Amphetamine Unlikely C.

As...o...b..c acid (vitamin C) None A*

Beta-carotene Low dose: none C.

Calcium salts Unlikely NA.

Chlorpromazine Unlikely C.

Cimetidine Unlikely B.

Cisapride Undetermined C.

Cyanocobalamin Undetermined NA.

Dexfenfluramine Undetermined C.

Diethylpropion None NA.

Famotidine Unlikely B.

Fenfluramine Undetermined NA.

Folic acid None A*

Iron None NA.

Isotretinoin High Xm Mazindol Undetermined NA.

Methamphetamine Unlikely (therapeutic dose) NA.

Metoclopromide Unlikely B.

Niacin Undetermined A*

Nizatidine Undetermined B.

Omeprazole Unlikely C.

Pantothenate Undetermined NA.

Phendimetrazine Unlikely NA.

Phentermine Undetermined C.

Prochlorperazine None NA.

Promethazine None C.

Pyridoxine None A.

Ranitidine Unlikely B.

Retinol (vitamin A) Low dose: none A*

High dose: undetermined Thiamine Undetermined A*

Vitamin D Unlikely A*

Vitamin E Undetermined A*

NA, not available.

Compiled from: Friedman et al., Obstet Gynecol 1990; 75 75: 594; Briggs et al., 2005; Friedman and Polifka, 2006.

gastric acid reflux. Therapy consists primarily of one of the antacid preparations discussed in the previous section. Frequent small feedings and elevation of the head of the bed at night may be beneficial. An H -receptor antagonist or omeprazole, as well as 2 metoclopramide, may also prove useful for severe forms of reflux. Esomeperazole and omeprazole are the most popular treatments for reflux esophagitis, and omeprazole is well studied during pregnancy.

Special considerations 237.

Box 12.4 Therapy for nausea and vomiting of pregnancya Chlorpramazine Chlorpramazine *

Suppositories, 50100 mg q 8 h *

Oral, 1025 mg q 4 h *

Parenteral, 12.525 mg IM q 4 h Ondansetron *

Intravenous, 32 mg as a single dose once a day *

Oral, 8 mg bid Prochlorperazine *

Suppositories, 510 mg two to three times per day *

Oral, 510 mg tid or gid *

Parenteral, 510 mg IM q 4 h Promethazine *

Suppositories, 12.525 mg q 4 h *

Oral, 510 mg tid or gid *

Parenteral, 25 mg IM q 4 h Thiethylperazine *

Suppositories, 10 mg gd to tid *

Oral, 10 mg qd to tid *

Parenteral, 10 mg IM qd to tid Trimethobenzamide *

Suppositories, 200 mg tid or gid *

Oral, 250 mg tid or gid *

Parenteral, 200 mg IM tid or gid aSee manufacturer's recommendations.

Peptic ulcer disease Peptic ulcer disease is not common during pregnancy and active ulcer disease may actually improve during pregnancy. The mainstay of therapy in patients with ulcer disease is reduction of gastric acid production. This can be accomplished with either antacids or the H -receptor antagonists. The most popular treatment is with PPIs.

2.Any of the antacids described can be used in pregnant women with peptic ulcer disease, but preference should be given to the best studied during pregnancy (i.e., ranitidine or omeprazole). The usual dosing regimen is given after meals and at bedtime. It is not generally recommended that pregnant women with inactive or asymptomatic disease be treated with 'prophylactic' antacids.

The H -receptor antagonists cimetidine and ranitidine inhibit gastric acid secretion and 2 may be used to treat peptic ulcer disease in pregnant women. Cimetidine is usually given in a dose of 300 mg orally four times a day, while ranitidine is usually given in a dose of 150 mg orally twice a day. Omeprazole may also be used with twice daily dosing.

Diarrhea Most cases of acute diarrhea require no specific therapy other than ensuring adequate hydration. When antidiarrheal therapy is required, the combination of kaolin and pectin 238 238 Nutritional and dietary supplementation during pregnancy Box 12.5 Therapy for uncomplicated diarrhea of pregnancya Box 12.5 Therapy for uncomplicated diarrhea of pregnancya Diphenoxylate and atropine, 2.55 mg orally three to four times per day. Diphenoxylate and atropine, 2.55 mg orally three to four times per day.

Kaolin, pectin, belladonna, opium, 30 mL initial dose, followed by 15 mL q 3 h.

Kaolin, pectin, paregone, 1530 mL after each diarrheal episode.

Kaolin plus pectin, 60120 cc of regular strength orally after each diarrheal episode.

Loperamide, 20 mL or two caplets after first diarrheal episode. Then 10 mL or 1 caplet after each diarrheal episode, not exceeding 40 mL or four caplets in 24 h.

aFrom manufacturer's recommendation.

(Kaopectate) can be used safely. If this fails and a stronger medications is indicated, an opioid-like preparation can be utilized (Box 12.5). However, narcotic preparations should not be used chronically, especially in pregnant women.

Traditional antidiarrheal medication should be used cautiously in pregnant women with diarrhea of an infectious etiology (i.e., Escherichia coli Escherichia coli, shigella, and salmonella).

It is generally accepted that infections may be increased in severity or prolonged when treated with these agents.

Diarrhea secondary to bacterial agents may or may not need specific antimicrobial therapy, and, when necessary, therapy should be directed towards the specific organism (see Chapter 2, Antimicrobials during pregnancy: bacterial, viral, fungal, and parasitic indications).

Diarrhea secondary to protozoan disease (i.e., amebiasis and giardiasis) can be treated with metronidazole (500 or 750 mg tid for 510 days for the former, and 250 mg tid for 510 days for the latter). Therapy need not be delayed until after the first trimester as first-trimester use of metronidazole does not increase the risk for congenital anomalies.

