Retrolental fibroplasia

Because nausea and vomiting of pregnancy peaks at about 8 weeks, right in the middle of organogenesis, some physicians worry about prescribing drugs to pregnant women, including those that have been shown to be safe in pregnancy.

In my opinion, all the antiemetic drugs can be used in pregnancy with the exception of corticosteroids and marijuana, as their benefits outweigh their risks.

I consider the combination of the antihistamine/anticholinergic doxylamine and pyridoxine (vitamin [B.sub.6]) to be the firstline pharmacologic treatment of nausea and vomiting of pregnancy (NVP). These were the components of Bendectin, which was withdrawn by the manufacturer from the U.S. market in 1983 because of adverse publicity and litigation surrounding allegations that it was as sociated with limb reduction defects in babies exposed in utero. But in 1999, thc Food and Drug Administration deter mined that it was not withdrawn for safety reasons and added the combination back to its list of approved drug products that are considered safe and effective.

Bendectin is probably the most thoroughly studied drug combination in human pregnancy Among the estimated 30 million pregnant women who took Bendectin, no increase in or clustering of birth defects were detected.

Until this combination is available again in the United States, NVP can be treated with doxylamine, the over-the-counter nighttime sleep aid marketed as Unisom. One half of a 25-mg Unisom tablet can be taken with 25 mg of vitamin [B.sub.6] once or twice a day (Bendectin contained 10 mg of doxylamine and 10 mg of vitamin [B.sub.6] and was a slow-release formulation.)

Other antihistamines are also generally safe during pregnancy Still, all antihistamines should be avoided if premature labor occurs because, of a possible association between retrolental fibroplasia in premature babies exposed to antihistamines within 2 weeks of birth.

If intravenous therapy is necessary diphenhydramine (Benadryl) is the 'parenteral drug of choice. It is safe during pregnancy, although neonatal withdrawal has been reported with chronic use. Diphenhydramine also interacts with temazepam (Restoril), and has oxytocic properties when administered intravenously near term.

Oral dimenhydrinate (Dramamine) has been used extensively for NVP in Canada but not in this country Like diphenhydramine, it is safe during pregnancy but is tied to oxytocic effects when given intravenously near term.

Other antiemetics that can be used are dopamine antagonists. Phenothiazines, butyrophenones, and metoclopramide (Reglan) have the most direct effect on blocking the pathway between the center in the medulla that controls vomiting and the chemoreceptor trigger. zone. The drawback of dopamine antagonists is their dystonic effects. Prochiorperazine (Compazine) is also safe and effective during pregnancy and is probably one of the more common agents used by physicians for NVP. Like other phenothiazines, this drug also causes dystonic reactions, even 'with a single dose, but, has the advantage of being available in oral, rectal, intramuscular, and intravenous formulations.

The butyrophenone derivative droperidol is the most potent m this 'class nd is the most effective drug available for severe NVP and hyperemesis gravidarum. It is not an animal teratogen, and we have not seen anyclustering of or increase in birth defects. An. advantage is that the type of extrapyramidal side effects seen with droperidol tends to be akathisia, 'which is common, but I have never seen a dystonic reaction.

Our protocol for hyperemesis gravidarum' includes treatment with intravenous droperidol and intravenous diphenhydramine, which usually elicits a quick response. We use this combination because' droperidol is an effective antiemetic, and diphenhydramine is an effective antiemetic and an antidote for akathisia. After 2 days, we discharge patients on oral metoclopramide and hydroxyzine (Vistaril) four times a day

Metoclopramide has been safe and effective for NVP in numerous studies but is no more effectiverhan any other NVP drug. Hydroxyzine is another antihistamine alternative to doxylamine-pyridoxine.

The selective serotonin receptor antagonists dolasetron (Anzemet), granisetron (Kytril), and ondansetron (Zofran) don't appear to be human teratogens, but most have not been studied for NVP. They also are expensive and do not' offer any advantage over other drugs. Herbal medicines are also used for NVP but except for ginger, no 'data exist on their effectiveness, and 'safety data are lacking.

GERALD C. BRIGGS, B.Pharm., is pharmacist clinical specialist, Women's Hospital, Long Beach. Memorial Medical Center; clinical professor of pharmacy, University of California, San Francisco; and adjunct associate professor of pharmacy, University of Southern California, Los Angeles. He is also coauthor of the textbook "Drugs in Pregnancy and Lactation."

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