Loratadine has been used as a therapeutic agent for more than 14 years. It is a tricyclic antihistamine with selective peripheral H1 receptor antagonist activity. It is marketed as a non-sedative antihistamine for the relief of symptoms associated with allergic rhinitis and ocular itching and burning.

In 1999, the Swedish Medical Products Agency (MPA) reported an increased in frequency of hypospadias in boys born to 2,780 Swedish women who took loratadine (Clarityn®, Schering Plough) during their pregnancy. Fifteen cases were observed among these births. Hypospadias is a developmental anomaly in which the urethra opens on the underside of the penis or on the perineum. It is a frequently found malformation with an incidence of 3 per 1,000 males and may be due to genetic or environmental factors.

Following these reports, a review was conducted by the Committee of Proprietary Medicinal Products (CPMP) of the European Agency for the Evaluation of Medicinal Products (EMEA). The concern for this adverse effect was also extended to the major metabolite of loratadine, i.e. desloratadine, which is also marketed as a non-sedative antihistamine and indicated for the relief of symptoms associated with seasonal allergic rhinitis.

The company's preclinical study showed that loratadine has no anti-androgenic activity. The scientific assessment of the safety signal of hypospadias following use of loratadine during pregnancy by CPMP concluded that based on the available data, a causal relationship between loratadine and hypospadias could neither be confirmed nor excluded. CPMP also considered that the benefit/risk balance of desloratadine containing medicinal products remains favourable.

To-date, other than the Swedish reports, the WHO ADR database, which captures ADR reports from more than 71 participating countries, reveals 10 other cases of hypospadias suspected to be associated with loratadine. There are no reports with desloratadine.