Long answer. Cut and pasted from Dynamed, an evidenced based medicine resource. Sorry about the formatting.
* other simple behavioral and dietary modifications
o avoid greasy and spicy foods, and possibly odors
o eat dry carbohydrates (crackers) upon awakening, soft, low-fat foods and protein snack at bedtime
o drink carbonated beverages
o avoiding fluids with meals may help
* prophylactic thiamine supplementation recommended in hyperemesis gravidarum based on case report of Wernicke’s encephalopathy in 1 case complicated by diabetic ketoacidosis and IV glucose administration (grade C recommendation [lacking direct evidence]) (Obstet Gynecol 2006 Feb;107(2):486)
Activity:
* avoid sudden movements when nauseated
Medications:
* hydroxyzine and thiethylperazine may reduce nausea and vomiting symptoms (level 2 [mid-level] evidence)
o based on Cochrane review with limited evidence
o systematic review of 27 randomized trials evaluating antiemetic interventions in 4,041 women ≤ 20 weeks gestation with mild or moderate nausea and vomiting (not hyperemesis gravidarum)
o meta-analysis not performed due to heterogeneity in patients, interventions, comparison groups, and outcomes
o 6 low-quality trials evaluated pharmacological interventions to reduce nausea and vomiting symptoms
+ pharmacological interventions associated with
# significantly improved nausea and vomiting symptoms in 2 individual placebo-controlled trials
* hydroxyzine (1 trial with 150 women)
* thiethylperazine (1 trial with 164 women)
# fluphenazine-pyridoxine did not significantly improve nausea and vomiting symptoms compared to placebo in 1 trial with 78 women
# inconsistent results for debendox (bendectin) vs. placebo in 2 trials
# symptom improvement on day 3 of treatment in 65% of pyridoxine-metoclopramide group vs. 38% of prochlorperazine group vs. 40% of promethazine group in 1 trial with 169 women (no p value reported)
o Reference – Cochrane Database Syst Rev 2010 Sep 8;(9):CD007575
* some pharmacological interventions may be safe and effective for treatment of nausea and vomiting in pregnancy
o based on review of randomized trials and observational studies
o randomized trials reviewed for effectiveness, observational controlled studies reviewed for safety
o safe and effective treatments for nausea and vomiting in pregnancy
+ Bendectin/Diclectin (doxylamine, pyridoxine, dicyclomine)
+ antihistamines (H1 blockers)
+ phenothiazines (though magnitude of effect in question)
o safe treatments that may be effective
+ pyridoxine
+ vitamin B12
o treatments which may be effective but have insufficient safety data to recommend first-line use
+ metoclopramide
+ droperidol
+ ondansetron
o corticosteroids appear to have limited benefit and may have small teratogenic risk
o insufficient evidence regarding comparative efficacy
o Reference – Am J Obstet Gynecol 2002 May;186(5 Suppl Understanding):S256
* delayed-release doxylamine and pyridoxine may decrease nausea and vomiting in pregnant women (level 2 [mid-level] evidence)
o based on randomized trial with high dropout rate
o 280 pregnant women with nausea and vomiting randomized to delayed-release doxylamine succinate 10 mg plus pyridoxine hydrochloride 10 mg (Diclectin) vs. placebo for 14 days
o 27.5% discontinued treatment or lost to follow-up
o Diclectin associated with significantly greater improvements in scores of
+ nausea and vomiting of pregnancy (p = 0.006)
+ global assessment of well-being (p = 0.005)
o continued use of medication requested by 48.9% with Diclectin vs. 32.8% with placebo (p = 0.009)
o Diclectin not associated with increased rate of adverse events
o Reference – Am J Obstet Gynecol 2010 Dec;203(6):571.e1
* ginger
o ginger 350 mg orally 3 times daily or 250 mg orally 4 times daily effective in reducing nausea and vomiting in early pregnancy
+ ginger appears to reduce nausea and vomiting in pregnancy, but limited data supporting safety (level 2 [mid-level] evidence)
