Individual responses to medications vary greatly due to many factors including genetics and hydration. Target the triggers of nausea/vomiting such as motion sensitivity, while ensuring adequate hydration and metabolic balance.

If a woman is vomiting constantly, oral dosing of medications will likely be ineffective and alternates such as transdermal (patch/cream), subcutaneous (subQ) or intravenous (IV) routes, should be considered along with hydration.

Intramuscular injections (shots) should be avoided during HG, especially in those with loss of muscle mass.

Top 5 Medication Strategies

Hydrate regularly with IV Multivitamins + B vitamins

Change the dose, frequency & route, then add/change Rx

Replace electrolytes & nutritional deficiencies

Prevent/proactively manage side-effects

Wean over 2 weeks in 2nd+ trimester after 2+ weeks without symptoms. (Kimber’s Rule of 2's)

HER Medication Weaning Rule of 2

Serotonin Antagonists

Highly selective antagonist of 5-HT3 receptors in the vagus, CTZ (chemotrigger zone) and gut. Mostly Class B drugs. Found to improve symptoms in > 80% of women. Use cautiously with metoclopramide (Reglan), and avoid use with other serotonin antagonists (e.g. SSRI’s, antidepressants) to prevent serotonin syndrome.

Zofran (ondansetron) & Kytril Tips:

Hydrate regularly with IV Multivitamins + B Complex

Change the dose, frequency & route, then add/change Rx

Replace electrolytes & nutritional deficiencies

Prevent/proactively manage side-effects

Wean over 2 weeks in 2nd+ trimester after 2+ weeks without symptoms. (Kimber’s Rule of 2's)

Mother's Note: If you have pre-existing medical conditions (diabetes, heart disease, etc.), a history of medication reactions, or are a smoker, please inform your physician before taking these medications.

More common side-effects: Headache, mild/moderate (reversible) liver function test abnormalities, constipation*, diarrhea
* Proactive, daily bowel management is very important.

Often effective in mothers who have multiple triggers (smell, motion, etc.), a history of hormone sensitivity, and/or moderate to severe vomiting. If a woman has a history of HG that responded to serotonin antagonists, it should be considered as a first line drug to minimize symptom severity. Dosing throughout pregnancy may prevent relapse or stabilize symptoms.

IMPORTANT: Best taken on a strict schedule and weaned very slowly.

Drug NameMin/Max DosageNotesResearch Studies
ZofranZuplenz
(Ondansetron)
 
(** Update on Zofran safety)
4 to 8 mg every 6 hours (or 2 to 4 mg every 3 hours)

Given via SQ pump, oral tablet, quick dissolve film or tablet (ODT), or IV. Suppository available outside US.

Can be compounded into a suppository or cream.

Quick dissolving tablets are sometimes prescribed vaginally.
Widely available around the world. 

Proactively treat with a daily regimen of stool softeners plus periodic laxatives as needed. 

Some report generic oral dissolvable tablets do not dissolve as well.
Ondansetron in pregnancy and risk of adverse fetal outcomes in the United States. (2016)

Ondansetron compared with doxylamine and pyridoxine (Diclegis/Diclectin) for treatment of nausea in pregnancy. (2014)

Antiemetic medications in pregnancy: a prospective investigation of obstetric and neurobehavioral outcomes. (2014)

Ondansetron in pregnancy and risk of adverse fetal outcomes. (2013)

Secular Trends in the Treatment of Hyperemesis Gravidarum. (2007)

Pharmacokinetics of Three Formulations of Ondansetron. (2000)

More research articles on PubMed.
KytrilSancuso
(Granisetron)
1 mg every 12 hours (IV or orally)

Twice a day dosing.

Available in transdermal patch form as Sancuso.
Kytril is available as a generic.


Patient Assistance info for patch
Observational Case Series Evaluation of the Granisetron Transdermal Patch System (Sancuso) for the Management of Nausea/Vomiting of Pregnancy. (2017)

Comparison of Efficacy of Granisetron and Promethazine [Phenergan] in Control of Hyperemesis Gravidarum. (2016)

Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy. (2016)

Research articles on PubMed.
Mirtazapine
(Remergil, Remeron)
15-45 mg/day in a single doseMay interact with sedatives, antihistamines, and tricyclic antidepressants.

