Ondansetron Injection

Ondansetron is a 5-HT₃ receptor antagonist. Although other neurotransmitters are involved, serotonin plays an important role in the emetogenic pathways associated with chemotherapy- and radiation-induced nausea and vomiting. During the early or acute phase, the primary site of emetogenesis in chemotherapy-induced nausea and vomiting (CINV) is thought to be the gut wall. Chemotherapy is cytotoxic to enterochromaffin cells in the small intestine. Enterochromaffin cell death leads to serotonin release and therefore increased serotonin binding on nerve endings, leading to sensory input that contributes to emesis.Culy CR, Bhana N, Plosker GL. Ondansetron: a review of its use as an antiemetic in children. Paediatr Drug 2001;3:441-479.Rojas C, Slusher BS. Pharmacological mechanisms of 5-HT3 and tachykinin NK1 receptor antagonism to prevent chemotherapy-induced nausea and vomiting. Eur J Pharmacol 2012;684:1-7. Peripherally, ondansetron preferentially blocks the serotonin 5-hydroxytryptamine, type 3 (5-HT₃) receptors at the peripheral vagal nerve terminals in the intestines, blocking the signal transmission to the central nervous system and antagonizing the effects of serotonin. Ondansetron is also a weak antagonist of the 5-HT_1B, 5-HT_1C, alpha-adrenergic, and opioid mu receptors; the clinical implications of these actions is uncertain. It has no activity at dopamine receptors.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.Culy CR, Bhana N, Plosker GL. Ondansetron: a review of its use as an antiemetic in children. Paediatr Drug 2001;3:441-479.

Much like chemotherapy-induced nausea and vomiting (CINV), postoperative nausea and vomiting (PONV) is not controlled by a single neurotransmitter, but serotonin is believed to play a major role. The process of postoperative nausea and vomiting is coordinated by the vomiting center in the central nervous system. Stimulation can be initiated centrally in areas such as the cerebral cortex and otic or vestibular nerves, or peripherally in areas such as the oropharynx, mediastinum, gastrointestinal track, renal pelvis, peritoneum, or genitalia. Stretching and inflammation that occur during or after surgery may trigger chemical stimulation that lead to nausea and vomiting. Centrally, ondansetron blocks the 5-HT₃ receptor site at the chemoreceptor trigger zone, stopping the vomiting reflex produced by the vomiting center. Because of multiple neurochemical receptor sites involved during surgery, combination antiemetic therapy with drugs of different mechanisms is often necessary.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.Kovac AL. Management of postoperative nausea and vomiting in children. Paediatr Drugs 2007;9:47-69.

Ondansetron is administered orally and parenterally. It is approximately 70—76% bound to plasma protein; circulating drug also distributes into erythrocytes (approximately 36%). Animal data indicate it distributes into breast milk. Systemic exposure does not increase proportionately to the dose. Less than 5% of a dose is excreted in the urine unchanged. The mean elimination half-life in adults ranges 3.1 to 5.8 hours.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Affected cytochrome P450 isoenzymes and drug transporters:  CYP3A4, CYP1A2, CYP2D6, CYP2C9, P-gp

Ondansetron undergoes extensive metabolism, mainly by hydroxylation, followed by glucuronide or sulfate conjugation. In vitro studies indicate that ondansetron is metabolized by hepatic cytochrome P450 (CYP450) drug-metabolizing enzymes, including CYP1A2, CYP2D6, and CYP3A4; with CYP3A4 playing the largest role. Because multiple enzymes are involved in the metabolism of ondansetron, inhibition or loss of any one enzyme may not affect the overall rate of metabolism. Additionally, it is likely that inhibition or loss of one enzyme (e.g., CYP2D6 genetic deficiency) will be compensated by others and may result in little change in overall rates of ondansetron elimination.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Interactions with inhibitors or inducers of these enzymes have not been reported clinically; however, the potential exists for these interactions to change the clearance and, hence, the half-life of ondansetron. On the basis of limited available data, no dosage adjustment is recommended for patients receiving CYP-interacting drugs. Ondansetron is also a substrate of P-glycoprotein.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. The inactive metabolites are eliminated in the urine.