# based on systematic review without assessment of allocation concealment
# systematic review of 6 randomized double-blind trials with 675 patients
# 4 trials with 246 patients showed ginger 250 mg 4 times daily (1 trial used 125 mg 4 times daily) to be more effective than placebo
# 2 trials with 429 patients showed ginger 350 mg 3 times daily or 500 mg 3 times daily to be as effective as vitamin B6
# studies reported in descriptive fashion only, no numerical data presented
# prospective cohort study of 187 patients plus all 6 trials showed absence of significant side effects or adverse pregnancy outcomes
# no case reports of adverse events found
# Reference – Obstet Gynecol 2005 Apr;105(4):849, commentary can be found in Obstet Gynecol 2005 Sep;106(3):640, Am Fam Physician 2005 Dec 1;72(11):2349
+ ginger 250 mg 4 times daily may reduce nausea and vomiting in pregnant women
# based on randomized trial with allocation concealment unclear
# 70 pregnant women (mean age 24 years) at mean gestational age 13 weeks were randomized to ginger 250 mg 4 times daily for 4 days vs. placebo
# 67 (96%) included in analysis
# ginger associated with
* higher rate of improvement (85% vs. 56% with placebo, p < 0.01)
* decreased vomiting frequency (50% vs. 9% with placebo, p < 0.05)
# Reference – J Altern Complement Med 2009 Mar;15(3):243
+ ginger 1 g/day appears as effective as vitamin B6 (level 2 [mid-level] evidence)
# based on randomized trial without intention-to-treat analysis
# 291 women at 8–16 weeks gestation with nausea or vomiting randomized to ginger 350 mg vs. vitamin B6 25 mg orally 3 times daily for 3 weeks
# 81% follow-up at 3 weeks
# no clinically significant differences in reduction of nausea, retching, or vomiting at 1, 2 or 3 weeks between groups
# differences favoring vitamin B6 were of borderline statistical significance but magnitude of differences not considered clinically significant
# no significant differences in adverse pregnancy outcomes but study too small to rule out clinically significant differences
# Reference – Obstet Gynecol 2004 Apr;103(4):639 PDF in ACOG News Release 2004 Mar 29, commentary can be found in Am Fam Physician 2005 Feb 1;71(3):587, Evidence-Based Medicine 2005 Jan-Feb;10(1):14
+ ginger may be more effective than vitamin B6 for reducing severity of nausea (level 2 [mid-level] evidence)
# based on small randomized trial
# 70 pregnant woman randomized to ginger 1 g/day vs. vitamin B6 40 mg/day for 4 days
# comparing ginger vs. vitamin B6
* 83% vs. 68% had improvement in nausea symptoms (not significant)
* ginger had significantly greater reduction in visual analog scores for nausea (p = 0.024)
* no significant difference in reduction in number of vomiting episodes
# Reference – Midwifery 2009 Dec;25(6):649
+ ginger reduced nausea and vomiting in early pregnancy; 70 Thai women with nausea and vomiting before 17 weeks gestation randomized to 250-mg capsules derived from fresh ginger root vs. placebo 4 times daily for 4 days, 87.5% vs. 28.6% felt their symptoms improved, no adverse effects identified (Obstet Gynecol 2001 Apr;97(4):577 in J Watch 2001 May 15;21(10);81), commentary can be found in J Fam Pract 2001 Aug;50(8):720, summary can be found in Am Fam Physician 2001 Nov 15;64(10):1745
+ randomized, double-blind, crossover trial using powdered root of ginger 250 mg orally 4 times daily vs. placebo for 4 days with 2-day washout period in 30 women with hyperemesis gravidarum found ginger significantly better in relieving symptoms; fetal loss rate not reported and not clear if investigated (Eur J Obstet Gynecol Reprod Biol 1991 Jan 4;38(1):19 in Alternative Medicine Alert 1998 Mar;1(3):30 and in Alternative Medicine Alert 1998 Dec;1(12):133)
+ ginger syrup reduced nausea in early pregnancy; 26 patients in first trimester with nausea were randomized to ginger syrup (250 mg ginger/tablespoon) vs. placebo syrup 1 tablespoon mixed in 4–8 oz hot or cold water 4 times daily for 2 weeks; based on intention to treat analysis including all subjects (extrapolated from data in original article), 10 of 14 (71%) ginger patients vs. 3 of 12 (25%) placebo patients had at least 4-point improvement on 10-point nausea scale (NNT 2.2) (Altern Ther Health Med 2002 Sep-Oct;8(5):89), commentary can be found in Altern Ther Health Med 2003 Jan-Feb;9(1):19
