Ondansetron (Zofron, Zofran, Onset) is used in the treatment and prevention of nausea and vomiting especially in cancer patients receiving emetogenic chemotherapy.

Ondansetron (Zofran) Uses:

• Cancer chemotherapy-induced nausea and vomiting:

  • IV:

    • Associated with initial, prevention of nausea and vomiting and repeat courses of emetogenic cancer chemotherapy (including high-dose cisplatin).

  • P/O:

    • Associated with highly emetogenic cancer chemotherapy, prevention of nausea and vomiting (including cisplatin ≥50 mg/m²).
    • Associated with initial, prevention of nausea and vomiting and repeat courses of moderately emetogenic cancer chemotherapy.

  • Postoperative nausea and/or vomiting:

    • P/O:
      • Prevention of postoperative nausea & vomiting (PONV).
      • If nausea/vomiting occurs in a patient who had not received prophylactic ondansetron, then to prevent further episodes, IV ondansetron may be administered.
  • Limitations of use:
    • In patients with minimal expectation of nausea & vomiting, routine prophylaxis for PONV is not recommended, although use is recommended in patients when nausea and vomiting must be avoided in the postoperative period, even if the incidence of PONV is low.

  • Radiotherapy-associated nausea and vomiting:

    • P/O:
      • Prevention of nausea and vomiting associated with radiotherapy, in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.

• Off Label Use of Ondansetron in Adults:

  • Carcinoid syndrome-associated diarrhea, severe, refractory
  • Symptomatic treatment of nausea and vomiting, Gastroparesis (alternative agent in patients with persistent symptoms refractory to prokinetic therapy)
  • Acute, severe nausea & vomiting,
  • Postoperative nausea & vomiting, treatment or rescue therapy
  • Pregnancy-associated nausea & vomiting, severe or refractory
  • Vertigo-associated nausea and vomiting

Ondansetron (Zofron) Dose in Adults

Note:

• Due to the potential for QT prolongation, single IV doses >16 mg are no longer recommended.

Ondansetron (Zofron) Dose in the treatment of severe, refractory carcinoid syndrome-associated diarrhea (alternative agent) (off-label):

• P/O:
  • 8 mg 3 times a day followed by a maintenance dose of 4 to 8 mg/day for 4 to 12 weeks
  • Or 8 mg twice daily for 3 days.
• IV:
  • 4 to 8 mg every 8 hours.

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Ondansetron (Zofron) Dose in the prevention of Chemotherapy-induced nausea and vomiting: Single-day IV chemotherapy regimens:

• Highly emetogenic chemotherapy (>90% risk of emesis [eg, cisplatin, breast cancer regimens that include an anthracycline combined with cyclophosphamide]).

  • Day of chemotherapy:

    • Administer prior to chemotherapy and in combination with a neurokinin 1 (NK ) receptor antagonist, dexamethasone, with or without olanzapine.
      • IV:
        • 8 mg or 0.15 mg/kg (max: 16 mg/dose) as a single dose (manufacturer's labeling)
      • P/O:
        • All oral formulations except for the oral soluble film:
        • 8 mg twice daily for 2 doses with the first dose administered prior to administration of chemotherapy.
        • Manufacturer’s labeling:
          • Dosing in the prescribing information may not reflect current clinical practice:
            • 24 mg as a single dose
        • Oral soluble film:
          • 24 mg (three 8 mg doses given together) as a single dose

  • Post-chemotherapy days:

    • 5-HT-3 receptor antagonist use is not recommended (alternative agents are recommended).

Moderately emetogenic chemotherapy (30% to 90% risk of emesis):

• Carboplatinbased regimens:

  • Day of chemotherapy:
    • Administer prior to chemotherapy and in combination with an NK receptor antagonist and dexamethasone
    • IV:
      • 8 mg or 0.15 mg/kg (max: 16 mg/dose) as a single dose (manufacturer's labeling)
    • P/O:
      • 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy (manufacturer's labeling)
  • Post-chemotherapy days:
    • Antiemetic use is not necessary (ASCO [Hesketh 2017]; MASCC/ESMO [Roila 2016]).