Has both anti-vomiting and anti-depressant effects.
Is Mirtazapine an Effective Treatment for Nausea and Vomiting of Pregnancy? (2017)

Treatment options for hyperemesis gravidarum. (2017)

Mirtazapine use in resistant hyperemesis gravidarum: report of three cases and review of the literature. (2005)

More research articles on PubMed.
EXPERIMENTAL: Aloxi
(Palonosetron)
No trials for HG yet conducted.

0.25 mg IV given for chemo.
None for HG yet. Research on PubMed.
Anzemet
(Dolasetron)
Dose not established in HG.

50-150 mg orally daily is reported.
Research articles on PubMed.

Antihistamines

Common side-effects: Drowsiness, dry mouth, blurred vision, constipation, urinary retention, restlessness, insomnia, sedation, upset stomach, nervousness, and headache.

Mostly Class A or B drugs
Effective for MILD cases of nausea and vomiting during pregnancy or as adjunctive therapy. Antihistamines with sedative effects can be helpful for sleep.

Drug NameMin/Max DosageNotesResearch Studies
Bonine, Antivert, Marezine
(Meclizine/Buclizine/Cyclizine)
Typical dose: 25-50 mg every 6 hours.
Dramamine
(Dimenhydrinate)
50-100 mg every 4-6 hoursUsed for motion sickness.
Doxylamine
(Unisom)
25 mg orally at bedtime,
1/2 tablet every 6 hours
Component of Diclegis/Diclectin. 

Often taken with vitamin B6 (pyridoxine).
Diclectin, Diclegis 
(doxylamine plus pyridoxine)
Average dose is 1 tablet in morning, one in afternoon and two at night.Differs from Unisom/B6 combo because it is a delayed release formula.Ondansetron compared with doxylamine and pyridoxine (Diclegis/Diclectin) for treatment of nausea in pregnancy. (2014)

Fox & NPR Reports. (2017)

More Research on PubMed.
Benadryl
(Diphenhydramine or Gravol)
25 mg IV/orally every 4–6 hours
Tigan
(Trimethobenzamide)
300 mg orally every 6-8 hoursIM (intramuscular injections not recommended during HG)
Vistaril, Atarax
(Hydroxyzine)
25 mg orally every 6 hours

Pill or syrup
Helpful for insomnia and reducing Rx side-effects such as restlessness and anxiety.

Antidopaminergics: Phenothiazines

Common side-effects: Drowsiness, hypotension, dry mouth, constipation, urinary retention, rash, extrapyramidal symptoms (EPS)*, restlessness, confusion, fatigue. Phenothiazines lower seizure threshold.

*Call your doctor immediately for involuntary movements, tremors and rigidity, restlessness, muscle contractions and changes in breathing and heart rate.

Mostly Class C drugs.
May be helpful in mild and moderate cases or used in conjunction with other medications.

Co-administer antihistamines to minimize side-effects.

Drug NameMin/Max Dosage>NotesResearch Studies
Compazine, Stemetil
(Prochlorperazine)
5–10 mg orally, IM, or IV every 6–8 hours

25 mg every 6–8 hours rectal
Risk of EPS increased with metoclopramide (Reglan).Research articles on PubMed.
Phenergan
(Promethazine)
12.5–25 mg IV/orally, PR every 4-6 hours

*IV dose contains sulfite

*Do not inject or use subcutaneously & use cautiously IV.
Warning: IV or injected doses can cause tissue damage. GIVE IV dose SLOWLY to avoid contractions.

Side-effects of anxiety, sedation, and restlessness common and may limit use.
Promethazine compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. (2010)

Research articles on PubMed.
Thorazine
(Chlorpromazine)
Oral/IM 12.5–25mg every 4–6 hours

Rectal 50–100 mg every 6–8 hours
May increase risk of fetal malformations. 

May cause muscle spasms in neck/face and/or difficulty with speech.
Research articles on PubMed.
Haldol
(Haloperidol)
1–2 mg orally/IM every 8 hoursExtrapyramidal symptoms (EPS) more common. May cause constipation.Research articles on PubMed.

Corticosteroids

Cortisone/Corticosteroids - Not recommended before 9 weeks of pregnancy.

Used for refractory hyperemesis gravidarum, usually in conjunction with ondansetron

Possible side-effects: blood sugar instability, weight loss, nausea and vomiting, increased risk of preeclampsia

Possible fetal complications: reduced birth weight, clefts (if early use), adrenal insufficiency (if exposed to large doses).

