Dosing and uses of Zofran, Zuplenz (ondansetron)
Adult dosage forms and strengths
injectable solution
- 2mg/mL
tablet
- 4mg
- 8mg
- 24mg
oral solution
- 4mg/5mL
oral soluble film
- 4mg
- 8mg
orally disintegrating tablets
- 4mg
- 8mg
Chemotherapy-Induced Nausea & Vomiting
Prophylaxis
PO
- Moderately emetogenic chemotherapy: 8 mg started 30 minutes before chemotherapy, then q12hr for 1-2 days after chemotherapy
- Highly emetogenic chemotherapy: 24 mg started 30 minutes before chemotherapy
- Zofran ODT: Using dry hands, carefully remove from blister pack immediately before use
IV
- 0.15 mg/kg over 15 min administered 30 min before chemotherapy, then 4 and 8 hr after first dose; not to exceed 16 mg (32 mg no longer recommended because of increased risk of QT prolongation)
Postoperative Nausea & Vomiting
Prophylaxis
4 mg IV/IM immediately before anesthesia or after procedure or 16 mg PO 1 hr before anesthesia; patients >80 kg may need additional 4 mg IV
Radiation-Induced Nausea & Vomiting
Prophylaxis
Total body radiation therapy: 8 mg PO 1-2 hours before radiation therapy; administered each day
Single high-dose fraction therapy to abdomen: 8 mg PO 1-2 hr before radiation therapy; administer subsequent doses every 8 hr after first dose 1-2 days after completion of therapy
Daily fractions to abdomen: Administer 8 mg PO 1-2 hr before radiotherapy; administer subsequent doses every 8 hr after first dose each day radiotherapy is given
Dosage modifications
Renal impairment: Dose adjustment not necessary
Severe hepatic impairment (Child-Pugh score ≥10): Not to exceed 8 mg/day
Cholestatic Pruritus (Off-label)
8 mg divided q12hr or 8 mg q8-12hr PO for 7 days up to 5 months
Alternatively, 4-8 mg intermittent short-term IV dosing used in adults; single dose of 4 mg single dose used in pregnancy
Uremic Pruritus (Off-label)
8 mg divided q12hr or 8 mg q8-12hr PO for 14 days up to 5 months
Spinal Opioid-Induced Pruritus (Off-label)
Prophylaxis: 4-8 mg IV 20-30 min prior to spinal opioid therapy; may repeat dosing at 12, 24, 36, 48 hr after spinal opioid dosing
Treatment: 4-8 mg IV
Rosacea (Off-label)
4-8 mg PO q12hr for up to 3 weeks
Alternatively, 12 mg IV daily for 4 days
Hyperemesis Gravidarum
10 mg IV q8hr PRn
Pediatric dosage forms and strengths
injectable solution
- 2mg/mL
tablet
- 4mg
- 8mg
oral solution
- 4mg/5mL
oral soluble film
- 4mg
- 8mg
orally disintegrating tablets
- 4mg
- 8mg
Chemotherapy-Induced Nausea & Vomiting
Prophylaxis
PO
- <4 years old: Safety and efficacy not established
- 4-12 years: 4 mg started 30 min before chemotherapy, then 4 and 8 hr after first dose, then q8hr for 1-2 days after chemotherapy
- >12 years: 8 mg started 30 min before chemotherapy, then q12hr for 1-2 days after chemotherapy, or single dose of 24 mg
IV
- <6 months: Safety and efficacy not established
- ≥6 months: 0.15 mg/kg over 15 min administered 30 min before chemotherapy, then repeated 4 and 8 hr after first dose; not to exceed 16 mg/dose (32 mg no longer recommended because of increased risk of QT prolongation)
Postoperative Nausea & Vomiting
Prophylaxis
1 month-12 years
- <40 kg, 0.1 mg/kg IV
- >40 kg, 4 mg IV
>12 years
- 4 mg IV/IM immediately before anesthesia or after procedure or 16 mg PO 1 hr before anesthesia; patients >80 kg may need additional 4 mg IV
Chemotherapy-Induced Nausea & Vomiting (Orphan)
Ondansetron inhalation powder: Prevention of chemotherapy-induced nausea and vomiting due to highly emetogenic chemotherapy in pediatric patients (aged birth through 16 yr)
Sponsor
- Luxena Pharmaceuticals, Inc; 1400 Coleman Avenue, Suite D27; Santa Clara, California 95050
Zofran, Zuplenz (ondansetron) adverse (side) effects
>10%
Headache (9-27%)
Malaise/fatigue (9-13%)
Constipation (6-11%)
1-10%
Hypoxia (9%)
Drowsiness (8%)
Diarrhea (2-7%)
Dizziness (7%)
Fever (2-8%)
Gynecologic disorder (7%)
Anxiety (6%)
Urinary retention (5%)
Pruritus (2-5%)
Injection-site pain (4%)
Paresthesia (2%)
Cold sensation (2%)
Elevated liver function test results (1-5%)
<1%
Cardiac: 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
Gastrointestinal: Nausea and vomiting
Anaphylaxis
ECG alterations: Arrhythmias; prolongation of PR, QRS, and QT intervals
Hepatobiliary: Specific hepatic enzyme abnormalities, hepatic necrosis, and abnormal hepatic function
General: Flushing, rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylactic reactions, angioedema, bronchospasm, cardiopulmonary arrest, hypotension, laryngeal edema, laryngospasm, shock, shortness of breath, stridor)
Local reactions: Pain, redness, and burning at injection site
Lower respiratory: Hiccups
Neurological: Oculogyric crisis, appearing alone, as well as with other dystonic reactions; transient dizziness during or shortly after intravenous infusion
Skin and subcutaneous tissue: Urticaria, Stevens-Johnson syndrome, and toxic epidermal necrolysis
Eye Disorders: Transient blindness (predominantly during IV administration) reported to resolve within a few minutes up to 48 hr; transient blurred vision
Musculoskeletal and connective tissue: Arthralgia
Warnings
Contraindications
Hypersensitivity