Moderately emetogenic chemotherapy (30% to 90% risk of emesis):

• Non-carboplatinbased regimens (alternative agent).

Note:

• In this setting, ASCO guidelines & MASCC/ESMO guidelines do not state a preference for which 5-HT-3 receptor antagonists should be used.
• However, it is recommended by some experts palonosetron as the preferred 5-HT receptor antagonist.
• Day of chemotherapy:
  • Administer prior to chemotherapy and in combination with dexamethasone.
    • IV:
      • 8 mg or 0.15 mg/kg (max: 16 mg/dose) as a single dose (manufacturer's labeling)
    • P/O:
      • 8 mg twice daily for 2 doses with the first dose administered prior to chemotherapy (manufacturer’s labeling)
• Post-chemotherapy days:
  • 5-HT-3 receptor antagonist use is not recommended (alternative agents, depending on the chemotherapy regimen administered, may be recommended).
  • However, if a first-generation 5-HT-3 receptor antagonist (eg, ondansetron, granisetron) was used on day 1 of chemotherapy rather than palonosetron, some experts suggest the first-generation 5HT-3 receptor antagonist be continued for post-chemotherapy emetic prophylaxis on days 2 and 3.

Low emetogenic risk (10% to 30% risk of emesis):

Note:

• For prophylaxis, single-agent ondansetron is one of many options.
• Day of chemotherapy:
  • Administer as a single dose prior to chemotherapy.
  • IV:
    • 8 mg or 0.15 mg/kg (max: 16 mg/dose).
  • P/O (off-label):
    • 8 mg.

• Post-chemotherapy days:
  • Prophylaxis is not necessary on subsequent days.

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Ondansetron (Zofron) Dose in the prevention of Chemotherapy-induced nausea & vomiting:

• Oral chemotherapy agents: Limited data.

  • High/moderate emetogenic risk oral agent:

    • P/O:
      • 8-16 mg/day administered before chemotherapy continued daily.

  • Low/minimal emetogenic risk oral agent:

    • P/O:
      • 8-16 mg/day on an as-needed basis.

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Ondansetron (Zofron) Dose in the symptomatic treatment of nausea and vomiting due to Gastroparesis (alternative agent) (off label):

Note:

• For patients with persistent symptoms refractory to prokinetic therapy.
• No data are available.
• Recommendations for use & dose are based on expert opinion.
• P/O:
  • 4-8 mg 3 times daily.

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Ondansetron (Zofron) Dose in the treatment of acute, severe nausea and/or vomiting (off-label):

Note:

• Use has primarily been evaluated in patients presenting to the emergency department with undifferentiated nausea/vomiting.
• However, due to viral gastroenteritis, clinical experience also suggests utility in nausea/vomiting, acute mountain sickness & a variety of other medical conditions associated with severe, self-limiting acute nausea/vomiting (.
• Oral, IV, IM:
  • 4 mg as a single dose.

Note:

• IV administration is preferred over IM when possible, for parenteral therapy. (Salvucci 2011).

Ondansetron (Zofron) Dose in the prevention of postoperative nausea and vomiting (PONV):

• Moderate- to high-risk patients:

Note:

• May combine ondansetron with other prophylactic interventions in patients at moderate risk (eg, another antiemetic agent from a different pharmacologic class, modification of anesthetic technique, and acupuncture).
• Combine 3 or more interventions in patients at high risk.
• Usual dose:
  • IV:
    • 4 mg as a single dose at the end of surgery.
• Alternative strategy:
  • P/O (oral disintegrating tablet or oral soluble film):
    •  8 mg as a single dose given 30-60 mins prior to surgery

• Low-risk patients:

  • Although in low-risk patients, prophylaxis is not always indicated, consensus guidelines acknowledge that some experts may administer an antiemetic in these patients.
  • However, clinicians are also advised that this strategy comes with the potentially unnecessary risk of rare adverse effects.
  • The dosing is the same as for moderate- to high-risk patients if ondansetron is given.

