Doxylamine 10mg / Pyridoxine 10mg gastro-resistant tablets

Nausea and vomiting during pregnancy (NVP) affect up to 85% of pregnant women and usually begin between the 4th and 7th weeks of gestation, and symptoms often peak around the 9th week and generally resolve by the 20th week in most cases, with severe cases termed hyperemesis gravidarum (HG) impacting physical and psychological health. This review aims to provide a structured dietary approach to managing NVP by developing a food pyramid specifically for this population, based on a systematic evaluation of dietary evidence. The findings highlight the beneficial effects of dietary patterns rich in fruits, vegetables, and protein sources in reducing NVP symptoms. Protein intake is shown to alleviate nausea and vomiting by stabilizing gastric motility and addressing nutritional deficiencies. The review also explores the potential benefits of herbal supplements, like ginger and vitamin B6. By integrating these dietary strategies with pharmacological treatments, a more holistic approach to managing NVP can be achieved, enhancing both maternal well-being and fetal health. The proposed food pyramid emphasizes glycemic stability, hydration, and gradual nutrient intake, offering a structured dietary guide for pregnant women experiencing NVP and HG.

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Background: Nausea and vomiting in pregnancy affects up to 80% of pregnant women and may progress to hyperemesis gravidarum, leading to maternal morbidity and adverse pregnancy outcomes. Despite numerous pharmacological and non-pharmacological options, the comparative efficacy and safety of these interventions remain unclear. Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials assessing pharmacological and non-pharmacological interventions for nausea and vomiting in pregnancy. The databases searched included CENTRAL, PubMed, and EMBASE (up to 28 May 2024). Eligible trials compared interventions with a placebo in pregnant women with nausea and vomiting in pregnancy. The primary outcomes were symptom severity, assessed using validated tools. Safety outcomes included adverse effects. Data were pooled using frequentist pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool, and the certainty of evidence was evaluated using the CINeMA framework. Results: Of 9844 records screened, 24 randomized controlled trials (3017 participants) met the inclusion criteria, encompassing 16 intervention categories. Network analysis ranked quince, vitamin B6 with pomegranate and mint, acupressure P6, dimenhydrinate, and acupuncture combined with doxylamine-pyridoxine as the most effective interventions for reducing symptoms of nausea and vomiting in pregnancy, with considerable uncertainty and low-to-moderate quality of evidence. Reporting of adverse events was limited. Risk of bias was low to moderate. Discussion: Most interventions demonstrated significant benefit over a placebo. However, high heterogeneity and sparse reporting of adverse effects warrant caution when translating these results into clinical practice. Conclusions: This study indicates that both pharmacological (vitamin B6, metoclopramide, dimenhydrinate) and non-pharmacological (ginger, quince, acupressure, acupuncture) interventions might be effective in reducing symptoms of nausea and vomiting in pregnancy.

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BackgroundHyperemesis gravidarum (HG) is the leading cause of hospitalization during early pregnancy, affecting approximately 0.3-3% of pregnancies. It represents the most severe end of the nausea and vomiting in pregnancy (NVP) spectrum and is associated with substantial maternal morbidity and potential adverse fetal outcomes. Despite extensive research, the exact pathophysiology remains poorly understood, and optimal management strategies continue to be debated.MethodsThis narrative review synthesizes current evidence on the complications and treatment approaches for HG. A literature search was conducted in PubMed, Scopus, and Medline up to October 2024 using predefined keywords. Eligible sources included observational studies, cohort studies, descriptive studies, and case reports. Systematic reviews, meta-analyses, and non-English articles were excluded.ResultsHG is associated with a broad spectrum of complications, including dehydration, electrolyte imbalances, Wernicke's encephalopathy, cardiac arrhythmias, thromboembolism, and adverse pregnancy outcomes such as fetal growth restriction and preterm birth. Pharmacological treatments-most notably doxylamine-pyridoxine (the only FDA-approved therapy), ondansetron, metoclopramide, and corticosteroids-have demonstrated varying efficacy and safety profiles. Non-pharmacological interventions such as acupressure, dietary adjustments, psychotherapy, and hypnosis have also been studied, although evidence remains limited.ConclusionsHG requires a comprehensive and individualized management approach. While doxylamine-pyridoxine remains the cornerstone of therapy, other pharmacologic and supportive measures may offer additional benefit. Continued research is essential to clarify the underlying mechanisms, improve therapeutic efficacy, and develop evidence-based guidelines that integrate both medical and psychosocial care for affected women.

