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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 -
Expert Opinion on Drug Safety Dec 2014Approximately 10 - 15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion.... (Review)
Review
INTRODUCTION
Approximately 10 - 15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion. Antihistamines include histamine H1-receptor and H2-receptor antagonists.
AREAS COVERED
This is a systematic evaluation of the peer-reviewed epidemiologic literature published through February 2014 on the association between prenatal exposure to antihistamines and birth defects. Papers addressing histamine H1- or H2-receptor antagonists are included. Papers addressing pyridoxine plus doxylamine (Bendectin in the United States, Debendox in the United Kingdom, Diclectin in Canada, Lenotan and Merbental in other countries) prior to the year 2001 were excluded post hoc because of several previously published meta-analyses and commentaries on this medication.
EXPERT OPINION
The literature on the safety of antihistamine use during pregnancy with respect to birth defects is generally reassuring though the positive findings from a few large studies warrant corroboration in other populations. The findings in the literature are considered in light of three critical methodological issues: i) selection of appropriate study population; ii) ascertainment of antihistamine exposures; and iii) ascertainment of birth defect outcomes. Selected antihistamines have been very well studied (e.g., loratadine); others, especially H2-receptor antagonists, require additional study before an assessment of safety with respect to birth defect risk could be made.
Topics: Congenital Abnormalities; Female; Histamine Antagonists; Humans; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 25307228
DOI: 10.1517/14740338.2014.970164 -
The Turkish Journal of Pediatrics 2018Derinöz-Güleryüz O. Doxylamine succinate overdose: Slurred speech and visual hallucination. Turk J Pediatr 2018; 60: 439-442. Doxylamine succinate is a commonly used...
Derinöz-Güleryüz O. Doxylamine succinate overdose: Slurred speech and visual hallucination. Turk J Pediatr 2018; 60: 439-442. Doxylamine succinate is a commonly used antihistamine for respiratory allergies including allergic rhinitis as well as for the management of insomnia. As it is available over-the-counter like other nonprescription antihistamines and sleep aids, there is a risk of overdose. It is believed that doxylamine succinate has both peripheral and central activity with its anticholinergic properties. Delirium, seizures, and coma are among the central adverse effects that are rare. This case was presented since it is the first case in the literature who developed slurred speech and visual hallucination after high dose doxylamine succinate use and received antidotal therapy for anticholinergic side effects.
Topics: Adolescent; Cholinesterase Inhibitors; Doxylamine; Drug Overdose; Female; Hallucinations; Histamine H1 Antagonists; Humans; Physostigmine; Speech; Speech Disorders
PubMed: 30859772
DOI: 10.24953/turkjped.2018.04.015 -
American Journal of Public Health Dec 1986In a case-control study spanning five years' experience at Group Health Cooperative of Puget Sound, we could demonstrate no plausible association between the use of...
In a case-control study spanning five years' experience at Group Health Cooperative of Puget Sound, we could demonstrate no plausible association between the use of spermicides, oral contraceptives, Bendectin, or antibiotics prior to conception and the occurrence of 73 nontraumatic stillbirths.
Topics: Abnormalities, Drug-Induced; Adult; Anti-Bacterial Agents; Contraceptives, Oral; Dicyclomine; Doxylamine; Drug Combinations; Female; Fetal Death; Health Surveys; Humans; Pregnancy; Pyridines; Pyridoxine; Spermatocidal Agents
PubMed: 3777291
DOI: 10.2105/ajph.76.12.1428 -
Neurology. Clinical Practice Oct 2021
PubMed: 34840894
DOI: 10.1212/CPJ.0000000000000956 -
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 -
Therapeutic Drug Monitoring Oct 2012Women often hesitate to take medications in pregnancy due to fears of perceived potential fetal damage. The authors' objective is to identify the determinants of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Women often hesitate to take medications in pregnancy due to fears of perceived potential fetal damage. The authors' objective is to identify the determinants of adherence to delayed-release doxylamine-pyridoxine (Diclectin) in patients with nausea and vomiting of pregnancy (NVP).
