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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 -
Annals of Internal Medicine Jul 2023An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking.
OBJECTIVE
To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP.
DESIGN
Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384).
SETTING
13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022.
PARTICIPANTS
352 women in early pregnancy with moderate to severe NVP.
INTERVENTION
Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days.
MEASUREMENTS
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications.
RESULTS
No significant interaction was detected between the interventions ( = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]).
LIMITATION
The placebo effects of the interventions and natural regression of the disease were not evaluated.
CONCLUSION
Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone.
PRIMARY FUNDING SOURCE
The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.
Topics: Pregnancy; Child; Female; Humans; Doxylamine; Pyridoxine; Antiemetics; Quality of Life; Vomiting; Nausea; Pregnancy Complications; Acupuncture Therapy
PubMed: 37335994
DOI: 10.7326/M22-2974 -
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 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023The article analyzes the current literature on the relationship of insomnia with affective disorders, in particular with depression and anxiety. Research shows that... (Meta-Analysis)
Meta-Analysis
The article analyzes the current literature on the relationship of insomnia with affective disorders, in particular with depression and anxiety. Research shows that there is a strong multi-channel relationship between insomnia, depression, and anxiety, with insomnia being considered a risk factor for mood disorders more often than vice versa. The so-called insomnia paradox of bipolar disorder is described, the essence of which is that in manic episodes the frequency of insomnia is higher than in depressive episodes. The data of a network meta-analysis, which found an evidence base for the use of a variety of drugs used for the pharmacological treatment of insomnia in adults, are presented. Efficiency and convenience in taking the drug Valocordin-Doxylamine are noted.
Topics: Adult; Humans; Sleep Initiation and Maintenance Disorders; Bipolar Disorder; Anxiety Disorders; Anxiety; Doxylamine
PubMed: 37275997
DOI: 10.17116/jnevro202312305243 -
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 -
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 -
The Medical Letter on Drugs and... Jan 2023
Topics: Humans; Sleep Initiation and Maintenance Disorders; Hypnotics and Sedatives
PubMed: 36630579
DOI: 10.58347/tml.2023.1667a -
European Review For Medical and... Dec 2022
Reply Letter - to Urso et al "Comment on: Comparative dissolution profiles of two anti-emetic delayed release dosage forms of doxylamine and pyridoxine: Xonvea® tablets vs. Cariban® capsules".
Topics: Doxylamine; Pyridoxine; Antiemetics; Solubility; Ursodeoxycholic Acid; Tablets; Capsules; Gastrointestinal Agents; Delayed-Action Preparations
PubMed: 36524482
DOI: 10.26355/eurrev_202212_30533