• Post-discharge management in high-risk patients:

  • Dosage regimen studied in a single clinical trial:
    • P/O (oral disintegrating tablet or oral soluble film):
      • 8 mg to be taken on discharge & in the morning of postoperative days 1 & 2

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Ondansetron (Zofron) Dose in the treatment of Postoperative nausea and vomiting (PONV), treatment or rescue therapy (off-label):

• IV:
  • 4 mg as a single dose (treatment) when a prophylactic agent was not utilized, or following failure of an agent utilized as prophylaxis (rescue therapy).

Note:

• Unless a potentially inadequate dose was initially administered or the effect of the first drug has worn off, rescue therapy should always include an antiemetic from a different class than the one used for prophylaxis (>6 hours since initial dose for most 5-HT-3 receptor antagonists).
• However, some experts do not recommend repeat administration of a 5-HT-3 antagonist unless triple therapy has been used for prophylaxis and no alternatives are available for a rescue that was not used for prophylaxis.

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Ondansetron (Zofron) Dose in the treatment of severe, refractory pregnancy-associated nausea and vomiting (off-label):

Note:

• Following initial pharmacologic therapy, may be considered for adjunctive treatment of nausea and vomiting when symptoms persist.

• Patients without hypovolemia:

  • P/O, IV (bolus):
    • 4 mg every 8 hours, added to the current treatment regimen, as needed.
    • Some experts increase to a maximum of 8 mg/dose if necessary

• Patients with hypovolemia:

Note

• For patients with persistent symptoms despite intravenous fluid replacement:
  • IV:
    • 8 mg administered over 15 mins every 12 hours, added to the current treatment regimen.
    • Some experts use 4-8 mg administered as an IV bolus every 8 hours until stabilization.

Ondansetron (Zofron) Dose in the prevention of radiation therapy-associated nausea and vomiting:

• High-emetogenic risk radiation therapy (total body irradiation):

  • Radiation day(s):

    • IV (off-label):
      • Prior to each fraction of radiation, 8 mg or 0.15 mg/kg (max: 16 mg/dose) once daily or twice daily.
      • Give in combination with dexamethasone.
    • P/O:
      • 8 mg once daily or twice daily administered 1-2 hours prior to each fraction of radiation.
      • Give in combination with dexamethasone (ASCO [Hesketh 2017]) or, in one clinical trial of 4 days of hypofractionated total body irradiation, 8 mg (without dexamethasone) were administered 1.5 hours prior to every fraction of radiation (3 times daily for the first 3 days and twice daily on day 4) (Spitzer 2000)

  • Post-radiation days:

    • IV (off-label), P/O:
      • The appropriate duration of therapy is not well defined following radiotherapy days.
      • It is recommended by ASCO guidelines to continue ondansetron once daily or twice daily on the day after each day of radiation (ASCO [Hesketh 2017])

• Moderate-emetogenic risk radiation therapy (upper abdomen, craniospinal irradiation [off-label use]):

  • Radiation day(s):

    • IV (off-label):
      • 8 mg or 0.15 mg/kg (max: 16 mg/dose) once daily or twice daily prior to each fraction of radiation.
      • Before the first 5 fractions, may give with or without dexamethasone.
    • P/O:
      • Administered 1 to 2 hours prior to each fraction of radiation 8 mg once daily or twice daily.
      • Before the first 5 fractions, may give with or without dexamethasone or, in clinical trials involving upper abdomen radiation (high-dose single exposure or multiple-day fractionated course), 8 mg 3 times daily (without dexamethasone) has been given.
      • Doses were administered 1 to 2 hours prior to radiation therapy.

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Ondansetron (Zofron) Dose in the treatment of Vertigo-associated nausea and vomiting (alternative agent) (off-label):

• IV (preferred), IM:
  • 4-8 mg once for acute symptoms.
• P/O:
  • 4 mg every 8-12 hours.

