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BMC Pregnancy and Childbirth Mar 2015Nausea 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... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Nausea 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.
METHODS
We 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.
RESULTS
Doxylamine 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.
CONCLUSIONS
Doxylamine 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 REGISTRATION
Clinical Trial Registration No: NCT00614445 .
Topics: Adult; Antiemetics; Delayed-Action Preparations; Dicyclomine; Double-Blind Method; Doxylamine; Drug Combinations; Drug Monitoring; Female; Histamine H1 Antagonists; Humans; Nausea; Pregnancy; Pregnancy Complications; Pyridoxine; Treatment Outcome; Vitamin B Complex; Vomiting
PubMed: 25884778
DOI: 10.1186/s12884-015-0488-1 -
BMC Chemistry Mar 2023A sequential spectrophotometric resolution technique (SSRT) was developed in this study without the use of systematic separation procedures to determine drug of a...
The simultaneous measurement of quaternary mixture in over-the-counter cold medications using sequential spectrophotometric resolution approach enhanced with in-lab sample enrichment.
A sequential spectrophotometric resolution technique (SSRT) was developed in this study without the use of systematic separation procedures to determine drug of a quaternary combination; caffeine (CAF), pseudoephedrine (PSE), doxylamine succinate (DOX), and paracetamol (PAR). Their presence in a tablet with a gap ratio of 3:3:1:150, respectively, and their overlapping spectra with low absorptivities make their resolution and determination impossible without prior separation. successive ratio subtraction technique (SRST) and constant multiplication method were used to solve these problems. Furthermore, an in-lab sample enrichment technique was applied to increase minor components concentration and consequently their absorbanses (CAF, PSE, and DOX). The D absorption spectra were generated by successive ratios followed by subtraction and multiplication of the constants. The maximum absorbances of the drugs tested, namely (CAF, PSE, DOX and PAR) were measured at wavelengths of 272.0, 257.0, 260.0, and 248.0 nm, respectively. The limits of detection (LOD) and limits of quantification (LOQ) were 0.021, 0.124, 0.186, 0.137 and 0.070, 0.414, 0.621, 0.456 (µg/mL), respectively. The linearitiy ranges (µg/mL) were 1.0-22.0, 1.0-24.0, 10.0-90.0 and 1.0-15.0 for CAF, PSE, DOX, and PAR, respectively. The International Conference on Harmonization (ICH) guidelines were applied for method validation, and the results obtained were within the limited parameters. The finding results were compared to official and/or published analytical methods to determine the procedure's reliability. It was noted that there was no actual difference in accuracy and precision between both meyhods. The proposed technique is sensitive, selective and economic;so it can be applied to the simultaneous analysis of these drugs in their commercial tablets and/or in quality-control laboratories.
PubMed: 36949535
DOI: 10.1186/s13065-023-00931-4 -
Clinical Toxicology (Philadelphia, Pa.) Mar 2015Doxylamine is a first-generation antihistamine similar in structure to diphenhydramine. Unlike diphenhydramine, however, there is a paucity of data regarding the risk of... (Observational Study)
Observational Study
BACKGROUND
Doxylamine is a first-generation antihistamine similar in structure to diphenhydramine. Unlike diphenhydramine, however, there is a paucity of data regarding the risk of toxicity following unintentional exposures in pediatric patients.
METHODS
We performed an observational case series with data collected retrospectively from a poison system database for all single-substance pediatric (5 years-old and younger) doxylamine ingestions for the period of 1997-2012. Data collected included age, gender, weight, reason for exposure, exact or estimated maximum dose, clinical effects and medical interventions.
RESULTS
A total of 140 cases were identified; 74 (53%) involved males. Ages ranged 6 months to 5 years. In 30 cases (21%), the exact amount ingested was documented and ranged from 6.25-50 mg with a maximum weight-based dose of 6.2 mg/kg. In 76 cases, the estimated maximum dose ranged from 12.5 to 375 mg with a maximum weight-based dose of 37 mg/kg. All symptoms were mild and self-limiting. The only documented intervention was the administration of activated charcoal in 13 cases.
CONCLUSION
Unintentional isolated pediatric doxylamine ingestions did not result in significant toxicity in our 140 cases. Reported doses of up to 6.2 mg/kg resulted in only transient drowsiness and tachycardia.
