LORATADINE

Fetal Risk Summary

Loratadine, a second-generation histamine H1-receptor antagonist, is used for the treatment of symptoms related to seasonal allergic rhinitis. Studies with rats and rabbits with oral doses up to 75 and 150 times, respectively, the maximum recommended human daily oral dose on a mg/m2 basis found no evidence of teratogenicity (1).

It is not known if loratadine crosses the human placenta. The molecular weight (about 383) is low enough, however, that passage to the fetus should be expected.

The FDA has received six reports of adverse outcomes following exposure during pregnancy, including two cases of cleft palate, and one case each of microtia and microphthalmia, deafness, tricuspid dysplasia, and diaphragmatic hernia (personal communication, F. Rosa, FDA, 1996). A relationship, if any, between loratadine and the outcomes cannot be determined from these data.

A 1998 non-interventional observational cohort study described the outcomes of pregnancies in women who had been prescribed one or more of 34 newly marketed drugs by general practitioners in England (2). Data were obtained by questionnaires sent to the prescribing physicians one month after the expected or possible date of delivery. In 831 (78%) of the pregnancies, a newly marketed drug was thought to have been taken during the 1st trimester with birth defectrs noted in 14 (2.5%) singleton births of the 557 newborns (10 sets of twins). In addition, two birth defects were observed in aborted fetuses. However, few of the aborted fetuses were examined. Loratadine was taken during the 1st trimester in 18 pregnancies. The outcomes of these pregnancies included 2 elective abortions and 16 normal, term infants (2).

Although no congenital malformations were observed in the above study, the data are too limited to assess the safety of loratadine. Moreover, the study lacked the sensitivity to identify minor anomalies because of the absence of standardized examinations. Late appearing major defects may also have been missed due to the timing of the questionnaires. If an oral antihistamine agent is required during pregnancy, first generation agents such as chlorpheniramine or tripelennamine should be considered. Loratadine and cetirizine are considered acceptable alternatives, except during the 1st trimester, if a first generation drug is not tolerated (3,4 and 5).

Breast Feeding Summary

Loratadine and its metabolite, descarboethoxyloratadine, are excreted into human milk (1,6). Six lactating women were given a single 40-mg dose (6). The peak milk concentration, 29.2 ng/mL, occurred within 2 hours of the dose, whereas the peak plasma level, 30.5 ng/mL, was measured 1 hour after the dose.

The mean milk:plasma area under the concentration curve (AUC) ratios for the parent compound and the active metabolite, measured during 48 hours, were 1.17 and 0.85, respectively (1,6). During 48 hours, the mean amounts of loratadine and metabolite recovered from the milk were 4.2 µg (0.010% of the dose) and 6.0 µg (equivalent to 7.5 µg of loratadine; 0.019% of the dose), respectively. A 4-kg infant ingesting this milk would have received a dose equivalent to 0.46% of the mother's dose on a mg/kg basis (6). Based on this estimate, and the fact that the dose used in the study was 4 times the current recommended dose, there is probably little clinical risk to a nursing infant whose mother was taking 10 mg of loratadine per day.

References

1. Product information. Claritin. Schering Corporation, 2001.
2. Wilton LV, Pearce GL, Martin RM, Mackay FJ, Mann RD. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol 1998;105:882–9.
3. Mazzotta P, Loebstein R, Koren G. Treating allergic rhinitis in pregnancy. Safety considerations. Drug Saf 1999;20:361–75.
4. Horak F, Stubner UP. Comparative tolerability of second generation antihistamines. Drug Saf 1999;20:385–401.
5. Position statement of a joint committee of the American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology. The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475–80.
6. Hilbert J, Radwanski E, Affrime MB, Perentesis G, Symchowicz S, Zampaglione N. Excretion of loratadine in human breast milk. J Clin Pharmacol 1988;28:234–9.