Doxylamine 10mg / Pyridoxine 10mg modified-release tablets

BACKGROUND: Hyperemesis 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. METHODS: This 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. RESULTS: HG 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. CONCLUSIONS: HG 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 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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Emesis (e.g., vomiting and nausea) can be a nebulous condition to treat, as it has many and highly varied etiologies. Understanding the underlying causes of emesis is crucial in selecting the appropriate antiemetic therapy. At present, there are a plethora of medications on the market to treat emesis, known as antiemetics. For the healthcare professionals managing emesis, key concerns include efficacy, the onset of effects, and potential adverse actions of these drugs. The present investigation reviews different classes of antiemetics and specific clinical uses for each based on pharmacological action. In addition, a few emerging treatment options are discussed, including cannabinoids, vitamin B6 (pyridoxine), and combination formulations such as Diclegis (doxylamine-pyridoxine), prompting avenues for future roles in the management of emesis.

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We report a case of a 36-year-old pregnant woman whose fetus exhibited frequent premature ventricular contractions (PVCs) and occasional probable premature atrial contractions (PACs) at 23 weeks' gestation. The patient was taking Unisom for nausea. After discontinuing the medication, the fetal arrhythmias resolved within a week. Postnatal evaluation showed a normal ECG, a normal QT interval, and no recurrence of arrhythmias. This case highlights the importance of thoroughly reviewing maternal medications when assessing fetal arrhythmia and suggests a possible proarrhythmic effect of doxylamine during pregnancy.

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Background: Nausea and Vomiting in Pregnancy (NVP) and Hyperemesis Gravidarum (HG) are common pregnancy-related conditions that can significantly impair maternal quality of life and, in severe cases, impact pregnancy outcomes. This study aimed to assess the prevalence of NVP and HG, evaluate their association with pregnancy progression and neonatal outcomes, and investigate the role of pharmacological therapy. Methods: A prospective observational study was conducted at the University Hospital of Siena between September 2023 and September 2024. Seventy-nine pregnant women aged 28–34 years were enrolled and followed throughout pregnancy. Symptom severity was assessed using the PUQE questionnaire during scheduled outpatient visits. Patients with NVP received pharmacological treatment with doxylamine succinate/pyridoxine hydrochloride. Results: Nausea and Vomiting in Pregnancy was reported by 59% of patients, with all cases categorized as mild or moderate; no severe HG cases were observed. Symptoms resolved by the third trimester. A significant association was observed between NVP and a positive family history of the condition (OR: 3.66, 95% CI: 1.20–11.21; p = 0.025). Logistic regression analysis also revealed that NVP was associated with an increased risk of gestational hypertension (15% vs. 0%, p = 0.04), and a decreased likelihood of gestational diabetes (OR: 0.24, 95% CI: 0.07–0.86) and cesarean section (OR: 0.34, 95% CI: 0.13–0.87). No significant differences were found in neonatal outcomes, including birth weight, Apgar scores, or fetal complications. Conclusions: While NVP may influence maternal outcomes, the condition does not significantly affect neonatal health. Early pharmacological treatment improves maternal well-being and may reduce hospitalization rates. Larger multicenter studies are needed to confirm these findings.

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Abstract Nausea and vomiting of pregnancy (NVP) is among the most common conditions that pregnant women encounter in the early stages of pregnancy. It can affect up to 85% of pregnant women, thus representing a significant public health concern. NVP results in substantial negative physical, emotional, and financial consequences. Despite its prevalence, the pathogenesis remains elusive. Few guidelines have been published; however, several interventions exist for the symptomatic treatment of NVP. The aim of this review is to provide an overview of modern treatment strategies of NVP with a special focus on the recently approved dual-release formulation of the doxylamine and pyridoxine combination. This combination was approved by the Food and Drug Administration (FDA) in November 2016 for the treatment of NVP when conservative management fails, and it has been introduced to the American market in April 2018. The maximum plasma concentration (Tmax) of doxylamine and pyridoxal-5-phosphate is reached 3.5 h and 15 h, respectively, after administration of one tablet twice daily, or 4.5 h and 0.5 h, respectively, when one tablet is administered just once daily. In addition, the delayed-release combination allows sufficient levels of doxylamine and the active metabolite pyridoxal-5-phosphate in the systemic circulation, providing symptoms relief in the subsequent morning. Hence, the dual-release formulation can improve the quality of life of pregnant women suffering from NVP. Additionally, large epidemiological trials have shown no increased risk of adverse effects to newborns, demonstrating that its use is not teratogenic.

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The quality by design enabled the development of cost-effective, simple, precise, and rapid RP-HPLC techniques for determining Pyridoxine (PRD) and Doxylamine (DXA) in the tablet dosage form. Systematic method optimization was performed through central composite design by altering the flow rate and composition of the organic phase in the mobile phase as the critical method parameters for evaluating the necessary analytical attributes, namely the tailing factor, theoretical plate count, and resolution. The optimal separation was achieved on a column with C18 in nature and dimensions of (250 mm length × 4.6 mm id × 5 μm particle size) composed of a blend of acetate buffer and acetonitrile in a volumetric composition of 35:65, at a flow rate of 1.0 ml/minute. Detection was carried out at 254 nm. The PRD and DXA have retention times of 3.053 and 4.357 minutes, respectively. The developed method was useful for the determination of bulk drugs and formulations.

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