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Medication Safety Issues
Sound-alike/look-alike issues:
Ondansetron may be confused with dolasetron, granisetron, palonosetron
Zofran® may be confused with Zantac®, Zosyn®
Pronunciation
(on DAN se tron)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use
Prevention of nausea and vomiting associated with moderately- to highly-emetogenic cancer chemotherapy; radiotherapy in patients receiving total body irradiation or fractions to the abdomen; prevention of postoperative nausea and vomiting (PONV); treatment of PONV if no prophylactic dose received
Use: Unlabeled/Investigational
Treatment of early-onset alcoholism; hyperemesis gravidarum
Pregnancy Risk Factor
B
Pregnancy Implications
Teratogenic effects were not observed in animal studies; however, there are no adequate and well-controlled studies in pregnant women. Use of ondansetron for the treatment of nausea and vomiting of pregnancy (NVP) has been evaluated. Additional studies are needed to determine safety to the fetus, particularly during the first trimester. Based on preliminary data, use is generally reserved for severe NVP (hyperemesis gravidarum) or when conventional treatments are not effective.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to ondansetron, other selective 5-HT3 antagonists, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Allergic reactions: Use with caution in patients allergic to other 5-HT3 receptor antagonists; cross-reactivity has been reported.
• ECG effects: Selective 5-HT3 antagonists, including ondansetron, have been associated with a number of dose-dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT), usually occurring 1-2 hours after I.V. administration. In general, these changes are not clinically relevant, however, when used in conjunction with other agents that prolong these intervals, arrhythmia may occur. When used with agents that prolong the QT interval (eg, Class I and III antiarrhythmics), clinically relevant QT interval prolongation may occur resulting in torsade de pointes. A number of trials have shown that 5-HT3 antagonists produce QT interval prolongation to variable degrees. Use with caution in patients at risk of QT prolongation and/or ventricular arrhythmia. Reduction in heart rate may also occur with the 5-HT3 antagonists. I.V. formulations of 5-HT3 antagonists have more association with ECG interval changes, compared to oral formulations.
Disease-related concerns:
• Long QT syndrome: Use with caution in patients with congenital long QT syndrome or other risk factors for QT prolongation (eg, medications known to prolong QT interval, electrolyte abnormalities [hypokalemia or hypomagnesemia], and cumulative high-dose anthracycline therapy).
Special populations:
• Pediatrics: Safety and efficacy have not been established in children <1 month of age.
Dosage form specific issues:
• Phenylalanine: Orally-disintegrating tablets contain phenylalanine.
Other warnings/precautions:
• Chemotherapy-related emesis: For chemotherapy, should be used on a scheduled basis, not on an “as needed” (PRN) basis, since data support the use of this drug only in the prevention of nausea and vomiting (due to antineoplastic therapy) and not in the rescue of nausea and vomiting. Should only be used in the first 24-48 hours of chemotherapy. Data does not support any increased efficacy in delayed nausea and vomiting.
• Ileus or gastric distention: Does not stimulate gastric or intestinal peristalsis; may mask progressive ileus and/or gastric distension.
Adverse Reactions
Note: Percentages reported in adult patients.
>10%:
Central nervous system: Headache (9% to 27%), malaise/fatigue (9% to 13%)
Gastrointestinal: Constipation (6% to 11%)
1% to 10%:
Central nervous system: Drowsiness (8%), fever (2% to 8%), dizziness (4% to 7%), anxiety (6%), cold sensation (2%)
Dermatologic: Pruritus (2% to 5%), rash (1%)
Gastrointestinal: Diarrhea (2% to 7%)
Genitourinary: Gynecological disorder (7%), urinary retention (5%)
Hepatic: ALT/AST increased (1% to 5%)
Local: Injection site reaction (4%; pain, redness, burning)
Neuromuscular & skeletal: Paresthesia (2%)
Respiratory: Hypoxia (9%)
<1%: Anaphylaxis, angina, bronchospasm, ECG changes, extrapyramidal symptoms, grand mal seizure, hypokalemia, tachycardia, vascular occlusive events
Postmarketing and/or case reports: Anaphylactoid reactions, angioedema, arrhythmia, blindness (transient/following infusion; lasting ?48 hours), blurred vision (transient/following infusion), bradycardia, cardiopulmonary arrest, dyspnea, dystonic reaction, electrocardiographic alterations (second degree heart block and ST-segment depression), flushing, hiccups, hypersensitivity reaction, hypotension, laryngeal edema, laryngospasm, oculogyric crisis, palpitation, premature ventricular contractions (PVC), QT interval increased, shock, stridor, supraventricular tachycardia, syncope, urticaria, ventricular arrhythmia
Drug Interactions
Substrate of CYP1A2 (minor), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (major); Inhibits CYP1A2 (weak), 2C9 (weak), 2D6 (weak)
Apomorphine: Due to reports of profound hypotension during concomitant therapy, the manufacturer of apomorphine contraindicates its use with ondansetron.
