PRAZIQUANTEL

Fetal Risk Summary

Praziquantel is a systemic anthelmintic used in the treatment of parasitic infections involving cestodes (tapeworms), including neurocysticercosis, and trematode (flukes) infestations of the liver and other tissues. The drug is rapidly and nearly completely (80%) absorbed following oral administration (1). The various metabolites are excreted primarily by the kidneys.

Praziquantel was not carcinogenic in rats and hamsters, but mutagenic effects in Salmonella tests were observed in one laboratory (1). The mutagenicity was not confirmed in the same tested strain by other laboratories (1). Similarly, a study published in 1982 found no mutagenic effects in five strains of Salmonella exposed to praziquantel (2). A 1984 review also described negative mutagenic results in a variety of tests, including those with mice, rats, and humans, and negative carcinogenic results in tests with rats and hamsters (3). A 1997 review, however, cited studies that observed a co-mutagenic effect between praziquantel and several mutagens and carcinogens (4). Praziquantel has also been shown in in vitro studies to induce micronuclei in hamster embryonic cells and lymphocytes (4). Moreover, in some pigs and humans, praziquantel was found to induce hyperploid lymphocytes and structural chromosomal aberrations (4).

Reproduction studies in mice, rats, and rabbits at doses up to 40 times the human dose (human dose 60–75 mg/kg over 1 day) showed no evidence of impaired fertility or teratogenicity (1,3). An increase in the abortion rate in rats, however, was observed at doses 3 times the single human therapeutic dose (1). No teratogenicity was observed in other studies in rats and rabbits with doses up to 300 mg/kg (5,6) or in rats with doses up to 450 mg/kg (2). Compared with controls, the administration of praziquantel and ivermectin (another anthelmintic agent) to possums at 8- to 10-week intervals throughout the breeding season to the time of emergence of young from the pouch had no significant effect on the number of births or survival of the young to emergence (7).

Authors of a study published in 1985 concluded that treatment of parasitic disease with potentially teratogenic or toxic drugs may not always be indicated in otherwise healthy pregnant women (8). For example, in their study, they found that treatment of some gastrointestinal parasites, including some tapeworms and liver flukes, could be postponed until after delivery unless the parasite was causing clinical disease or public health problems (8). Similarly, reviews in 1996 and 1997 recommended avoiding praziquantel during pregnancy (9,10).

The authors are aware of two cases of neurocysticercosis treated with praziquantel during gestation, but no outcome information is available in either case. A 1996 case report, however, described the use of praziquantel for the treatment of neurocysticercosis in a 17-year-old pregnant woman (11). She received praziquantel, 1050 mg three times daily, for 21 days starting at about 8 weeks' gestation. Seizures, which occurred at the time of presentation and again 4 days after the start of anticysticercus therapy, were successfully controlled with phenytoin and carbamazepine. She eventually delivered a 2.5-kg girl at term. Other than documented anemia, no other abnormalities or malformations were found. The placenta appeared normal on gross examination.

In summary, praziquantel is not an animal teratogen, but human data are limited to one case. The lack of published human data prevents any assessment of a human risk. Recent data have indicated that the agent may be mutagenic and carcinogenic in humans, especially in developing countries where infections of trematodes and cestodes are frequent and multiple treatment courses may be prescribed. Moreover, the presence of other environmental mutagens combined with praziquantel may increase the risk for mutagenicity (4). Because of this potential toxicity, the use of praziquantel during pregnancy should be reserved for those cases in which the parasite is causing clinical illness or public health problems.

Breast Feeding Summary

Because praziquantel is excreted into breast milk at a concentration of about one-fourth that of the maternal serum, the manufacturer advises holding nursing on the day of treatment and during the subsequent 72 hours (1). The drug is excreted primarily in the urine with 80% of the dose being eliminated within 4 days (12). About 90% of this elimination, however, occurs in the first 24 hours (12).

No reports describing the use of praziquantel during nursing have been located, but a 1996 review recommended avoiding praziquantel during lactation (9). The effects, if any, on a healthy, noninfected nursing infant from exposure to the drug via breast milk are unknown. Because adverse reactions induced by the death of an infecting parasite have been observed in treated adults (7), nursing infants with parasitic infections sensitive to praziquantel may be at risk for similar adverse effects. Moreover, the potential for mutagenic and carcinogenic effects of the drug should be considered (see Fetal Risk Summary).

References

1. Product information. Biltricide. Bayer Corporation, 1999.
2. Ni YC, Shao BR, Zhan CQ, Xu YQ, Ha SH, Jiao PY. Mutagenic and teratogenic effects of anti-schistosomal praziquantel. Chin Med J 1982;95:494–8.
3. Frohberg H. Results of toxicological studies on praziquantel. Arzneimittelforschung 1984;34:1137–44.
4. Montero R, Ostrosky P. Genotoxic activity of praziquantel. Mutat Res 1997;387:123–39.
5. Muermann P, Von Eberstein M, Frohberg H. Notes on the tolerance of Droncit. Summary of trial results. Ved Med Rev 1976;2:142–65. As cited by Schardein JL. Chemical Induced Birth Defects. 2nd ed. New York, NY: Marcel Dekker, 1993:402–15.
6. Muermann P, Von Eberstein M, Frohberg H. Notes on the tolerance of Droncit. Summary of trial results. Vet Med Rev 1976;2:142–65. As cited by Shepard TH. Catalog of Teratogenic Agents. 8th ed. Baltimore, MD: Johns Hopkins University Press, 1995:350.
7. Viggers KL, Lindenmayer DB, Cunningham RB, Donnelly CF. The effects of parasites on a wild population of the Mountain Brushtail possum (Trichosurus caninus) in south-eastern Australia. Int J Parasitol 1998;28:747–55.
8. D'Alauro F, Lee RV, Pao-In K, Khairallah M. Intestinal parasites and pregnancy. Obstet Gynecol 1985;66:639–43.
9. Volkheimer G. Intestinal helminthiasis–general practice problem of the gastroenterologist. Z Gastroenterol 1996;34:534–41.
10. de Silva N, Guyatt H, Bundy D. Anthelmintics. A comparative review of their clinical pharmacology. Drugs 1997;53:769–88.
11. Paparone PW, Menghetti RA. Case report: neurocysticercosis in pregnancy. N J Med 1996;93:91–4.
12. Reynolds JEF, editor. Martindale. The Extra Pharmacopoeia. 31st ed. London, England:Royal Pharmaceutical Society, 1996:123–5.