human pregnancy has not been established. Evaluation of experimental animal studies does not indicate direct or indirect harmful effects with respect to the development of the embryo, or foetus, the course of gestation pre-and post-natal development. However as animal studies are not always predictive of human response the use of Ondansetron in pregnancy is not recommended.
Injection: Pregnancy Category B. Reproduction studies have been performed in pregnant rats and rabbits at intravenous doses up to 4 mg/kg per day (approximately 1 and 2 times the recommended human intravenous dose of 32 mg/day, respectively, based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Lactation: Tablet: Tests have shown that Ondansetron passes into the milk of lactating animals. It is therefore, recommended that mothers receiving Ondansetron should not breastfeed their babies.
Injection: Ondansetron is excreted in the breast milk of rats. It is not known whether ondansetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ondansetron is administered to a nursing woman.
Fertility: Tablet: There is no information on the effects of Ondansetron on human fertility.

Tablet: Ondansetron may cause headache, a sensation of flushing or warmth, hiccups, and constipation. A transient rise in liver enzymes has occasionally occurred.
There have been rare reports of immediate hypersensitivity reactions, including anaphylaxis, chest pain, hypotension, tachycardia, and bradycardia have been reported rarely.
Ondansetron should be used with care in patients with signs of subacute intestinal obstruction or ileus. Ondansetron should be given in reduced doses to patients with moderate to severe hepatic impairment.
Injection: Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The following adverse reactions have been reported in clinical trials of adult patients treated with ondansetron, the active ingredient of intravenous Ondansetron Injection at a dosage of three 0.15-mg/kg doses or as a single 32-mg dose. A causal relationship to therapy with Ondansetron Injection was unclear in many cases.
Chemotherapy-Induced Nausea and Vomiting: See Table 2.

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Cardiovascular: Rare cases of angina (chest pain), electrocardiographic alterations, and tachycardia have been reported.
Gastrointestinal: Constipation has been reported in 11% of chemotherapy patients receiving multiday ondansetron.
Hepatic: In comparative trials in cisplatin chemotherapy patients with normal baseline values of aspartate transaminase (AST) and alanine transaminase (ALT), these enzymes have been reported to exceed twice the upper limit of normal in approximately 5% of patients. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur.
Integumentary: Rash has occurred in approximately 1% of patients receiving ondansetron.
Neurological: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving Ondansetron Injection, and rare cases of grand mal seizure.
Other: Rare cases of hypokalemia have been reported.
Postoperative Nausea and Vomiting: The adverse reactions in Table 3 have been reported in ≥ 2% of adults receiving ondansetron at a dosage of 4 mg intravenous over 2 to 5 minutes in clinical trials. (See Table 3.)

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Pediatric Use: Rates of adverse reactions were similar in both the ondansetron and placebo groups in pediatric patients receiving ondansetron (a single 0.1-mg/kg dose for pediatric patients weighing 40 kg or less, or 4 mg for pediatric patients weighing more than 40 kg) administered intravenously over at least 30 seconds. Diarrhea was seen more frequently in patients taking Ondansetron Injection (2%) compared to placebo (< 1%) in the 1 month to 24 month age group. These patients were receiving multiple concomitant perioperative and postoperative medications.
Postmarketing Experience: The following adverse reactions have been identified during post-approval use of ondansetron. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ondansetron.
Cardiovascular: Arrhythmias (including ventricular and supraventricular tachycardia, premature ventricular contractions, and atrial fibrillation), bradycardia, electrocardiographic alterations (including second degree heart block, QT/QTc interval prolongation, and ST segment depression), palpitations and syncope. Rarely and predominantly with intravenous ondansetron, transient ECG changes including QT/QTc interval prolongation have been reported.
General: Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylactic reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, stridor) have also been reported. A positive lymphocyte transform test to ondansetron has been reported, which suggests immunologic sensitivity to ondansetron.
Hepatobiliary: Liver enzyme abnormalities have been reported. Liver failure and death have been reported in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics.
Local Reactions: Pain, redness, and burning at site of injection.
Lower Respiratory: Hiccups.
Neurological: Oculogyric crisis, appearing alone, as well as with other dystonic reactions. Transient dizziness during or shortly after intravenous infusion.
Skin: Urticaria.
Eye Disorders: Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours. Transient blurred vision, in some cases associated with abnormalities of accommodation, have also been reported.

Tablet: There is no evidence that Ondansetron either induces or inhibits the metabolism of other medical products commonly co-administered with it. Specific studies have shown that Ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lignocaine, propofol and thiopental. Ondansetron is metabolised by multiple hepatic cytochrome P-450 enzymes: CYP3A4, CYP2D6 and CYP1A2. Due to the multiplicity of metabolic enzymes capable of metabolising Ondansetron, enzyme inhibition or reduced activity of one enzyme (e.g. CYP2D6 genetic deficiency) is normally compensated by other enzymes and should result in little or no significant change in overall Ondansetron clearance or dose requirement.
Caution should be exercised when Ondansetron is co-administered with drugs that prolong the QT interval and/or cause electrolyte abnormalities.
Use of Ondansetron with QT prolonging drugs may result in additional QT prolongation. Concomitant use of Ondansetron with cardiotoxic drugs (e.g. anthracyclines (such as doxorubicin, daunorubicin or trastuzumab), antibiotics (such as erythromycin), antifungals (such as ketoconazole), antiarrhythmics (such as amiodarone) and beta blockers (such as atenolol or timolol) may increase the risk of arrhythmias.
Serotonergic Drugs (e.g. SSRIs and SNRIs): There have been post-marketing reports describing patients with serotonin syndrome (including altered mental status, autonomic instability and neuromuscular abnormalities) following the concomitant use of Ondansetron and other serotonergic drugs (including SSRIs and SNRIs).
Apomorphine: Based on reports of profound hypotension and loss of consciousness when Ondansetron was administered with apomorphine hydrochloride, concomitant use with apomorphine is contraindicated.
Phenytoin, Carbamazepine and Rifampicin: In patients treated with potent inducers of CYP3A4 (i.e. phenytoin, carbamazepine, and rifampicin), the oral clearance of ondansetron was increased and Ondansetron blood concentrations were decreased.
Tramadol: Data from small studies indicate that Ondansetron may reduce the analgesic effect of tramadol.
Injection: Drugs Affecting Cytochrome P-450 Enzymes: Ondansetron does not 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. On the basis of limited available data, no dosage adjustment is recommended for patients on these drugs.
Apomorphine: Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with ondansetron is contraindicated.
Phenytoin, Carbamazepine, and Rifampin: 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 there are no data on pharmacokinetic drug interactions between ondansetron and tramadol, data from two small studies indicate that concomitant use of ondansetron may result in reduced analgesic activity of tramadol. Patients on concomitant ondansetron self administered tramadol more frequently in these studies, leading to an increased cumulative dose in patient controlled administration (PCA) of tramadol.
Chemotherapy: In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of ondansetron.
In a crossover study in 76 pediatric patients, intravenous ondansetron did not increase blood levels of high-dose methotrexate.
Temazepam: The coadministration of ondansetron had no effect on the pharmacokinetics and pharmacodynamics of temazepam.
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.

Store at temperatures not exceeding 30°C. Protect from light.

Antiemetics / Supportive Care Therapy

A04AA01 - ondansetron ; Belongs to the class of serotonin (5HT3) antagonists. Used for the prevention of nausea and vomiting.

Rx