Inconclusive concerns over impact on fetal brain development and oral/lip clefts with prolonged dosing at high levels, and use during the first trimester. (Collaborative Perinatal Project)

Typical treatment is a steroid burst with a rapid taper similar to what is used in acute asthma attacks. [Most studies of asthma patients using steroids show no adverse fetal effects.]

Hypothyroid mothers may have an exaggerated response to corticosteroids.

Diabetic mothers may require as much as a 40% increase in their insulin when high dose steroids are started.

Drug Classification:
Methylprednisolone: C  Prednisone: B
(See below for FDA-Assigned Pregnancy Categories.)

Drug NameMin/Max DosageNotesResearch Studies
Medrol or Solu-Medrol (Methylprednisolone or Prednisone)Typical oral dosage is 48 mg per day for three to five days, followed by slow tapering over two to three weeks.

Limit to one month of therapy if possible. Continued use in small doses is sometimes beneficial.

See article for more on dosing.
Consider use with serotonin antagonists and/or during weaning from steroids to prevent relapse.Management of hyperemesis gravidarum: the importance of weight loss as a criterion for steroid therapy. (2002)

Termination is not the treatment of choice for severe hyperemesis gravidarum: Successful management using prednisolone. (2009)

The efficacy low dose of prednisolone in the treatment of hyperemesis gravidarum. (2004)

More Research on PubMed.

Antireflux Medications

Common side-effects: Headache, dizziness, difficulty sleeping, constipation, diarrhea.

Helpful both for reflux and for prevention of gastric (stomach & throat) irritation which worsens nausea

Use when a woman is vomiting frequently and/or cannot eat and drink sufficiently.

Studies suggest they are generally safe during pregnancy and may relax uterine contractions, however recent research suggests there may be some increased risk of asthma in the child. Mostly Class B drugs. Omeprazole (Prilosec, Zegerid) are class C

Drug NameMin/Max DosageNotesResearch Studies
H2 Histamine Blocker (Acid Reducers)

Pepcid
(Famotidine)


20 mg IVP/orally every 12 hours
The safety of H(2)-blockers use during pregnancy.
(2012)
Tagamet
(Cimetidine)
Not recommended during pregnancy due to anti-androgenic effects in humans.
Proton Pump Inhibitors (PPI)

Prevacid
(Lansoprazole)


Nexium (Esomeprazole)

Prilosec
(Omeprazole)


30-60 mg/day

Omeprazole ODT available



20-40 mg/day



20 mg/day
Turns off acid pump in stomach. Stronger than above H2 Blocking meds.The safety of fetal exposure to proton-pump inhibitors during pregnancy. (2012)

Are proton pump inhibitors safe during pregnancy and lactation? Evidence to date. (2012)

Prokinetic Agents

Reglan blocks dopamine receptors in the CTZ (chemoreceptor trigger zone) and increases the CTZ threshold & decreases the sensitivity of visceral nerves that transmit afferent impulses from the GI tract to the vomiting center.

Helpful in women who vomit after eating/drinking.

Sometimes used with meds such as Zofran, but must monitor for serotonin syndrome.

Use with antihistamines to minimize side-effects.

Side-effects are very common and can be severe, especially if medication is given quickly through an IV.

Common side-effects:
Drowsiness, dizziness, abdominal pain, diarrhea, restlessness, EPS*, depression

(*Report extrapyramidal symptoms immediately: involuntary movements, tremors and rigidity, body restlessness, muscle contractions and changes in breathing and heart rate.)

Drug NameMin/Max DosageNotesResearch Studies
Reglan or Maxeran
(Metoclopramide)
10–20 mg IV/orally every 6 hours; ODT available

May be given orally, SQ pump, IV (SLOWLY)
FDA recommends this drug only be taken for up to 12 weeks. Risks of serious side-effects increase thereafter.

Increased CNS side effects when used with phenothiazines.

Side-effects common and may limit use. Use with antihistamines.

Class B drug.
Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. (2014)

Ondansetrone or metoclopromide? Which is more effective in severe nausea and vomiting of pregnancy? (2013)

Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. (2010)

Home Infusion of Reglan.
Propulsid
(Cisapride)
10 mg orally every 6 hours, before meals and at bedtime (maximum dose 20 mg every 6 hours)No CNS side effects. Limited availability in US.

Anticholinergics/Antispasmodics

Common side-effects: Confusion; dizziness, lightheadedness (continuing) or fainting; eye pain; skin rash or hives.

