Pyridoxine/doxylamine: Difference between revisions

{{short description|Prescription drug for pregnancy morning sickness}}

{{Infobox drug

| verifiedrevid = 447569357

| class1 = [[Vitamin]]

| class2 = [[Antihistamine]]

| tradename = Diclegis, Bendectin, Debendox, Lenotan, Merbental, Diclectin, others

| pregnancy_category = Compatible

| legal_CA = Approved

| legal_US = Approved

| legal_status = Prescription only; approved drug in Israel

| routes_of_administration = By mouth

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 65-23-6

| CAS_number2_Ref = {{cascite|correct|CAS}}

| CAS_number2 = 469-21-6

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = KV2JZ1BI6Z

| UNII2_Ref = {{fdacite|correct|FDA}}

| UNII2 = 95QB77JKPL

| KEGG = D10357

'''Pyridoxine/doxylamine''', sold under the brand name '''Diclectin''' among others, is a combination of [[pyridoxine hydrochloride]] ([[vitamin B6|vitamin B₆]]) and [[doxylamine succinate]]. It is generally used for [[nausea and vomiting of pregnancy]] (morning sickness); even though its efficacy has not been proven and subsequent research has led to the removal of recommendations in medical journals.<ref name="Doxylamine-pyridoxine for nausea an">{{cite journal | vauthors = Persaud N, Meaney C, El-Emam K, Moineddin R, Thorpe K | title = Doxylamine-pyridoxine for nausea and vomiting of pregnancy randomized placebo controlled trial: Prespecified analyses and reanalysis | journal = PLOS ONE | volume = 13 | issue = 1 | pages = e0189978 | date = 17 January 2018 | pmid = 29342163 | pmc = 5771578 | doi = 10.1371/journal.pone.0189978 | bibcode = 2018PLoSO..1389978P | doi-access = free }}</ref><ref>[https://www.cbc.ca/news/health/diclectin-pregnancy-nausea-vomiting-persaud-duchesnay-confidential-industry-documents-health-canada-1.4491300 Morning sickness drug Diclectin doesn't work, confidential industry documents reviewed by doctor show] &mdash; Article published in "''CBC news''" on 17 January 2018</ref>

==Medical uses==

The combination of [[pyridoxine]], commonly referred to as vitamin B6 and [[doxylamine]] may be an effective for the management of [[nausea and vomiting of pregnancy]],<ref>{{cite journal | vauthors = Madjunkova S, Maltepe C, Koren G | title = The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin ®) for the treatment of nausea and vomiting of pregnancy | journal = Paediatric Drugs | volume = 16 | issue = 3 | pages = 199–211 | date = June 2014 | pmid = 24574047 | pmc = 4030125 | doi = 10.1007/s40272-014-0065-5 }}</ref> but it is only recommended for use in a small number of cases after lifestyle, diet and vitamin B6. A 2018 review found the benefit was small.<ref name="Doxylamine-pyridoxine for nausea an"/>

Doxylamine and pyridoxine are pregnancy compatible drugs,<ref name=":1">Briggs GG, Freeman RK. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition. 2015. Published by: Wolters Kluwer Health.</ref> consistent with FDA's safety assessment of the combination product. They have been categorized by the FDA as a category A drug (no evidence of risk to the fetus). This letter classification system for risk in pregnancy is no longer being utilized and is currently being phased out by the FDA.<ref>{{cite web | publisher = US Food and Drug Administration | title = Pregnancy and Lactation Labeling (Drugs) Final Rule | date = 2 March 2020 | url = https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Labeling/ucm093307.htm }}</ref>

