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Obstetric Medicine Mar 2016Nausea and vomiting of pregnancy (NVP) is a common condition affecting 75% of pregnant women. NVP generally commences early in the first trimester, peaking in severity... (Review)
Review
Nausea and vomiting of pregnancy (NVP) is a common condition affecting 75% of pregnant women. NVP generally commences early in the first trimester, peaking in severity between 7 and 12 weeks and in over 90% symptoms will have abated by week 20. Thus, the time when women are most likely to have NVP and require treatment coincides with the embryonic period when there is maximum susceptibility to any teratogenic risk. Following the thalidomide tragedy of 55 years ago there is a particular awareness and sensitivity about these potential risks, especially in relation to any medication used to treat NVP. Despite several studies showing no clear benefits of ondansetron over other NVP treatments such as doxylamine, and the paucity of safety data, the off-label prescribing and use of ondansetron to treat NVP has increased significantly worldwide. Albeit based on limited human pregnancy data, ondansetron has not been associated with a significantly increased risk of birth defects or other adverse pregnancy outcomes. This review attempts to highlight some of the difficulties in interpreting the available data and the need to follow practical guidelines regarding treatment of NVP.
PubMed: 27512487
DOI: 10.1177/1753495X15621154 -
P & T : a Peer-reviewed Journal For... Jan 2017Olaratumab (Lartruvo) for the treatment of soft tissue sarcoma; bezlotoxumab (Zinplava) for use with an antibiotic to reduce recurrence of infection; and doxylamine...
Olaratumab (Lartruvo) for the treatment of soft tissue sarcoma; bezlotoxumab (Zinplava) for use with an antibiotic to reduce recurrence of infection; and doxylamine succinate/pyridoxine hydrochloride (Bonjesta) for the treatment of nausea and vomiting during pregnancy.
PubMed: 28090157
DOI: No ID Found -
Maedica Dec 2020Prescribing drugs in pregnancy is a challenging approach for doctors. To evaluate drugs used in pregnancy. A prospective, cross-sectional, descriptive study was carried...
Prescribing drugs in pregnancy is a challenging approach for doctors. To evaluate drugs used in pregnancy. A prospective, cross-sectional, descriptive study was carried out by collecting and evaluating prescriptions on various parameters. More than 50% of antenatal care attendees belonged to the 18-24 age group, and 102 (41.46%) were primigravidae. The main presenting complaints were abdominal pain (25.16%), followed by nausea and vomiting (22.60%) and fever (11.14%); the maximum number of visits to hospital was seen in the first trimester (40.53%), followed by the third trimester (38.42%). It was observed that 25.78% of prescriptions did not contain any medicine. The average number of prescribed medicines was 2.32, with the lowest in the first trimester (1.77) and the highest in the second trimester (2.78). It was noticed that 74.11% and 71.26% of all prescribed medicines were from essential medicine list and generics, respectively. Of all prescribed drugs, 11.52% were antimicrobials, and 4.11% injectable dosage forms. Vitamins and minerals were the preferred prescribed medicines (34.82%), followed by antimicrobial agents (11.52%) and doxylamine plus pyridoxine (10.16%). Also, doctors who made the drug choice during antenatal visits were more confident in evidence-based safety as per New Pregnancy and Lactation Rule (PPLR); 45.37% of drugs were prescribed from category A, followed by 38.25% from category B and none from group X. Doctors were concerned about prescribing safer drugs in pregnancy and were more confident in evidence-based medication.
PubMed: 33603908
DOI: 10.26574/maedica.2020.15.4.503 -
Geburtshilfe Und Frauenheilkunde Feb 2024Nausea 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...
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 (T ) 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.