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of ondansetron. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins. The manufacturer does not recommend dosage adjustment in patients receiving CYP3A4 inducers.
Ethanol/Nutrition/Herb Interactions
Food: Food increases the extent of absorption. The Cmax and Tmax do not change much.
Herb/Nutraceutical: St John's wort may decrease ondansetron levels.
Storage
Oral solution: Store between 15°C and 30°C (59°F and 86°F). Protect from light.
Premixed bag: Store between 2°C and 30°C (36°F and 86°F). Protect from light.
Tablet: Store between 2°C and 30°C (36°F and 86°F).
Vial: Store between 2°C and 30°C (36°F and 86°F). Protect from light. Stable when mixed in D5W or NS for 48 hours at room temperature.
Reconstitution
Prior to I.V. infusion, dilute in 50 mL D5W or NS.
Compatibility
Stable in D51/2NS, D5NS, D5W, mannitol 10%, LR, NS, sodium chloride 3%; do not mix injection with alkaline solutions.
Y-site administration: Compatible: Alatrofloxacin, aldesleukin, amifostine, amikacin, aztreonam, bleomycin, carboplatin, carmustine, cefazolin, cefotaxime, cefoxitin, ceftazidime, ceftizoxime, cefuroxime, chlorpromazine, cimetidine, cisatracurium, cisplatin, cladribine, clindamycin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dexamethasone sodium phosphate, diphenhydramine, docetaxel, dopamine, doxorubicin, doxorubicin liposome, doxycycline, droperidol, etoposide, etoposide phosphate, famotidine, filgrastim, floxuridine, fluconazole, fludarabine, gatifloxacin, gemcitabine, gentamicin, haloperidol, heparin, hydrocortisone sodium phosphate, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, ifosfamide, imipenem/cilastatin, linezolid, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, mesna, methotrexate, metoclopramide, mitomycin, mitoxantrone, morphine, paclitaxel, paclitaxel with ranitidine, pentostatin, piperacillin/tazobactam, potassium chloride, prochlorperazine edisylate, promethazine, ranitidine, remifentanil, sodium acetate, streptozocin, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, topotecan, vancomycin, vinblastine, vincristine, vinorelbine, zidovudine. Incompatible: Acyclovir, allopurinol, aminophylline, amphotericin B, amphotericin B cholesteryl sulfate complex, ampicillin, ampicillin/sulbactam, amsacrine, cefepime, cefoperazone, furosemide, ganciclovir, lorazepam, methylprednisolone sodium succinate, piperacillin, sargramostim, sodium bicarbonate. Variable (consult detailed reference): Fluorouracil, meropenem.
Mechanism of Action
Selective 5-HT3-receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone
Pharmacodynamics/Kinetics
Onset of action: ?30 minutes
Distribution: Vd: Children: 1.7-3.7 L/kg; Adults: 2.2-2.5 L/kg
Protein binding, plasma: 70% to 76%
Metabolism: Extensively hepatic via hydroxylation, followed by glucuronide or sulfate conjugation; CYP1A2, CYP2D6, and CYP3A4 substrate; some demethylation occurs
Bioavailability: Oral: 56% to 71%; Rectal: 58% to 74%
Half-life elimination: Children <15 years: 2-7 hours; Adults: 3-6 hours
Mild-to-moderate hepatic impairment: Adults: 12 hours
Severe hepatic impairment (Child-Pugh C): Adults: 20 hours
Time to peak: Oral: ?2 hours
Excretion: Urine (44% to 60% as metabolites, 5% to 10% as unchanged drug); feces (?25%)
Dosage
Note: Studies in adults have shown a single daily dose of 8-12 mg I.V. or 8-24 mg orally to be as effective as mg/kg dosing, and should be considered for all patients whose mg/kg dose exceeds 8-12 mg I.V.; oral solution and ODT formulations are bioequivalent to corresponding doses of tablet formulation
Children:
I.V.:
Prevention of chemotherapy-induced emesis: 6 months to 18 years: 0.15 mg/kg/dose administered 30 minutes prior to chemotherapy, 4 and 8 hours after the first dose or 0.45 mg/kg/day as a single dose
Prevention of postoperative nausea and vomiting: 1 month to 12 years:
?40 kg: 0.1 mg/kg as a single dose
>40 kg: 4 mg as a single dose
Oral: Prevention of chemotherapy-induced emesis:
4-11 years: 4 mg 30 minutes before chemotherapy; repeat 4 and 8 hours after initial dose, then 4 mg every 8 hours for 1-2 days after chemotherapy completed
?12 years: Refer to adult dosing.