ginger may reduce nausea and vomiting compared to placebo and may be as effective as B6 (level 2 [mid-level] evidence)
o based on Cochrane review with limited evidence
o systematic review of 27 randomized trials evaluating antiemetic interventions in 4,041 women ≤ 20 weeks gestation with mild or moderate nausea and vomiting (not hyperemesis gravidarum)
o heterogeneity of patients, interventions, comparison groups, and outcomes limited analys
o ginger evaluated in 8 trials
+ ginger improved nausea compared to placebo in 2 trials with 93 women but no significant effect in 1 other trial with 70 women
+ no significant difference in nausea symptom scores on day 3 compared to vitamin B6 in analysis of 2 trials 624 women or in analysis of symptom improvement additional 2 trials with 360 women
o Reference – Cochrane Database Syst Rev 2010 Sep 8;(9):CD007575, previous version withdrawn (Cochrane Library 2003 Issue 4:CD000145)
o ginger use not recommended by some during pregnancy because of possible harms (grade C recommendation [lacking direct evidence])
+ amount of ginger in food appears safe in pregnancy, but insufficient evidence to establish safety or harm of medicinal use of ginger in pregnancy
+ use of ginger controversial in pregnancy; concern due to effect on testosterone binding and thromboxane synthetase activity, 2 Japanese studies showed in vitro mutagenic properties of isolated ginger compounds, no conclusive data about ginger in pregnancy (Alternative Medicine Alert 1998 Dec;1(12):133)
o available as ginger ale, ginger snaps, gingerbread, crystallized ginger candy, ginger sprinkled on food, capsules and syrup
o wide variation in gingerol composition and suggested serving sizes (ranging from 250 mg to 4.77 g per day) found in 10 different ginger root dietary supplements (Obstet Gynecol 2006 Jun;107(6):1337)
o candied ginger usually not dried well enough to be therapeutic, pickled and candied forms not tested, liquid sources (ginger ale, ginger tea) have such low concentrations of ginger that large quantities of liquid required (Alternative Medicine Alert 1998 Dec;1(12):133)
o ginger can increase risk of bleeding with concurrent aspirin use (Prescriber’s Letter 1997;4:1 in Am Fam Physician 1998 Apr 1;57(7):1527)
o review of ginger can be found in Am Fam Physician 2007 Jun 1;75(11):1689 full-text
* pyridoxine (vitamin B6) alone or in combination has been used
o pyridoxine 10–25 mg 3 times daily appears to improve nausea and vomiting based on trials lasting 3–5 days
+ pyridoxine may improve severe nausea and vomiting, based on 3-day trial; 74 women with nausea and vomiting of pregnancy randomized to pyridoxine 25 mg vs. placebo orally every 8 hours for 3 days, 59 (80%) completed the trial and were analyzed; no significant differences between pyridoxine and placebo in overall response based on nausea scores (1–10); among subgroup of 22 women with severe nausea at baseline (nausea score > 7), mean decrease in nausea score was 4.3 with pyridoxine vs. 1.8 with placebo (p < 0.01), 8% vs. 50% continued to have severe nausea after 3 days (p < 0.05, NNT 3); 26% pyridoxine vs. 54% placebo women had vomiting after 3 days of therapy (p < 0.05, NNT 4) (Obstet Gynecol 1991 Jul;78(1):33)
+ pyridoxine 10 mg 3 times daily modestly improves nausea, based on 5-day trial; 342 women < 17 weeks gestation with nausea (with or without vomiting) randomized to pyridoxine hydrochloride 10 mg vs. placebo orally 3 times daily for 5 days; mean nausea score (on 10-cm scale) was 5.2 vs. 4.9 at baseline and 1.9 vs. 2.9 at 5 days, pyridoxine significantly reduced mean nausea scores compared to placebo over composite of 5 days (mean change -2.9 vs. -2, p = 0.008); no differences in incidence of vomiting, but pyridoxine may have reduced mean number of vomiting episodes (p = 0.0552) (Am J Obstet Gynecol 1995 Sep;173(3):881); patients taking iron tablets were excluded, use of prenatal vitamins not mentioned but may not be common practice in Thailand where this trial was done (DynaMed commentary)
o pyridoxine (B-natal) is non-prescription product for morning sickness relief; available as cherry-flavored TheraPops or green apple lozenges (Monthly Prescribing Reference 2007 Jun:A-13); both formulations are 25 mg per dose
