-
The New England Journal of Medicine Apr 1998
Review
Topics: Abnormalities, Drug-Induced; Animals; Counseling; Dicyclomine; Doxylamine; Drug Combinations; Drug Evaluation, Preclinical; Drug-Related Side Effects and Adverse Reactions; Epidemiologic Studies; Female; Fetus; Humans; Infant, Newborn; Information Services; Isotretinoin; Pharmaceutical Preparations; Pregnancy; Pregnancy Complications; Pyridoxine; Risk; Teratogens; Thalidomide
PubMed: 9545362
DOI: 10.1056/NEJM199804163381607 -
Teratology Apr 1983
Review
Topics: Abnormalities, Drug-Induced; Animals; Dicyclomine; Doxylamine; Drug Combinations; Drug Utilization; Female; Fetus; Health Education; Humans; Pregnancy; Pyridines; Pyridoxine; Rabbits; Rats; Teratogens
PubMed: 6346560
DOI: 10.1002/tera.1420270216 -
PloS One 2017We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and...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We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of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 -
Clinical Pharmacology and Therapeutics May 1985The separate and combined effects of doxylamine succinate (25 mg) and acetaminophen (1 gm) on sleep were studied by interview procedures and information from medical... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The separate and combined effects of doxylamine succinate (25 mg) and acetaminophen (1 gm) on sleep were studied by interview procedures and information from medical records of 2,931 postoperative patients. The sample contained 1,617 patients with mild or moderate pain and 1,314 who were free of pain. Each received either doxylamine alone (S), acetaminophen alone (A), a combination of both drugs (C), or placebo (P). Drug treatment was double blind and randomized separately for the pain and pain-free subsamples. Twelve measures of sleep were determined. C was more beneficial than S or A, and S and A were each superior to P. For all 12 sleep measures, the effect of the combination (C - P) approximated or exceeded the sum of the two separate effects (S - P) + (A - P). The presence of either drug tended to enhance the sleep benefit of the other. The sedative and analgesic benefits to sleep were at least additive, and some outcome measures suggested synergism. In the total sample, the contributions of sedative and analgesic similar. Among patients with pain, contributions of the analgesic surpassed those of the sedative. For patients free of pain, the sedative was better, but even pain-free patients had enhanced sleep after the analgesic. The analgesic, but not the sedative, reduced pain; the analgesic induced the feeling of being well rested and not tired; the sedative induced a feeling of being drugged. Nondrug variables (e.g., pain, sex, age, and sleep expectations) influenced sleep outcome at least as much as drugs, but randomization and the large sample prevented those extraneous variables from biasing drug comparisons.
Topics: Acetaminophen; Administration, Oral; Adolescent; Adult; Aged; Double-Blind Method; Doxylamine; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Medical Records; Middle Aged; Pain, Postoperative; Pyridines; Random Allocation; Sleep; Surveys and Questionnaires
PubMed: 3987179
DOI: 10.1038/clpt.1985.87 -
Journal of Clinical Pharmacology Jul 2015Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin... (Comparative Study)
Comparative Study
Nausea and vomiting of pregnancy (NVP) is a common gestational condition. This is the first study to compare the use of vitamin B6 (pyridoxine) versus Diclectin (doxylamine succinate-pyridoxine HCl) for NVP symptoms. Participants were pregnant women with NVP who used either pyridoxine or doxylamine succinate-pyridoxine HCl for ≥4 days prior to calling the Motherisk NVP Helpline. Women receiving pyridoxine only (n = 80) were matched to a woman taking doxylamine succinate-pyridoxine HCl only (n = 80), accounting for potential confounders and baseline level of NVP, measured by the Pregnancy Unique Quantification of Emesis (PUQE) score. Change in NVP severity after a week of therapy with either pyridoxine or doxylamine succinate-pyridoxine HCl was quantified using the PUQE-24 scale, which describes NVP symptoms 24 hours prior to their call. Doxylamine succinate-pyridoxine HCl use found a significant reduction in PUQE score, compared with pyridoxine (+0.5 versus -0.2, P < .05; negative denotes worsening). This association was especially prominent in women with more severe symptoms, where doxylamine succinate-pyridoxine HCl use saw a mean improvement of 2.6 versus 0.4 with pyridoxine (P < .05). As well, doxylamine succinate-pyridoxine HCl use was associated with fewer women experiencing moderate to severe scores after a week of treatment, compared with the pyridoxine group (7 versus 17, P < .05), despite similar baseline PUQE scores.
Topics: Adult; Antiemetics; Cohort Studies; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Morning Sickness; Pregnancy; Prospective Studies; Pyridoxine; Severity of Illness Index; Treatment Outcome
PubMed: 25663469
DOI: 10.1002/jcph.480 -
Lancet (London, England) Jul 1984
Topics: Abnormalities, Drug-Induced; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Pregnancy; Pyridines; Pyridoxine
PubMed: 6146759
DOI: No ID Found -
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 -
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 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2017Evaluate the efficiency of reslip (doxylamine) in short-term insomnia in comparison with donormyl in multicenter comparative randomized study. (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
Evaluate the efficiency of reslip (doxylamine) in short-term insomnia in comparison with donormyl in multicenter comparative randomized study.
MATERIAL AND METHODS
The study was conducted in 6 medical centers and included 60 patients aged from 30 to 59 years with short-term insomnia. Patients were divided into two groups: in first one patients took reslip and in the second one donormyl in same dosage and regimen.
RESULTS
The complete clinical remission of insomnia was achieved in majority of patients in both groups. Indicators of insomnia severity, sleep quality and daytime sleepiness in both groups improved with a high significance. Side effects were mild and in most cases did not result in treatment cessation. No significant differences between the groups in terms of clinical efficacy were found.
CONCLUSION
Short-term doxylamine intake causes significant positive clinical effect in short-term insomnia with satisfactory acceptability by patients. Russian doxylamine Reslip correlates well with donormil regarding the clinical efficacy and acceptability and can be used in clinical practice for the short-term insomnia treatment.
Topics: Adult; Doxylamine; Histamine H1 Antagonists; Humans; Middle Aged; Russia; Sleep Initiation and Maintenance Disorders; Treatment Outcome
PubMed: 28777365
DOI: 10.17116/jnevro20171174256-59 -
Journal of Pharmaceutical Sciences Aug 1983A rapid and sensitive high-performance liquid chromatographic (HPLC) assay for the quantitative determination of doxylamine in plasma is described. The drug levels of...
A rapid and sensitive high-performance liquid chromatographic (HPLC) assay for the quantitative determination of doxylamine in plasma is described. The drug levels of doxylamine in plasma were monitored after the oral administration of a single 25-mg tablet of doxylamine succinate to each of 20 male volunteers. The compound was extracted from the plasma samples, concentrated under a nitrogen stream, and analyzed by HPLC using normal-phase chromatography with detection at 254 nm. The detection limit is approximately 5 ng/ml.
Topics: Adult; Chromatography, High Pressure Liquid; Doxylamine; Humans; Kinetics; Male; Middle Aged; Pyridines
PubMed: 6620159
DOI: 10.1002/jps.2600720834