Ondansetron In Pregnancy Research Articles

Signal mining of adverse reactions in the antiemetic drug ondansetron during pregnancy:A Real-World analysis of the FDA adverse Event Reporting System (FAERS)

ABSTRACT Background The aim of this study is to assess the risks associated with the use of ondansetron in pregnant women in real-world based on the Food and Drug Administration adverse Event Reporting System (FAERS). Methods The FAERS data from the 2017Q1 to the 2023Q1, which was used by the ratio-of-reporting (ROR) and Bayesian confidence interval progressive neural network (BCPNN) to assess the safety of ondansetron in pregnancy. Results A total of 15,727 pregnancy population reports were reported, with a total of 1,064 reports of adverse reactions with ondansetron as the primary suspected drug. Ondansetron was involved in a total of 10 system organ classifications (SOCs) of signal generation, and the top three signal intensities were Congenital, familial and genetic disorders (ROR=19.1, ROR025=17.03; IC=1.23, IC025=1.16), Ear and labyrinth disorders (ROR=17.11, ROR025=12.46; IC=1.22, IC025=1.03), and Cardiac disorders (ROR=9.48, ROR025=8.38; IC=1.12, IC025=1.03); signals of adverse reactions obtained of 216, of which the main ones were Anhedonia (IC=1.34, IC025=1.08), Injury (IC=1.34, IC025=1.19), Left-to-right cardiac shunt (IC=1.33, IC025=1.05). Conclusion The adverse reactions of Ondansetron involve multiple systems and organs, which should cause clinical vigilance. However, due to the limitations of the data, the causal relationship and risk level of adverse reactions cannot be accurately inferred.

Ondansetron in pregnancy revisited: Assessment and pregnancy labelling by the European Medicines Agency (EMA) & Pharmacovigilance Risk Assessment Committee (PRAC).

Ondansetron is an effective antiemetic that is being widely used as a second-line treatment option for severe nausea and vomiting of pregnancy in accordance with clinical guidelines. The safety of ondansetron during pregnancy has-following publication of controversial and seemingly contradictory results-been subject to considerable academic turmoil, specifically with respect to the risk of congenital cardiac malformations and oral cleft. In July 2019, the European Medicines Agency (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) released an updated, comprehensive assessment report on the use of ondansetron in the first trimester. The ensuing Summary of Product Characteristics (SmPC) was updated in November 2019 with important changes to section on "Fertility, pregnancy and lactation." The SmPC now states that ondansetron should not be used in the first trimester of pregnancy. ENTIS, The European Network of Teratology Information Services, believes that the implementation of this regulatory step-which has important clinical consequences-is insufficiently substantiated and is not serving the interest of pregnant women with severe nausea and vomiting. Herein, we discuss the underlying evidence and argue the case against the EMA decision.

Intravenous Ondansetron in Pregnancy and Risk of Congenital Malformations

(JAMA. 2020;323:372–374) A prior study found no significant association between oral ondansetron exposure during the first trimester and cardiac malformations or overall congenital malformations, except for a small association with oral clefts. Subsequent research, however, has suggested that the intravenous administration of ondansetron may be associated with adverse neonatal events. The aim of this study was to examine the association between intravenous ondansetron and congenital malformations.

Intravenous Ondansetron in Pregnancy and Risk of Congenital Malformations

This pharmacoepidemiology study uses Medicaid data to estimate associations between first-trimester use of intravenous ondansetron and risk of cardiac malformations and oral cleft in children of exposed mothers.

Ondansetron in Pregnancy and the Risk of Congenital Malformations: A Systematic Review.

Ondansetron, not approved for use in pregnancy, is increasingly being prescribed for nausea and vomiting in pregnancy and hyperemesis gravidarum. A number of recent lawsuits have highlighted the possibility that ondansetron may cause congenital malformations. The aim of this study was to systematically review epidemiological evidence on the potential association of prenatal exposure to ondansetron and congenital malformations. Systematic searches in Medline and Embase were performed in June 2017 using controlled vocabulary and key words, and references of search results were reviewed. Full papers (RCTs, cohort, and case-control studies) were eligible for inclusion if they reported fetal outcomes of prenatal ondansetron exposure in humans. Excluded were: case reports, studies involving pre-medication with ondansetron prior to CS, animal studies, and foreign languages studies. Ten epidemiologic studies were included: five large retrospective cohort studies, two prospective observational studies, two population-based case-controls. and a retrospective case series. Sample sizes ranged from 17 to 1 501 434 infants exposed to ondansetron. A case-control study identified an association between prenatal exposure to ondansetron and cleft palate, and one cohort study found an increased risk of cardiovascular defects. These findings were not reproduced in the other studies. While further investigation of the literature is needed, our results highlight the paucity of evidence linking prenatal exposure to ondansetron to an increased risk of congenital malformations. There is a need for additional epidemiologic studies to confirm whether ondansetron represents a safe and effective alternative treatment for nausea and vomiting in pregnancy and hyperemesis gravidarum.

