Hyperemesis Gravidarum in Emergency Medicine Medication

Updated: Feb 04, 2021
  • Author: Feras H Khan, MD; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD  more...
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Medication Summary

The American College of Obstetrics and Gynecology recommends that first-line treatment of nausea and vomiting of pregnancy should start with pyridoxine (vitamin B6) with or without doxylamine. [11]  Pyridoxine has been found to be effective in significantly reducing severe vomiting but is less effective with milder vomiting. Pyridoxine in combination with doxylamine 10 mg, the active ingredient in many over-the-counter sleep agents, has been shown in randomized, placebo-controlled trials to have a 70% reduction in nausea and vomiting. The combination of pyridoxine 10 mg and doxylamine 10 mg was originally available in the United States from 1956 until 1983 as Bendectin, when it was voluntarily removed from the market by the manufacturer due to litigation. Multiple studies have shown no increased risk of birth defects with the pyridoxine-doxylamine combination.

The only FDA-approved drug for treating nausea and vomiting in pregnancy is doxylamine/pyridoxine (Diclegis). Originally sold between 1956 and 1983 with the brand name Bendectin, it was pulled from the market because of safety concerns, which have since been disproved. The new dosage form approved in April 2013 is a delayed-release tablet, that when taken at bedtime, is at its peak serum concentrations in the morning when nausea and vomiting may be worse. Approval was based on a study of pregnant women between 7-14 weeks gestation who were suffering from nausea and vomiting. Compared with placebo, doxylamine/pyridoxine significantly improved both the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) scores and quality of life of trial participants. [14]

Doxylamine/pyridoxine’s approval did not include hyperemesis gravidarum, but a study by Koren and Maltepe showed the drug may work best when administered before the onset of symptoms. A greater reduction in the recurrence of hyperemesis gravidarum was observed in those who used the doxylamine/pyridoxine combination preemptively compared to those who took the drug at symptom onset (43% vs 17%). [15]

Ondansetron (Zofran), while pregnancy Class B, has become the most common parenteral and oral antiemetic used in US emergency departments due to its efficacy, and it has become the first choice in hyperemesis in the last several years—especially since it became available in a generic form. The Orally Dissolving Tablet (ODT) formulation, while not yet available in generic form, is very helpful in patients who are having a hard time tolerating oral forms. It is a serotonin antagonist and is dose responsive. Starting dosage is 4 mg, either IV or PO, and that dose may be repeated every 15-30 minutes until symptoms improve. Other typical antiemetics such as promethazine 12.5-25 mg IV or PO every 4 hours or prochlorperazine 25 mg rectally every 12 hours are also acceptable second-line agents.

Anticholinergics are supported by some data attesting to their safety, but they are not as well studied. Meclizine and dimenhydrinate have both been shown to be more effective than placebo in controlling nausea and vomiting of pregnancy. Metoclopramide, a promotility agent, has been demonstrated to be more effective than placebo in the treatment of hyperemesis gravidarum, and it has not been shown to be associated with increased incidence of congenital malformations.

Corticosteroids have a possible benefit in the treatment of hyperemesis gravidarum. [16] Steroids have been considered a last resort in patients who will require enteral or parenteral nutrition due to weight loss. The most common regimen is methylprednisolone 16 mg, orally or intravenously, every 8 hours for 3 days. Patients who do not respond within 3 days are not likely to respond. For those who do respond, the course may be tapered over 2 weeks. Some recent studies have demonstrated an association between oral clefts and methylprednisolone use in the first trimester. The current recommendation is that corticosteroids be used with caution and avoided before 10 weeks' gestation. [11]

In addition to the medications mentioned below, ginger is a common remedy for nausea and vomiting in pregnancy. Ginger capsules of 250 mg taken 4 times a day have been demonstrated to be effective against nausea and vomiting of pregnancy as well as hyperemesis when compared with placebo, without evidence of significant side effects or adverse effects on pregnancy outcomes. [17, 18] However, no clinical or experimental data about adverse effects of ginger in pregnancy exist. The Food and Drug Administration (FDA) does not regulate ginger products.

Practitioners of traditional Chinese medicine believe that stimulation of acupuncture point P6 can relieve nausea. Acupressure can be used as an alternative or complement to Western medications. However, the data about acupressure for nausea are equivocal. Sea Band is an easy over-the-counter product that stimulates the P6 site.


Nutritional supplements

Class Summary

Pyridoxine deficiency may have an etiologic role. Severe nutritional deficiencies may lead to thiamine deficiency and result in Wernicke encephalopathy.

Pyridoxine (Vitamin B6, Hexa-Betalin)

Some use pyridoxine with doxylamine (active ingredients in Benedictine, an antiemetic no longer available in the United States but still widely used in Europe). In the United States, doxylamine can be found in the over-the-counter medication Unisom (effective dose is half tablet).

Thiamine (Vitamin B1, Thiamilate)

Used in the treatment of thiamine deficiency including Wernicke encephalopathy syndrome.



Class Summary

Useful in the treatment of symptomatic nausea and vomiting.

Doxylamine/pyridoxine (Diclegis)

Mechanism of action for efficacy to treat morning sickness is unknown. It contains doxylamine, an ethanolamine antihistamine derivative, and pyridoxine, a vitamin B6 analog. It is the only FDA-approved medication for treatment of nausea and vomiting of pregnancy who have not adequately responded to dietary and lifestyle changes.

Promethazine (Phenergan)

Antidopaminergic agent effective in treating emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to the brainstem reticular system. Not to be administered SC or intra-arterially, because necrotic lesions may develop.

Prochlorperazine (Compazine)

Antidopaminergic drug that may relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors with its anticholinergic effects and by depressing the reticular activating system.

Metoclopramide (Reglan)

Works as an antiemetic by blocking dopamine receptors in chemoreceptor trigger zone of the CNS. Usually reserved for use when other therapies fail to control symptoms. Stimulates intestinal motility and is metabolized in the kidneys.

Dimenhydrinate (Dramamine)

Used as an antimotion sickness agent, dimenhydrinate has been demonstrated to be effective in reducing hyperemesis and is an acceptable second-line agent.

Diphenhydramine (Benadryl)

Used for the treatment and prophylaxis of vestibular disorders that may cause nausea and vomiting.

Meclizine (Antivert, Antrizine, Meni-D, Dramamine, Marezine)

Decreases excitability of the middle-ear labyrinth and blocks conduction in middle-ear vestibular-cerebellar pathways. These effects are associated with relief of nausea and vomiting.

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally, used in the prevention of nausea and vomiting. It is metabolized in the liver with P-450 mechanism.