-
International Journal of Women's Health 2014Nausea and vomiting in pregnancy (NVP) is common and often undertreated, in part due to fears of adverse effects of medications on the fetus during early pregnancy. In... (Review)
Review
Nausea and vomiting in pregnancy (NVP) is common and often undertreated, in part due to fears of adverse effects of medications on the fetus during early pregnancy. In April 2013, the US Food and Drug Administration (FDA) approved doxylamine succinate 10 mg and pyridoxine hydrochloride (a vitamin B6 analog) 10 mg as a delayed-release combination pill called Diclegis for the treatment of NVP. Diclegis is currently the only medication that is FDA-approved for the indication of NVP. This review addresses the historical context, safety, efficacy, pharmacology, and practical role of doxylamine and pyridoxine for the management of NVP. The reintroduction of this doxylamine-pyridoxine combination pill into the American market fills a therapeutic gap in the management of NVP left by the removal of the same active drugs marketed over 30 years ago in the form of Bendectin. The substantial amount of safety data accumulated over the years makes it one of the few drugs that qualify for FDA Pregnancy Category A status. In the hierarchical approach to pharmacological treatment of NVP, the combination of doxylamine and pyridoxine should thus be first-tier.
PubMed: 24748822
DOI: 10.2147/IJWH.S46653 -
The New England Journal of Medicine Mar 2014
Topics: Antiemetics; Congenital Abnormalities; Dicyclomine; Doxylamine; Drug Approval; Drug Combinations; Female; History, 20th Century; Humans; Morning Sickness; Pregnancy; Pyridoxine; United States; United States Food and Drug Administration
PubMed: 24645939
DOI: 10.1056/NEJMp1316042 -
Paediatric Drugs Jun 2014Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for... (Review)
Review
Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis(®), and has been on the Canadian market since 1979, currently under the brand name Diclectin(®). The efficacy of Diclegis(®)/Diclectin(®) has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis(®)/Diclectin(®) for the treatment of NVP to justify its use as first-line treatment for NVP.
Topics: Antiemetics; Delayed-Action Preparations; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Nausea; Pregnancy; Pregnancy Complications; Pyridoxine; Treatment Outcome; Vomiting
PubMed: 24574047
DOI: 10.1007/s40272-014-0065-5 -
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 -
Hospital Pharmacy Oct 2013Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The...
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available online. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The October 2013 monograph topics are afatinib, ferric carboxymaltose, cangrelor, vedolizumab, and albiglutide. The DUE/MUE is on afatinib.
PubMed: 24421551
DOI: 10.1310/hpj4809-762 -
Hospital Pharmacy Jul 2013Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The...
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The July 2013 monograph topics are prothrombin complex concentrate (human), cysteamine bitartrate delayed-release capsules, doxylamine succinate/pyridoxine hydrochloride, tedizolid phosphate, and sofosbuvir. The DUE/MUE is on canaglifozin.
PubMed: 24421524
DOI: 10.1310/hpj4807-580 -
Journal of Korean Medical Science Oct 2013Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the... (Comparative Study)
Comparative Study
Social factors may affect the available sources of toxic substances and causes of poisoning; and these factors may change over time. Additionally, understanding the characteristics of patients with acute toxic poisoning is important for treating such patients. Therefore, this study investigated the characteristics of patients with toxic poisoning. Patients visiting one of 3 hospitals in 2003 and 2011 were included in this study. Data on all patients who were admitted to the emergency departments with acute toxic poisoning were retrospectively obtained from medical records. Total 939 patients were analyzed. The average age of patients was 40.0 ± 20 yr, and 335 (36.9%) patients were men. Among the elements that did not change over time were the facts that suicide was the most common cause, that alcohol consumption was involved in roughly 1 of 4 cases, and that there were more women than men. Furthermore, acetaminophen and doxylamine remained the most common poisoning agents. In conclusion, the average patient age and psychotic drug poisoning has increased over time, and the use of lavage treatment has decreased.
Topics: Acetaminophen; Adolescent; Adult; Aged; Aged, 80 and over; Alcohol Drinking; Child; Child, Preschool; Doxylamine; Emergency Service, Hospital; Female; Hospitals, University; Humans; Infant; Infant, Newborn; Male; Middle Aged; Poisoning; Retrospective Studies; Sex Factors; Suicide, Attempted; Young Adult
PubMed: 24133344
DOI: 10.3346/jkms.2013.28.10.1424 -
PloS One 2013Given the growing worldwide market of non-prescription drugs, monitoring their misuse in the context of self-medication represents a particular challenge in Public...