PubMed: 38344043
DOI: 10.1055/a-2225-5883 -
PloS One 2018Doxylamine-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... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Doxylamine; Drug Therapy, Combination; Female; Humans; Morning Sickness; Placebos; Pregnancy; Pyridoxine
PubMed: 29342163
DOI: 10.1371/journal.pone.0189978 -
American Family Physician Nov 2018Women often see their primary care physicians for common acute conditions during pregnancy. These conditions may be caused by pregnancy (obstetric problems) or worsened... (Review)
Review
Women often see their primary care physicians for common acute conditions during pregnancy. These conditions may be caused by pregnancy (obstetric problems) or worsened by pregnancy (obstetrically aggravated problems), or they may require special consideration during pregnancy because of maternal or fetal risks (nonobstetric problems). Primary care physicians should know the differential diagnosis for common conditions during pregnancy and recognize the important findings of obstetric and urgent nonobstetric problems. The family physician can evaluate and treat most nonobstetric problems, although obstetric problems require referral to a primary maternity care clinician. A tiered approach, including routinely looking for all-cause red flag symptoms and signs, while remaining aware of estimated gestational age, allows for high-quality care and shared decision making between the family physician and the pregnant patient. When treating common causes of nausea and epigastric pain/gastroesophageal reflux, lifestyle modifications are considered the safest and first-choice therapy, followed by well-established low-risk therapies, such as vitamin B6 (pyridoxine) and doxylamine for nausea, and antacids not containing salicylates (found in bismuth combination products) for gastroesophageal reflux. Other common conditions during pregnancy are best treated with low-risk therapies, such as using antihistamines or topical steroids for rashes, first-generation cephalosporins or amoxicillin for cystitis, and physical therapy and acetaminophen for low back pain and headaches.
Topics: Acute Disease; Diagnosis, Differential; Female; Humans; Pregnancy; Pregnancy Complications; Primary Health Care
PubMed: 30325641
DOI: No ID Found -
PloS One 2022To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014.
OBJECTIVE
To compare patterns in use of different antiemetics during pregnancy in Canada, the United Kingdom, and the United States, between 2002 and 2014.
METHODS
We constructed population-based cohorts of pregnant women using administrative healthcare data from five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, and Saskatchewan), the Clinical Practice Research Datalink from the United Kingdom, and the IBM MarketScan Research Databases from the United States. We included pregnancies ending in live births, stillbirth, spontaneous abortion, or induced abortion. We determined maternal use of antiemetics from pharmacy claims in Canada and the United States and from prescriptions in the United Kingdom.
RESULTS
The most common outcome of 3 848 734 included pregnancies (started 2002-2014) was live birth (66.7% of all pregnancies) followed by spontaneous abortion (20.2%). Use of antiemetics during pregnancy increased over time in all three countries. Canada had the highest prevalence of use of prescription antiemetics during pregnancy (17.7% of pregnancies overall, 13.2% of pregnancies in 2002, and 18.9% in 2014), followed by the United States (14.0% overall, 8.9% in 2007, and 18.1% in 2014), and the United Kingdom (5.0% overall, 4.2% in 2002, and 6.5% in 2014). Besides use of antiemetic drugs being considerably lower in the United Kingdom, the increase in its use over time was more modest. The most commonly used antiemetic was combination doxylamine/pyridoxine in Canada (95.2% of pregnancies treated with antiemetics), ondansetron in the United States (72.2%), and prochlorperazine in the United Kingdom (63.5%).
CONCLUSIONS
In this large cohort study, we observed an overall increase in antiemetic use during pregnancy, and patterns of use varied across jurisdictions. Continued monitoring of antiemetic use and further research are warranted to better understand the reasons for differences in use of these medications and to assess their benefit-risk profile in this population.
Topics: Pregnancy; Female; Humans; Antiemetics; Abortion, Spontaneous; Cohort Studies; Retrospective Studies; Gastrointestinal Agents; Alberta
PubMed: 36454900
DOI: 10.1371/journal.pone.0277623 -
Frontiers in Microbiology 2020Pharmaceutical contaminants (PCs) have been recognized as emerging contaminants causing unexpected consequences to environment and humans. There is an urgent need for...
Pharmaceutical contaminants (PCs) have been recognized as emerging contaminants causing unexpected consequences to environment and humans. There is an urgent need for development of efficient technologies to treat these PCs from water. The current study has investigated the removal capacity of a green microalgal species, , for doxylamine, chemical oxygen demand (COD), and nutrients from real wastewater. Results have indicated that can grow well in the doxylamine-polluted wastewater with the achievement of 56, 78.5, 100, and 89% removal of doxylamine, COD, total nitrogen (TN), and total phosphorus (TP). Addition of 2 g L bicarbonate enhanced the removal of doxylamine up to 63% and slightly inhibited the removal of COD. Decreased carbohydrate (28-26%) and increased protein content (30-33%) of the harvested biomass have been observed after cultivation in the wastewater. The current study has shown the feasibility of using microalgae-based biotechnologies for PC-contaminated wastewater.
