How long has ondansetron been on the market

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She provided confidence and security in all matters. Blog February The History of Zofran. Sensitivity analyses were conducted to test the robustness of the primary results. The reference group was changed to women who filled a prescription for a different antiemetic medication during the first trimester because they might be more comparable with women exposed to ondansetron than women who were never treated with antiemetic agents during pregnancy.

To evaluate the potential effect of exposure misclassification, exposure was redefined as having filled 2 or more prescriptions for ondansetron during the first trimester. Because the period of greatest sensitivity to teratogens for oral clefts is likely the later part of the first trimester, we redefined the exposure window as 6 to 12 weeks after the date of last menstrual period.

In a negative control analysis, we assessed the risk of malformations in women who filled their first ondansetron prescription in gestational months 5 to 8, which is after the etiologically relevant window. A null finding in this analysis provides indirect evidence of no substantial residual confounding.

We also used this group with first ondansetron exposure in months 5 to 8 as an alternative reference group. Because the cohort included live births only, the potential effect of differences in the proportion of pregnancy losses among women treated with ondansetron vs those untreated within levels of covariates used in the adjustment were conducted, as previously described eAppendix in the Supplement : Quantifying the potential effect of restriction to livebirths.

All analyses were conducted using SAS version 9. No adjustments were made for multiple comparisons, and results of secondary analyses should be interpreted as exploratory.

Use increased from 0. Exposed women were more likely to be white, to have a diagnosis of psychiatric and neurological conditions, and to smoke. They were also more likely to fill a prescription for other medications used to treat nausea and vomiting during pregnancy metoclopramide, promethazine, pyridoxine , for psychotropic medications, for corticosteroids, and for suspected teratogens. Most markers of comorbid illness and disease severity were also elevated among ondansetron-exposed compared with unexposed women Table 1 and eTable 3 in the Supplement.

The risk of cardiac malformations was Among exposed pregnancies, the risks of oral clefts were The increase in risk of cardiac malformations associated with ondansetron in the unadjusted analyses was related to ventricular septal defects exposed and unexposed cases; RR, 1. The other specific cardiac malformations were less common, ranging between less than 11 and exposed cases, and none of the unadjusted RR suggested an increased risk.

The increased risk for oral clefts was attributable to cleft palate 65 exposed; unexposed cases; RR, 1. There was no evidence of an increased risk for cleft lip 33 exposed; unexposed cases; RR, 1. The risk for any congenital malformation was After stratification on the propensity score, all measured patient characteristics were balanced between the ondansetron-exposed and unexposed groups judged by an absolute standardized difference of less than 0.

Although adjusting for the treatment indications and associated factors propensity score level 1 did not substantially change the crude risk estimates, accounting for all prespecified potential confounding variables propensity score level 2 resulted in a null point estimate for cardiac malformations RR, 0.

These findings were confirmed in analyses that adjusted for proxies for unmeasured confounders through use of high-dimensional propensity scores Figure 1. Results when using women exposed to other antiemetics as the reference group were consistent with the main analyses adjusted RR for cardiac malformations, 1.

Results were similar across the individual antiemetic agents Figure 2 and eTables in the Supplement. Requiring 2 or more prescriptions to be filled during the first trimester did not strengthen the association for oral clefts adjusted RR, 1. In the negative control analyses, which evaluated the association with exposure to ondansetron after the etiologically relevant time window, no increased risk was observed for oral clefts RR, 0.

When using these women with exposure to ondansetron after the etiologically relevant window as an alternative reference group, adjusted estimates were consistent with the main analyses Figure 2 and eTables in the Supplement. We quantified the potential for selection bias due to the restriction of the cohort to livebirths. Based on these assumptions, the RR estimate would shift from 0. In exploratory analyses, we screened for associations with other specific malformations eTable 4 in the Supplement.

In the context of multiple comparisons, the risk of ear malformations was elevated: the absolute risks were 3. Quiz Ref ID In this national cohort of publicly insured pregnant women, there was no association between exposure to ondansetron during the first trimester of pregnancy and increased risk of cardiac malformations or congenital malformations overall, after accounting for potentially confounding conditions.

These findings were consistent across a broad range of sensitivity analyses. This study expands on the evidence available to date. The largest and most recent cohort study published in the peer-reviewed literature included 19 cardiac malformations, 1 oral cleft, and 49 malformations overall among exposed women eTable 1 in the Supplement. Other studies did not account for important potential confounding variables, such as the underlying indication or its severity, maternal comorbidities eg, diabetes and concomitant medication use.

For this same reason, a cautious interpretation of the finding of a potential increase in the risk of ear deformities that emerged in exploratory analyses is warranted.

It should be viewed as a potential safety signal that requires replication in other studies. Apart from the large cohort size, this study has several strengths. First, information on medication exposures was collected in a prospective manner based on filled prescriptions for medications and is thus free from recall bias.