Topics: Accidents; Age Factors; Antidotes; California; Charcoal; Child, Preschool; Dose-Response Relationship, Drug; Doxylamine; Female; Histamine H1 Antagonists; Humans; Infant; Male; Poisoning; Retrospective Studies; Risk Assessment; Risk Factors; Sleep Stages; Tachycardia; Treatment Outcome
PubMed: 25661472
DOI: 10.3109/15563650.2015.1006400 -
Journal of Hazardous Materials Aug 2024Ubiquitous distribution of pharmaceutical contaminants in environment has caused unexpected adverse effects on ecological organisms; however, how microorganisms recover...
Ubiquitous distribution of pharmaceutical contaminants in environment has caused unexpected adverse effects on ecological organisms; however, how microorganisms recover from their toxicities remains largely unknown. In this study, we comprehensively investigated the effect of a representative pollutant, doxylamine (DOX) on a freshwater microalgal species, Chlorella sp. by analyzing the growth patterns, biochemical changes (total chlorophyll, carotenoid, carbohydrate, protein, and antioxidant enzymes), and transcriptomics. We found toxicity of DOX on Chlorella sp. was mainly caused by disrupting synthesis of ribosomes in nucleolus, and r/t RNA binding and processing. Intriguingly, additional bicarbonate enhanced the toxicity of DOX with decreasing the half-maximum effective concentrations from 15.34 mg L to 4.63 mg L, which can be caused by inhibiting fatty acid oxidation and amino acid metabolism. Microalgal cells can recover from this stress via upregulating antioxidant enzymatic activities to neutralize oxidative stresses, and photosynthetic pathways and nitrogen metabolism to supply more energies and cellular signaling molecules. This study extended our understanding on how microalgae can recover from chemical toxicity, and also emphasized the effect of environmental factors on the toxicity of these contaminants on aquatic microorganisms.
Topics: Chlorella; Water Pollutants, Chemical; Transcriptome; Microalgae; Chlorophyll; Photosynthesis; Oxidative Stress; Carotenoids; Antioxidants
PubMed: 38815390
DOI: 10.1016/j.jhazmat.2024.134752 -
JAMA Otolaryngology-- Head & Neck... Sep 2020Sinonasal remedies are the most frequently purchased category of over-the-counter (OTC) drugs in the United States. A variety of options for relief are available under...
IMPORTANCE
Sinonasal remedies are the most frequently purchased category of over-the-counter (OTC) drugs in the United States. A variety of options for relief are available under proprietary names, although the actual number of available options may not be readily appreciated by the consumer or the clinician.
OBJECTIVE
To determine the prevalence of specific ingredients in OTC sinonasal products.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study took physical inventory of brand-name and generic OTC drugs marketed as sinus, cold, allergy, or nasal remedies. Retail pharmacies in New Orleans, Louisiana, commercial websites, and the Drugs, Herbs and Supplements section of MedlinePlus and drugs.com were searched. Data were collected and analyzed from July 1 to 31, 2018.
MAIN OUTCOMES AND MEASURES
Frequency of active ingredients in OTC formulations.
RESULTS
Five pharmacies were visited to identify 18 brands, for which the commercial websites were then searched. The 14 most common brands represented 211 unique products. Only 8 unique nonanalgesic ingredients were identified among these products, with many products sold under the same brand name and with the same active ingredient. Phenylephrine hydrochloride, dextromethorphan hydrobromide, pseudoephedrine hydrochloride, guaifenesin, chlorpheniramine maleate, brompheniramine maleate, diphenhydramine hydrochloride, and doxylamine succinate were the common active ingredients, with all available OTC sinonasal remedies consisting of 1 or more of these ingredients. The frequency of occurrence of each ingredient ranged from 10 to 261 different products. Combinations of 2, 3, or 4 active ingredients occurred frequently in OTC sinonasal products.
CONCLUSIONS AND RELEVANCE
These findings suggest that proliferation of brand extension products under a common name is pervasive. Clinicians should be aware of the large array of redundant OTC formulations and lack of specificity when discussing brand-name sinonasal remedies with their patients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Drug Combinations; Histamine Antagonists; Humans; Nonprescription Drugs; Respiratory System Agents; United States
PubMed: 32672802
DOI: 10.1001/jamaoto.2020.1836 -
American Journal of Obstetrics and... May 2016
Randomized Controlled Trial
Topics: Delayed-Action Preparations; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Morning Sickness; Pregnancy; Pyridoxine
PubMed: 26844757
DOI: 10.1016/j.ajog.2016.01.186 -
Spectrochimica Acta. Part A, Molecular... Feb 2021The combination of pyridoxine HCl (PYR) and doxylamine succinate (DOX) was proved to be effective and safe acting as the first line of pregnancy medication for vomiting...