Adults:
I.V.:
Prevention of chemotherapy-induced emesis:
0.15 mg/kg 3 times/day beginning 30 minutes prior to chemotherapy or
0.45 mg/kg once daily or
8-10 mg 1-2 times/day or
24 mg or 32 mg once daily
Treatment of hyperemesis gravidum (unlabeled use): 8 mg administered over 15 minutes every 12 hours or 1 mg/hour infused continuously for up to 24 hours
I.M., I.V.: Postoperative nausea and vomiting: 4 mg as a single dose approximately 30 minutes before the end of anesthesia, or as treatment if vomiting occurs after surgery
Note: Repeat doses given in response to inadequate control of nausea/vomiting from preoperative doses are generally ineffective.
Oral:
Chemotherapy-induced emesis:
Highly-emetogenic agents/single-day therapy: 24 mg given 30 minutes prior to the start of therapy
Moderately-emetogenic agents: 8 mg every 12 hours beginning 30 minutes before chemotherapy, continuously for 1-2 days after chemotherapy completed
Total body irradiation: 8 mg 1-2 hours before daily each fraction of radiotherapy
Single high-dose fraction radiotherapy to abdomen: 8 mg 1-2 hours before irradiation, then 8 mg every 8 hours after first dose for 1-2 days after completion of radiotherapy
Daily fractionated radiotherapy to abdomen: 8 mg 1-2 hours before irradiation, then 8 mg 8 hours after first dose for each day of radiotherapy
Postoperative nausea and vomiting: 16 mg given 1 hour prior to induction of anesthesia
Treatment of hyperemesis gravidum (unlabeled use): 8 mg every 12 hours
Elderly: No dosing adjustment required
Dosage adjustment in renal impairment: No dosing adjustment required
Dosage adjustment in hepatic impairment: Severe liver disease (Child-Pugh C): Maximum daily dose: 8 mg
Administration: Oral
Oral dosage forms should be given 30 minutes prior to chemotherapy; 1-2 hours before radiotherapy; 1 hour prior to the induction of anesthesia.
Orally-disintegrating tablets: Do not remove from blister until needed. Peel backing off the blister, do not push tablet through. Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva.
The I.V. preparation has been successful when administered orally.
Administration: I.M.
Should be given undiluted.
Administration: I.V.
IVPB: Dilute in 50 mL D5W or NS. Infuse over 15-30 minutes; 24-hour continuous infusions have been reported, but are rarely used.
Chemotherapy-induced nausea and vomiting: Give first dose 30 minutes prior to beginning chemotherapy.
I.V. push: Prevention of postoperative nausea and vomiting: Single doses may be administered I.V. injection over 2-5 minutes as undiluted solution.
Administration: I.V. Detail
pH: 3-4
Monitoring Parameters
Closely monitor patients <4 months of age
Dietary Considerations
Take without regard to meals.
Orally-disintegrating tablet contains <0.03 mg phenylalanine
Patient Education
This drug is given to reduce the incidence of nausea and vomiting. Do not take any other medication for nausea and vomiting with this medication unless approved by prescriber. If self-administered, take as directed. May cause headache, drowsiness, or dizziness (do not change position rapidly, request assistance when getting up or changing position and do not perform activities requiring alertness) or diarrhea (request appropriate treatment from prescriber). Report persistent headache, excessive drowsiness, fever, numbness or tingling, or changes in elimination patterns (constipation or diarrhea); and chest pain or palpitations.
Orally-disintegrating tablets: Do not remove from blister until needed. Peel backing off the blister, do not push tablet through. Using dry hands, place tablet on tongue and allow to dissolve. Swallow with saliva. Contains <0.03 mg phenylalanine/tablet.
Geriatric Considerations
Elderly have a slightly decreased hepatic clearance rate. This does not, however, require a dose adjustment.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness
Mental Health: Effects on Psychiatric Treatment
Barbiturates and carbamazepine may increase the metabolism of ondansetron; monitor for diminished effects
Nursing: Physical Assessment/Monitoring
To be used on a scheduled basis, not on an "as needed" (PRN) basis for prevention of nausea and vomiting associated with moderately- to highly-emetogenic cancer chemotherapy; not recommended for treatment of existing chemotherapy-induced emesis. Assess potential for interactions with other pharmacological agents and herbal products patient may be taking (eg, increase or decrease levels/effects of ondansetron). See Administration for specifics according to formulation. Assess effectiveness (avoidance of nausea and vomiting) and adverse effects (dizziness, constipation, diarrhea, urinary retention, hypoxia). Teach patient possible side effects/appropriate interventions, and adverse symptoms to report.