===Medical organizations’ position===

The [[American Congress of Obstetricians and Gynecologists]] (ACOG) states "Safe and effective treatments are available for more severe cases, and mild cases of nausea and vomiting of pregnancy may be resolved with lifestyle and dietary changes."<ref>{{cite journal | author = American College of Obstetricians and Gynecologists (ACOG). | title = Nausea and vomiting of pregnancy. | location = Washington (DC) | publisher = American College of Obstetricians and Gynecologists (ACOG) | date = April 2004 | journal = ACOG Practice Bulletin | issue = 52 }}</ref> The [https://www.aafp.org/ American Family Medicine] recommends, "Initial treatment is conservative and includes dietary changes, emotional support, and vitamin B6 supplementation."<ref name=":5">{{Cite journal |last=Herrell |first=Howard Ernest |date=2014-06-15 |title=Nausea and Vomiting of Pregnancy |url=https://www.aafp.org/pubs/afp/issues/2014/0615/p965.html |journal=American Family Physician |language=en-US |volume=89 |issue=12 |pages=965–970|pmid=25162163 }}</ref> This treatment has a Grade A, "''consistent, good-quality patient-oriented evidence "'' <ref name=":5" /> while the addition of prescribing doxylamine has a Grade C, "''consensus, disease-oriented evidence, usual practice, expert opinion, or case series."<ref name=":5" />''

[[Canadian Family Physician]] issued a correction stating previous articles which stated Diclectin should be used as a first line therapy were incorrect, based upon undisclosed conflicts of interest with the manufacturer, and not peer-reviewed studies:<blockquote>"Recommendations in 2 articles published in ''Canadian Family Physician'', “Nausea and vomiting of pregnancy. Evidence-based treatment algorithm” and “Treatment of nausea and vomiting in pregnancy. An updated algorithm,” '''have subsequently come under critical scrutiny'''. '''These articles were not subjected to standard peer review''', and ''Canadian Family Physician'' acknowledges that upon '''closer inspection these articles did not provide satisfactory evidence that would have justified the recommendation of doxylamine-pyridoxine as a sole first-line treatment for nausea and vomiting in pregnancy''' (NVP). More recent Canadian NVP guidelines have been published; however, a subsequent re-analysis questions the conclusions of 1 of the studies cited in these guidelines to justify doxylamine-pyridoxine as a recommended first-line treatment for NVP. Additionally, '''for the articles in ''Canadian Family Physician'' there was an undisclosed conflict of interest with Duchesnay, the manufacturer of Diclectin, the combination of doxylamine-pyridoxine'''. ''Canadian Family Physician'' encourages readers to interpret previously published NVP recommendations with caution. Readers are also referred to the commentary “Motherisk and ''Canadian Family Physician''” in the January 2017 issue of ''Canadian Family Physician''."<ref name=":7">{{Cite journal |date=January 2019 |title=Recommendations in 2 articles published in Canadian Family Physician, "Nausea and vomiting of pregnancy. Evidence-based treatment algorithm"1 and "Treatment of nausea and vomiting in pregnancy. An updated algorithm,"2 have subsequently come under critical scrutiny. |journal=Canadian Family Physician |volume=65 |issue=1|page=8 |pmid=30674506 |pmc=6347327 }}</ref> [Ed: bolding to help summarize information, note please follow link to article to see the footnotes from this article]</blockquote>

==Adverse effects==

[[Pyridoxine]], vitamin B6, is a [[water-soluble vitamins|water-soluble vitamin]] and is generally recognized as having no adverse effects.<ref>{{cite book | chapter = Vitamin B6 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK114313/#ch7.s51 | title = Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. | author = Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine. | location = Washington, DC | publisher = The National Academies Press | date = 1998}}</ref><ref name="webprod5.hc-sc.gc.ca">{{cite book | title = Diclectin Product Monograph | via = Health Canada’s Drug Product Database | url = https://pdf.hres.ca/dpd_pm/00033994.PDF | author = Duchesnay Inc. | date = 8 March 2016 }}</ref> After diet changes, it alone is recommended as the secondary treatment plan.

The most commonly reported adverse reaction of doxylamine is drowsiness.<ref name=":3" /> Other adverse drug reactions associated with doxylamine succinate may include: vertigo, nervousness, epigastric pain, headache, palpitation, diarrhea, disorientation, irritability, convulsions, urinary retention or insomnia.<ref name="webprod5.hc-sc.gc.ca" />

It is not recommended to take doxylamine with other medications of the same class, medications that act on the central nervous system (CNS) or with alcohol as this may increase the risk of adverse effects.<ref name="webprod5.hc-sc.gc.ca" /><ref name=":3">American Society of Health-System Pharmacists (AHFS) Drug Information 2014, Antihistamine Drugs. pgs 1-8.</ref> To minimize the risk of particular adverse effects, doxylamine should not be used when taking any medication classified as a monoamine oxidase inhibitor (MAOI), and should be used with caution, if at all, when certain medical conditions are present.<ref name="webprod5.hc-sc.gc.ca" /><ref name=":3" />