o combination pyridoxine and doxylamine
+ Bendectin (doxylamine and pyridoxine) orally twice daily was safe and effective for treating nausea and vomiting of pregnancy, and is still FDA approved; however, due to lawsuits over associated congenital anomalies (which have not been shown to be associated in published studies), manufacturer removed drug from market (Alternative Medicine Alert 1998 Mar;1(3);30)
+ Diclectin (doxylamine and pyridoxine) is available in Canada, and manufacturer is working with United States FDA to market in United States (Reprotox, March of Dimes)
+ hospitalizations for nausea and vomiting in pregnancy increased after Bendectin withdrawn from market and appear to be decreasing with introduction of Diclectin (Nausea and Vomiting of Pregnancy: State of the Art 2000;1:9)
+ both pyridoxine (vitamin B6) and doxylamine (Unisom Nighttime Sleep Aid) now considered pregnancy risk category “A”, both available without a prescription in 25 mg tablets, recommended dose is pyridoxine 12.5 mg (half tablet) and doxylamine 25 mg twice daily plus full tablet (25 mg) of each at bedtime, caution that doxylamine causes drowsiness, caution that other Unisom products contain diphenhydramine so important to specifically look for doxylamine (Prescriber’s Letter 2000 Apr;7(4);23)
+ doxylamine available without a prescription in products named Unisom Nighttime Sleep Aid, Decapryn, Nighttime Sleep Aid, Sleep Aid; be careful to look at ingredients to ensure presence of doxylamine and not diphenhydramine, and note that doses may vary between products
+ Unisom SleepGels contain diphenhydramine, not doxylamine (Prescriber’s Letter 2004 Jun;11(6):35)
o PremesisRx is prescription product for morning sickness containing sustained-release pyridoxine (vitamin B6) 75 mg, folic acid 1 mg, vitamin B12 12 mcg and calcium carbonate 200 mg; useful for pregnant women who have nausea and vomiting despite usual dietary recommendations; costs $32 for 100 tablets; cheaper alternative may be pyridoxine 25 mg 3 times daily and folic acid or prenatal vitamin if tolerated (Prescriber’s Letter 1999 Dec;6(12):68, Monthly Prescribing Reference 1999 Dec;A-19)
* consider starting prenatal vitamins
* prenatal vitamins may also aggravate nausea
o try taking at night (to sleep through nausea) instead of in the morning
o try dividing doses if scored tablets
* antiemetics (for example, antihistamines) occasionally needed, especially if dehydration, ketosis or electrolyte abnormalities occur
* antihistamines
o H1 antihistamines
+ FDA Pregnancy Categories for H1 antihistamines
# A for doxylamine (available as Unisom or Unisom-2 in Canada, and combined with pyridoxine as Diclectin in Canada)
# B for dimenhydrinate (Dramamine; PMS-dimenhydrinate in Canada), diphenhydramine (Benadryl), and meclizine (Antivert; Bonamine in Canada)
# C for hydroxyzine (Atarax, Vistaril; PMS-Hydroxyzine in Canada)
+ antihistamine exposure during last 2 weeks of pregnancy has been associated with retrolental fibroplasia in premature infants, based on textbook citation
+ dimenhydrinate and diphenhydramine use anytime in pregnancy not associated with major or minor malformations, based on textbook citation
+ hydroxyzine associated with 5.8% rate of major birth defects in 828 newborns with first-trimester exposure in retrospective study and 2 major heart malformations in 53 first-trimester exposures in prospective study, based on textbook citation
+ Reference – Prescriber’s Letter 2006 Dec;13(12):71
o ranitidine (Zantac) 150 mg orally twice daily effective for third-trimester GERD, but safety in human pregnancy not studied; 20 women with reflux in third trimester given ranitidine 150 mg twice daily, 150 mg once daily or placebo in crossover study, 18 women completed study; ranitidine 150 mg twice daily significantly improved heartburn; animal studies show no adverse effects on pregnancy outcomes (Obstet Gynecol 1997 Jul;90(1):83 in J Watch Women’s Health 1997 Aug;2(8):62); Zantac is FDA Pregnancy Category C
* 5 HT3 agonists
o dolasetron (Anzemet), granisetron (Kytril) and ondansetron (Zofran) are FDA Pregnancy Category B