Ondansetron (Zofron) Dose in Childrens

Ondansetron (Zofron) Dose in the prevention of Chemotherapy-induced nausea and vomiting:

Manufacturer's labeling:

• IV:

  • Infants ≥6 months, Children, and Adolescents:

    • 0.15 mg/kg/dose;(Max Dose:16mg/dose)
    • Administer the first dose 30 minutes before the start of chemotherapy, with subsequent doses administered 4 and 8 hours after the first dose for 3 doses total

• P/O: Moderately emetogenic antineoplastic therapy:

  • Children 4-11 years:
    • 4 mg beginning 30 mins before chemotherapy
    • Repeat 4 and 8 hours after the initial dose, then 4 mg every 8 hours for 1-2 days after chemotherapy completed.
  • Children ≥12 years and Adolescents:
    • 8 mg beginning 30 mins before chemotherapy
    • Repeat dose 8 hours after initial dose, then 8 mg every 12 hours for 1 to 2 days after chemotherapy completed

Alternate dosing:

• Weight-directed dosing: Infants, Children, and Adolescents:

  • Highly emetogenic antineoplastic therapy:

    • IV, P/O:
      • 0.15 mg/kg/dose(Max Dose:16mg/dose)
        • Administer first dose before the start of chemotherapy, and then every 8 hours.
        • A once-daily single dose of 0.3 mg/kg or 0.45 mg/kg (max dose: 16 mg) dependent upon emetogenic potential of chemotherapy has also been reported (Holdsworth 2006)

• Moderately emetogenic antineoplastic therapy:

  • IV, P/O:
    • 0.15 mg/kg/dose (Max dose:8 mg/dose)
    • Administer the first dose before the start of chemotherapy with subsequent doses every 12 hours.

• Low emetogenic antineoplastic therapy:

  • IV, P/O:
    • 0.3 mg/kg/dose once(Max dose: 16 mg/dose.)
    • Administered 30 minutes before the start of chemotherapy.

• BSA-directed dosing:

  • Highly emetogenic antineoplastic therapy:

    • Infants, Children, and Adolescents:
      • IV, P/O:
        • 5 mg/m²/dose(Max dose:16 mg/dose)
        • Administer the first dose before the start of chemotherapy with subsequent doses administered every 8 hours.

• Moderately emetogenic antineoplastic therapy:

  • Infants, Children, and Adolescents:
    • IV, P/O:
      • 5 mg/m²/dose (Max dose: 8 mg/dose).
      • Administer first before the start of chemotherapy with subsequent doses every 12 hours.

• Low emetogenic antineoplastic therapy:

  • Infants, Children, and Adolescents:
    • IV, P/O:
      • 10 mg/m²/dose once (Max dose:16 mg/dose).
      • Administered before the start of chemotherapy.

Ondansetron (Zofron) dose in the treatment of acute attack of cyclic vomiting syndrome:

• Children >2 years and Adolescents:

  • Low dose:
    • IV:
      • 0.15 mg/kg every 4 hours as needed for up to 3 doses (Max dose:16 mg/dose)

• High dose:
  • IV:
    • 0.3 to 0.4 mg/kg/dose every 4-6 hours (Max dose:16 mg/dose).
    • Should not exceed 3 doses in a 24-hour period as per manufacturer labeling.

Ondansetron (Zofron) Dose in the treatment of Acute Gastroenteritis:

Note:

•  In most cases of acute gastroenteritis, routine use of ondansetron is not recommended.

• Infants and Children ≥1 month:

  • IV:
    • 15 or 0.3 mg/kg/dose once (Max dose:16 mg/dose)

• Infants and Children 6 months to 10 years, ≥8 kg:

  • P/O:
    • 8-15 kg:
      • 2 mg/dose once
  • P/O:
    • >15 to 30 kg:
      • 4 mg/dose once
  • P/O:
    • >30 kg:
      • 8 mg/dose once

Ondansetron (Zofron) Dose in the prevention of Postoperative nausea and vomiting:

• If the patient is symptomatic, administer immediately before or following induction of anesthesia, or postoperatively.
• Repeat doses given in response to inadequate control of nausea/vomiting from preoperative doses are generally ineffective.