Because doxylamine is small enough on a molecular weight basis to pass into breastmilk, women should not breastfeed while using products with doxylamine as this may lead to adverse effects in the breastfed infant.<ref name="webprod5.hc-sc.gc.ca" />

===Safety in pregnancy===

Due to the extensive scientific evidence demonstrating that there is no difference in the risk for birth defects or other adverse pregnancy outcomes between infants whose mothers take pyridoxine/doxylamine during pregnancy and those infants whose mothers do not take this drug combination, the two ingredients of the drug are considered pregnancy compatible<ref name=":1" /> (or category A drugs with the previous pregnancy risk factor classification system).

Since the mid-1950s, over 33 million women have used the combination drug of pyridoxine/doxylamine in pregnancy, and scientific analysis on more than 200,000 exposed pregnancies has been conducted to determine if the combination of pyridoxine and doxylamine is harmful to the unborn baby.<ref name=":0">{{cite journal | vauthors = Koren G, Clark S, Hankins GD, Caritis SN, Miodovnik M, Umans JG, Mattison DR | title = Effectiveness of delayed-release doxylamine and pyridoxine for nausea and vomiting of pregnancy: a randomized placebo controlled trial | journal = American Journal of Obstetrics and Gynecology | volume = 203 | issue = 6 | pages = 571.e1–7 | date = December 2010 | pmid = 20843504 | doi = 10.1016/j.ajog.2010.07.030 }}</ref><ref name=":2">{{cite journal | vauthors = Kutcher JS, Engle A, Firth J, Lamm SH | title = Bendectin and birth defects. II: Ecological analyses | journal = Birth Defects Research. Part A, Clinical and Molecular Teratology | volume = 67 | issue = 2 | pages = 88–97 | date = February 2003 | pmid = 12769504 | doi = 10.1002/bdra.10034 | hdl-access = free | hdl = 2027.42/35295 }}</ref> No epidemiological studies have found any [[teratogenic]] effect.<ref name=":2" />

Two separate [[Meta analysis|meta-analyses]] have been conducted that have assessed pregnancy outcomes following the use of a combination of pyridoxine and doxylamine with or without dicyclomine during the first trimester of pregnancy.<ref name="ReferenceA">{{cite journal | vauthors = Einarson TR, Leeder JS, Koren G | s2cid = 33156399 | title = A method for meta-analysis of epidemiological studies | journal = Drug Intelligence & Clinical Pharmacy | volume = 22 | issue = 10 | pages = 813–24 | date = October 1988 | pmid = 3229352 | doi = 10.1177/106002808802201021 }}</ref><ref name="ReferenceB">{{cite journal | vauthors = McKeigue PM, Lamm SH, Linn S, Kutcher JS | title = Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies | journal = Teratology | volume = 50 | issue = 1 | pages = 27–37 | date = July 1994 | pmid = 7974252 | doi = 10.1002/tera.1420500105 }}</ref> The initial meta-analysis, published in 1988, combined data from 12 cohort and 5 case-control studies,<ref name="ReferenceA"/> and the subsequent meta-analysis, published in 1994, combined data from 16 cohort studies and 11 case control studies.<ref name="ReferenceB"/> These studies included over 200,000 Bendectin-exposed pregnancies and did not observe an increased risk for major malformations.<ref name="ReferenceA"/><ref name="ReferenceB"/> Separate analyses were conducted for specific defects including cardiac defects, limb reduction defects, oral clefts, and genital tract malformations; no increased risks for these defects were found.<ref name="ReferenceB"/>

