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BMJ Case Reports Nov 2012Doxylamine succinate, an H(1)-antihistamine drug, is commonly used as sleep-inducing agent as well as therapy for nausea and vomiting in pregnancy. At usual doses, it...
Doxylamine succinate, an H(1)-antihistamine drug, is commonly used as sleep-inducing agent as well as therapy for nausea and vomiting in pregnancy. At usual doses, it may cause impairment of cognitive and psychomotor performance, anticholinergic effects, agitation and postural hypotension. Besides, since this drug is frequently involved in either accidental or intentional overdoses, it seems relevant to bear in mind other possible toxic effects. We report a case of acute severe hyponatremia in the setting of a syndrome of inappropriate antidiuresis (SIAD), an apparent new adverse effect linked to doxylamine overdose. The Naranjo adverse drug reaction probability scale indicated a probable relationship between doxylamine intake and SIAD development. SIAD may be considered as a potential, serious adverse reaction of doxylamine overdose. Clinicians should consider this aetiological possibility when attending patients suffering from hyponatremia.
Topics: Aged; Dose-Response Relationship, Drug; Doxylamine; Drug Overdose; Female; Glasgow Coma Scale; Humans; Hypnotics and Sedatives; Hyponatremia; Inappropriate ADH Syndrome; Saline Solution, Hypertonic; Sleep Initiation and Maintenance Disorders
PubMed: 23166178
DOI: 10.1136/bcr-2012-007428 -
Canadian Family Physician Medecin de... Oct 1984Nausea and/or vomiting affect 50% of all pregnant women. For most women, this is a self-limited problem which responds well to conservative management. However, there...
Nausea and/or vomiting affect 50% of all pregnant women. For most women, this is a self-limited problem which responds well to conservative management. However, there are some situations where the risk to the mother and fetus posed by the illness are greater than the possible risks of teratogenicity of antinauseant drugs. Antihistamines have had the widest testing, and to date, there has been no evidence linking doxylamine, dimenhydrinate or promethazine to congenital malformations. Since no available drugs have official approval for use in nausea and vomiting of pregnancy the physician is left alone to make this difficult decision.
PubMed: 21279128
DOI: No ID Found -
Canadian Medical Association Journal Feb 1981
Topics: Abnormalities, Drug-Induced; Antiemetics; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Infant, Newborn; Maternal-Fetal Exchange; Pregnancy; Pyridines; Pyridoxine; Teratogens
PubMed: 7459786
DOI: No ID Found -
PloS One 2015There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine...
BACKGROUND
There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in '90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines.
AIM
To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries.
METHODS
We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance.
RESULTS
Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible.
CONCLUSIONS
Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators and clinicians should consider risk-minimisation activities. Also antihistamines without signal but with peculiar use in a few Countries (e.g., levocetirizine) or with increasing consumption (e.g., rupatadine) deserve careful surveillance.
Topics: Administration, Oral; Adverse Drug Reaction Reporting Systems; Arrhythmias, Cardiac; Databases, Factual; Drug Utilization; Europe; Histamine H1 Antagonists; Humans; Pharmacovigilance
PubMed: 25785934
DOI: 10.1371/journal.pone.0119551 -
The Journal of Allergy and Clinical... 2013Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects.
BACKGROUND
Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects.
OBJECTIVE
To test 16 previously hypothesized associations between specific antihistamines and specific birth defects, and to identify possible new associations.
METHODS
We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within 6 months of delivery about demographic, reproductive, medical, and behavioral factors, and details on the use of prescription and nonprescription medications. We compared first trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6982 nonmalformed controls by using conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use.
RESULTS
Overall, 13.7% of controls were exposed to antihistamines during the first trimester. The most commonly used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). When estimates were stable, none supported the previously hypothesized associations. Among more than 100 exploratory comparisons of other specific antihistamine-defect pairs, 14 had odds ratios ≥1.5, of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons.
CONCLUSION
Our findings do not provide meaningful support for previously posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation that may also apply to our new findings.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Case-Control Studies; Female; Histamine Antagonists; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Risk Factors; Young Adult
PubMed: 24565715
DOI: 10.1016/j.jaip.2013.07.008 -
Indian Journal of Pharmaceutical... 2008Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine...
Two UV spectrophotometric methods have been developed, based on first derivative spectrophotometry for simultaneous estimation of doxylamine succinate, pyridoxine hydrochloride, and folic acid in tablet formulations. In method I, the concentrations of these drugs were determined by using linear regression equation. Method II is also based on first derivative spectrophotometry however simultaneous equations (Vierdot's method) were derived on derivative spectra. The first derivative amplitudes at 270.0, 332.8 and 309.2 nm were utilized for simultaneous estimation of these drugs respectively by both methods. In both the methods, linearity was obtained in the concentration range 2.5-50 mug/ml, 1-40 mug/ml and 1-30 mug/ml for doxylamine succinate, pyridoxine hydrochloride, and folic acid respectively. The developed methods show best results in terms of linearity, accuracy, precision, LOD, LOQ and ruggedness for standard laboratory mixtures of pure drugs and marketed formulations. The common excipients and additives did not interfere in their determinations.