In vitro analytical dissolution profiling of antiemetic delayed release tablets in two different dissolution media: Validated spectrophotometric methods versus reported HPLC.
The combination of pyridoxine HCl (PYR) and doxylamine succinate (DOX) was proved to be effective and safe acting as the first line of pregnancy medication for vomiting and nausea under a trade name; Vomibreak® delayed release tablets. This combination has been available in the Egyptian market since 2016. Dissolution study is a meaningful tool that represents a predictor of output because the rate controlling steps in any drug's absorption is the rate of discharging from its medicinal formulation. Generally, the dissolution test of all delayed release tablets is operated at two stages: first the acid stage then the buffer stage. In our work, the acid stage was performed in 0.1 N hydrochloric acid (0.1 M HCl) and the buffer one was in 0.2 M sodium phosphate buffer (0.2 M Na-PB), pH = 6.8, according to FDA guidelines. In present work, for the first time, this binary mixture was quantitatively determined by applying four spectrophotometric methods. PYR was directly determined by zero order spectra method (D) at 291.0 nm in the range 2.0-26.0 μg/mL in the acid stage and at 325.0 nm in the range 5.0-35.0 μg/mL in the buffer stage, where DOX show no interference in both cases. However, DOX was determined by three methods, namely, Dual wavelength (DW), Ratio difference (RD) and Derivative ratio (DD). DD was the chosen method for determination of DOX in the two-phase dissolution study of Vomibreak® tablets at 249.0 nm in the range 2.0-44.0 μg/mL and 273.0 nm in the range 5.0-100.0 μg/mL in acid and buffer phases, respectively. All of the suggested methods were tested in compliance with ICH guidelines, where all methods were found to be reliable, reproducible, and selective. A statistical comparison was computed between two analytical techniques of critical importance in the development of two media dissolution profile: proposed UV- spectrophotometric and reported HPLC methods where no significant difference was found. Difference (ƒ) and similarity (ƒ) factors were calculated for PYR and DOX and shown that ƒ was 1.490 and 1.654 and ƒ was 94.431 and 92.396 for PYR and DOX, respectively.
Topics: Antiemetics; Chromatography, High Pressure Liquid; Egypt; Female; Humans; Pregnancy; Solubility; Tablets
PubMed: 33049467
DOI: 10.1016/j.saa.2020.119013 -
Journal of Clinical Epidemiology Dec 2019The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics.
OBJECTIVES
The aim of the study was to quantify the risk of major congenital malformations (MCM) associated with first-trimester exposure to antiemetics.
STUDY DESIGN AND SETTING
Using the Quebec Pregnancy Cohort (1998-2015), first-trimester doxylamine-pyridoxine, metoclopramide, and ondansetron exposures were assessed for their association with MCM. Generalized estimating equations were used to estimate odds ratios (OR), adjusting for potential confounders (aOR).
RESULTS
Within 17 years of follow-up, the prevalence of antiemetic use during pregnancy increased by 76%. Within our cohort, 45,623 pregnancies were exposed to doxylamine-pyridoxine, 958 to metoclopramide, and 31 to ondansetron. Doxylamine-pyridoxine and metoclopramide use were associated with an increased risk of overall MCM (aOR 1.07, 95% confidence interval [CI]: 1.03-1.11; 3,945 exposed cases) and (aOR 1.27, 95% CI: 1.03-1.57; 105 exposed cases), respectively. Doxylamine-pyridoxine exposure was associated with increased risks of spina bifida (aOR 1.87, 95% CI: 1.11-3.14; 23 exposed cases), nervous system (aOR 1.25, 95% CI: 1.06-1.47; 225 exposed cases), and musculoskeletal system defects (aOR 1.08, 95% CI: 1.02-1.14; 1,735 exposed cases). Metoclopramide exposure was associated with an increased risk of genital organ defects (aOR 2.26, 95% CI: 1.14-4.48; 10 exposed cases). No statistically significant association was found between ondansetron exposure and the risk of overall MCM.
CONCLUSION
First-trimester doxylamine-pyridoxine and metoclopramide exposure was associated with a significantly increased risk of overall and specific MCM.
