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American Family Physician Jul 2003Nausea and vomiting of pregnancy, commonly known as "morning sickness," affects approximately 80 percent of pregnant women. Although several theories have been proposed,... (Review)
Review
Nausea and vomiting of pregnancy, commonly known as "morning sickness," affects approximately 80 percent of pregnant women. Although several theories have been proposed, the exact cause remains unclear. Recent research has implicated Helicobacter pylori as one possible cause. Nausea and vomiting of pregnancy is generally a mild, self-limited condition that may be controlled with conservative measures. A small percentage of pregnant women have a more profound course, with the most severe form being hyperemesis gravidarum. Unlike morning sickness, hyperemesis gravidarum may have negative implications for maternal and fetal health. Physicians should carefully evaluate patients with nonresolving or worsening symptoms to rule out the most common pregnancy-related and nonpregnancy-related causes of severe vomiting. Once pathologic causes have been ruled out, treatment is individualized. Initial treatment should be conservative and should involve dietary changes, emotional support, and perhaps alternative therapy such as ginger or acupressure. Women with more complicated nausea and vomiting of pregnancy also may need pharmacologic therapy. Several medications, including pyridoxine and doxylamine, have been shown to be safe and effective treatments. Pregnant women who have severe vomiting may require hospitalization, orally or intravenously administered corticosteroid therapy, and total parenteral nutrition.
Topics: Acupressure; Antiemetics; Diagnosis, Differential; Doxylamine; Female; Zingiber officinale; Humans; Hyperemesis Gravidarum; Nausea; Ondansetron; Pregnancy; Pregnancy Complications; Vomiting
PubMed: 12887118
DOI: No ID Found -
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 -
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 -
PloS One 2017We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and... (Randomized Controlled Trial)
Randomized Controlled Trial
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.
Topics: Cooperative Behavior; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Nausea; Physicians; Placebos; Pregnancy; Pregnancy Complications; Publication Bias; Publications; Pyridoxine; Research Report; Risk; Vomiting
PubMed: 28052111
DOI: 10.1371/journal.pone.0167609 -
International Journal of Clinical... Aug 2017Background The unintentional misuse of over-the-counter sleep aids among older adults is an important public health problem and a focus of Healthy People 2020....
Background The unintentional misuse of over-the-counter sleep aids among older adults is an important public health problem and a focus of Healthy People 2020. Accordingly, the 2015 Beers Criteria for Potentially Inappropriate Medication Use in Older Adults recommends that individuals 65 years or older avoid use of diphenhydramine and doxylamine; however, many over-the-counter sleep products contain these active ingredients. Objective To identify the proportion of older adults using an over-the-counter medication containing diphenhydramine or doxylamine, and compare their characteristics with older adults using an over-the-counter medication that does not contain these ingredients. Setting Study participants were recruited from the Community Registry of the Pittsburgh Claude D. Pepper Older Americans Independence Center. Method The study sample was taken from a larger survey of 1025 participants on sleep health and over-the-counter sleep medication use conducted from February to April 2015. A subset of 169 participants aged 65 and older reporting taking at least one over-the-counter product to improve sleep within the past 30 days (16.5%) were selected for our analysis on associations between participant characteristics and potentially inappropriate use of over-the-counter sleep medications. Main outcome measure The proportion and characteristics of older adults taking at least one over-the-counter medication containing diphenhydramine or doxylamine. Results Of the 223 over-the-counter sleep medications listed by participants, 115 (52%) contained diphenhydramine or doxylamine. Using the Beers Criteria, we found that more than half of participants (59%) had used a potentially inappropriate over-the-counter medication containing diphenhydramine or doxylamine to improve sleep within the past 30 days. Participants taking at least one diphenhydramine or doxylamine containing medication were less likely to be aware of any safety risks in taking over-the-counter sleep medications than participants not taking these products (38 vs 49%, p = 0.016). Conclusion A majority of older adults in a limited sample from the United States taking an over-the-counter medication to improve sleep are taking a product containing diphenhydramine or doxylamine, both of which are classified as potentially inappropriate for older adults. Awareness of the safety risks of over-the-counter medications and addressing conditions that impact sleep quality could be facilitated through consultation with pharmacists and other healthcare providers.
Topics: Age Factors; Aged; Aged, 80 and over; Cross-Sectional Studies; Diphenhydramine; Doxylamine; Female; Histamine H1 Antagonists; Humans; Male; Nonprescription Drugs; Sleep Aids, Pharmaceutical; Sleep Wake Disorders; Surveys and Questionnaires
PubMed: 28466395
DOI: 10.1007/s11096-017-0467-x -
The Israel Medical Association Journal... Jan 2013Diclectin (pyridoxine 10 mg and doxylamine 10 mg) has traditionally been used to treat nausea and vomiting of pregnancy (NVP); however, this drug is unavailable in many... (Comparative Study)
Comparative Study
BACKGROUND
Diclectin (pyridoxine 10 mg and doxylamine 10 mg) has traditionally been used to treat nausea and vomiting of pregnancy (NVP); however, this drug is unavailable in many countries.
OBJECTIVES
To evaluate the efficacy and safety of a simple bi-daily treatment regimen with the combination of pyridoxine (50 mg twice daily) and doxylamine (25-50 mg) as an alternative treatment for NVP.
