This is my fourth and final installment on anti-infectives

* Anthelmintics. All three agents in the benzimidazole class of the anthelmintics are rated pregnancy category C. In humans, their bioavailability is extremely low, but increases substantially when taken with fatty foods.

There are few data concerning use of these three drugs during lactation, although it is likely that they are safe because of their low bioavailability.

Albendazole (Albenza) is embryotoxic, fetotoxic, and teratogenic in rabbits and rats at doses less than the recommended human dose. There are only about 60 reports of human pregnancy exposures, including 10 in the first trimester; all had normal outcomes. But because of limb reduction effects observed with all doses in one animal study and the potential for greater bioavailability if taken with a fatty meal, this drug should be avoided during pregnancy especially in the first trimester.

Mebendazole (Vermox) is also teratogenic in rats at doses about equal to the dose in humans, but not in other animal species. Because the more than 5,000 reports of human pregnancy exposures to this drug have found no association with abortions or birth defects, mebendazole is preferred over albendazole during pregnancy.

The third benzimidazole, thiabendazole (Mintezol), was not teratogenic in mice, rats, or rabbits at doses equal to the human dose, but birth defects were seen when it was suspended in olive oil, indicating that it may pose a danger when the patient has a fatty diet. There are no reported human exposures to thiabendazole in the first trimester.

Another anthelmintic, pyrantel, rated C, is not teratogenic in rats or rabbits, but there are no human reports of its use in pregnancy or lactation.

* Antifungals. Amphotericin B, which is administered intravenously and crosses the human placenta, can be used in pregnancy when indicated. Reports have found no evidence of fetal harm in animals or humans, and it is rated B. There are no breast-feeding reports.

There are no human reports of pregnancy exposures to caspofungin (Cancidas), rated C, which is embryotoxic in rats and rabbits at systemic exposures equal to those used in humans. It crosses the placenta in both animals, so I recommend avoiding this drug in the first trimester.

At dosages below 400 mg a day fluconazole (Diflucan), which is rated C, does not appear to be associated with birth defects in humans, but it is teratogenic and toxic in rats. At daily dosages of 400 mg or more for systemic fungal infections, case reports in humans have consistently associated in utero exposure with congenital anomalies. The small amount excreted into breast milk does not seem to pose a problem for nursing infants.

Itraconazole (Sporanox), rated C, also causes dose-related embryotoxicity and teratogenicity in mice and rats. No reports have linked human malformations to this drug, but because human data are limited, I would avoid it during the first trimester. The drug is excreted into breast milk with continuous daily dosing, which could result in widespread tissue accumulation in the nursing infant, the toxicity of which has not been studied.

Ketoconazole, rated C, is embryotoxic and teratogenic in rats, but does not appear to be a human teratogen. It has been used during the first trimester for vaginal candidiasis without apparent harm and has been used at high doses in the third trimester for hypercortisolism in one patient without any harm to the infant.

Griseofulvin, rated C, is tumorigenic, embryotoxic, and teratogenic in mice and rats, but does not appear to have these effects in humans. There was a report of two sets of conjoined twins after first-trimester exposure to griseofulvin, which was not confirmed by other studies. Still, the safest course is to avoid it during pregnancy because it is taken for a long period of time and usually an alternative can be used. There are no breast-feeding data for griseofulvin or ketoconazole.

Nystatin, rated B, is poorly absorbed with oral administration, so it poses no risk to the fetus and nursing infant.

In rats and rabbits, no evidence of impaired fertility or fetal harm was found for terbinafine (Lamisil). It is rated B, but there are no reports of its use in human pregnancy or lactation.

Flucytosine (Ancobon), rated C, is metabolized by fungi to 5-fluorouracil (5-FU), which may be a human teratogen. No adverse effects were seen in three case reports of women who took flucytosine after the first trimester, but I would avoid this drug in the first trimester and lactation because of the potential adverse effects of its metabolite.

GERALD G. BRIGGS 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.