Route-Specific Pharmacokinetics

Intravenous Route: In adults, a single 4-mg dose administered as a 5-minute intravenous (IV) infusion demonstrated a mean AUC of 156 ng x h/ml. Mean peak plasma concentrations were 42.9 ng/ml at 10 minutes after IV infusion.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

The fixed dose of ondansetron recommended for post-operative nausea and vomiting was established in patients weighing less than 80 kg. Patients weighing more than 80 kg or with obesity have not been studied extensively.

Ondansetron is extensively metabolized in the liver and should be used with caution in patients with hepatic disease, hepatitis, or elevated hepatic enzymes because of possible increased plasma levels, reduced clearance, and subsequent toxicity.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Ondansetron should not be used in patients with a known ondansetron hypersensitivity. Use with caution in patients with known granisetron hypersensitivity, palonosetron hypersensitivity, dolasetron hypersensitivity, or sensitivity to related drugs.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Cross-sensitivity is possible between these agents; there have been several reports of anaphylactic/anaphylactoid reactions associated with the use of drugs in this class.Chen M, Tanner A, Gallo-Torres H. Anaphylactoid-anaphylactic reactions associated with ondansetron. Ann Intern Med 1993;119:862. Kataja V, Bruijn. Hypersensitivity reactions associated with 5-hydroxytriptamine3-receptor antagonists: a class effect? Lancet 1996;347:584-585. Antagonism at serotonin (5-HT) receptors, and the subsequent increased concentrations of serotonin, may increase the risk of developing bronchospasm and/or vasoconstriction.Cazzola M, Matera MG. 5-HT modifiers as a potential treatment of asthma. Trends Pharmacol Sci 2000;21:13-16. Tsuneyuki T, Ward JK, Tadjkarimi S. 5-hydroxytryptamine facilitates cholinergic bronchoconstriction in human and guinea pig airways. Am J Respir Care Med 1995;152:377-380. Saxena PR, Villalon CM. Cardiovascular effects of serotonin agonists and antagonists. J Cardiovasc Pharmacol 1991;15: S17-34.

Patients with phenylketonuria should be informed that ondansetron orally disintegrating tablets (ODT) contain phenylalanine (a component of aspartame). Each 4 mg and 8 mg ODT contains less than 0.03 mg phenylalanine.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

The use of ondansetron may mask the symptoms of adynamic ileus, GI obstruction, or gastric distention after abdominal surgery or during use to prevent chemotherapy-induced nausea and vomiting.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron is not a drug that stimulates gastric or intestinal peristalsis; it should not be used instead of nasogastric suction.Zuplenz (ondansetron) package insert. Woodcliff Lake, NJ: Par Pharmaceutical, Inc.; 2021 Aug.