Should not be used in treatment of hyperemesis gravidarum. These agents slow gastric emptying and prolong GI transit time.

Drug NameMin/Max DosageNotesResearch Studies
Scopolamine, Belladonna
(Hyoscine Hydrobromide)
0.3 to 0.65 mg administered IV, intramuscularly or subcutaneously every 6 to 8 hours as needed
1.5 mg transdermal disc behind the ear every 3 days
Effectiveness studies are lacking.

Optimal management of nausea and vomiting of pregnancy. (2012)

Miscellaneous & New Medications

Drug NameMin/Max DosageNotesResearch Studies
Catapres-TTS
(Clonidine)
New medication being used for HG.Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI. (2014)

Research articles on PubMed.
Gabapentin
(Neurontin)
In trials for use in HG. Considered as last resort in patients who have exhausted other medication categories.

May cause neonatal withdrawal.
Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy. (2014)

A case of treatment refractory hyperemesis gravidarum in a patient with comorbid anxiety, treated successfully with adjunctive gabapentin. (2012)

Research articles on PubMed.
Thiamine
(Vitamin B1)
5 mg/day minimum.

For HG: 100-500 mg BID IV. IM contraindicated.

Can be taken as a single pill if prenatal vitamins are not tolerated.
Body's stores depleted in < 3 weeks.

Infographic on thiamin deficiency in HG.

Should be given orally before and during pregnancy as tolerated.
Iatrogenic wernicke encephalopathy in a patient with severe hyperemesis gravidarum. (2015)

Mortality Secondary to Hyperemesis Gravidarum: A Case Report (2015)
Pyridoxine
(Vitamin B6, Hexa-Betalin)

Cobalamin, Cyanocobalamin, Hydroxocobalamin
(Vitamin B12)
20-75 mg/day
Doses up to 150 mg are being used.

100 mcg/day
Paresthesias may occur if B6 is taken in high doses. 

Note: reactions to B vitamins are rare but possible.
Reprivex
Each tablet contains 25mg of Vitamin B6 (as Pyridoxine Hydrochloride) and 100mg of Ginger Root PE 5% Gingerois (Zingiber Officinalis)
3 tablets dailyA prescription is NOT required for this medication.
Ginger250 mg orally every 6 hoursMay be helpful as adjunctive therapy.
Emetrol
(Fructose, Dextrose, and Phosphoric Acid)
One or two tablespoonfuls upon arising and every three hours as needed.May be helpful as adjunctive therapy.
Marijuana
(Cannabis)
or the pharmaceutical extract: Marinol
(Dronabinol)
Dose not established for HG.Use with caution. Potential fetal effects – see studies at right.Cannabis and pregnancy: Maternal child health implications (2017)

The effects of cannabis on embryological development. (2016)

Prenatal Cannabis and Tobacco Exposure in Relation to Brain Morphology: A Prospective Neuroimaging Study in Young Children. (2016)

Research on PubMed.
Benzodiazepine Derivatives:
Valium
(Diazepam)
Dose not established for HG.Class D drug.Use of diazepam for hyperemesis gravidarum. (2009)
Neuroleptic:
Inapsine
(Droperidol)
Gerald G. Briggs
Briggs (LBMMC) Hyperemesis Protocol
Use with diphenhydramine to avoid side-effects.

Category C drug.
Droperidol and diphenhydramine in the management of hyperemesis gravidarum (1996)

** IM = Intramuscular (injection/shot)
** IV = Intravenous
** IVP = Intravenous push (injected into an IV)
** PR = Per rectum
** PR = Per vaginally
** SQ = subcutaneous (injected under the skin)
** TD = Transdermal 

Substance P/Neurokinin 1 (NK1) Receptor Antagonist

This is a NEWER class of drugs that are effective for nausea and vomiting in non-pregnant patients.

NO safety data is available during pregnancy or HG.

We strongly caution the use of this medication class.

Drug NameMin/Max DosageNotesResearch Studies
EXPERIMENTAL: Emend
(Aprepitant)
80-125 mg per day is dose for chemotherapy

Oral and IV
Typical protocol (prevention of vomiting due to chemotherapy) includes combining with a serotonin antagonists and steroids.None for HG yet. Research on PubMed.

FORMER FDA Pregnancy Categories for Drugs (United States)

Category A

Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).

Category B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Category C

Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category D

There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Category X

Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.

Excerpted from Drug Information for the Health Care Professional, USP-DI, Volume 1A, 11th ed., 1991.