Anti-Infective (Antiprotozoal)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of nitazoxanide in human pregnancy have been located. Although the animal data are suggestive of low risk, the absence of human pregnancy experience prevents an assessment of risk that the drug represents to an embryo or fetus. If indicated, nitazoxanide should not be withheld during pregnancy. However, until human pregnancy data are available, exposure to the agent should be avoided in the 1st trimester, if possible.
FETAL RISK SUMMARY
Nitazoxanide is an oral synthetic antiprotozoal agent approved for the treatment of diarrhea caused by Cryptosporidium parvum and Giardia lamblia in pediatric patients between the ages of 1 and 11 years (1). However, the drug has been used in children and adults for a wide variety of gastrointestinal and hepatic infections, including those associated with AIDS (2–10). Nitazoxanide is a prodrug that is rapidly hydrolyzed during absorption to the active metabolites, tizoxanide and tizoxanide glucuronide (1). The parent compound, nitazoxanide, is not detected in plasma. Tizoxanide is extensively bound to plasma proteins (>99.9%) (1). The terminal elimination half-life of tizoxanide is 7.3 hours (11).
Reproduction studies have been conducted in rats and rabbits. In rats, doses up to 48 times the human clinical dose based on BSA (HCD) revealed no evidence of fetal harm. Higher doses (up to 66 times the HCD) had no effect on fertility in male and female rats. In rabbits, doses up to three times the HCD revealed no evidence of impaired fertility or fetal harm (1).
It is not known if the active metabolites of nitazoxanide cross the human placenta (nitazoxanide itself is not detected in the plasma). The molecular weight of one of the active metabolites, tizoxanide (about 265), is low enough for placental passage, but the extensive plasma protein binding will limit the amount of drug transferred to the embryo or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of nitazoxanide during human lactation have been located. It is not known if the active metabolites of nitazoxanide are excreted into breast milk (nitazoxanide itself is not detected in the plasma). The molecular weight of one of the active metabolites, tizoxanide (about 265), is low enough to be excreted into breast milk, but the extensive plasma protein binding (>99.9%) will limit the amount. The effect of this exposure on a nursing infant is unknown, but probably is not clinically significant. However, the nursing infant should be monitored for gastrointestinal symptoms.
References
1.Product information. Alinia. Romark Pharmaceuticals, 2004.
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10.Bicart-See A, Massip P, Linas MD, Datry A. Successful treatment with nitazoxanide of Enterocytozoon bieneusi microsporidiosis in a patient with AIDS. Antimicrob Agents Chemother 2000;44:167–8.
11.Stockis A, Deroubaix X, Lins R, Jeanbaptiste B, Calderon P, Rossignol JF. Pharmacokinetics of nitazoxanide after single oral dose administration in 6 healthy volunteers. Int J Clin Pharmacol Ther 1996;34:349–51.