Myocardial ischemia has been reported in patients treated with ondansetron. In some cases, predominantly during intravenous administration, the symptoms appeared immediately after administration but resolved with prompt treatment. Coronary artery spasm (coronary vasospasm) appears to be the most common underlying cause. Therefore, monitor for or advise patients of signs or symptoms of myocardial ischemia during use of ondansetron.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. Ondansetron also increases the risk of developing QT prolongation in a dose-dependent manner, which can lead to abnormal and potentially fatal heart rhythms, including torsade de pointes. In June 2012, the FDA announced preliminary results from a study suggesting that intravenous (IV) ondansetron given as a single 32 mg dose causes QT prolongation. Single IV doses should not exceed 16 mg; the 32 mg IV single-dose regimen is no longer indicated for chemotherapy-induced nausea and vomiting prophylaxis. Oral dosing recommendations have not changed and the use of single oral doses up to 24 mg may be used for the prevention of chemotherapy-induced nausea and vomiting (CINV). Avoid ondansetron in patients with congenital long QT syndrome. Electrocardiogram (ECG) monitoring and cautious use is recommended in patients with hypokalemia, hypomagnesemia, congestive heart failure, significant bradycardia, or in patients taking other medications known to prolong the QT interval. Use ondansetron with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, stress-related cardiomyopathy, myocardial infarction, stroke, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Little information is available about dosage in children 4 years of age or younger. Furthermore, there is no experience with the use of 24 mg ondansetron tablets in pediatric patients.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Infants younger than 4 months of age may accumulate ondansetron and should be closely monitored for toxicity. Limited information is available on the use of ondansetron in neonates younger than 1 month of age receiving surgery or in pediatric cancer patients who are infants younger than 6 months of age. The clearance of ondansetron in infants 1 to 4 months of age is slower and the half-life is roughly 2.5-fold longer than infant patients who are 4 to 24 months of age.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Data on the use of ondansetron during human pregnancy from published clinical and epidemiological studies are inconsistent and have important methodological limitations, including the uncertainty of whether women who filled a prescription actually took the medicine, the concomitant use of other medications or treatments, recall bias, and other unadjusted confounders, that do not reliably inform a drug associated risk of adverse fetal outcomes. In aggregate analysis, ondansetron exposure in utero has not been associated with major congenital malformations. Some studies have not shown a statistically significant increase in the risk of birth defects with the use of ondansetron; however, others have shown a possible increased risk of cleft palate and cardiovascular malformations.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. Ondansetron has been shown to cross the placenta in early pregnancy with a median fetal to maternal ratio of 0.41. Evidence is limited on the safety or efficacy of the serotonin 5-HT3 inhibitors for nausea and vomiting of pregnancy. There are more published data for ondansetron use during pregnancy than with other 5HT-3 antagonists. The American College of Obstetricians and Gynecologists (ACOG) includes oral ondansetron as a third-line pharmacologic treatment option for nausea and vomiting of pregnancy in patients who are not dehydrated and have failed other therapies and IV ondansetron for patients who are dehydrated, require IV fluid replacement, and have failed other therapies. Although some studies have shown an increased risk of birth defects with early ondansetron use, other studies have not and the absolute risk to any fetus is considered, per ACOG, to be low. Some studies have suffered from small sample sizes and potential methodological bias. However, women should be counseled regarding the available data, and the use of ondansetron before 10 weeks of gestation should be individualized weighing the risks and benefits.American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin Number 189: Nausea and vomiting of pregnancy. Obstet Gynecol 2018;131:15-30. Reaffirmed 2019. Danielsson B, Wikner BN, Kallen B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol 2014;50:134-7. Anderka M, Mitchell AA, Louik C, et al. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth defects Res A Clin Mol Teratol 2012;94:22-30. Pasternak B, Svanstrom H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med 2013;368:814-23.

It is not known whether ondansetron is excreted in human milk. However, because of its low molecular weight, transfer into breast milk should be expected.Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Briggs GG, Freeman RK, Yaffe SJ, (eds.) 7th ed., Philadelphia PA: Lippincott Williams and Wilkins 2005;:742-3. Caution should be exercised when administering ondansetron to a breastfeeding woman.

No differences in responses for safety or efficacy have been observed between geriatric and younger patients during clinical trials or other reported clinical experience. Of the total number of patients enrolled in US and foreign-controlled clinical trials for postoperative and chemotherapy-induced nausea and vomiting, for which there were subgroup analyses, 938 were 65 years of age or older. However, greater sensitivity of some older individuals cannot be ruled out. The manufacturer states that no dosage adjustments are needed in elderly patients. Geriatric patients may be at increased risk for developing a prolonged QT interval when using ondansetron. Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Data on the use of ondansetron during human pregnancy from published clinical and epidemiological studies are inconsistent and have important methodological limitations, including the uncertainty of whether women who filled a prescription actually took the medicine, the concomitant use of other medications or treatments, recall bias, and other unadjusted confounders, that do not reliably inform a drug associated risk of adverse fetal outcomes. In aggregate analysis, ondansetron exposure in utero has not been associated with major congenital malformations. Some studies have not shown a statistically significant increase in the risk of birth defects with the use of ondansetron; however, others have shown a possible increased risk of cleft palate and cardiovascular malformations.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. Pasternak B, Svanstrom H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med 2013;368:814-23. Danielsson B, Wikner BN, Kallen B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol 2014;50:134-7. Anderka M, Mitchell AA, Louik C, et al. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth defects Res A Clin Mol Teratol 2012;94:22-30. Ondansetron has been shown to cross the placenta in early pregnancy with a median fetal to maternal ratio of 0.41. Evidence is limited on the safety or efficacy of the serotonin 5-HT3 inhibitors for nausea and vomiting of pregnancy. There are more published data for ondansetron use during pregnancy than with other 5HT-3 antagonists. The American College of Obstetricians and Gynecologists (ACOG) includes oral ondansetron as a third-line pharmacologic treatment option for nausea and vomiting of pregnancy in patients who are not dehydrated and have failed other therapies and IV ondansetron for patients who are dehydrated, require IV fluid replacement, and have failed other therapies. Although some studies have shown an increased risk of birth defects with early ondansetron use, other studies have not and the absolute risk to any fetus is considered, per ACOG, to be low. Some studies have suffered from small sample sizes and potential methodological bias. However, women should be counseled regarding the available data, and the use of ondansetron before 10 weeks of gestation should be individualized weighing the risks and benefits.American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin Number 189: Nausea and vomiting of pregnancy. Obstet Gynecol 2018;131:15-30. Reaffirmed 2019. Danielsson B, Wikner BN, Kallen B. Use of ondansetron during pregnancy and congenital malformations in the infant. Reprod Toxicol 2014;50:134-7. Anderka M, Mitchell AA, Louik C, et al. Medications used to treat nausea and vomiting of pregnancy and the risk of selected birth defects. Birth defects Res A Clin Mol Teratol 2012;94:22-30. Pasternak B, Svanstrom H, Hviid A. Ondansetron in pregnancy and risk of adverse fetal outcomes. N Engl J Med 2013;368:814-23.

