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Am Fam Physician. 2011;83(7):842

Background: Hyperemesis gravidarum is a severe form of nausea and vomiting during pregnancy that can cause dehydration, electrolyte abnormalities, and weight loss. It affects 0.3 to 2.3 percent of all pregnancies. Less severe forms of nausea and vomiting affect up to 85 percent of all pregnancies. Treatment for hyperemesis gravidarum may require hospitalization, and includes intravenous rehydration, antiemetic medications, and psychosocial support. The American College of Obstetricians and Gynecologists recommends intravenous dimenhydrinate (Dramamine), metoclopramide (Reglan), and promethazine (Phenergan) as first-line medications. Previous studies have evaluated promethazine, ondansetron (Zofran), corticosteroids, metoclopramide, and diphenhydramine (Benadryl), but no trial has directly compared metoclopramide and promethazine. Tan and colleagues assessed the effectiveness and adverse effect profiles of these drugs as treatment for hyperemesis gravidarum.

The Study: This randomized controlled study included women admitted to a hospital in Malaysia with presumed hyperemesis. Patients who were no more than 16 weeks pregnant and were admitted to the hospital for the first time in their current pregnancy with dehydration and ketonuria were eligible to participate. Women who had a multiple gestation pregnancy, nonviable pregnancy, a preexisting medical condition that could cause nausea and vomiting, or an allergy to either study medication were excluded. Patients received an initial dose of 10 mg of metoclopramide or 25 mg of promethazine, and additional doses at eight, 16, and 24 hours. Participants recorded their vomiting episodes and reported their nausea on a 10-point visual numeric scale before starting the drug and after each dose. At 24 hours, patients also recorded their overall sense of well-being during the study period and answered a questionnaire about symptoms. After 24 hours, patients could continue their study medication or switch to the other as open-label treatment. Primary end points were the frequency of vomiting and the overall well-being score. Secondary end points included adverse effects and nausea scores at each dose.

Results: A total of 73 women were assigned to the metoclopramide group and 76 to the promethazine group. There were no significant differences in vomiting episodes, nausea scores at each dose, or overall sense of well-being after 24 hours. However, the metoclopramide group reported significantly fewer adverse effects, mainly drowsiness (number needed to treat [NNT] = 5), dizziness (NNT = 3), and dystonia (NNT = 8), compared with the promethazine group. The seven women who did not complete the trial because of adverse effects were all in the promethazine group. Limitations of the study include the possibility that intravenous rehydration therapy alone is equally effective in treating hyperemesis. Additionally, the authors cite a Cochrane review that found no benefit with any specific treatment for hyperemesis gravidarum.

Conclusion: The authors conclude that when metoclopramide is given in a dosage of 10 mg every eight hours, it is as effective as and better tolerated than promethazine for hyperemesis gravidarum.

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