METHODS
The authors performed a prespecified secondary analysis of a multicenter double-blind randomized controlled trial of Diclectin versus placebo for the treatment of NVP. Data on adherence to study medication were collected in all patients. The primary outcome of this analysis was adherence to study medication, which was determined by pill counting and patient diaries. The treatment regimen in the original trial was not fixed and depended on patient's symptoms. There was no difference in the adherence rates between subjects in the Diclectin or placebo arms of the study, so the 2 arms were analyzed as one cohort. The degree of adherence was analyzed in the various subgroups. Subsequently, a multiple linear regression model was constructed to identify predictors to adherence.
RESULTS
Two hundred fifty-eight women were included in this analysis. There were no differences in adherence rates according to ethnicity, race, or the presence of adverse events. Gravidity, average number of prescribed tablets per day, site of enrollment, and change in NVP severity measured by the pregnancy unique-quantification of emesis score were associated with adherence. In multivariable analysis, average number of tablets per day, change in pregnancy unique-quantification of emesis, number of treatment days, site of enrollment were significantly predictive of adherence, with the former being negatively correlated.
CONCLUSION
Adherence to antinauseants for NVP is affected by number of tablets prescribed per day, and treatment duration and effectiveness.
Topics: Adult; Antiemetics; Cohort Studies; Delayed-Action Preparations; Dicyclomine; Double-Blind Method; Doxylamine; Drug Combinations; Female; Humans; Medication Adherence; Nausea; Pregnancy; Pregnancy Complications; Pyridoxine; Vomiting
PubMed: 22972538
DOI: 10.1097/FTD.0b013e31826e7997 -
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 -
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 -
Drugs in R&D Jun 2013Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose... (Randomized Controlled Trial)
Randomized Controlled Trial
Pharmacokinetic dose proportionality between two strengths (12.5 mg and 25 mg) of doxylamine hydrogen succinate film-coated tablets in fasting state: a single-dose, randomized, two-period crossover study in healthy volunteers.
BACKGROUND
Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of doxylamine are available, although this drug has been marketed in European countries for more than 50 years.
OBJECTIVE
The objective of this study was to evaluate and compare the dose proportionality between two marketed strengths (12.5 mg and 25 mg) of doxylamine hydrogen succinate after a single oral dose administration under fasting conditions in healthy human subjects.
STUDY DESIGN
This was a single-center, randomized, single dose, laboratory-blinded, two-period, two-sequence, crossover study.
SETTING
The study was conducted in a phase I clinical unit.
SUBJECTS AND METHODS
A single oral dose of doxylamine hydrogen succinate of 12.5 mg (equivalent to 8.7 mg of doxylamine base) or 25 mg (equivalent to 17.4 mg of doxylamine base) was administered to healthy volunteers under fasting conditions in each study period. The drug administrations were separated by a wash-out period of 7 calendar days. Blood samples were collected for up to 60 h post-dose, and plasma doxylamine levels were determined by an ultra high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using non-compartmental analysis. Dose proportionality was assessed based on the parameter area under the concentration-time curve (AUCt normalized). Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs and 12-lead electrocardiogram (ECG).
RESULTS
In total, 12 healthy volunteers (3 male; 9 female) were included in the study. Mean maximum observed plasma concentration (Cmax) and area under the concentration-time curve from time zero to time t (AUCt ) of doxylamine hydrogen succinate 12.5 mg and 25 mg tablets increased linearly and dose-dependently [12.5 mg: mean Cmax 61.94 ng/mL, coefficient of variation (CV) 23.2%; mean AUCt 817.33 ng·h/mL, CV 27.4%; and 25 mg: mean Cmax 124.91 ng/mL, CV 18.7%; mean AUCt 1630.85 ng·h/mL, CV 22.8%]. Mean AUCt normalized was 815.43 ng·h/mL, CV 22.8% for 25 mg. The dose-normalized geometric mean ratio (%, 12.5 mg/25 mg) of AUCt was 98.92 (90% CI: 92.46, 105.83). The most common adverse event was somnolence.
CONCLUSIONS
Exposure to doxylamine was proportional over the therapeutic dose range of 12.5-25 mg in healthy volunteers. Based on the results, a predictable and linear increase in systemic exposure can be expected. Doxylamine hydrogen succinate was safe and well tolerated.
Topics: Adult; Biological Availability; Cross-Over Studies; Dose-Response Relationship, Drug; Doxylamine; Fasting; Female; Healthy Volunteers; Histamine H1 Antagonists; Humans; Male; Medication Adherence; Middle Aged; Tablets
PubMed: 23633146
DOI: 10.1007/s40268-013-0015-7