In 1989, a report on the safety of the drug combination of pyridoxine/doxylamine for use in the management of NVP was prepared by a panel of Canadian and American experts for the Special Advisory Committee on Reproductive Physiology to the Health Protection Branch of [[Health Canada]] (currently called the Health Products and Food Branch).<ref name="ReferenceC">{{cite journal | vauthors = Ornstein M, Einarson A, Koren G | title = Bendectin/diclectin for morning sickness: a Canadian follow-up of an American tragedy | journal = Reproductive Toxicology | volume = 9 | issue = 1 | pages = 1–6 | year = 1995 | pmid = 8520127 | doi = 10.1016/0890-6238(94)00050-7 }}</ref> These scientific experts concluded that “numerous studies in animals and in humans that have been reported in the scientific and medical literature demonstrate that Bendectin is not a teratogen. The safety of Bendectin/Diclectin in the management of nausea and vomiting of pregnancy has been established by its use in many thousands of pregnant women”.<ref name="ReferenceC"/>

A study was conducted to determine whether the combination drug of pyridoxine and doxylamine had an effect on the neurodevelopment of children exposed in utero. Results from this study observed no difference in [[intelligence quotient]] scores between children who were exposed to pyridoxine/doxylamine in utero and children who were not exposed.<ref>{{cite journal | vauthors = Nulman I, Rovet J, Barrera M, Knittel-Keren D, Feldman BM, Koren G | title = Long-term neurodevelopment of children exposed to maternal nausea and vomiting of pregnancy and diclectin | journal = The Journal of Pediatrics | volume = 155 | issue = 1 | pages = 45–50, 50.e1-2 | date = July 2009 | pmid = 19394042 | doi = 10.1016/j.jpeds.2009.02.005 }}</ref>

The combination of doxylamine and vitamin B6 was first introduced to the US market as Bendectin in 1956. At that time, Bendectin was a 3 ingredients prescription medication. The third one, [[dicyclomine]], a [[Pregnancy Category]] B [[anticholinergic]]/[[antispasmodic]], was omitted from the formulation starting in 1976 due to its lack of efficacy.<ref>{{cite journal |last1=Sanders |first1=Joseph | name-list-style = vanc |title=The Bendectin Litigation: A Case Study in the Life Cycle of Mass Torts |journal=Hastings Law Journal |date=January 1992 |volume=43 |issue=2 |pages=301–418 |url=https://repository.uchastings.edu/cgi/viewcontent.cgi?article=3055&context=hastings_law_journal}}</ref>{{rp|317}} Bendectin (doxylamine/vitamin B6) was voluntarily removed from the market in 1983 by its manufacturer, [[Merrell Dow Pharmaceuticals]], following numerous lawsuits alleging that it caused [[birth defects]], although an [[Food and Drug Administration|FDA]] panel concluded that no association between Bendectin and birth defects had been demonstrated.<ref name=brody>{{cite news| title=Shadow of Doubt Wipes Out Bendectin | first = Jane E. | last = Brody | name-list-style = vanc | url=https://query.nytimes.com/gst/fullpage.html?sec=health&res=9A02E6DC123BF93AA25755C0A965948260 | work=New York Times | date=1983-06-19}}</ref> In litigation, Bendectin was implicated as the cause of various fetal malformations and problems including limb and other musculoskeletal deformities, facial and brain damage, defects of the respiratory, gastrointestinal, cardiovascular and genital-urinary systems, blood disorders and cancer.<ref name=brody/> The most famous case involving the drug is ''[[Daubert v. Merrell Dow Pharmaceuticals]]'' (1993). These suits were led by celebrity plaintiff attorney [[Melvin Belli]] .<ref>{{cite journal | vauthors = Korcok M | title = The Bendectin debate | journal = Canadian Medical Association Journal | volume = 123 | issue = 9 | pages = 922–8 | date = November 1980 | pmid = 7437993 | pmc = 1704894 }}</ref> The star witness for the case against Bendectin, [[William McBride (doctor)|William McBride]], was later found to have falsified research on teratogenic effects of the drug, and was struck off the medical register in Australia.<ref>[https://www.newscientist.com/article/mg13718620.800-thalidomide-hero-found-guilty-of-scientific-fraud-.html Thalidomide hero found guilty of scientific fraud] &mdash; Article published in "''New Scientist''" on 27 February 1991</ref><ref>[https://www.independent.co.uk/news/world/thalidomide-doctor-guilty-of-medical-fraud-william-mcbride-who-exposed-the-danger-of-one-antinausea-drug-has-been-disgraced-by-experiments-with-another-writes-robert-milliken-in-sydney-1474190.html Thalidomide doctor guilty of medical fraud] &mdash; Article published in "''The Independent''" on 20 February 1993</ref>

