Ondansetron vs. Metoclopramide in Hyperemesis

I hate to say it, but this is one of the first randomized trials I’ve stumbled across from Obstetrics and Gynecology – so, even though it’s not terribly profound, I felt compelled to cover it.

This is a double-blind, randomized trial of women admitted to observation with hyperemesis gravidarum.  They received either 4mg of ondansetron or 10mg of metoclopramide every 8 hours for 24 hours, and patient were tracked for vomiting episodes and self-reported nausea.  With regard to these co-primary outcomes, there was no difference between study drugs – most had full resolution, and most in each group had 2 episodes of vomiting or fewer.  However, secondary outcomes and adverse effects – drowsiness, xerostomia, and persistent ketonuria – favored ondansetron.

The authors therefore conclude ondansetron ought probably be favored – all else being equal.  But, for these authors, all else is not equal – ondansetron is markedly more expensive.  Therefore, the ultimate conclusion of these authors is rather in favor of metoclopramide, considering their similar efficacy.

Of other interesting note, one patient, despite admission and supportive care, had 23 episodes of vomiting during the study period.  Oy.

“Ondansetron Compared With Metoclopramide for Hyperemesis Gravidarum
A Randomized Controlled Trial”
http://www.ncbi.nlm.nih.gov/pubmed/24807340

4 thoughts on “Ondansetron vs. Metoclopramide in Hyperemesis”

  1. It is important to note that in this study, only 12 mg of ondansetron (Zofran) was given which is a very small dose. Zofran works best if given on a strict schedule and in doses of at least 16 mg, but up to 32 mg. Given this study did not administer Zofran this way, it's results are far from conclusive. Most women cannot live in a drug-induced, half comatose state for months as they might with metoclopramide. In the case of mothers, many have small children at home and their ability to ambulate safely is of concern. Kimber MacGibbon, RN (www.HelpHER.org)

  2. 12 mg isn't a very small dose IMHO.
    32 mg is a lot and according to one source isn't recommended anymore
    because of increased QT prolongation.
    http://reference.medscape.com/drug/zofran-zuplenz-ondansetron-342052

    Do we have safety studies for long term use of ondansetron at a high dosage ?
    As the label is for Chemotherapy or post surgery nausea and vomiting , I doubt there is .

    I have seen widely widened QT after 4 mg IV , if the clinical significance is questionable, t'is a bit scary.

    But patients vomiting for days such as in HG have another risk factor which is … vomiting induced alcalosis and transfer hypokalaemia, and possibly hypomagnesemia .

    QT prolongation is dose dependant.
    Other side effects aren't nihil.
    http://reference.medscape.com/drug/zofran-zuplenz-ondansetron-342052#4

    In addition (I dn't know in the US and elsewhere) , but in France it s only licensed for chemotherapy induced vomiting up to 5 days only. ANd never > 16 mg IV.

    I wonder why they did not test the classic time and RCT honoured pyridoxine/doxylamine treatment.

  3. Thanks both for your comments – I tend to agree with Axel regarding the uncertain additive efficacy of higher doses of ondansetron. Routine dosing for nausea in the Emergency Department is merely 4mg IV – with 4mg and 8mg ODT available. While I've absolutely seen 16mg and 32mg used, and used safely, I'm not familiar with the evidence supporting such doses.

    Re: the doxylamine/B6 combination, it's uncertain what adjunctive therapy was used. At the point of hospitalization, however, oral medications are likely not as valuable.

  4. 16 – 32mg doses of ondansetron seem very large. In surgical (theatres and PACU) we only give up to 8mg usually, after that it is metoclopramide, cyclizine, droperidol, dexamethasone and maybe a scopolamine patch.

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