Oncology: Emetic Potential
Very low (<10%)
Oncology: Vesicant
No
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Infusion [premixed in D5W, preservative free]: 32 mg (50 mL)
Zofran®: 32 mg (50 mL)
Injection, solution: 2 mg/mL (2 mL, 20 mL)
Zofran®: 2 mg/mL (2 mL, 20 mL)
Injection, solution [preservative free]: 2 mg/mL (2 mL)
Solution, oral: 4 mg/5 mL (50 mL)
Zofran®: 4 mg/5 mL (50 mL) [contains sodium benzoate; strawberry flavor]
Tablet: 4 mg; 8 mg
Zofran®: 4 mg; 8 mg
Tablet, orally disintegrating: 4 mg; 8 mg
Zofran® ODT: 4 mg, 8 mg [each strength contains phenylalanine <0.03 mg/tablet; strawberry flavor]
Pricing: U.S. (www.drugstore.com)
Tablet, orally-disintegrating (Ondansetron)
4 mg (30): $549.00
Tablet, orally-disintegrating (Zofran ODT)
4 mg (30): $659.95
Tablets (Ondansetron HCl)
4 mg (30): $569.99
8 mg (30): $1048.95
Tablets (Zofran)
4 mg (10): $244.63
8 mg (30): $1169.97
24 mg (10): $1008.41
Extemporaneously Prepared
A 0.8 mg/mL syrup may be made by crushing ten 8 mg tablets; flaking of the tablet coating occurs. Mix thoroughly with 50 mL of the suspending vehicle, Ora-Plus® (Paddock), in 5 mL increments. Add sufficient volume of any of the following syrups: Cherry syrup USP, Syrpalta® (Humco), Ora-Sweet® (Paddock), or Ora-Sweet® Sugar-Free (Paddock) to make a final volume of 100 mL. Stability is 42 days refrigerated.
Trissel LA, “Trissel's Stability of Compounded Formulations,” American Pharmaceutical Association, 1996.
Rectal suppositories: Calibrate a suppository mold for the base being used. Determine the displacement factor (DF) for ondansetron for the base being used (Fattibase® = 1.1; Polybase® = 0.6). Weigh the ondansetron tablet. Divide the tablet weight by the DF. Subtract the weight of base displaced from the calculated weight of base required for each suppository. Grind the ondansetron tablets to a fine powder in a mortar. Weigh out the appropriate weight of suppository base. Melt the base over a water bath (<55°C). Add the ondansetron powder to the suppository base and mix well. Pour the mixture into the suppository mold and cool. Stable for at least 30 days under refrigeration.
Allen LV, “Ondansetron Suppositories,” US Pharm, 20(7):84-6.
References
American College of Obstetrics and Gynecology, ACOG (American College of Obstetrics and Gynecology) Practice Bulletin: “Nausea and Vomiting of Pregnancy,” Obstet Gynecol, 2004, 103(4):803-14.
Chaffee BJ and Tankanow RM, “Ondansetron - the First of a New Class of Antiemetic Agents,” Clin Pharm, 1991, 10(6):430-6.
Kris MG, Hesketh PJ, Somerfield MR, et al, “American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006,” J Clin Oncol, 2006, 24(18):2932-47.
Levichek Z, Atanackovic G, Oepkes D, et al, “Nausea and Vomiting of Pregnancy. Evidence-Based Treatment Algorithm,” Can Fam Physician, 2002, 48:267-8, 277.
Navari RM and Koeller JM, “Electrocardiographic and Cardiovascular Effects of the 5-Hydroxytryptamine3 Receptor Antagonists,” Ann Pharmacother, 2003, 37(9):1276-86.
Roila F and Del Favero A, “Ondansetron Clinical Pharmacokinetics,” Clin Pharmacokinet, 1995, 29(2):95-109.
Siu SS, Yip SK, Cheung CW, et al, “Treatment of Intractable Hyperemesis Gravidarum by Ondansetron,” Eur J Obstet Gynecol Reprod Biol, 2002, 105(1):73-4.
Tramer MR, Moore RA, Reynolds DJ, et al, “A Quantitative Systematic Review of Ondansetron in Treatment of Established Postoperative Nausea and Vomiting,” BMJ, 1997, 314(7087):1088-92.
Wilde MI and Markham A, “Ondansetron. A Review of Its Pharmacology and Preliminary Clinical Findings in Novel Application,” Drugs, 1996, 52(5):773-94.
International Brand Names
Lexi-Comp.com
Last full review/revision June 2008
Content last modified June 2008
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