Antiemetic use among pregnant women in the United States: the escalating use of ondansetron

To examine ondansetron use in pregnancy in the context of other antiemetic use among a large insured United States population of women delivering live births. We assessed ondansetron and other antiemetic use among pregnant women delivering live births between 2001 and 2015 in 15 data partners contributing data to the Mini-Sentinel Distributed Database. We identified live birth pregnancies using a validated algorithm, and all forms of ondansetron and other available antiemetics were identified using National Drug Codes or procedure codes. We assessed the prevalence of antiemetic use by trimester, calendar year, and formulation. In over 2.3 million pregnancies, the prevalence of ondansetron, promethazine, metoclopramide, or doxylamine/pyridoxine use anytime in pregnancy was 15.2, 10.3, 4.0, and 0.4%, respectively. Ondansetron use increased from <1% of pregnancies in 2001 to 22.2% in 2014, with much of the increase attributable to oral ondansetron beginning in 2006. Promethazine and metoclopramide use increased modestly between 2001 (13.8%, 3.2%) and 2006 (16.0%, 6.0%) but decreased annually through 2014 (8.0%, 3.2%). Doxylamine/pyridoxine, approved for management of nausea and vomiting in pregnancy in 2013, was used in 1.8% of pregnancies in 2014. For all antiemetics, use was highest in the first trimester. We observed a marked increase in ondansetron use by study year, prescribed to nearly one-quarter of insured pregnant women in 2014, occurring in conjunction with decreased use of promethazine and metoclopramide. Given the widespread use of ondansetron in pregnancy, data establishing product efficacy and methodologically rigorous evaluation of post-marketing safety are needed. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States.

This is an analysis of fetal outcome in pregnancies exposed to ondansetron to treat Hyperemesis Gravidarum (HG). In this retrospective cohort study, U.S. data on outcome were collected on 1070 pregnancies exposed to ondansetron and compared to outcomes in two control groups: 771 pregnancies in women with a history of HG with no ondansetron exposure and 1555 pregnancies with neither a history of HG nor ondansetron exposure. Ventricular septal defects were reported in 2/952 of infants in the HG/Ondansetron-exposure group and 4/1286 in the No HG/No Ondansetron-exposure group. Cleft palate was reported in 1/952 live births in the HG/Ondansetron and 2/1286 in the No HG/No Ondansetron-exposure groups. Women with a history of HG who took ondansetron reported less miscarriages and terminations, and higher live birth rates. The overall results do not support evidence of teratogenicity of ondansetron.

Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes

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Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes

Survey of Anesthesiology: October 2013 - Volume 57 - Issue 5 - p 231-232 doi: 10.1097/01.sa.0000433222.96883.5b

Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes

Nausea and vomiting affect more than 50% of all pregnant women. Although ondansetron is often used for treatment, data on its safety for the fetus are limited. The drug is administered during the period the fetus is most susceptible to teratogenic effects (7–12 weeks’ gestation). This historical cohort study was performed to determine whether use of ondansetron during pregnancy led to an increased risk of adverse fetal outcomes. Danish registries were used to establish a nationwide cohort of all pregnancies that resulted in a singleton live birth or stillbirth or ended with any abortive outcome during 2004 to 2011. Data were extracted for women given ondansetron. Specific exposure times were defined as the first trimester through 12 weeks’ gestation for any major birth defect, any time before 37 completed weeks for preterm delivery, any time during pregnancy for analyses involving birth weight, weeks 7 to 22 for spontaneous abortion, and week 7 until birth for stillbirth. Women who did not receive ondansetron were categorized as “unexposed.” Outcomes were spontaneous abortion, stillbirth, any major birth defects, preterm delivery, and infants of low birth weight or small for gestational age (SGA). Cox proportional hazards regression models were used to estimate hazard ratios (HRs) for the comparison of pregnancies in which women were and were not exposed to ondansetron. The analyses of birth defects, preterm delivery, and birth weight were based on live births; logistic regression was used to estimate prevalence odds ratios (ORs). Women exposed to ondansetron were matched, in a 1:4 ratio, to unexposed women in accordance with the nearest-neighbor–matching algorithm. Exposure to ondansetron occurred in 1970 (0.3%) of 608,385 women in the cohort. The first prescription was filled at a median of 70 gestational days (interquartile range, 57–88 days). In unadjusted analyses conducted before propensity score matching, the risk of spontaneous abortion was significantly decreased among women who were exposed to ondansetron compared with unexposed women. No increased risk of stillbirth, any major birth defects, infant born at low birth weight, or infant born SGA was associated with ondansetron exposure, whereas the risk of preterm delivery was significantly increased. The propensity score–matched analyses included spontaneous abortion (1849 exposed vs 7396 unexposed women), stillbirth (1915 vs 7660), any major birth defect (1233 vs 4932), preterm delivery (1792 vs 7168), and birth of infants at low birth weight and SGA (1784 vs 7136). The matched groups were similar in baseline characteristics. More than 50% of women given ondansetron were hospitalized for hyperemesis or nausea and vomiting, and almost half received another antiemetic. An analysis that included 215 cases occurring in weeks 7 to 12 and 139 cases in weeks 13 to 22 found that women exposed to ondansetron were not at increased risk for spontaneous abortion compared with unexposed women, with an adjusted HR of 0.49 (95% confidence interval [CI], 0.27–0.91) in weeks 7 to 12 and of 0.60 (95% CI, 0.29–1.21) in weeks 13 to 22. Six stillbirths occurred among 1915 women exposed to ondansetron (0.3%) and 27 among 7660 women not exposed (0.4%; adjusted HR, 0.42; 95% CI, 0.10–1.73). Among 1233 women given ondansetron in the first trimester, 36 infants (2.9%) had a major birth defect compared with 141 of 4932 unexposed infants (2.9%; adjusted prevalence OR, 1.12; 95% CI, 0.69–1.82). No cases of cleft palate occurred in the exposed group. Among 1792 women exposed to ondansetron before 37 weeks’ gestation, 111 had preterm deliveries (6.2%) compared with 374 among 7168 unexposed women (5.2%; adjusted prevalence OR, 0.90; 95% CI, 0.66–1.25). Exposure to ondansetron at any time during pregnancy was not associated with low birth weight (4.1% exposed vs 3.7% unexposed; adjusted prevalence OR, 0.76; 95% CI, 0.51–1.13) or with infants who were SGA (10.4% exposed vs 9.2% unexposed; adjusted prevalence OR, 1.13; 95% CI, 0.89–1.44). Compared with pregnancies with exposure to antihistamine antiemetics, those having exposure to ondansetron had no significantly different risk of spontaneous abortion. These results indicate that ondansetron exposure in pregnancy is not associated with a significantly increased risk of major adverse fetal outcomes, including spontaneous abortion, stillbirth, any major birth defects, preterm delivery, or low birth weight or SGA. These results may offer some reassurance for using ondansetron as treatment for nausea and vomiting during pregnancy.

Ondansetron in pregnancy, no adverse fetal outcomes

Ondansetron in pregnancy, no adverse fetal outcomes

Ondansetron in Pregnancy and Risk of Adverse Fetal Outcomes

BackgroundOndansetron is frequently used to treat nausea and vomiting during pregnancy, but the safety of this drug for the fetus has not been well studied.MethodsWe investigated the risk of adverse fetal outcomes associated with ondansetron administered during pregnancy. From a historical cohort of 608,385 pregnancies in Denmark, women who were exposed to ondansetron and those who were not exposed were included, in a 1:4 ratio, in propensity-score–matched analyses of spontaneous abortion (1849 exposed women vs. 7396 unexposed women), stillbirth (1915 vs. 7660), any major birth defect (1233 vs. 4932), preterm delivery (1792 vs. 7168), and birth of infants at low birth weight and small for gestational age (1784 vs. 7136). In addition, estimates were adjusted for hospitalization for nausea and vomiting during pregnancy (as a proxy for severity) and the use of other antiemetics.ResultsReceipt of ondansetron was not associated with a significantly increased risk of spontaneous abortion, which occurred in 1.1% of exposed women and 3.7% of unexposed women during gestational weeks 7 to 12 (hazard ratio, 0.49; 95% confidence interval [CI], 0.27 to 0.91) and in 1.0% and 2.1%, respectively, during weeks 13 to 22 (hazard ratio, 0.60; 95% CI, 0.29 to 1.21). Ondansetron also conferred no significantly increased risk of stillbirth (0.3% for exposed women and 0.4% for unexposed women; hazard ratio, 0.42; 95% CI, 0.10 to 1.73), any major birth defect (2.9% and 2.9%, respectively; prevalence odds ratio, 1.12; 95% CI, 0.69 to 1.82), preterm delivery (6.2% and 5.2%; prevalence odds ratio, 0.90; 95% CI, 0.66 to 1.25), delivery of a low-birth-weight infant (4.1% and 3.7%; prevalence odds ratio, 0.76; 95% CI, 0.51 to 1.13), or delivery of a small-for-gestational-age infant (10.4% and 9.2%; prevalence odds ratio, 1.13; 95% CI, 0.89 to 1.44).ConclusionsOndansetron taken during pregnancy was not associated with a significantly increased risk of adverse fetal outcomes. (Funded by the Danish Medical Research Council.)