Coadministration with apomorphine; combination reported to cause profound hypotension and loss of consciousness
Cautions
Hypersensitivity reactions including anaphylaxis and bronchospasm may occur: discontinue therapy if suspected; monitor and treat promptly per standard of care until signs and symptoms resolve
Reduce dose with severe hepatic impairment
Use according to schedule, not PRn
Do not use instead of nasogastric suction
Ondansetron may mask progressive ileus or gastric distention in patients who are undergoing abdominal surgery or experiencing chemotherapy-induced nausea and vomiting; monitor for decreased bowel activity, particularly in patients with risk factors for gastrointestinal obstruction
Serotonin syndrome reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs including SSRIs, SNRIs, MAO inhibitors, lithium, tramadol, methylene blue IV, and mirtazapine; if concomitant use with other serotonergic drugs is clinically warranted, patients should be made aware of potential increased risk for serotonin syndrome
Cross-sensitivity among selective serotonin antagonists may occur
Zofran ODT contains phenylalanine (caution for phenylketonurics)
Dose-dependent QT prolongation; avoid in patients with congenital long QT syndrome; ECG monitoring recommended in patients who have electrolyte abnormalities, CHF, or bradyarrhythmias or who are also receiving other medications that cause QT prolongation
Pregnancy and lactation
Pregnancy: Available data do not reliably inform of association with adverse fetal outcomes; published epidemiological studies on the association between ondansetron and fetal outcomes have reported inconsistent findings and have important methodological limitations hindering interpretation
Lactation: It is not known whether ondansetron is present in human milk; there are no data on effects of ondansetron on breastfed infant or effects on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for ondansetron and any potential adverse effects on breast-fed infant from therapy or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Zofran, Zuplenz (ondansetron)
Mechanism of action
Mechanism not fully characterized; selective 5-HT3 receptor antagonist; binds to 5-HT3 receptors both in periphery and in CNS, with primary effects in GI tract
Has no effect on dopamine receptors and therefore does not cause extrapyramidal symptoms
Absorption
Bioavailability: 56-71% (PO); food increases extent of absorption (17%)
Onset: 30 min
Peak plasma time: IV, end of infusion; IM, 30 min; PO, 2 hr (tablet) or 1 hr (soluble film)
Distribution
Protein bound: 70-76%
Vd: Children, 1.7-3.7 L/kg; adults, 2.2-2.5 L/kg
Metabolism
Extensive hepatic metabolism, with hydroxylation followed by glucuronide (indole ring) or sulfate conjugation; metabolized by CYP2D6 and partly by CYP1A2 and CYP3A4
Metabolites: Glucuronide conjugate, sulfate conjugate (inactive)
Elimination
Half-life: 2-7 hr (children <15 years); 3-7 hr (adults); patients with mild to moderate hepatic impairment, 12 hr; patients with severe hepatic impairment (Child-Pugh class C), 20 hr
Renal Clearance: 0.26-0.38 L/hr/kg
Total body clearance: 600-700 mL/min
Excretion: Primarily urine (30-70%); feces (25%)
Administration
IV Incompatibilities
Syringe: DroperidoL
Y-site: Acyclovir, allopurinol, aminophylline, amphotericin B, amphotericin B cholesteryl sulfate, ampicillin, ampicillin/sulbactam, amsacrine, cefepime, cefoperazone, 5-fluorouracil (5-FU; at 1 mg/mL ondansetron and 16 mg/mL 5-FU; may be compatible at 0.8 mg/mL 5-FU and up to 160 mcg/mL ondansetron), furosemide, ganciclovir, lorazepam, meropenem (at 50 mg/mL meropenem and 1 mg/mL ondansetron; may be compatible at 1 mg/mL each), methylprednisolone, piperacillin, sargramostim, sodium bicarbonate
IV Compatibilities
Solution: Compatible with most common solvents
Additive (partial list): Cisplatin, cyclophosphamide, cytarabine, decarbazine, dacarbazine with doxorubicin(?), doxorubicin, etoposide, hydromorphone, meropenem (incompatible at 20 g/L meropenem), methotrexate, morphine sulfate
Syringe: Alfentanil, atropine, dexamethasone (incompatible at 0.67 mg/mL dexamethasone and 1.07 mg/mL ondansetron), fentanyl, glycopyrrolate, meperidine, metoclopramide, midazolam, morphine sulfate, naloxone, neostigmine, propofoL
Y-site (partial list): Alatrofloxacin, aldesleukin, azithromycin, bleomycin, carboplatin, cisplatin, cladribine, clindamycin, cyclophosphamide, cytarabine, dactinomycin, dopamine, heparin, hydromorphone, magnesium sulfate, meperidine, morphine sulfate, paclitaxel, potassium chloride, topotecan, vancomycin, vinblastine, vincristine, zidovudine
IV Preparation
No dilution necessary for premixed injection
Postoperative nausea and vomiting: No dilution necessary for 2 mg/mL vials
Chemotherapy-induced nausea and vomiting: Dilute IV injection (2 mg/mL vials, not premixed injection) in 50 mL D5W or Ns
IV Administration
Infuse over 15 minutes after further dilution with 50 mL NS/D5W
Inject undiluted over at least 30 seconds, preferably over 2-5 minutes
IM Administration
No dilution necessary for premixed injection
Storage
Store at room temperature or refrigerate
Protect from light, excessive heat, and freezing