An extensive review of the evidence submitted in legal proceedings regarding Bendectin has been summarized and found no evidence that the drug in clinical use was linked to birth defects.<ref name=":4">{{cite journal|url=http://www.voteview.com/Bendectin_Tortogen_Litigen.pdf|journal=Reproductive Toxicology|volume=9 |issue=4 |pages=337–349 |year=1995|title=Bendectin: Review of the medical literature of a comprehensively studied human nonteratogen and the most prevalent tortogen-litigen| vauthors = Brent RL |access-date=2010-07-30|archive-url=https://web.archive.org/web/20110716111731/http://www.voteview.com/Bendectin_Tortogen_Litigen.pdf|archive-date=2011-07-16|url-status=dead|doi=10.1016/0890-6238(95)00020-B|pmid=7496090}}</ref>

The FDA, in 1999, published a statement in the [http://www.gpo.gov/fdsys/pkg/FR-1999-08-09/pdf/99-20362.pdf Federal Register] that summarized their opinion regarding the safety of pyridoxine/doxylamine during pregnancy: “The FDA has determined that the drug product Bendectin, a tablet composed of pyridoxine hydrochloride 10 mg, and doxylamine succinate 10 mg, for the prevention of nausea of pregnancy was not withdrawn from the market for reasons of safety or effectiveness”.

On Monday April 8, 2013, the FDA approved the return of the [[Doxylamine|doxylamine-pyridoxine]] combination under the new trademark name of Diclegis. The medication is manufactured by Duchesnay Inc, a company later shown to not disclose conflict of interests with authors, leading to Canadian Family Physician to correct several articles because of their behavior and the lack of research that shows that there was medically significant results.<ref name=":7" />

In July 2015, the drug company came under considerable scrutiny for promoting its drug through the American celebrity [[Kim Kardashian]] through the social media platforms [[Facebook]] and [[Instagram]].<ref>{{cite news|last1=Kroll|first1=David | name-list-style = vanc |title=The Kim Kardashian-Endorsed Morning Sickness Drug Is The Real Deal|url=https://www.forbes.com/sites/davidkroll/2015/07/31/the-kim-kardashian-endorsed-morning-sickness-drug-is-the-real-deal/|access-date=15 October 2015|work=Forbes|date=July 31, 2015}}</ref><ref>{{cite news|title=Kim Kardashian drug endorsement may break Canadian law: experts|url=https://ca.news.yahoo.com/blogs/dailybrew/kim-kardashian-drug-endorsement-may-break-canadian-230010432.html|access-date=15 October 2015|agency=Yahoo news|date=7 Aug 2015}}</ref><ref>{{cite news|last1=Rinkunas|first1=Susan | name-list-style = vanc |title=How Safe Is the Morning-Sickness Drug Diclegis?|url=http://nymag.com/thecut/2015/07/how-safe-is-the-morning-sickness-drug-diclegis.html|access-date=15 October 2015|publisher=New York Magazine|date=19 July 2015}}</ref><ref>{{cite news|last1=Blackwell|first1=Tom | name-list-style = vanc |title=FDA lashes out at drug company for promoting Canadian morning-sickness pill on Kardashian Instagram feed|url=http://news.nationalpost.com/health/kim-kardashian-morning-sickness-pill|access-date=15 October 2015|publisher=National Post|date=11 August 2015}}</ref><ref>{{cite news|title=Kim Kardashian's social media posts for morning-sickness violate drug promotion rules: FDA|url=http://www.cbc.ca/news/health/kim-kardashian-s-social-media-posts-for-morning-sickness-violate-drug-promotion-rules-fda-1.3187449|access-date=15 October 2015|agency=The Associated Press|publisher=Canadian Broadcasting Corporation|date=11 August 2015}}</ref>

