Antihistamines and birth defects: a systematic review of the literature

Abstract

Introduction Approximately 10-15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion. Antihistamines include histamine H1-receptor and H2-receptor antagonists. Areas covered This is a systematic evaluation of the peer-reviewed epidemiologic literature published through February 2014 on the association between prenatal exposure to antihistamines and birth defects. Papers addressing histamine H1- or H2-receptor antagonists are included. Papers addressing pyridoxine plus doxylamine (Bendectin in the United States, Debendox in the United Kingdom, Diclectin in Canada, Lenotan and Merbental in other countries) prior to the year 2001 were excluded post-hoc because of several previously published meta-analyses and commentaries on this medication. Expert opinion The literature on the safety of antihistamine use during pregnancy with respect to birth defects is generally reassuring though the positive findings from a few large studies warrant corroboration in other populations. The findings in the literature are considered in light of three critical methodological issues: (1) selection of appropriate study population; (2) ascertainment of antihistamine exposures; and (3) ascertainment of birth defects outcomes. Selected antihistamines have been very well-studied (e.g. loratadine); others, especially H2- receptor antagonists, require additional study before an assessment of safety with respect to birth defects risk could be made.

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…Efletirizine, however, was developed as a topical agent to fit the pharmacophores for H 1 receptor antagonists and inhibitors of lipoxygenase (an enzyme involved in the production of leukotrienes) (Salmun, 2002;Lewis et al, 2004b) but was discontinued in the late phases of development. Regarding the H 1 receptor antagonists already in the pharmacopoeia, few studies have been conducted on teratogenicity or embryotoxicity with high doses of antihistamines in animal testing, and it is recommended that antihistamines should not be used in pregnancy (Gilboa et al, 2014). The lack of any teratogenic effects reported thus far gives some confidence, but there should still be a note of caution because of the lack of controlled studies in children or pregnancy for the first-generation compounds (Church et al, 2010).…”

Nausea and vomiting of pregnancy - What's new?

“…Antihistamines, are commonly used during early pregnancy for the treatment of nausea and vomiting (Gilboa et al, 2014). First generation H1-receptor antagonists diphenhydramine (Benadryl), dimenhydrinate (Dramamine), meclizine (anitvert) and doxylamine indirectly affect the vestibular system, decreasing stimulation of the vomiting center (Badell et al, 2006).…”

“…These antihistamines are pregnancy category B and have been shown to be effective in controlling NVP symptoms (Leathem, 1986; Mazzotta et al, 2000a). The majority of 31 cohort studies and 23 case-control studies that aimed at identifying positive associations between antihistamines and birth defects demonstrated a lack of association between prenatal antihistamine exposure and birth defects (Gilboa et al, 2014; Milkovich et al, 1976; Seto et al, 1997). …”

Management and treatment of chronic urticaria (CU)

“…With respect to potential drug‐exposure in (breastfeeding) infants, loratadine and cetirizine are the preferred choice for lactating, as well as pregnant women. Furthermore, the related antihistamines, desloratadine and levocetirizine can also be recommended …”