It is not known whether ondansetron is excreted in human milk. However, because of its low molecular weight, transfer into breast milk should be expected.Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Briggs GG, Freeman RK, Yaffe SJ, (eds.) 7th ed., Philadelphia PA: Lippincott Williams and Wilkins 2005;:742-3. Caution should be exercised when administering ondansetron to a breastfeeding woman.

Diarrhea (2—16%) and constipation (6—11%) were among the most frequently reported adverse events in patients receiving ondansetron during clinical trials for chemotherapy-induced nausea and vomiting (CINV) with moderate-high emetogenic agents.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. Hiccups have been reported during post-marketing experience with ondansetron.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Urinary retention (5%) and gynecological disorder (7%) have been reported in patients receiving oral ondansetron for postoperative nausea and vomiting (PONV) during clinical trials.Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Headache (9—27%) was the most frequently reported adverse event during clinical trials of ondansetron and appeared to be more common in patients receiving the drug for chemotherapy-induced nausea and vomiting (CINV). Preliminary observations in a small number of subjects suggest a higher incidence of headache when ondansetron orally disintegrating tablets are taken with water, when compared to without water. Other neurologic side effects reported include drowsiness (8—20%), malaise and fatigue (9—13%), anxiety or agitation (<= 6%), paresthesias (2%), and dizziness (4—7%). Transient dizziness associated with intravenous infusion has been reported post-marketing. Rarely, extrapyramidal reactions, including oculogyric crisis appearing alone or with other types of dystonic reaction, have been reported with ondansetron use.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. In one case, extrapyramidal reactions were confirmed by rechallenge. In addition, there have been rare reports of grand mal seizures in patients receiving ondansetron, although a casual relationship has not been established.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Elevated hepatic enzymes were reported in patients receiving either cisplatin- or cyclophosphamide-based chemotherapy during clinical trials. The elevation did not appear to be related to ondansetron dose or duration of therapy. The enzyme levels exceeded twice the upper limit of normal (ULN) in approximately 5% of chemotherapy patients receiving injection dosing, and 1—2% of patients receiving oral therapy, but the increases were transient in nature and did not cause symptomatic hepatic disease. Repeat exposure showed similar elevations in some instances. In addition, hepatic failure and death have been reported in patients with cancer receiving concomitant medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics; the etiology of the hepatic failure is unclear.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Rare cases of hypokalemia have been reported following treatment with ondansetron in oncology patients; the relationship to ondansetron is unclear.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. It may be prudent to monitor serum electrolytes in select patients, as hypokalemia is a risk factor for electrocardiogram (ECG) changes.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Ondansetron has been associated with QT prolongation and torsade de pointes. Patients at risk for developing torsade de pointes include those with underlying heart conditions, such as congenital long QT syndrome (avoid use), those who are predisposed to hypokalemia and hypomagnesemia, and those taking other medications that lead to QT prolongation. Other cardiovascular adverse events reported during clinical trials with ondansetron include angina, chest pain (unspecified), ECG alterations (including second-degree AV block, QT prolongation, and ST-T wave changes), hypotension (5%), and sinus tachycardia. Bradycardia (6% vs. 6% placebo) was reported in patients receiving oral ondansetron for postoperative nausea and vomiting (PONV). Syncope, palpitations, and arrhythmias, including ventricular tachycardia and supraventricular tachycardia (SVT), bradycardia, premature ventricular contractions (PVCs), atrial fibrillation, and acute myocardial ischemia have been reported during postmarketing use of ondansetron. In some cases, predominantly during intravenous administration, the symptoms of myocardial ischemia appeared immediately after administration but resolved with prompt treatment. Coronary vasospasm (coronary artery spasm) appears to be the most common cause of the ischemia. To minimize the risk of these adverse events in patients receiving intravenous treatment, do not exceed the recommended ondansetron infusion rate and monitor patients for signs and symptoms of myocardial ischemia during and after administration. In patients receiving oral therapy, monitor or advise patients of these symptoms.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. Intravenous (IV) ondansetron given as a single 32 mg dose causes QT prolongation in a dose-dependent manner; therefore, single IV doses should not exceed 16 mg/dose IV; the 32 mg IV single-dose regimen is no longer indicated for chemotherapy-induced nausea and vomiting (CINV). Oral dosing recommendations have not changed. ECG monitoring is recommended in patients with electrolyte imbalance (e.g., hypokalemia or hypomagnesemia), congestive heart failure, significant bradycardia, or in patients taking other medications that can lead to QT prolongation.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Several reports of anaphylactoid reactions have been associated with serotonin (5-HT₃) receptor antagonists, such as ondansetron.Chen M, Tanner A, Gallo-Torres H. Anaphylactoid-anaphylactic reactions associated with ondansetron. Ann Intern Med 1993;119:862. Kataja V, Bruijn. Hypersensitivity reactions associated with 5-hydroxytriptamine3-receptor antagonists: a class effect? Lancet 1996;347:584-585. Manifestations of anaphylactoid reactions have included angioedema, bronchospasm, dyspnea, hypotension, laryngeal edema, stridor, and/or urticaria. Laryngospasm, shock, cardiac arrest, and respiratory arrest have been reported during allergic reactions in patients receiving injectable ondansetron. Rash (unspecified) (1%), pruritus (2—5%), and flushing have been reported in clinical trials with both oral and injectable formulations.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. Stevens-Johnson syndrome and toxic epidermal necrolysis (TENS) have been reported with post-marketing use of ondansetron.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