In October 2015, Toronto, Canada physicians Drs. Navindra Persaud, Jessica Chin, and Mark Walker wrote a public letter to the Journal of Obstetrics and Gynaecology of Canada and raised concerns over the risks of Diclectin and recommended reconsidering it as the "first-line pharmacological treatment" against the nausea and vomiting of pregnancy.<ref name=Persaud>{{cite journal | vauthors = Persaud N, Chin J, Walker M | title = Should doxylamine-pyridoxine be used for nausea and vomiting of pregnancy? | journal = Journal of Obstetrics and Gynaecology Canada | volume = 36 | issue = 4 | pages = 343–348 | date = April 2014 | pmid = 24798673 | doi = 10.1016/s1701-2163(15)30611-3 | doi-access = free }}</ref> Dr. Persaud shared with news agencies that his only source of research data for this drug came from [[Health Canada]] and claimed he was only able to access the document by signing a confidentiality agreement.<ref>{{Cite web | url=https://www.ledevoir.com/societe/sante/405801/un-antinauseeux-a-utiliser-avec-prudence |title = Un antinauséeux à utiliser avec prudence?| date=17 April 2014 }}</ref><ref>{{cite web | url=http://www.cbc.ca/radio/asithappens/as-it-happens-wednesday-edition-1.3270429/health-canada-confidentiality-pact-forces-doctor-to-withhold-drug-data-1.3270432 |title = Health Canada confidentiality pact forces doctor to withhold drug data | date = 15 October 2015 | work = CBC Radio }}</ref><ref>{{Cite news | url=https://www.thestar.com/news/canada/2015/10/14/health-canada-hands-over-documents-but-muzzles-doctor.html | title=Health Canada hands over documents but muzzles doctor &#124; the Star| newspaper=The Toronto Star| date=14 October 2015}}</ref>

In January 2019, Canadian Family Physician issued a correction stating "Recommendations in 2 articles published in ''Canadian Family Physician'', “Nausea and vomiting of pregnancy. Evidence-based treatment algorithm” and “Treatment of nausea and vomiting in pregnancy. An updated algorithm,” '''have subsequently come under critical scrutiny'''. '''These articles were not subjected to standard peer review''', and ''Canadian Family Physician'' acknowledges that upon '''closer inspection these articles did not provide satisfactory evidence that would have justified the recommendation of doxylamine-pyridoxine as a sole first-line treatment for nausea and vomiting in pregnancy''' (NVP). More recent Canadian NVP guidelines have been published; however, a subsequent re-analysis questions the conclusions of 1 of the studies cited in these guidelines to justify doxylamine-pyridoxine as a recommended first-line treatment for NVP. Additionally, '''for the articles in ''Canadian Family Physician'' there was an undisclosed conflict of interest with Duchesnay, the manufacturer of Diclectin, the combination of doxylamine-pyridoxine'''. ''Canadian Family Physician'' encourages readers to interpret previously published NVP recommendations with caution. Readers are also referred to the commentary “Motherisk and ''Canadian Family Physician''” in the January 2017 issue of ''Canadian Family Physician''."<ref name=":7" /> [Ed: bolding to help summarize information, note please follow link to article to see the footnotes from this article]

==Society and culture==

From a legal perspective, the case through [[Daubert v. Merrell Dow Pharmaceuticals]], 509 U.S. 579 (1993) set a new standard for admitting expert testimony in federal courts in lieu of the [[Frye standard]].<ref>{{cite journal |last1=McCarthy |first1=Leigh Stephens | name-list-style = vanc |title=Life After Daubert v. Merrell Dow: Maine as a Case Law Laboratory for Evidence Rule 702 Without Frye |journal=Maine Law Review |date=June 1994 |volume=46 |issue=2 |url=https://digitalcommons.mainelaw.maine.edu/cgi/viewcontent.cgi?article=1626&context=mlr}}</ref>

== See also ==

*[[Daubert v. Merrell Dow Pharmaceuticals]]

== References ==

== External links ==

* [http://www.gpo.gov/fdsys/pkg/FR-1999-08-09/pdf/99-20362.pdf FDA FederalRegister/Vol. 64, No. 152/August 9,1999/Determination That Bendectin Was Not Withdrawn From Sale for Reasons of Safety or Effectiveness]

* [https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm347087.htm FDA approves Diclegis for pregnant women experiencing nausea and vomiting, April 8, 2013]

* [http://www.motherisk.org/women/morningSickness.jsp About Morning Sickness from MOTHERISK at the Hospital for Sick Children in Toronto]

{{DEFAULTSORT:Pyridoxine doxylamine}}