Hyperemesis Gravidarum Medication

Updated: Apr 12, 2022
  • Author: Dotun A Ogunyemi, MD; Chief Editor: Christine Isaacs, MD  more...
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Medication Summary

Antihistamines, antiemetics of the phenothiazine class, and promotility agents (eg, metoclopramide) have been used in the treatment of nausea and vomiting during pregnancy.

Vitamin B-6 (pyridoxine) has also been studied in the treatment of nausea and vomiting during pregnancy and reduced nausea and vomiting when compared with placebo.

Ondansetron (Zofran), a serotonin-receptor antagonist, showed no benefit over the antiemetic promethazine (Phenergan), at much greater cost. It may be reserved for refractory cases. A meta-analysis of 6 randomized, double-blind trials showed that ginger was an effective treatment for hyperemesis gravidarum.

Steroids may be used in patient's refractory to standard therapy. Promethazine (Phenergan) was compared with methylprednisolone in a randomized, double-blind, controlled trial. Methylprednisolone appeared to decrease the rate of readmission for hyperemesis gravidarum; however, the patients randomized to promethazine had a significantly longer duration of symptoms prior to treatment.

However, concerns exist about association between oral clefts and methylprednisolone use in the first trimester; thus, it should be used with caution before 10 weeks of gestation.



Class Summary

Essential for normal DNA synthesis and play a role in various metabolic processes.

Pyridoxine (Nestrex)

Marketed in combination formulations with doxylamine (Benedectin, Dilectin).

Benedectin was taken off the market in the United States in the 1980s because of liability issues, but it is available in Canada. Doxylamine is probably not teratogenic and can be used in combination with pyridoxine at a dose of 10-12.5 mg PO qd/bid.


Herbal medications

Class Summary

Not approved by the US Food and Drug Administration but are remedies believed to improve symptoms.


A randomized, double-blind, crossover trial of a ginger extract was shown to be more beneficial for reducing symptoms than placebo.



Class Summary

Useful in the treatment of symptomatic nausea.

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.

Prochlorperazine (Compazine)

May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system. In a placebo-controlled study, 69% of patients given prochlorperazine reported significant symptom relief, compared to 40% of patients in the placebo group.

Promethazine (Phenergan)

For symptomatic treatment of nausea in vestibular dysfunction. Antidopaminergic agent effective in treating emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to brainstem reticular system.

Chlorpromazine (Thorazine, Ormazine)

Mechanisms responsible for relieving nausea and vomiting include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of RAS. Blocks alpha-adrenergic receptors and depresses release of hypophyseal and hypothalamic hormones.

Trimethobenzamide: (Tebamide, Tigan)

Acts centrally to inhibit the medullary chemoreceptor trigger zone.

Metoclopramide (Reglan)

Blocks dopamine receptors and (when given in higher doses) also blocks serotonin receptors in chemoreceptor trigger zone of the CNS; enhances the response to acetylcholine of tissue in upper GI tract causing enhanced motility and accelerated gastric emptying without stimulating gastric, biliary, or pancreatic secretions; increases lower esophageal sphincter tone.

Ondansetron: (Zofran)

Selective 5-HT3-receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone.



Class Summary

These agents have profound and varied metabolic effects.

Methylprednisolone (Medrol, Solu-Medrol)

May improve symptoms of nausea and vomiting.



Class Summary

Studied in nausea and vomiting during pregnancy and in small numbers of patients with hyperemesis gravidarum, providing relief in 82% of patients. Appears to be as efficacious as pyridoxine in another study.

Meclizine (Antivert)

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

Diphenhydramine (Benadryl)

Competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract; anticholinergic and sedative effects are also seen