Antiemetics and QTc Prolongation

Prolonged QT interval reflects prolonged myocyte repolarization due to ion channel malfunction and gives rise to early

after-depolarizations.1

Prolonged QTc is defined as > 470 msec in males and > 480 msec in females.1

The danger of a prolonged QTc interval is a life-threatening polymorphic ventricular rhythm known as Torsades de Pointes

(TdP), the risk of TdP is 2-3 times higher when QTc is > 500 msec.1

Multiple factors can contribute to QTc prolongation including advancing age, bradyarrhythmias, underlying cardiac

disease, electrolyte abnormalities (e.g. hypokalemia, hypomagnesaemia, hypocalcemia), and medications (e.g.

antiarrhythmics, antidepressants, antimicrobials, antipsychotics, and many others).1-2

Medication induced QT prolongation is dose and route related, with higher doses and IV administration being associated

with more QT prolongation

Medication

Ondansetron

(Zofran)

Promethazine

(Phenergan)

Metoclopramide

(Reglan)

Prochlorperazine

(Compazine)

Dose

4 mg

5 to 10 mg

5 to 10 mg

Route of

Administration

PO (ODT + Tab), IV, IM

PO, IV, IM, Rectal

PO, IV, IM

PO, IV, IM, Rectal

PK/PD

Onset: ~30 min

Half-life: 3-6 hours

Metabolism: Extensive

hepatic,

CYP1A2/2D6/3A4

Excretion: Urine (44-

60%), feces (~25%)

Onset: PO/IM ~20 min,

IV ~5 min

Duration: 4-6 hours

Metabolism: Hepatic,

CYP2D6/2B6

Excretion: Urine & feces

as inactive metabolites

Onset: PO 30-60 min, IV 1-3

min, IM 10-15 min

Duration: 1-2 hours

Metabolism: Hepatic,

CYP2D6

Excretion: Urine (~85%),

feces

Author,

year

Design/ sample

size

Intervention & Comparison

Outcome

Li,

2018

Prospective,

observational

study

(n=20)

IV ondansetron 4 mg

A single administration of ondansetron was associated with a mean QTc

increase of 16.2 msec (p=0.01)

Zero related cardiac events reported

Moffett,

2016

Prospective,

observational

study

(n=22)

IV ondansetron 4 mg

A single administration of ondansetron was associated with a mean QTc

increase of 20 msec

Zero related cardiac events reported

Owczuk,

2009

Prospective,

double-blind,

randomized study

(n=40)

IV promethazine 25 mg

IV midazolam 2.5 mg

Promethazine had a statically significant increase in QTc interval

compared to midazolam at 5,10,15,& 20 min (p<0.001)

Significantly higher number of patients with a QTc > 450 in the

promethazine group compared to the midazolam group (11 vs 7; p=0.007)

No cardiac events were reported

Kai Li, Kathy, et al. J of Health-System Pharm. 2018;

75(5):276-282.

Moffett P, et al. Acad Emerg Med. 2016; 23(1):102-5.

Owczuk R, , et al. Anaesthesia. 2009; 64(6):609-614.

Charbit B, et al. Anesthesiology. 2008; 109:206-12.

Drew BJ, et al. Circulation. 2010 Mar 2;121(8):1047-60

Viskin S et al. Lancet. 1999;354:1625-33.

Chan A et al. An International J of Med. 2007. 100(10)609-

Drew BJ, et al. Circulation. 2010; 121:1047.

Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc.

Riverwoods, IL. Available

at: http://online.lexi.com. Accessed May 22, 2019.

Kai Li, Kathy, et al. J of Health-System Pharm. 2018;

75(5):276-282.

Moffett P, et al. Acad Emerg Med. 2016; 23(1):102-5.

Owczuk R, , et al. Anaesthesia. 2009; 64(6):609-614.

Charbit B, et al. Anesthesiology. 2008; 109:206-12.