Off-Label Use of Ondansetron in Pregnancy in Western Australia

Aims. Nausea and vomiting of pregnancy is the most common medical condition in pregnancy. There is an increasing trend to prescribe ondansetron although its safety for use in pregnancy has not been established. Methods. Exposed pregnancies were all births in Western Australia, 2002–2005, where the mother was dispensed ondansetron under the Australian Pharmaceutical Benefits Scheme, compared with all other births during the same period. Outcomes investigated include maternal and child characteristics, birth defects, pregnancy, and delivery characteristics. Results. There were 96,968 births from 2002 to 2005. Ondansetron was dispensed to 251 pregnant women during this period. The women dispensed ondansetron were more likely to be privately insured (OR: 5.8; 95% CI: 4.3–7.9), to be Caucasian (3.3; 1.9–5.7), not to smoke during their pregnancy (2.9; 1.8–4.7), to have a multiple birth (2.7; 1.5–5.0), and to have used fertility treatment (1.8; 1.0–3.4). There was a small but not significantly increased risk of a major birth defect with first trimester exposure (1.2; 0.6–2.2). Conclusions. Our study did not detect any adverse outcomes from the use of ondansetron in pregnancy but could not conclude that ondansetron is safe to use in pregnancy.

Ms. Einarson Replies

Back to table of contents Previous article Next article Letters to the EditorFull AccessMs. Einarson RepliesADRIENNE EINARSON R.N.,ADRIENNE EINARSON R.N.Search for more papers by this author,Published Online:1 Nov 2008https://doi.org/10.1176/appi.ajp.2008.08040573rAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We thank Drs. Mintzes and Jureidini for their interest in our study. They felt that the statement “appropriate treatment of depression during pregnancy is essential and if this includes taking paroxetine, this information should reassure women and their health care providers” was an endorsement, which is at odds with regulatory warnings. This is an incorrect assumption because we do not endorse any drugs used in pregnancy; we only examine safety. Critically, the regulatory warnings they reference (1 , 2) are based on the results of preliminary findings, which have not been updated because new data, including our study, has been published, refuting these early findings (3 , 4) . The design employed in our study is one that has been used over many years to examine the safety of numerous drugs in pregnancy (5) . It is widely considered to be an optimal design in the absence of randomized control trials that cannot be ethically conducted among pregnant women. The study design was discussed in detail in our article, documenting that the maternal characteristics were similar in both the exposed group and the unexposed comparison group. We also detailed the limitations in the discussion section. The data Drs. Mintzes and Jureidini state were missing would have only been available if our study had been a randomized control trial. The results of the previously published data were included—since we documented that there was a 1.5% increased risk for heart defects as opposed to approximately 1% in the general population—both in the abstract and in the body of the article. As we discussed, 50% of all pregnancies are unplanned, and all the women who participated in our study were receiving paroxetine prior to becoming pregnant. We cited the JAMA study conducted by Cohen et al., since it illustrated the importance of treating depression during pregnancy when appropriate. The treatment of depression during pregnancy with antidepressants is a complicated decision for both the physician and the pregnant patient. Being “on the safe side” by not using these drugs during pregnancy because of unproven potential harm is not always an option, especially if a woman is already pregnant and receiving an antidepressant. Each case requires individual evaluation, and a risk/benefit assessment must be conducted in order to serve the best interest of both the pregnant mother and her unborn child.Toronto, Ontario, CanadaThis letter (doi: 10.1176/appi.ajp.2008.08040573r) was accepted for publication in August 2008.Errors in the Journal"s editorial office resulted in the disclosures of Ms. Einarson and her co-authors not accompanying the original article and so they are presented here: Dr. Koren and Ms. Einarson have received research support from Janssen-Ortho and Wyeth. Dr. Koren has received research support from Apotex, Duchesnay, Novartis, and Pfizer. Ms. Einarson has received unrestricted research grants from GlaxoSmithKline for studying ondansetron in pregnancy and from Organon for studying mirtazapine in pregnancy. Dr. Einarson has received research support from Bristol-Myers Squibb, Eli Lilly, Janssen-Ortho, Lundbeck, Novo Nordisk, and Organon. The remaining authors report no competing interests.