Drug products: Ondansetron 2care4, Ondansetron Accord, Ondansetron Alternova, Ondansetron Aristo, Ondansetron Aurobindo, Ondansetron B. Braun, Ondansetron Bluefish, Ondansetron Copyfarm, Ondansetron Ebb, Ondansetron Fresenius Kabi, Ondansetron Hameln, Ondansetron Hexal, Ondansetron Mylan, Ondansetron Nycomed, Ondansetron Orifarm, Ondansetron Sandoz, Ondansetron STADA, Ondansetron Teva, Ondansetron Vian, Setofilm, Zofran, Zofran munlöslig, Zofran®, Zofran® munlöslig, Zofron munlöslig, Zotrix
ATC code: A04AA01
Substances: ondansetron, ondansetron hydrochloride, ondansetron hydrochloride dihydrate
Women have a slower excretion and higher bio availability and AUC after single dose ondansetrone. Women have more nausea and vomiting after surgery and chemo therapy compared to men. As with many other antiemetic drugs men have usually better effect of ondansetrone treatment.
Ondansetrone, particularly when administered IV in high doses is associated with QT prolongation on ECG and thus a risk of developing the serious arrhythmia “Torsade de Pointes” ventricular tachycardia. No difference in risk has been shown regarding ondansetrone but one risk factor of Torsade de Pointes is female sex.
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.
In a pharmacokinetic study of healthy volunteers with normal body weight (17 men, 17 women) divided in three age groups; 21-38 years; 61-74 years; and 75-82 years of age, AUC and Cmax values were higher in women than in men after a single oral dose of ondansetron. In women, clearance was found to be lower, oral bioavailability higher due to reduced first-pass uptake of parent drug, and apparent volume of distribution smaller than in men . A cross over study between oral and rectal ondansetron (8 men, 8 women) found similar results with higher AUC and lower clearance in women for both administration forms . Despite the pharmacokinetic differences of ondansetron, the clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested by the manufacturer .
In an open prospective multicenter study of the effect on ondansetron on cisplatin-induced emesis and nausea (16 men, 76 women), 50% of the women had delayed emesis compared to 19% of the men. Treatment failure on worst day was 30% in women and 0% in men . Similar results were found in another randomized study comparing the antiemetic effect after cisplatine induced nausea of ondansetron with metoclopramide+lorazepam (53 men, 68 women). Treatment success was found in 95% of men and 65% of women . In a cross-over study of chemotherapy induced emesis (270 men, 130 women), women had less chance of complete recovery from emesis .
Several studies have shown ondansetron to prolong the electric repolarization (QT-interval) in the heart, increasing the risk of ventrical arrhythmias [7-9]. In an observational study (17 men, 25 women) on QT-prolongation after ondansetron treatment of post-operative nausea, 9 men and 9 women had ondansetron-induced prolonged QTc-interval . With a few exceptions all ondansetron induced Torsades de pointes have been associated with IV-administration of high doses [8-9]. A warning for 32 mg ondansetron IV has been issued by the FDA . Among the known risk factors of drug induced ventrical arrhythmias are female sex, hypokalemia, bradycardia, and base line QT-prolongation .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2015-01-13
Reviewed by: Karin Schenck-Gustafsson
Approved by: Karin Schenck-Gustafsson