Celiac disease Celiac disease is a characterized by diarrhea, bloating, anemia, weight loss, and gluten intolerance. Usually, folic acid, iron, and other essential nutrients are not adequately absorbed from the gastrointestinal tract. Patients usually improve when placed on a gluten-free diet. One large series of 94 women with celiac disease during pregnancy showed that with untreated celiac disease there were nine times more miscarriages than among women on a gluten-free diet. Low birth weight was approximately six times more frequent among untreated women compared to those maintained on a gluten-free diet. Severity of celiac disease during pregnancy was apparently not related to pregnancy outcome; maintenance of a gluten-free diet during gestation was the important determinant of pregnancy outcome (Ciacci et al et al., 1996).

Inflammatory bowel disease Ulcerative colitis and Crohn's disease commonly occur in pregnant women. Among 30 percent of more than 1000 pregnant women with inactive inflammatory bowel disease, Key references Key references 239.

the condition worsened during pregnancy. Of the 320 patients with active disease at the start of pregnancy, 143 (45 percent) became worse, 84 (26 percent) remained the same, and 93 (29 percent) improved (Miller, 1986).

Ulcerative colitis, a chronic disease of unknown etiology, is a.s.sociated with two life-threatening conditions: fulminant disease and adenocarcinoma of the colon. Ulcerative colitis therapy includes sulfasalazine (Azulfidine), glucocorticoids, azathioprine, and mercaptopurine. Sulfasalazine is comprised of sulfapyridine and aminosalicylic acid, and usually used for mild or moderate disease (Hanauer, 1996). Sulfapyridine, a sul-fanamide, crosses the placenta (Azad and Truelove, 1979) and theoretically could cause hyperbilirubinemia or kernicterus, but there are no publications of these complications.

According to its manufacturer, the usual initial treatment dose is 0.51 g orally four times a day for active disease, and maintenance doses are usually lower.

Glucocorticoids (e.g., prednisone) in large doses may be necessary for active disease.

Azathioprine, an immunosuppressant, may be necessary in the small number of patients who do not respond to the usual regimen. Cyclosporine has also been used to treat patients refractory to intravenous steroids (Hanauer, 1996).

Aminosalicylate, metronidazole, corticosteroids, azathioprine, and cyclosporine may also be used to treat pregnant patients with Crohn's disease.

Key references Berkovitch M, Mazzota P, Greenberg R et al. Metoclopramide for nausea and vomiting of pregnancy. A prospective multicenter international study. Am J Perinatol 2002; 19 19: 311.

Diav-Citrin O, Arnon J, Shechtman S et al. The safety of proton pump inhibitors in pregnancy. a multicentre prospective controlled study. Aliment Pharmacol Ther 2005; 21 21: 269 Einarson A, Maltepe C, Navioz Y, Kennedy D, Tan MP, Koren G. The safety of ondansetron for nausea and vomiting of pregnancy. a prospective comparative study. BJOG 2004; 111 111: 940.

Grosse SD, Waitzman NJ, Romano PS, Mulinare J. Reevaluating the benefits of folic acid fortification in the United States. Economic a.n.a.lysis, regulation, and public health. Am J Public Health 2005; 95 95: 1917.

Jones KL, Johnson KA, d.i.c.k LM, Felix RJ, Kao KK, Chambers CD. Pregnancy outcomes after first trimester exposure to phentermine/fenfluramine. Teratology 2002; 65 65: 125.

Kallen B. Delivery outcome after the use of acid-suppressing drugs in early pregnancy with special reference to omeprazole. Br J Obstet Gynaecol 1998; 105 105: 877.

Lalkin A, Loebstein R, Addis A et al. The safety of omeprazole during pregnancy. A multicenter prospective controlled study. Am J Obstet Gynecol 1998; 179 179: 727.

Little BB. Pharmac.o.kinetics during pregnancy. Evidence-based maternal dose formulation.

Obstet Gynecol 1999; 93 93: 858.

Rothman KUJ, Moore LL, Singer MR, Nguyen US, Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. N Engl J Med 1995; 333 333: 1369.

Ruigomez A, Garcia Rodriguez LA, Cattaruzzi C et al. Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes. Am J Epidemiol 1999; 150 150: 476.

Further references are available on the book's website at http://www.drugsandpregnancy.com 13.Use of dermatologics during pregnancy Vitamin A derivatives 240.

Antiseborrheic agents 244.

Antibiotics 243.

Adrenocorticosteroids 245.

Antifungals 244.

Other agents 248.

Antiparasitics 244.

Special considerations 249.

Keratolytics, astringents, and Key references 253.

defatting agents 244.

Dermatologic disorders are frequent among pregnant women, but few conditions are unique to pregnancy. However, pruritic urticarial papules and plaques of pregnancy, herpes gestation, and papular dermat.i.tis of pregnancy do occur and are unique to pregnancy.

A number of dermatologic preparations are available for local and systemic use. Most of these agents can be used with little or no risk to the unborn child. Two of the most potent human teratogens known, etretinate and isotretinoin, are dermatologic drugs.

Six major categories of dermatologic preparations are reviewed: (1) vitamin A derivatives, (2) antibiotics, (3) antifungals, (4) antiseborrheics, (5) adrenocorticosteroids, and (6) keratolytics, astringents, and defatting agents. Dermatologic conditions unique to pregnancy and common dermatologic conditions that may occur during pregnancy are discussed under Special Considerations.

VITAMIN A DERIVATIVES.

Three retinoic acid derivatives, vitamin A a.n.a.logs (two oral agents and one topical agent), are currently available to treat cystic acne, acne vulgaris, or psoriasis.