Ondansetron

Question 1

Ondansetron

Class

Answer 1

Antiemetic

Selective 5-HT3 Receptor Antagonist

Question 2

Ondansetron

Dose

Adults

Answer 2

Usual dose:
IV: 4 mg as a single dose at the end of surgery (Gan 2014)

OR

Alternative strategy: Oral (oral disintegrating tablet or oral soluble film): 8 mg as a single dose given 30 to 60 minutes prior to surgery (Gan 2014; Grover 2009; Kenny 1992)

Question 3

For rescue therapy, when should you use Ondansetron again if given for prophylaxis?

Answer 3

> 6 hours since initial dose for most 5-HT3 receptor antagonists

(Feinleib 2018; Gan 2014).

Question 4

Ondansetron

Renal Impairment: Adult

Dosing Adjustments or Clinical indications?

Answer 4

IV: No dosage adjustment is necessary.

Oral: No dosage adjustment is necessary; however, according to the manufacturer, there is no experience for oral ondansetron in renal impairment beyond first-day administration (has not been studied beyond day 1).

Question 5

Ondansetron

Hepatic Impairment: Adult

Dosing Adjustments or Clinical indications?

Answer 5

1. Mild to moderate impairment: No dosage adjustment necessary.
2. Severe impairment (Child-Pugh class C):

IV: Day 1: Maximum daily dose: 8 mg; however, according to the manufacturer, there is no experience beyond first-day administration (has not been studied beyond day 1)

Oral: Maximum daily dose: 8 mg

Question 6

Ondansetron

Dose

infants and children

Answer 6

≤40 kg: 0.1 mg/kg/dose as a single dose; maximum dose: 4 mg/dose

> 40 kg: 4 mg/dose as a single dose

Question 7

Ondansetron

Dose

Adolescents

Answer 7

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

Question 8

When should zofran be administered in peds during surgery?

Answer 8

Administer immediately before or following induction of anesthesia, or postoperatively if the patient is symptomatic.

Question 9

How effective is repeat dosing of Zofran if N/V uncontrolled?

Answer 9

Repeat doses given in response to inadequate control of nausea/vomiting from preoperative doses are generally ineffective.

Question 10

1 CNS Side Effect of Zofran

> 10%

Answer 10

Central nervous system:

1. Headache (oral: 9% to 27%; IV: 17%)
2. Fatigue (oral: ≤9% to 13%)
3. Malaise (oral: ≤9% to 13%)

Question 11

1 GI Side Effect of Zofran

> 10%

Answer 11

Gastrointestinal: Constipation (6% to 11%)

Question 12

Common CNS Side Effect of Zofran

1-10%

Answer 12

Drowsiness (IV: ≤8%)

Sedation (IV: ≤8%)

Dizziness (7%)

Agitation (oral: ≤6%)

Anxiety (oral: ≤6%)

Paresthesia (IV: 2%)

Sensation of cold (IV: 2%)

Question 13

Common Dermatological Side Effect of Zofran

1-10%

Answer 13

1. Pruritus (2% to 5%)

2. Skin rash (1%)

Question 14

Common GI Side Effect of Zofran

1-10%

Answer 14

Gastrointestinal:

Diarrhea (oral: 6% to 7%; IV: Children 1 to 24 months of age: 2%)

Question 15

Common Genitourinary Side Effect of Zofran

1-10%

Answer 15

Genitourinary:

Gynecologic disease (oral: 7%)

Urinary retention (oral: 5%)

Question 16

Common Hepatic Side Effect of Zofran

1-10%

Answer 16

1. Increased serum ALT (>2 times ULN: 1% to 5%; transient)

2. Increased serum AST (>2 times ULN: 1% to 5%; transient)

Question 17

Zofran

Pregnancy Class

Answer 17

B

No evidence of risk in studies
Either animal reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester and there is no evidence of a risk in later trimesters.

Question 18

Zofran

Mechanism of Action

Answer 18

Ondansetron is a selective 5-HT3-receptor antagonist which blocks serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone

Question 19

Zofran

Onset of Action

Answer 19

~30 minutes

Question 20

Zofran
Adults
Volume of Distribution

Answer 20

Adults: 1.9 L/kg

Question 21

Zofran

Volume of Distribution
1 to 4 months:

5 to 24 months:

3 to 12 years:

Answer 21

1 to 4 months: 3.5 L/kg

5 to 24 months: 2.3 L/kg

3 to 12 years: 1.65 L/kg

Question 22

Zofran

Protein Binding

Answer 22

Protein binding, plasma: 70% to 76%

Question 23

Zofran

Metabolism

Answer 23

Extensively hepatic via hydroxylation, followed by glucuronide or sulfate conjugation;

CYP1A2
CYP2D6
CYP3A4 substrate

Some demethylation occurs