PubMed: 20046784
DOI: 10.4103/0250-474X.44607 -
Canadian Medical Association Journal Nov 1983
Topics: Abnormalities, Drug-Induced; Canada; Dicyclomine; Doxylamine; Drug Combinations; Drug Industry; Female; Humans; Infant, Newborn; Legislation, Drug; Male; Pregnancy; Public Opinion; Pyridines; Pyridoxine; United States
PubMed: 6627167
DOI: No ID Found -
American Journal of Obstetrics and... Dec 2014Presently, 97.7% of prescriptions for the treatment of nausea and vomiting in pregnancy in the United States are with medications not labeled for use in pregnancy, not...
Presently, 97.7% of prescriptions for the treatment of nausea and vomiting in pregnancy in the United States are with medications not labeled for use in pregnancy, not indicated for nausea and vomiting in pregnancy, and not classified as safe in pregnancy by the Food and Drug Administration. The use of ondansetron for nausea and vomiting in pregnancy has increased from 50,000 monthly prescriptions in 2008 to 110,000 at the end of 2013, despite unresolved issues regarding fetal safety and Food and Drug Administration warnings about serious dysrhythmias. In April 2013, the Food and Drug Administration approved the combination of doxylamine and pyridoxine, specifically for nausea and vomiting in pregnancy symptoms. Now that a safe and effective drug is available in the United States, there is no reason for women to be exposed to a drug of unproven maternal and fetal safety.
Topics: Antiemetics; Dicyclomine; Doxylamine; Drug Approval; Drug Combinations; Female; Heart Defects, Congenital; Humans; Morning Sickness; Ondansetron; Practice Patterns, Physicians'; Pregnancy; Pyridoxine; Serotonin Syndrome; Torsades de Pointes; United States; United States Food and Drug Administration
PubMed: 25151184
DOI: 10.1016/j.ajog.2014.08.017 -
Emergency Medicine Journal : EMJ Apr 2007To compare the effectiveness and side effects of lactated Ringer's solution (LR) and 0.9% saline (NS) in the treatment of rhabdomyolysis induced by doxylamine... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To compare the effectiveness and side effects of lactated Ringer's solution (LR) and 0.9% saline (NS) in the treatment of rhabdomyolysis induced by doxylamine intoxication.
METHODS
In this 15-month-long prospective randomised single-blind study, after excluding 8 patients among 97 doxylamine-intoxicated patients, 28 (31%) patients were found to have developed rhabdomyolysis and were randomly allocated to NS group (n = 15) or LR group (n = 13).
RESULTS
After 12 h of aggressive hydration (400 ml/h), urine/serum pH was found to be significantly higher in the LR group, and serum Na+/Cl- levels to be significantly higher in the NS group. There were no significant differences in serum K+ level and in the time taken for creatine kinase normalisation. The amount of sodium bicarbonate administered and the frequency administration of diuretics was significantly higher in the NS group. Unlike the NS group, the LR group needed little supplemental sodium bicarbonate and did not develop metabolic acidosis.
CONCLUSION
LR is more useful than NS in the treatment of rhabdomyolysis induced by doxylamine intoxication.
Topics: Adult; Doxylamine; Female; Fluid Therapy; Histamine H1 Antagonists; Humans; Isotonic Solutions; Male; Prospective Studies; Rhabdomyolysis; Ringer's Lactate; Single-Blind Method; Sodium Chloride; Statistics, Nonparametric; Treatment Outcome
PubMed: 17384382
DOI: 10.1136/emj.2006.043265 -
Canadian Family Physician Medecin de... Oct 2012While I usually prescribe doxylamine-pyridoxine for morning sickness, some of my patients with severe nausea and vomiting of pregnancy (NVP) receive ondansetron in...
QUESTION
While I usually prescribe doxylamine-pyridoxine for morning sickness, some of my patients with severe nausea and vomiting of pregnancy (NVP) receive ondansetron in hospital. I have read some new precautions recommended by the US Food and Drug Administration (FDA). Is ondansetron safe to use during pregnancy?
ANSWER
During the past decade ondansetron has been increasingly used in the United States for NVP, owing to the lack of an FDA-approved drug for this condition. While fetal safety data for doxylamine-pyridoxine are based on more than a quarter of a million pregnancies, the fetal safety data for ondansetron are based on fewer than 200 births. Moreover, a recent case-control study suggested there was an increased risk of cleft palate associated with ondansetron. Recently, the FDA issued a warning about potentially serious QT prolongation and torsade de pointes associated with ondansetron use; the warning included a list of precautions and tests that must be followed. The drug is not labeled for use in NVP in either the United States or Canada. Based on the data available today, ondansetron use cannot be assumed to be safe during pregnancy.
Topics: Antiemetics; Canada; Cleft Palate; Female; Fetus; Humans; Long QT Syndrome; Morning Sickness; Nausea; Ondansetron; Pregnancy; Pregnancy Complications, Cardiovascular; United States; Vomiting
PubMed: 23064917
DOI: No ID Found