o dolasetron and granisetron have no human data, ondansetron has limited human data, animal data suggest low risk
o Reference – Prescriber’s Letter 2006 Dec;13(12):71
o ondansetron appears no more effective than promethazine (level 2 [mid-level] evidence)
+ based on small randomized trial
+ 30 women hospitalized for hyperemesis gravidarum were randomized to ondansetron IV vs. promethazine IV
+ no significant differences in
# relief of nausea
# weight gain
# days of hospitalization (4.5 vs. 4.5)
# medication doses per hospitalization (2.1 vs. 1.9)
+ Reference – Am J Obstet Gynecol 1996 May;174(5):1565
o ondansetron during pregnancy does not appear to increase risk for major malformations (level 2 [mid-level] evidence)
+ based on observational study
+ 176 pregnancies exposed to ondansetron compared to 176 pregnancies exposed to other antiemetics and 176 non-teratogen exposures
+ ondansetron cohort had 169 live births, 5 miscarriages, 2 therapeutic abortions, 6 (3.6%) major malformations, and mean birth weight 3,362 g
+ none of these outcomes were statistically different than either comparison group
+ Reference – BJOG 2004 Sep;111(9):940
* other antiemetics
o FDA Pregnancy Categories for other antiemetics
+ B for metoclopramide (Reglan; APO-Metoclop in Canada)
+ C for droperidol (Inapsine), trimethobenzamide (Tigan)
+ C for phenothiazines—chlorpromazine (Thorazine; Novo-Chlorpromazine in Canada), perphenazine (Trilafon; APO-Perphenazine in Canada), prochlorperazine (Compazine; AP-prochlorperazine in Canada), promethazine (Phenergan; Histantil in Canada)
+ D for diazepam (Valium; Vivol in Canada)
+ C for corticosteroids, but D in first trimester
+ Reference – Prescriber’s Letter 2006 Dec;13(12):71
o phenothiazines have mixed results in prospective studies, recommended only when nausea and vomiting threaten maternal nutrition
o metoclopramide appears safe during first trimester
+ metoclopramide during first trimester not associated with increased risk for fetal adverse effects (level 2 [mid-level] evidence)
# based on data review of 81,703 infants born in 1 healthcare system in Israel
# 4.2% exposed to metoclopramide during first trimester of pregnancy
# no significant differences comparing infants exposed vs. not exposed to metoclopramide
* major congenital malformations in 5.3% vs. 4.9%
* low birth weight in 8.5% vs. 8.3%
* preterm delivery in 6.3% vs. 5.9%
* perinatal death in 1.5% vs. 2.2%
# Reference – N Engl J Med 2009 Jun 11;360(24):2528
+ no fetal adverse effects identified with metoclopramide in case-control study with 126 pregnant women exposed to metoclopramide during first trimester and 126 controls (N Engl J Med 2000 Aug 10;343(6):445)
o metoclopramide has similar therapeutic effect but fewer adverse effects compared with promethazine in women hospitalized with hyperemesis gravidarum (level 1 [likely reliable] evidence)
+ based on randomized trial
+ 159 pregnant women at < 16 weeks gestation at initial hospitalization for hyperemesis gravidarum randomized to metoclopramide 10 mg vs. promethazine 25 mg 3 times daily for 24 hours
+ no significant difference in median number of vomiting episodes
+ comparing metoclopramide vs. promethazine
# drowsiness in 58.6% vs. 83.6% (p = 0.001, NNT 5)
# dizziness in 34.3% vs. 71.2% (p < 0.001, NNT 3)
# dystonia in 5.7% vs. 19.2% (p = 0.02, NNT 8)
# therapy curtailment due to adverse events in 0% vs. 9.2% (p = 0.014, NNT 11)
+ Reference – Obstet Gynecol 2010 May;115(5):975
o Trimethobenzamide (Tigan) suppositories withdrawn from market due to lack of evidence of effectiveness, oral and injectable formulations not affected (FDA Press Release 2007 Apr 6, FDA MedWatch 2007 Apr 6)
o droperidol (Inapsine) has BLACK BOX WARNING due to fatal cardiac arrhythmias (QT prolongation, torsades de pointes) (FDA Talk Paper 2001 Dec 5)
o IV promethazine associated with risk of serious tissue injury
+ strategies to reduce risk with injectable promethazine include intramuscular use, lower doses (6.25–12.5 mg), dilution with normal saline 10–20 mL, or administration through free-flowing IV
+ Reference – Prescriber’s Letter 2006 Oct;13(10):56
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