• Infants and Children:

  • IV:

    • ≤40 kg:
      • 0.1 mg/kg/dose as a single dose (Max dose:4 mg/dose).
    • >40 kg:
      • 4 mg/dose as a single dose

• Adolescents:

  • IM, IV:
    • 4 mg/dose as a single dose

Ondansetron (Zofron) Dose in the prevention of Radiation-induced nausea and vomiting: Oral:

• Weight-directed dosing:

  • Infants ≥5 months, Children, and Adolescents:

    • 2 mg/kg/dose (maximum dose: 8 mg/dose) administered every 8 hours throughout total body irradiation (TBI) prior to HSCT.
    • In clinical trials, the doses were generally rounded to 4 mg/dose in children 4 to 11 years and 8 mg/dose in children ≥12 years and adolescents.

• Alternate weight-based dosing:

  • Children and Adolescents:

    • 15 mg/kg/dose administered 3 to 4 times daily throughout TBI.

• Fixed-dose:

Note:

• Derived from rounding weight-based (0.2 mg/kg/dose) doses.
  • Children 4-11 years:
    • 4 mg every 8 hours throughout total body irradiation (TBI) prior to HSCT
  • Children ≥12 years and Adolescents:
    • 8 mg every 8 hours throughout total body irradiation(TBI) prior to HSCT

• Alternate fixed-dosing:

  • Children ≥9 years and Adolescents:
    • 8 mg every 12 hours on days of TBI prior to bone marrow transplantation.
  • Note:
    • Administered in combination with dexamethasone.

Pregnancy Risk Factor B

• Negative events were not seen in animal reproduction studies.
• Ondansetron crosses the human placenta easily in the first trimester and is detected in fetal tissue.
• Due to pregnancy-induced physiological changes, the clearance of ondansetron could increase.
• Ondansetron has been approved for treatment of nausea and vomiting during pregnancy.
• However, the current guidelines state that data regarding fetal safety are inconsistent. Ondansetron should only be used when other agents fail.
• ECG monitoring is recommended for patients with electrolyte anomalies. Dose-dependent QT-interval prolongation can occur with use, which may be associated with NVP.
• A consensus panel of experts recommends that pregnant patients receiving chemotherapy to treat gynecologic tumors should not receive 5-HT antagonists (including Ondansetron), if chemotherapy is administered according to the general guidelines for chemotherapy use during pregnancy.

Ondansetron use during breastfeeding:

• It is unknown if ondansetron can be found in breast milk.
• According to the manufacturer, when deciding whether to continue or stop breastfeeding during therapy, it is important to consider the risks to infants, the benefits to the mother and the benefits to the mother.

Ondansetron (Zofron) Dose in Kidney Disease:

• IV:
  • No dosage adjustment is necessary.
• P/O:
  • No dosage adjustment is necessary.
  • However, according to the manufacturer, there is no experience for oral ondansetron in renal impairment beyond the first-day of administration (has not been studied beyond day 1).

Ondansetron (Zofron) Dose in Liver Disease:

• Mild to moderate impairment:

  • No dosage adjustment is necessary.

• Severe impairment (Child-Pugh class C):

  • IV:
    • Day 1: Max daily dose:
      • • 8 mg.
        • However, according to the manufacturer, there is no experience beyond first-day of administration (has not been studied beyond day 1)
  • P/O:
    • Max daily dose:
      • 8 mg

Note: Percentages reported in adult patients unless otherwise specified.

Common Side Effects of Ondansetron (Zofron):

• Central nervous system:

  • Headache
  • Fatigue
  • Malaise

• Gastrointestinal:

  • Constipation

Less Common Side Effects of Ondansetron (Zofron):

• Central Nervous System:

  • Drowsiness
  • Sedation
  • (Dizziness
  • Agitation
  • Anxiety
  • Paresthesia
  • Sensation Of Cold

• Dermatologic:

  • Pruritus
  • Skin Rash

• Gastrointestinal:

  • Diarrhea

• Genitourinary:

  • Gynecologic Disease
  • Urinary Retention

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST

• Local:

  • Injection Site Reaction

• Respiratory:

  • Hypoxia

• Miscellaneous:

  • Fever

Contraindications to Ondansetron (Zofron):

• Hypersensitivity to any component of the formulation or ondansetron.
• Use apomorphine concurrently

Warnings and precautions

• Hypersensitivity

  • Reports of hypersensitivity reactions, including anaphylaxis or bronchospasm, have been made.
  • If hypersensitivity develops, discontinue use.
  • Patients who are allergic to 5-HT receptor antagonists should be cautious.
  • It has been reported that cross-reactivity is possible.

