Letters 3. To measure improvement, the authors used a 100-mm visual analog scale and not one of the validated tools for measuring effectiveness in nausea and vomiting in pregnancy.3 4. The sample size of the study (18/arm) is grossly suboptimal to discern effects. It has been shown repeatedly that randomized controlled trails with small sample sizes are more sensitive to bias against the null hypothesis. 5. There are still major unresolved issues around maternal and fetal safety of ondansetron that must be acknowledged.4 Speciﬁcally, new studies show increased cardiovascular malformation risks.5
Ondansetron Compared With Doxylamine and Pyridoxine for Treatment of Nausea in Pregnancy: A Randomized Controlled Trial To the Editor: Oliveira and colleagues compared, in a double-blind, placebo-controlled trial, ondansetron with doxylamine–pyridoxine for treating symptoms of morning sickness.1 The authors should be congratulated for conducting a study in an area that sees very few studies. There are, however, major issues in the methodology of the study that diminish its clinical interpretation: 1. The authors compare ondansetron with the doxylamine–pyridoxine combination, which are the components of the only U.S. Food and Drug Administration (FDA)– approved drug for this condition. Yet, they did not use the delayedrelease form of doxylamine– pyridoxine, which is critical for its efﬁcacy, but rather an immediaterelease form.2 2. Even more serious, Oliveira et al used only 12.5 mg of doxylamine, which is half of the dose of the H1 blocker contained in the FDA-approved medication Diclegis.2 Guidelines for Letters. Letters posing a question or challenge to an article appearing in Obstetrics & Gynecology should be submitted within 8 weeks of the article’s publication online. Letters received after 8 weeks will rarely be considered. Letters should not exceed 350 words, including signatures and 5 references. A word count should be provided. The maximum number of authors permitted is four, and a corresponding author should be designated (and contact information listed). Letters will be published at the discretion of the Editor. The Editor may send the letter to the authors of the original paper so their comments may be published simultaneously. The Editor reserves the right to edit and shorten letters. A signed author agreement form is required from all authors before publication. Letters should be submitted using the Obstetrics & Gynecology online submission and review system, Editorial Manager (http://ong.edmgr.com).
Financial Disclosure: The authors have been supported by research grants from Duchesnay Inc. producer of Diclegis. Dr. Koren was the co-private investigator of the Diclegis Phase 3 trial.
Gideon Koren, MD, FRCPC Caroline Maltepe, BSc Svetlana Madjunkova, MD The Motherisk program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada
REFERENCES 1. Oliveira LG, Capp SM, You WB, Riffenburgh RH, Carstairs SD. Ondansetron compared with doxylamine and pyridoxine for treatment of nausea in pregnancy: a randomized controlled trial. Obstet Gynecol 2014;124:735–42. 2. Madjunkova S, Maltepe C, Koren G. The delayed-release combination of doxylamine and pyridoxine (DiclegisÒ/DiclectinÒ) for the treatment of nausea and vomiting of pregnancy. Paediatr Drugs 2014;16: 199–211. 3. Ebrahimi N, Maltepe C, Bournissen FG, Koren G. Nausea and vomiting of pregnancy: using the 24-hour pregnancyunique quantiﬁcation of emesis (PUQE-24) scale. J Obstet Gynaecol Can 2009;31: 803–7. 4. Koren G. Treating morning sickness in the United States-changes in prescribing are needed. Am J Obstet Gynecol 2014; 211:602–6. 5. Danielsson B, Wikner BN, Källén B. Use of ondansetron during pregnancy and
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congenital malformations in the infant. Reprod Toxicol 2014;50:134–7.
Odansetron Compared With Doxylamine and Pyridoxine for Treatment of Nausea in Pregnancy: A Randomized Controlled Trial To the Editor: It is with interest that I read the article by Oliveira et al.1 The authors compare odansetron with doxylamine plus pyridoxine in the treatment of nausea in pregnancy and conclude that odansetron is superior, suggesting its use as ﬁrst-line therapy for nausea in pregnancy. However, because the study uses only the lowest dose and lowest frequency of both doxylamine and pyridoxine, it may be premature to conclude that odansetron is superior. In the American College of Obstetricians and Gynecologists Practice Bulletin No. 52,2 the authors recommend doxylamine and pyridoxine as ﬁrst-line therapy and suggest a dosage and frequency titration based on the patient’s symptoms. In addition, the combination of doxylamine and pyridoxine has been approved by the U.S. Food and Drug Administration (FDA) as safe for treatment of nausea in pregnancy.3 The FDA has not approved odansetron as safe in pregnancy and has issued warnings about dysrhythmias.4 Before suggesting the ﬁrst-line use of a medication that is not approved by the FDA and has potential risks, there needs to be a more extensive comparison of all suggested dosages and dosing frequencies and resolution of any safety concerns. Financial Disclosure: The author did not report any potential conﬂicts of interest.
Kirstie Cunningham, MD, FACOG Department of Family Medicine, Morehouse School of Medicine, Atlanta, Georgia
REFERENCES 1. LG Oliveira, Capp SM, You WB, Riffenburgh RH, Carstairs SD. Ondansetron compared with doxylamine and pyridoxine for treatment of nausea
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