PubMed: 33224120
DOI: 10.3389/fmicb.2020.584020 -
JNCI Cancer Spectrum Mar 2023Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as... (Review)
Review
BACKGROUND
Incidence rates of colorectal cancer (CRC) are increasing among adults born in and after the 1960s, implicating pregnancy-related exposures introduced at that time as risk factors. Dicyclomine, an antispasmodic used to treat irritable bowel syndrome, was initially included in Bendectin (comprising doxylamine, pyridoxine, and dicyclomine), an antiemetic prescribed during pregnancy in the 1960s.
METHODS
We estimated the association between in utero exposure to Bendectin and risk of CRC in offspring of the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in Oakland, CA, between 1959 and 1966 (n = 14 507 mothers and 18 751 liveborn offspring). We reviewed prescribed medications from mothers' medical records to identify those who received Bendectin during pregnancy. Diagnoses of CRC in adult (aged ≥18 years) offspring were ascertained by linkage with the California Cancer Registry. Cox proportional hazards models were used to estimate adjusted hazard ratios, with follow-up accrued from birth through cancer diagnosis, death, or last contact.
RESULTS
Approximately 5% of offspring (n = 1014) were exposed in utero to Bendectin. Risk of CRC was higher in offspring exposed in utero (adjusted hazard ratio = 3.38, 95% confidence interval [CI] = 1.69 to 6.77) compared with unexposed offspring. Incidence rates of CRC were 30.8 (95% CI = 15.9 to 53.7) and 10.1 (95% CI = 7.9 to 12.8) per 100 000 in offspring exposed to Bendectin and unexposed, respectively.
CONCLUSIONS
Higher risk of CRC in offspring exposed in utero may be driven by dicyclomine contained in the 3-part formulation of Bendectin used during the 1960s. Experimental studies are needed to clarify these findings and identify mechanisms of risk.
Topics: Adult; Female; Humans; Pregnancy; Antiemetics; Colorectal Neoplasms; Dicyclomine; Mothers; Prenatal Exposure Delayed Effects
PubMed: 36895101
DOI: 10.1093/jncics/pkad021 -
Drugs in R&D Jun 2023Nausea and vomiting is a very prevalent condition during pregnancy. Combination of doxylamine and pyridoxine is placed as first-line pharmacological option for its...
BACKGROUND
Nausea and vomiting is a very prevalent condition during pregnancy. Combination of doxylamine and pyridoxine is placed as first-line pharmacological option for its treatment in most clinical guidelines. Among different release forms available, Cariban is a fixed-dose combination of doxylamine/pyridoxine 10/10 mg, formulated as modified-release capsules.
OBJECTIVES
In the present study, we aimed to characterize the bioavailability performance of Cariban in vitro and in vivo.
METHODS
An in vitro dissolution test was performed to evaluate the release profile of Cariban, together with immediate- and delayed-release formulations available on the market. A single-center, single-dose, open-label bioavailability study following Cariban administration in 12 healthy adult female patients was carried out to explore the drug behavior in vivo (protocol NBR-002-13; EUDRA-CT 2013-005422-35). These data were additionally used to perform a computational pharmacokinetic simulation of the posology approved for this drug.
RESULTS
Cariban capsules demonstrate a prolonged-release performance, with an early, gradual, and progressive release of both actives until reaching a complete dissolution after 4-5 h in solution. The pharmacokinetic features of these capsules show that doxylamine and pyridoxine metabolites are early absorbed, being all detectable in plasma within 1 h following oral administration. Computational pharmacokinetic simulation predicts that different posology provides distinct profiles of metabolites in plasma, with 1-1-2 (morning-midafternoon-night) being the one that concentrates higher plasma levels but lower dose dumping for 24 h.
CONCLUSION
Cariban behaves as a prolonged-release formulation, which correlates with rapid absorption and arising of the actives in the plasma, but also long-lasting and sustained bioavailability, especially when administered following the complete posology. These results would underlie its demonstrated efficacy to relieve nausea and vomiting of pregnancy (NVP) under clinical settings.
Topics: Adult; Female; Humans; Pregnancy; Antiemetics; Biological Availability; Capsules; Delayed-Action Preparations; Doxylamine; Drug Combinations; Nausea; Pregnancy Complications; Pyridoxine; Vomiting
PubMed: 37318714
DOI: 10.1007/s40268-023-00425-7