Medications are needed to manage hyperemesis gravidarum. Individual responses to medications vary greatly due to many factors including genetics, vitamin levels, and hydration.

One helpful strategy with HG is to target the triggers of nausea/vomiting such as motion sensitivity while ensuring adequate hydration and improving nutrition.

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, due to pain sensitivity and lack of muscle mass for storage.

What if I'm Breastfeeding?

More often than not, the majority of medications can be safely taken while breastfeeding. Lactmed and Infant Risk Center are updated with the latest research on the safety of medications while breastfeeding. You can ask your healthcare provider to check before prescribing a medication or if you have concerns about any effects your medications may have on your baby. Learn more about breastfeeding and HG here.

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)


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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
(** 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, liquid, 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 used vaginally.
Widely available around the world. 

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

Some report generic oral disintegrating tablets do not dissolve as well.

If headaches, consider granisetron.
Mother to Baby Fact Sheet (2022)

Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort (2021)

Intravenous Ondansetron in Pregnancy and Risk of Congenital Malformations (2020)

Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring (2018)

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.
1 mg every 12 hours (IV or orally)

Twice a day dosing.

Available in transdermal patch form as Sancuso.

**May need additional single oral/IV dose of granisetron on days 1-2 until Sancuso patch is full strength.**
Kytril is available as a generic.

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

Side-effects may be less with transdermal patch. Headaches may be less with granisetron than ondansetron.

**READ Sancuso instructions carefully. Apply to arm. Avoid heat/sun on patch/application site during use and for 10 additional days.

Prescriber info

Insurance info & sample patch

Request sample to see if Sancuso is effective. Generic may be available in 2025. Cash price is about $700 USD per weekly 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.
(Remergil, Remeron)
Dose not established for HG. 15 mg up to 3 times per day typically used.

Oral options: pill and oral dissolving tablet.
May interact with sedatives, antihistamines, and tricyclic antidepressants. Do not use with other serotonin-antagonistic medications.

Has both anti-vomiting and anti-depressant effects.
Mother to Baby Fact Sheet (2021)

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.
No trials for HG yet conducted.

0.25 mg IV given for chemo.
A few patient reports of Aloxi so far have not shown much benefit. No None for HG yet. Research on PubMed.
Dose not established in HG.

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


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
Typical dose: 25-50 mg every 6 hours.Widely available and often available with a prescription.

Cyclizine IV and 50 mg pills available in some countries.

Meclizine marketed as Dramamine Low Drowsy.
Mother to Baby Fact Sheet (2021)
Dramamine or Gravol
50-100 mg every 4-6 hoursUsed for motion sickness.
25 mg orally at bedtime,
1/2 tablet every 6 hours
Component of Diclegis/Diclectin. 

Often taken with vitamin B6 (pyridoxine).

Causes sleepiness.
Diclectin, Diclegis, Xonvea, Cariban, Bonjesta (higher dose) 
(doxylamine plus pyridoxine)
Average dose is 1 tablet in morning, one in afternoon and two at night.

Bonjesta is usually 1 pill in morning and 1 at night.
Differs from Unisom/B6 because it is a delayed release formula. Different brands are slightly different in release. Mother to Baby Fact Sheet (2023)

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

Fox & NPR Reports. (2017)

More Research on PubMed.
25 mg IV/orally every 4–6 hoursOften causes sleepiness.Mother to Baby Fact Sheet (2021)
300 mg orally every 6-8 hoursIM (intramuscular injections not recommended during HG)
Vistaril, Atarax
25 mg orally every 6 hours

Pill or syrup
Helpful for insomnia and reducing 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
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.
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. (See FDA Warning) GIVE IV dose SLOWLY to avoid contractions.

Side-effects of anxiety, sedation, and restlessness common and may limit use.
Mother to Baby Fact Sheet (2021)

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

Research articles on PubMed.
Zyprexa (olanzapine)No dose established

5 mg every 8-12 hours as needed

Available as an oral dissolving tablet (ODT)
Usage for HG is new and experimental. Is sometimes used for breakthrough vomiting and vomiting related to cannabis use.

Causes sedation. Less risk of some side effects compared to other medications in this category.
No research for HG. Mother to Baby Fact Sheet (2022)
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.
1–2 mg orally/IM every 8 hoursExtrapyramidal symptoms (EPS) more common. May cause constipation.Research articles on PubMed.

Mother to Baby Fact Sheet (2022)


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.Mother to Baby Fact Sheet (2022)

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)

Take at bedtime.

