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Individual responses to medications vary greatly. 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.

Read our brochure on medication strategies!
Learn how to get the most from medications & use them to manage HG most effectively!

Zofran (ondansetron) & Kytril Tips:

  • most effective class of drugs for HG & multi-trigger patients,
  • dose-dependent drugs - benefits and side-effects increase with the dose,
  • often works better if hydrated and combined with other meds,
  • higher doses may decrease need for IV's and hospitalization,
  • gradual reduction in dose, then frequency, is critical to avoid relapse,
  • prevent side-effects like constipation exacerbated by dehydration.
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 medications.


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.

More common side-effects: Headache, mild liver function abnormalities, constipation*, diarrhea
* Proactive, daily bowel management is very important. For information on managing these symptoms, see this article on MedicineNet.

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.

IMPORTANT: Effects are dose dependent. Best taken on a strict schedule and weaned very slowly when asymptomatic for two weeks. May be needed until delivery.

Drug Name Min/Max Dosage Notes Research Studies

Zofran, Zuplenz


(** Update on Zofran lawsuits)

4 to 8 mg every 6 hours

Given via SQ pump, oral tablet, liquid,NEW Researchquick dissolve film, or IV. Suppository available outside US.

Can be compounded into a suppository or other form.

Dosing throughout pregnancy may prevent relapse or stabilize symptoms.

Zofran tablets are available as a generic.

Widely available around the world.

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

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

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

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

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

More research articles on PubMed.

Kytril, Sancuso
1 mg every 12 hours (IV or orally)

Allows twice a day dosing.

Also available in transdermal patch form as Sancuso.NEW Research
Kytril is available as a generic.

Research articles on PubMed.
Mirtazapine (Remergil, Remeron)   May interact with sedatives, antihistamines, and tricyclic antidepressants.

Has both anti-vomiting and anti-depressant effects.

Mirtazapine (Remergil) for treatment resistant hyperemesis gravidarum: rescue of a twin pregnancy.

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

More research articles on PubMed.

Dose not established in HG. 0.25 mg IV given for chemo. Half-life: 40 hr. & only given once in 5 days.
Reimbursement Support Network.
None for HG yet. Research on PubMed.
Dose not established in HG. 50-150 mg orally daily is reported.   Research articles on PubMed.


This is a NEWER class of drugs so minimal safety data is available. No studies for its use in pregnancy are available. We caution the use of this medication class and suggest use as last resort.

Research Links:

Drug Name Min/Max Dosage Notes Research Studies
EmendNEW Research (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.


Cortisone/Corticosteroids - Not recommended until after 8-10 weeks
- 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 Name Min/Max Dosage Notes Research 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.

See article for more on dosing.
Consideration use with serotonin antagonists and/or during weaning from steroids to prevent relapse.

Corticosteroid therapy in hyperemesis gravidarum

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

More Research on PubMed


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

Mostly Class 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.

Research Links:

Drug Name Min/Max Dosage Notes Research Studies
Bonine, Antivert, Marezine
Follow directions on the label. See Medline Plus  
50-100 mg every 4-6 hours Used for motion sickness.  
25 mg orally at bedtime,
1/2 tablet every 6 hours as needed
Component of Diclegis/Diclectin.

Often taken with vitamin B6.
Diclectin, Diclegis NEW Research
(doxylamine plus pyridoxine)
Average dose is 1 tablet in morning, one in afternoon and two at night.

May be given in higher doses up to 12 tablets daily - see research links on right.
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

The return to the USA of doxylamine-pyridoxine delayed release combination (Diclegis®) for morning sickness.

(Diphenhydramine or Gravol)
25 mg IVP/orally every 4–6 hours      
25 mg orally every 6-8 hours
200 mg IM every 6-8 hours
Vistaril, Atarax
25 mg orally every 6 hours Syrup available
Helpful for insomnia


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, body 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 Name Typical Min/Max Dosage Notes Research 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). Treat/prophylax for EPS with Benadryl. Research articles on PubMed.

12.5–25 mg IVP/orally, IM/PR every 4-6 hours

*IV dose contains sulfite

NEW Research Warning: IV or injected doses can cause tissue damage. More info available on fda.gov. GIVE IV dose SLOWLY to avoid contractions.

