Second-generation oral antihistamines are the preferred first-line treatment option for allergic rhinitis and urticaria. Patients taking SGAHs report relatively little and mild adverse events even after long-term continuous treatments. An antihistamine should ideally possess high selectivity for the H(1)-receptor, high PrH1R occupancy and low to no BrH1R occupancy.

Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post‐marketing surveillance and continued evaluation of the benefit‐risk of long‐established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re‐evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real‐world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration‐dependent effects of hydroxyzine on a range of human cardiac ion channels. Based on a review of pharmacovigilance data between 14th December 1955 and 1st August 2016, we identified 59 reports of QT prolongation and/or TdP potentially linked to hydroxyzine use. Aside from intentional overdose, all cases involved underlying medical conditions or concomitant medications that constituted at least 1 additional risk factor for such events. The combination of cardiovascular disorders plus concomitant treatment of drugs known to induce arrhythmia was identified as the greatest combined risk factor. Parallel patch‐clamp studies demonstrated hydroxyzine concentration‐dependent inhibition of several human cardiac ion channels, including the ether‐a‐go‐go‐related gene (hERG) potassium ion channels. Results from this analysis support the listing of hydroxyzine as a drug with “conditional risk of TdP” and are in line with recommendations to limit hydroxyzine use in patients with known underlying risk factors for QT prolongation and/or TdP.

Levocetirizine is considered an effective and well tolerated option for treating allergic disease by patients and physicians alike, particularly when the best available effectiveness and tolerability are required.

Managing symptoms of allergic rhinitis (AR) and urticaria in pregnant women is important to reduce complications and negative outcomes. The objective of this study was to provide information on the pregnancy outcomes of women exposed to the antihistamine cetirizine (CTZ). The UCB Pharma Patient Safety Database was searched for pregnancies up to 28 February 2015. Maternal CTZ exposure reports were extracted, and pregnancy outcomes were examined, including exposure, comorbidities and infant events. 228 of 522 pregnancies with maternal CTZ exposure had available outcomes; 49 were prospective. The majority (83.7%) resulted in live births; four spontaneous miscarriages, three induced abortions and one stillbirth were reported. Most pregnancies were exposed during the first trimester. Two congenital malformations were reported. The results suggest that CTZ exposure is not associated with adverse pregnancy outcomes above the background rates. While reassuring, the strengths and limitations of a safety database study need to be considered. Impact statement What is already known on this subject? AR and urticaria can substantially affect pregnant women, and adequately managing their symptoms is important to reduce maternal and foetal complications. Antihistamines are efficacious, however, there is still a lack of data regarding use during pregnancy. Although current evidence indicates that antihistamines are well-tolerated during pregnancy, data regarding foetal safety are inconclusive. What do the results of this study add? Our study suggests that CTZ exposure during pregnancy is not linked to an increase in adverse outcomes. CTZ exposure mainly happened during the first trimester only, when most organogenesis takes place. Most of the maternally exposed, prospective pregnancies resulted in live births (83.7%). Congenital malformations occurred in 2/41 live births from the CTZ-exposed pregnancies. What are the implications of these findings for clinical practice and/or further research? Our study presents a detailed data analysis from a large number of CTZ-exposed pregnancies, and its results are in line with those from previous reports. While the limitations of a safety database study need to be considered, the results shown here are reassuring. Further prospectively reported pregnancies are required, before definite conclusions on the risks of CTZ exposure during pregnancy can be drawn.

Differences between an oral antihistamine and placebo in clinical studies of allergic rhinitis might be due to a different response to placebo rather than to the active drug. Levocetirizine seems to have consistent efficacy regardless of age, gender, and baseline scores.