Topics: Abnormalities, Drug-Induced; Adult; Antiemetics; Cohort Studies; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Male; Maternal Age; Metoclopramide; Nausea; Ondansetron; Pregnancy; Pregnancy Trimester, First; Prevalence; Pyridoxine; Quebec; Vomiting; Young Adult
PubMed: 31352006
DOI: 10.1016/j.jclinepi.2019.07.014 -
Drugs in R&D Jun 2018Doxylamine tablets are approved as an over-the-counter sleep aid. We developed a doxylamine succinate intranasal metered-dose delivery system with the expectation of a... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Doxylamine tablets are approved as an over-the-counter sleep aid. We developed a doxylamine succinate intranasal metered-dose delivery system with the expectation of a more rapid onset of action with reduced side-effect potential compared with the oral tablet.
METHODS
This phase I study randomized 24 adults with chronic intermittent sleep impairment to receive either single doses of intranasal doxylamine succinate 3.2, 6.3, or 12.7 mg or doxylamine succinate 25-mg oral tablet. Doxylamine pharmacokinetics were assessed using noncompartmental methods; pharmacodynamics were evaluated using the Karolinska Sleepiness Scale (KSS) and numerous psychomotor tests. Adverse events (AEs) were monitored.
RESULTS
None of the intranasal dose levels produced a mean maximum plasma concentration (C) above the 50 ng/mL target level or a time to maximum concentration shorter than that of the oral tablet. At the highest intranasal dose, C and area under the doxylamine concentration-time curve were approximately 25% of the values achieved with the oral dose. Variation in most pharmacokinetic parameters was higher with intranasal compared with oral dosing. A relationship between plasma doxylamine concentration and KSS change from baseline was evident for the 25-mg tablet and, to a lesser extent, for the 12.7-mg intranasal dose. Changes from baseline in psychomotor parameters did not show a relationship to intranasal dose, and did not distinguish between intranasal versus oral dosing. The most common AEs with intranasal dosing were nasal congestion, nasal dryness, and frontal headache.
CONCLUSION
The nasal spray did not increase doxylamine absorption or systemic bioavailability compared with the oral tablet.
Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Biological Availability; Cross-Over Studies; Dose-Response Relationship, Drug; Doxylamine; Female; Histamine H1 Antagonists; Humans; Male; Metered Dose Inhalers; Middle Aged; Sleep Initiation and Maintenance Disorders; Young Adult
PubMed: 29671128
DOI: 10.1007/s40268-018-0232-1 -
Expert Review of Clinical Pharmacology Nov 2018Several drugs were explored for their utility in treating nausea and vomiting in pregnancy (NVP). The present study is a network meta-analysis of such drugs. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Several drugs were explored for their utility in treating nausea and vomiting in pregnancy (NVP). The present study is a network meta-analysis of such drugs.
METHODS
Electronic databases were searched for randomized clinical trials that have compared active interventions (with placebo or other active interventions) for treating NVP. Nausea scores were the primary outcome and changes in nausea scores, emetic episodes, adverse events, and vomiting control were the key secondary outcomes. Weighted mean difference was the effect estimate for continuous variable and odds ratio for the numerical variable. Random-effects model was used and the strength of the evidence was graded.
RESULTS
Fifty studies were included in the systematic review and 42 in the meta-analysis. Acupuncture, chamomile, dimenhydrinate, doxylamine/vitamin B6, ginger, quince, metoclopramide, and vitamin B6 were associated with reduced nausea scores compared to placebo. Of these interventions, ginger and vitamin B6 were also associated with better vomiting control and less incidence of adverse events. Adequate evidence supporting the use exists only for ginger and the quality of evidence for this comparison is moderate. Strength of evidence for all other comparisons is very low.
CONCLUSION
Present evidence is conclusive on the therapeutic benefits of ginger in treating NVP. Although favorable results were obtained for several other interventions, the strength of evidence is very low. The results of this network meta-analysis should be interpreted with extreme caution as it might change with the advent of data from future head-to-head clinical trials.
Topics: Acupuncture Therapy; Antiemetics; Female; Zingiber officinale; Humans; Hyperemesis Gravidarum; Morning Sickness; Network Meta-Analysis; Pregnancy; Randomized Controlled Trials as Topic; Vitamin B 6
PubMed: 30261764
DOI: 10.1080/17512433.2018.1530108