• Extension of QT

  • ECG changes have been observed with ondansetron, including a dose-dependent QT interval extension.
  • Reports also mention cases of torsades-de-pointes.
  • Most commonly, the effects of selective 5-HT antagonists, such as ondansetron and QRS duration, usually occur within 1-2 hours following IV administration.
  • Single doses of more than 16 mg ondansetron IV should be avoided due to the increased risk of QT prolongation.
  • These changes aren't clinically significant in most patients.
  • Arrhythmia can occur when arrhythmia is combined with agents that prolong these intervals, or are at risk of QT prolongation.
  • Patients with heart disease or patients who have a prolongation of the QT interval that is clinically relevant may experience torsades d'pointes.
  • Numerous trials have demonstrated that 5-HT antagonists can prolong the QT interval to variable degrees.
  • Patients with congenital long QT syndrome should not take ondansetron.
  • Patients with QT prolongation risk factors (eg, medication known to prolong QT interval, electrolyte anomalies [hypokalemia and hypomagnesemia], heart disease, bradyarrhythmias, cumulative high-dose Anthracycline treatment) should be monitored carefully.
  • A reduction in heart rate can also be possible with 5-HT-3 antagonists
  • IV formulations of 5-HT-3 inhibitors are more associated with ECG interval changes than oral formulations.

• Serotonin syndrome:

  • Predominantly when used in combination with other serotonergic agents, serotonin syndrome has been reported with 5-HT receptor antagonists (eg, SSRIs, SNRIs, MAOIs, mirtazapine, fentanyl, lithium, tramadol, and/or methylene blue).
  • Some cases were fatal.
  • The majority of serotonin-related reports were made in a postanesthesia or infusion center setting due to 5-HT-3 receptor antagonists.
  • Serotonin syndrome was also reported after an overdose on Dansetron.
  • Serotonin syndrome symptoms should be monitored by your patients, including:
    • Mental status changes (eg: agitation, hallucinations and delirium, coma).
    • Autonomic instability (eg tachycardia and labile blood pressure; diaphoresis; dizziness; flushing; hyperthermia)
    • Neuromuscular changes (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination).
    • Gastrointestinal symptoms include nausea, vomiting, diarrhea, and/or
    • seizures.
  • If serotonin syndrome is present, discontinue 5-HT-3 antagonist treatment and start supportive management.

• Hepatic impairment

  • Patients with severe hepatic impairment should be advised to limit their dose (Child-Pugh Class C).
  • You should be cautious if you have mild-moderate liver impairment.
  • Clearance is reduced and half-life is increased in hepatic impairment.

Ondansetron: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Haloperidol	Ondansetron may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
MetFORMIN	Ondansetron may increase the serum concentration of MetFORMIN.
Panobinostat	Ondansetron may enhance the arrhythmogenic effect of Panobinostat.
Pentamidine (Systemic)	May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
QT-prolonging Antidepressants (Moderate Risk)	Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Antipsychotics (Moderate Risk)	Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Pimozide.
QT-prolonging Class IC Antiarrhythmics (Moderate Risk)	May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Kinase Inhibitors (Moderate Risk)	Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Miscellaneous Agents (Moderate Risk)	May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone.
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)	Ondansetron may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Quinolone Antibiotics (Moderate Risk)	Ondansetron may enhance the QTcprolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Serotonin Modulators	Antiemetics (5HT3 Antagonists) may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Tapentadol	Antiemetics (5HT3 Antagonists) may diminish the analgesic effect of Tapentadol.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
TraMADol	Antiemetics (5HT3 Antagonists) may diminish the analgesic effect of TraMADol.
Risk Factor D (Consider therapy modification)
Amiodarone	May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Domperidone	May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
QT-prolonging Agents (Highest Risk)	May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Ajmaline; Amiodarone; Disopyramide; Dofetilide; Dronedarone; Ibutilide; Procainamide; QuiNIDine; Sotalol; Vernakalant.
QT-prolonging Class IA Antiarrhythmics (Highest Risk)	May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Class III Antiarrhythmics (Highest Risk)	May enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Risk Factor X (Avoid combination)
Apomorphine	Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine.
Pimozide	May enhance the QTc-prolonging effect of Ondansetron.