Side-effects of anxiety, sedation, and restlessness common and may limit use.
Research articles on PubMed.
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 hours Extrapyramidal symptoms (EPS) more common. May cause constipation. Research articles on PubMed.


- Common side-effects: Headache, dizziness, difficulty sleeping, constipation, diarrhea.
- Helpful both for reflux and for prevention of gastric irritation which worsens nausea.
- Use when a woman is vomiting frequently and/or cannot eat and drink sufficiently.
- Studies suggest they are safe during pregnancy. Mostly Class B drugs. Omeprazole (Prilosec, Zegerid) are class C.

Drug Name Min/Max Dosage Notes Research Studies
50 mg IV every 8 hours or 150 mg orally daily or twice a day   Reprod Toxicol. 2005 Pregnancy outcome after exposure to ranitidine and other H2-blockers.
  Not recommended during pregnancy due to anti-androgenic effects in humans.  
20 mg IVP/orally every 12 hours   Reprod Toxicol. 2005 Pregnancy outcome after exposure to ranitidine and other H2-blockers.
30-60 mg/day   AAFP 2002
Proton Pump Inhibitors: An Update.

Use of proton pump inhibitors during pregnancy and rates of major malformations: a meta-analysis.


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, and who do not respond to Zofran alone.
- Sometimes used in conjunction with meds such as Zofran.
- Use with antihistamines to minimize side-effects.

- Side-effects are very common and can be severe, especially when 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 Name Min/Max Dosage Notes Research Studies
Reglan or Maxeran
10–20 mg IV/orally every 6 hours

May be given orally, SQ pump, IV (SLOWLY)
NEW ResearchFDA recommends this drug 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.

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

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

The safety of metoclopramide during pregnancy

Home Infusion of Reglan

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 Name Min/Max Dosage Notes Research 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


Clonidine New medication being used for HG.
Drug Name Min/Max Dosage Notes Research Studies
Catapres-TTS (Clonidine)   New medication being used for HG. Transdermal clonidine in the treatment of severe hyperemesis. A pilot randomised control trial: CLONEMESI.
Gabapentin (Neurontin)   In trials for use in HG. Considered as last resort in patients who have exhausted other medication categories.

Potential maternal symptomatic benefit of gabapentin and review of its safety in pregnancy.

A case of treatment refractory hyperemesis gravidarum in a patient with comorbid anxiety, treated successfully with adjunctive gabapentin: a review and the potential role of neurogastroentereology in understanding its pathogenesis and treatment.

Research articles on PubMed.

(Vitamin B1)

5 mg/day minimum; Considered non-toxic. For HG: 100-500 mg BID IV. IM contraindicated.

Should be given orally before and during pregnancy as tolerated.

Body's stores depleted in < 3 weeks.

Infographic on thiamin deficiency in HG.

Iatrogenic wernicke encephalopathy in a patient with severe hyperemesis gravidarum.

Wernicke's encephalopathy induced by hyperemesis gravidarum.

Neurological complications in hyperemesis gravidarum.

(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 vitamins are rare but possible.
Serious adverse drug reaction in a woman with hyperemesis gravidarum after first exposure to vitamin B complex containing vitamins B1, B6 and B12.


Each tablet contains 25mg of Vitamin B6 (as Pyridoxine Hydrochloride) and 100mg of Ginger Root PE 5% Gingerois (Zingiber Officinalis)

3 tablets daily


A prescription is NOT required for this medication.  
Ginger 250 mg orally every 6 hours Helpful as adjunctive therapy.  
(Fructose, Dextrose, and Phosphoric Acid)
One or two tablespoonfuls upon arising and every three hours as needed. Helpful as adjunctive therapy.  
or the pharmaceutical extract: Marinol
Dose not established for HG.  

Effects of prenatal exposure to marijuana.

Research on PubMed

International Association for Cannabis as Medicine
Does cannabis/THC do harm to the fetus if it is used during pregnancy?

Benzodiazepine Derivatives:
Dose not established for HG. Class D drug. Evaluation of treatment of hyperemesis gravidarum using parenteral fluid with or without diazepam.
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.

Droperidol-diphenhydramine for hyperemesis gravidarum.

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

FDA-Assigned Pregnancy Categories for Drugs (United States Classification)

  • 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.

Updated on: Aug. 17, 2019

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