BACKGROUND
Given the growing worldwide market of non-prescription drugs, monitoring their misuse in the context of self-medication represents a particular challenge in Public Health. The aim of this study was to investigate the prevalence of misuse, abuse, and dependence on non-prescription psychoactive drugs.
METHOD
During one month, in randomly solicited community pharmacies, an anonymous questionnaire was offered to adults requesting paracetamol (control group), codeine combined with paracetamol in analgesics, or sedative H1 antihistamines. Responses about misuse (drug use not in agreement with the Patient Information Leaflet) abuse (excessive drug use having detrimental consequences), and dependence (established according to questions adapted from the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria) on psychoactive drugs were compared to those of the paracetamol control group.
RESULTS
295 patients (mean age 48.5 years, 68.5% of women) having used one of the studied drugs during the previous month were included. Misuse and dependence to codeine analgesics concerned 6.8% and 17.8% of the patients exposed to these drugs, respectively, (n = 118), which was significantly higher than for paracetamol. 19.5% had used codeine analgesics daily for more than six months. Headache was the most frequent reason for persistent daily use. A high prevalence of persistent daily users of sedative H1 antihistamines was also observed. Whereas these drugs are recommended only for short treatment courses of occasional insomnia, 72.2% of the participants having taken doxylamine (n = 36) were daily users, predominantly for more than six months.
CONCLUSIONS
Results on misuse and dependence on non-prescription codeine analgesics suggest that chronic pain, in particular chronic cephalalgia, requires better medical care. In addition, as for hypnotics on prescription, persistent use of doxylamine for self-medication is not justified until an acceptable benefit-risk ratio for chronic sleep disturbance is shown by clinical data.
Topics: Acetaminophen; Adult; Aged; Analgesics, Opioid; Codeine; Cross-Sectional Studies; Female; France; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nonprescription Drugs; Prevalence; Self Medication; Substance-Related Disorders; Surveys and Questionnaires
PubMed: 24098516
DOI: 10.1371/journal.pone.0076499 -
European Journal of Obstetrics,... Sep 2013The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors.
OBJECTIVE
The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors.
STUDY DESIGN
This is a case-control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test.
RESULTS
Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p<0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p<0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p<0.0089). Poor outcomes were associated with early start of symptoms (p<0.019), and treatment with methylprednisolone (p<0.0217), promethazine (p<0.0386), and other antihistamines [diphenhydramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p<0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome.
CONCLUSION
Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy.
Topics: Adult; Case-Control Studies; Female; Histamine Antagonists; Humans; Hyperemesis Gravidarum; Pregnancy; Pregnancy Outcome; Prognosis; Treatment Outcome; United States
PubMed: 23751910
DOI: 10.1016/j.ejogrb.2013.04.017 -
Obstetrics and Gynecology International 2013Background. Nausea and vomiting of pregnancy (NVP) is the most common medical condition of pregnancy, affecting up to 85% of expecting mothers. In the USA, there is no...
Background. Nausea and vomiting of pregnancy (NVP) is the most common medical condition of pregnancy, affecting up to 85% of expecting mothers. In the USA, there is no FDA-approved medication for the treatment of NVP. Objective. To identify the primary concerns of American women leading them to contact the Motherisk NVP Helpline and to characterize the severity of their symptoms and therapy offered in order to develop improved and customized counseling for them. Methods. We reviewed the intake forms of the American women who called the NVP Helpline from 2008 to 2012. We extracted their state of residence, demographic data, severity of NVP symptoms, and other available clinical characteristics. Results. A total of 195 forms were reviewed. Of these, 86% called for information on management of NVP with/without questions about fetal drug safety, while 14% called solely about drug safety during pregnancy/breastfeeding. The majority of women were Caucasian, in their thirties, educated, employed, married and in their second pregnancy. Of them 95% were suffering from moderate-to-severe condition with 13% having hyperemesis gravidarum. Conclusion. American women need more information on the management of NVP and on a variety of its aspects in addition to the safety and effectiveness of antiemetic medications. Their leading concern was the use of doxylamine and vitamin B6 combination for NVP treatment followed by the use of ondansetron.
PubMed: 23690784
DOI: 10.1155/2013/752980