Monitoring Parameters:

• ECG (if applicable in high-risk or elderly patients).
• potassium, magnesium.
• Monitor for signs of serotonin syndrome.
• Monitor for decreased bowel activity.

How to administer Ondansetron (Zofron)?

• P/O:

  • Oral dosage forms should be administered 30 minutes prior to chemotherapy,
  • 1-2 hours before radiation.
  • 30-60 minutes prior to surgery or induction of anesthesia
• Orally disintegrating tablets:
  • Do not remove from the blister until needed.
  • Peel backing off the blister, do not attempt to push the tablet through the foil.
  • Using dry hands place tablet on tongue and allow to dissolve.
  • Swallow with saliva (no need to administer with liquids).
• Oral soluble film:
  • Do not remove from the pouch until immediately before use.
  • Using dry hands, place the film on top of the tongue, and allow to dissolve (4 to 20 seconds).
  • Swallow with or without liquid.
  • If using more than one film, each film should be allowed to dissolve completely before administering the next film.

• IM:

  • Should be administered undiluted.

• IV:

  • IVPB:
    • Infuse diluted solution over 15 mins
  • Chemotherapy-induced nausea and vomiting:
    • Give first dose 30 mins prior to beginning chemotherapy.
  • IV push: Prevention of postoperative nausea and vomiting:
    • Single doses may be administered IV injection as an undiluted solution over at least 30 seconds but preferably over 2-5 mins

Mechanism of action of Ondansetron (Zofron):

• Ondansetron, a 5-HT-receptor antagonist selectively blocks serotonin, is found both peripherally at vagal nerve terminals as well centrally in the trigger zone of the chemoreceptor.

The onset of action:

• ~30 mins

Absorption:

• P/O:
  • 100%.
  • Nonlinear absorption occurs with increasing oral doses.
  • Zofran ODT tablets are bioequivalent to Zofran tablets.
  • Absorption does not occur via oral mucosa

Plasma Protein binding:

• 70%-76%

Metabolism:

• Extensively hepatic via hydroxylation, followed by glucuronide or sulfate conjugation.
• CYP1A2, CYP2D6 & CYP3A4 substrate.
• Some demethylation occurs.

Bioavailability:

• P/O:
  • 50%-70% due to some first-pass metabolism.
  • In cancer patients (adults), 85%-87% bioavailability possibly related to changes in metabolism

Half-life elimination:

• Children:
  • Cancer patients:
    • Children & Adolescents:
      • 4-18 years:
        • 2.8 hours.
  • Surgical patients:
    • Infants 1-4 months:
      • 6.7 hours.
• Infants and Children 5 months to 12 years:
  • 2.9 hours
• Adults:
  • 3-6 hours.
• Mild-to-moderate hepatic impairment (Child-Pugh classes A and B):
  • 12 hours.
• Severe hepatic impairment (Child-Pugh class C):
  • 20 hours

Time to peak:

• P/O:
  • ~2 hours.
• Oral soluble film:
  • ~1 hour

Excretion:

• Urine (44% to 60% as metabolites, ~5% as unchanged drug).
• Feces (~25%)

Clearance:

• Cancer patients:
• Children and Adolescents 4-18 years:
  • 0.599 L/kg/hour

Surgical patients:

• Infants and Children:
  • 1-4 months:
    • 0.401 L/kg/hour.
  • 5-24 months:
    • 0.581 L/kg/hour.
  • 3-12 years:
    • 0.439 L/kg/hour
• Adult (normal):
  • 19-40 years:
    • 0.381 L/kg/hour.
  • 61 to 74 years:
    • 0.319 L/kg/hour.
  • >75 years:
    • 0.262 L/kg/hour