METHODS
A prospective case-controlled observational study of mother-infant pairs was conducted between February 2008 and December 2010. All women who contacted the Beilinson Teratology Information Service (BELTIS) regarding treatment of NVP were eligible for inclusion. Using data on NVP severity, treatment efficacy and outcomes, we compared the two groups of women: those treated with the combination of pyridoxine and doxylamine (treatment group, n=29) and those treated with metoclopramide (control group, n=29).
RESULTS
Moderate to severe symptoms were present in 97% of the treatment group women vs. 69% of control group women (P < 0.01). Despite increased symptom severity in the treatment group, the combination regimen was efficacious: 20/29 (69%) vs. 18/25 (72%) in the treatment vs. control women respectively (P = 0.65). There were no congenital anomalies in the treatment group. Follow-up was normal for all infants.
CONCLUSIONS
Bi-daily combination therapy with pyridoxine and doxylamine for NVP is safe, has comparable efficacy to metoclopramide, and is a treatment alternative in countries where Diclectin is not available. Despite symptoms warranting counseling by a teratology information service, more than a third of women do not take the suggested treatment.
Topics: Administration, Oral; Adult; Antiemetics; Case-Control Studies; Dicyclomine; Dose-Response Relationship, Drug; Doxylamine; Drug Administration Schedule; Drug Combinations; Female; Humans; Nausea; Pregnancy; Pregnancy Complications; Prospective Studies; Pyridoxine; Surveys and Questionnaires; Treatment Outcome; Vitamin B Complex; Vomiting
PubMed: 23484234
DOI: No ID Found -
Cureus Aug 2023A 52-year-old male with acute onset right-sided weakness, numbness, and buttock pain after consuming 30 tablets of doxylamine antihistamine the night prior. Laboratory...
A 52-year-old male with acute onset right-sided weakness, numbness, and buttock pain after consuming 30 tablets of doxylamine antihistamine the night prior. Laboratory tests showed elevated creatinine kinase, blood urea nitrogen, creatinine, troponins, liver transaminases, and phosphate. The patient was admitted to the medical intensive care unit for severe rhabdomyolysis, acute liver failure, and acute kidney injury secondary to doxylamine intoxication. Studies describe symptoms of severe doxylamine intoxication, such as impaired consciousness (coma), grand mal seizures, and cardiopulmonary arrest. Circulating myoglobin causes oxidative injury to the kidney through the formation of F2-isoprostanes leading to renal vasoconstriction. One study explained drug-induced rhabdomyolysis via two mechanisms: direct drug injury to the striated muscle and local muscle compression in seizure, coma, and metabolic abnormality. Treatment involves aggressive hydration with monitoring of serum electrolytes and renal function. Aggressive volume expansion via intravenous fluids remains critical in preventing rhabdomyolysis-associated nephrotoxicity and myoglobin-induced acute renal failure. Alkalinization of urine may prevent renal vasoconstriction resulting in enhanced excretion of the toxic metabolites of doxylamine and myoglobin via renal tubules, thereby reducing peak serum concentration time and preventing direct renal tissue damage.
PubMed: 37581198
DOI: 10.7759/cureus.43395 -
British Medical Journal (Clinical... Oct 1985
Topics: Abnormalities, Drug-Induced; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Infant, Newborn; Pregnancy; Pyridines; Pyridoxine; Risk; United Kingdom
PubMed: 3929963
DOI: 10.1136/bmj.291.6500.918 -
Hospital Pharmacy Oct 2013Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The...
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The October 2013 monograph topics are afatinib, ferric carboxymaltose, cangrelor, vedolizumab, and albiglutide. The DUE/MUE is on afatinib.
PubMed: 24421551
DOI: 10.1310/hpj4809-762 -
European Review For Medical and... Jun 2022Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose...
OBJECTIVE
Nausea and vomiting of pregnancy is a common disease that affects many women suffering from mild to severe symptoms. Amongst the different treatments, a fixed dose combination of doxylamine and pyridoxine has been proven safe and effective although the mechanism of action is not well established. There are different pharmaceutical dosage forms in the European market. The objective of this study was to compare the characteristics of a capsule formulation, Cariban® and a tablet formulation, Xonvea® to evaluate the potential impact of their release profiles on their onset of action.
MATERIALS AND METHODS
10 mg/10 mg of doxylamine succinate/pyridoxine hydrochloride capsules (Cariban®) and tablets (Xonvea®) were used as reference materials. Appearance, mass, composition, and in vitro dissolution profiles were compared. Bibliographic data from 4 pharmacokinetic studies of Xonvea® and 1 pharmacokinetic study of Cariban® was reviewed.
RESULTS
In vitro dissolution studies showed significant differences in dissolution profiles of tablets and capsules. The later exhibiting some release of both drug substances in acid conditions followed by a non-complete release after a total of 3 hours while the tablets demonstrated gastro-resistant properties and rapid API release in about 20-30 minutes after the acid stage. Comparison of PK data showed greater Cmax for pyridoxine.
CONCLUSIONS
At pH 6.8, complete and faster release of the fixed dose combination for Xonvea® gastro-resistant tablets compared to Cariban® capsules could possibly explain the greater Cmax observed in vivo for the tablet's formulation. This could translate into faster onset of action and relief of nausea for pregnant women taking the tablets vs. the capsules.
Topics: Antiemetics; Doxylamine; Female; Gastrointestinal Agents; Humans; Nausea; Pregnancy; Pyridoxine; Solubility; Tablets
PubMed: 35776043
DOI: 10.26355/eurrev_202206_29081