20 mg IVP/orally every 12 hours
Mother to Baby Fact Sheet

The safety of H(2)-blockers use during pregnancy.
Not recommended during pregnancy due to anti-androgenic effects in humans.
Proton Pump Inhibitors (PPI)


Nexium (Esomeprazole)

Take at bedtime.

30-60 mg/day
ODT available

20-40 mg/day

20 mg/day
Turns off acid pump in stomach. Stronger than above H2 acid reducing medications.Mother to Baby Fact Sheet (2020)

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
2.5–10 mg IV/orally every 6 hours; ODT (oral dissolving tablet) available

May be given orally, SQ (subcutaneous) infusion pump, IV (SLOWLY)
Often causes panic attacks if given IV push. Infuse SLOWLY instead.

Oral use may have less anxiety, especially if a low dose is used. Start with low dose of 2.5 to 5 mg to see if tolerated. 20 mg doses sometimes used.

FDA recommends this drug be used for less than 12 weeks. Risks of serious side-effects may increase thereafter.

Increased CNS side effects when used with phenothiazines.

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

Class B drug.
Mother to Baby Fact Sheet (2021)

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.
Motilium (Domperidone) 10-20 mg orally every 6-8 hours

May be used to increase milk production in breastfeeding.
Not available in the US due to concerns over heart issues. Special use request info for FDA.

Check with pharmacist on dosing when combining with other anti-vomiting medications. Correct electrolytes if needed.

May be combined with acid reducing medication.
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.


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
Thiamine or Thiamin
(Vitamin B1)
5 mg/day minimum for normal diet. NON TOXIC.

For HG: 100-500 mg up to TID IV or oral. IM contraindicated due to volume and low muscle mass.

***All women with HG should be on at least 100 mg daily orally (ideally Lipothiamine or Benfotiamine), and 250 mg per day after 20 weeks. If prolonged HG, continue taking for 3 months after delivery or breastfeeding.

Take as a single supplement because prenatal vitamins do not have enough.
Body's stores depleted in < 3 weeks.

Important info on B1 deficiency.

Should be given orally before and during pregnancy as tolerated. Protective of mother's brain and heart, and baby's development. See more info and Fact Sheets.
Iatrogenic wernicke encephalopathy in a patient with severe hyperemesis gravidarum. (2015)

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

Cobalamin, Cyanocobalamin, Hydroxocobalamin
(Vitamin B12)
20-150 mg/day oral/IV

100 mcg/day
Paresthesias (nerve issues) may occur if B6 is taken in high doses. 

Note: reactions to B vitamins are rare but possible.
Dose not established for HG. Studies use 300-600 mg orally up to 2400 mg per day.May be compounded into a suppository or cream.

May lower folic acid levels.

Causes sleepiness. Side-effects increase with dose. Is sometimes combined with other antiemetics.

Use with caution.

In trials for use in HG. Considered in patients who have not responded to optimized doses of other medications.

May cause neonatal withdrawal.
Mother To Baby Fact Sheet

Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes (2020)

Effect of gabapentin on hyperemesis gravidarum:
a double-blind, randomized controlled trial.

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.
0.625 - 2.5 mg IV or injectionUse with diphenhydramine to avoid side-effects.

May cause severe anxiety or restlessness.

Category C drug.
Droperidol and diphenhydramine in the management of hyperemesis gravidarum (1996)
Benzodiazepine Derivatives:
Dose not established for HG.Class D drug.

Also helps with anxiety but dependency occurs after regular use.
Mother to Baby Fact Sheet (2022)

Use of diazepam for hyperemesis gravidarum. (2009)
or the pharmaceutical extract: Marinol
Dose not established for HG.Use with caution. Potential fetal effects – see studies at right.

May cause cannabinoid hyperemesis syndrome.

Acute care rates may increase with use.
Mother to Baby Fact Sheet (2022)

Patterns of Use and Self Reported Effectiveness of Cannabis for Hyperemesis Gravidarum

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.
Each tablet contains 25mg of Vitamin B6 (as Pyridoxine Hydrochloride) and 100mg of Ginger Root PE 5% Gingerois (Zingiber Officinalis)
3 tablets dailyLimited benefit in HG.Mother to Baby Fact Sheet (2021)
New medication being tried for HG.Mother to Baby Fact Sheet (2022)

Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI. (2014)

Research articles on PubMed.
(Fructose, Dextrose, and Phosphoric Acid)
One or two tablespoonfuls upon arising and every three hours as needed.Benefit not established in HG.
Ginger250 mg orally every 6 hoursRarely helpful as adjunctive therapy.

Can be painful to vomit.

** 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
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.