Second, the MAX data contain rich patient-level information for confounding control, including maternal demographic characteristics, medical conditions, and medication exposures. Third, in addition to comparing exposed to unexposed women, ondansetron-exposed women were compared with women exposed to other antiemetics and consistent results were documented. Aside from reducing the likelihood of confounding, this analysis also addressed the clinically relevant question of which treatment is preferred for women whose symptoms are not self-limiting and do not resolve with nonpharmacological conservative measures.

Fourth, both cardiac malformations and oral clefts have been shown to have a high positive predictive value when identified using computerized records. This study has several limitations. First, filling a prescription does not mean that the medication was actually consumed, which could bias the results toward the null. To address this limitation, sensitivity analyses in which women were required to have filled at least 2 prescriptions during the first trimester were conducted based on the notion that if a woman refills a prescription she is likely to have consumed the prescribed medication.

This approach did not result in stronger associations. Second, in nonrandomized studies, there is always concern about residual confounding due to unmeasured or poorly measured characteristics. For example, absence of a recorded diagnosis is equated with absence of the disease. It is possible, however, that the clinician did not record the diagnosis.

This may have resulted in some misclassification of the confounder information and hence affect our ability to control for confounding. Although negative residual confounding is typically not a concern for null findings because drug exposure is not expected to be associated with factors protective against congenital malformations ie, cardiac malformations or congenital malformations overall , positive residual confounding could be a potential explanation for the increased risk in oral clefts.

An attempt was made to refute this alternative explanation using different strategies including adjustment for proxies of unmeasured confounders through high-dimensional propensity scores, use of alternate reference groups, and a negative control analysis.

No increased risk of oral clefts was observed using the negative control exposure window, supporting the validity of this association. Third, because the cohort was restricted to livebirths, severe congenital malformations that result in pregnancy losses or terminations will be missed. Nonsyndromic oral clefts do not result in fetal deaths and are rarely a reason for terminations.

For cardiac malformations and any congenital malformation, formal quantification of the potential for selection bias revealed that the differences in the proportion of nonlive births among ondansetron users vs the reference groups within levels of covariates used in the adjustment would have to be unrealistically strong in order to dilute a clinically meaningful increase in risk.

The cohort inclusion criteria resulted in the selection of a more disadvantaged subpopulation within Medicaid, mostly composed of low-income adults, multiparae, and women with disabilities. The characteristics of this Medicaid-eligible population of pregnant women, ie, a young, racially diverse, and vulnerable population with a high burden of disabilities, are not expected to affect the biological relations studied.

Therefore, the results should be generalizable to the broader Medicaid population, as well as to commercially insured pregnant women in the United States, and pregnant populations in other countries. Fifth, the study was based on data from through , but the biological association between ondansetron exposure and malformations should not change over time.

Among offspring of mothers enrolled in Medicaid, first-trimester exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall after accounting for measured confounders but was associated with a small increased risk of oral clefts. Corresponding Author: Krista F. Author Contributions : Dr Huybrechts had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Critical revision of the manuscript for important intellectual content: All authors. Dr Desai reports receiving grants to his institution from Merck, Bayer, and Vertex. Dr Bateman reports receiving grants to his institution from Eli Lilly, GlaxoSmithKline, Pacira, Baxalta, Pfizer, and Aetion and having served on an expert panel for a postpartum hemorrhage quality improvement project that was conducted by the Association of Women's Health, Obstetric, and Neonatal Nurses and funded by a grant from Merck for Mothers.

Dr Gray reports consulting for Quest Diagnostics. No other conflicts of interest were reported. Our website uses cookies to enhance your experience.

By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Figure 1. View Large Download. Ondansetron is in a class of medications called serotonin 5-HT 3 receptor antagonists. It works by blocking the action of serotonin, a natural substance that may cause nausea and vomiting.

Ondansetron comes as a tablet, a rapidly disintegrating dissolving tablet, film, and an oral solution liquid to take by mouth. The first dose of ondansetron is usually taken 30 minutes before the start of chemotherapy, 1 to 2 hours before the start of radiation therapy, or 1 hour before surgery. Additional doses are sometimes taken one to three times a day during chemotherapy or radiation therapy and for 1 to 2 days after the end of treatment.

Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take ondansetron exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. If you are taking the rapidly disintegrating tablet, remove the tablet from the package just before you take your dose.

To open the package, do not try to push the tablet through the foil backing of the blister. Instead, use dry hands to peel back the foil backing.

Gently remove the tablet and immediately place the tablet on the top of your tongue. The tablet will dissolve in a few seconds and can be swallowed with saliva.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information. Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one. Ondansetron may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.

Keep this medication in the container it came in, tightly closed, and out of reach of children.