International Brands of Ondansetron:

• Zofran
• Zofran ODT
• Zuplenz
• ACT Ondansetron
• APO-Ondansetron
• CCP-Ondansetron
• DOM-Ondansetron
• JAMP-Ondansetron
• Mar-Ondansetron
• MINT-Ondansetron
• MYLAN-Ondansetron
• NAT-Ondansetron
• Ondansetron ODT
• Ondansetron Omega
• Ondansetron-ODAN
• Ondissolve ODF
• PHL-Ondansetron
• PMSOndansetron
• RAN-Ondansetron
• RATIO-Ondansetron
• SANDOZ Ondansetron
• SeptaOndansetron
• TEVA-Ondansetron
• VAN-Ondansetron
• VPI-Ondansetron ODT
• Zofran
• Zofran ODT
• Antivon
• Apulset
• Avessa
• Avessaron
• Cedantron
• Cetron
• Danac
• Danset
• Dantron
• Emeset
• Emeton
• Emetron
• Emiset
• Emistop
• Emizof
• Emodan
• Enset
• Finaber
• Frazon
• Glotron
• Invomit
• Izofran
• Krindor
• Lartron
• Mefoz
• Modifical
• Nalisen
• Narfoz
• Nausedron
• Ofran
• Ondak
• Ondan
• Ondant
• Ondavell
• Ondawi
• Ondran
• Onetic
• Onsat
• Onset-8
• Onsetron
• Onsett
• Onsia
• Onzet
• Onzod
• Osetron
• Periset
• Setofilm
• Setron
• Setronax
• Trondamet
• Vomceran
• Vometron
• Vomiof
• Vomiz
• Yatrox
• Zetron
• Zilfujim
• Zofran
• Zofran Melt
• Zofran ODT
• Zofran Zydis
• Zofron
• Zofsetron
• Zophren

Ondansetron Brand Names in Pakistan:

Ondansetron Injection 2 mg
Danwrd	Welwrd Pharmaceuticals

Ondansetron Injection 8 mg
O-Tron	Bio Pharma
Ondansetron	Novartis Pharma (Pak) Ltd

Ondansetron Injection 1 mg/ml
Ondanles	Neo Medix

Ondansetron Injection 2 mg/ml
Anomed	Evergreen Pharmaceuticals Pvt Limited
Nes-8	Welmark Pharmaceuticals
Ondanles	Neo Medix
Ondavell ®	Icon Pharma
Ondiemetic	Zafa Pharmaceutical Laboratories (Pvt) Ltd.
Onset	Pharmedic (Pvt) Ltd.
Osetron	Wns Field Pharmaceuticals
Zofran	Glaxosmithkline

Ondansetron suspension 4 mg/5ml
Sharon	Rasco Pharma

Ondansetron oral solution 4 mg/5ml
Ondanles	Neo Medix

Ondansetron 4 mg Tablets
Espasevit	Rotex Medica Pakistan (Pvt) Ltd
Ondanles	Neo Medix
Onden	Macter International (Pvt) Ltd.
Onden	Macter International (Pvt) Ltd.
Onderon Sr	Wilsons Pharmaceuticals
Oniron	Genome Pharmaceuticals (Pvt) Ltd
Sharon	Rasco Pharma
Zofran	Glaxosmithkline

Ondansetron 8 mg Tablets
Averon	Aries Pharmaceuticals (Pvt) Ltd
Espasevit	Rotex Medica Pakistan (Pvt) Ltd
Odanso	Mediate Pharmaceuticals (Pvt) Ltd
Ondamex	Neo Medix
Ondanles	Neo Medix
Onden	Macter International (Pvt) Ltd.
Ondigo	Goodman Laboratories
Ondison	Pulse Pharmaceuticals
Oniron	Genome Pharmaceuticals (Pvt) Ltd
Onset	Pharmedic (Pvt) Ltd.
Setron	Bio Pharma
Zofran	Glaxosmithkline

Ondansetron 8 mg Tablets
Osetron	Wns Field Pharmaceuticals