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Background: Nausea and vomiting in pregnancy (NVP), or emesis gravidarum, is a frequent complication of early gestation with unclear causes, suspected to involve genetic, hormonal, and gastrointestinal factors. Our study investigated the association of human chorionic gonadotropin (hCG), histamine, diamine oxidase (DAO), thyroxine and pyridoxine and the severity of NVP symptoms and assessed the efficacy of a vitamin C-containing chewing gum as a potential NVP treatment. Methods: In this prospective, double-blinded, randomized, controlled trial, 111 participants were assigned to receive vitamin C-containing chewing gum, placebo gum, or no treatment at two follow-ups during early pregnancy. Maternal serum levels of hCG, histamine, DAO, thyroxine, and pyridoxine were measured and correlated with NVP severity using the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE-24) score. Results: Elevated maternal hCG levels were significantly associated with an increased PUQE-24 score (p p = 0.68). Maternal DAO levels negatively correlated with NVP symptoms (p p p p = 0.62) and second follow-up visits (p = 0.87). Conclusions: Our study underscores the complexity of factors contributing to NVP, highlighting the significant roles of hCG and DAO, while histamine levels appear unrelated. Maternal thyroxine and pyridoxine levels also significantly correlate with NVP symptoms. Vitamin C-containing chewing gum was not effective as a treatment for NVP. Further large-scale studies are needed to better understand these interactions and develop targeted treatments in the future.

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Background Doxylamine-pyridoxine is recommended as a first line treatment for nausea and vomiting during pregnancy and it is commonly prescribed. We re-analysed the findings of a previously reported superiority trial of doxylamine-pyridoxine for the treatment of nausea and vomiting during pregnancy using the clinical study report obtained from Health Canada. Methods and findings We re-analysed individual level data for a parallel arm randomized controlled trial that was conducted in six outpatient obstetrical practices in the United States. Pregnant women between 7 and 14 weeks of gestation with moderate nausea and vomiting of pregnancy symptoms. The active treatment was a tablet containing both doxylamine 10 mg and pyridoxine 10 mg taken between 2 and 4 times per day for 14 days depending on symptoms. The control was an identical placebo tablet taken using the same instructions. The primary outcome measure was improvement in nausea and vomiting of symptoms scores using the 13-point pregnancy unique quantification of emesis scale between baseline and 14 days using an ANCOVA. 140 participants were randomized into each group. Data for 131 active treatment participants and 125 control participants were analysed. On the final day of the trial, 101 active treatment participants and 86 control participants provided primary outcome measures. There was greater improvement in symptoms scores with doxylamine-pyridoxine compared with placebo (0.73 points; 95% CI 0.21 to 1.25) when last observation carried forward imputation was used for missing data but the difference is not statistically significant using other approaches to missing data (e.g. 0.38; 95% CI -0.08 to 0.84 using complete data). Conclusions There is a trend towards efficacy for nausea and vomiting symptoms with doxylamine-pyridoxine compared with placebo but the statistical significance of the difference depends on the method of handling missing data and the magnitude of the difference suggests that there is no clinically important benefit employing the prespecified minimal clinically important difference or “expected difference” of 3 points. Trial registration Clinical Trial NCT00614445

Abstract licence: CC BY 4.0

Objectives We report information about an unpublished 1970s study (“8-way” Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published. Design Double blinded, multi-centred, randomized placebo-controlled study. Setting 14 clinics in the United States. Participants 2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled. Interventions Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights. Outcomes Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians. Results Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were “evaluated moderate or excellent” was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity. Conclusion The available information about this “8-way Bendectin” trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias. Trial registration Not registered.

Abstract licence: CC BY 4.0

BackgroundNausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting up to 80% of expecting mothers. In April 2013 the FDA approved the delayed release combination of doxylamine succinate and -pyridoxine hydrochloride (Diclegis®) for NVP, following a phase 3 randomized trial in pregnant women. The fetal safety of this medication has been proven by numerous studies. However, because it is the only FDA-approved medication for NVP that is likely to be used by a large number of pregnant women, its maternal safety is an important public health question. The Objective is to evaluate the maternal safety of doxylamine succinate -pyridoxine hydrochloride delayed-release preparation (Diclegis® as compared to placebo.MethodsWe randomized women suffering from NVP to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from 2–4 tablets a day, based on a pre-specified titration protocol response to symptoms. Adverse events were collected through patient diaries, clinical examination and laboratory testing.ResultsDoxylamine succinate 10 mg and pyridoxine hydrochloride 10 mg use was not associated with an increased rate of any adverse event over placebo, including CNS depression, gastrointestinal or cardiovascular involvement.ConclusionsDoxylamine succinate–pyridoxine hydrochloride delayed release combination is safe and well tolerated by pregnant women when used in the recommended dose of up to 4 tablets daily in treating nausea and vomiting of pregnancy.Trial RegistrationClinical Trial Registration No: NCT00614445.

Abstract licence: CC BY 4.0