An injection site reaction (4%) was reported in patients receiving ondansetron injection intravenously over 2 to 5 minutes during clinical trials for post-operative nausea/vomiting (PONV); symptoms included pain, erythema, and burning at the site.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Visual impairment has occurred with ondansetron use. Cases of transient blindness, predominantly during intravenous (IV) administration, have been reported; resolution occurred within minutes up to 48 hours. Sudden blindness (amaurosis) of 2—3 minute duration occurred in one patient who was administered ondansetron 72 mg IV as a single dose.Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April. Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. In another case, transient blindness was reported in a patient who received ondansetron 4mg as a post-operative rapid IV bolus dose. The mechanism by which ondansetron may cause visual impairment is not well understood. Clinicians in the latter case suggest that it may be related to the rate of administration. Transient blurred vision, in some cases associated with accommodation disorder, has also been reported during post-marketing experience.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct.

Fever (2—8%) and shivers or chills (2—5%) were reported in patients receiving ondansetron during clinical trials. Wound problems (28% vs. 31% placebo) were reported in patients receiving oral ondansetron for postoperative nausea and vomiting (PONV).Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Serotonin syndrome has been reported with 5-HT₃ receptor antagonists, such as ondansetron, during concurrent use of other medications known to increase CNS or peripheral serotonin levels or during overdose. Some of the reported cases were fatal; most occurred in a post-anesthesia care unit or infusion center. If serotonin syndrome becomes evident during treatment, discontinue ondansetron and any other serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is a range of signs and symptoms that can include mental status changes (e.g., agitation, hallucinations, delirium, coma), gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), and/or seizures. Cases consistent with serotonin syndrome have been reported in pediatric patients after inadvertent overdose of oral ondansetron (estimated ingestion > 5 mg/kg). Symptoms reported in these cases included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizures. Patients required supportive care, including intubation in some cases, with complete recovery in 1—2 days.Zofran (ondansetron) injection package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 Oct. Ondansetron hydrochloride (Zofran) tablets and oral solution package insert. Research Triangle Park, NC: GlaxoSmithKline; 2021 April.

Store this medication in its original container at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond-use date. Do not flush unused medications or pour down a sink or drain.