What is the preferred antihistamine, Cetirizine (Citrizine) or Levocetirizine (Levocitrizine), for a pregnant patient with allergies?

Cetirizine vs Levocetirizine in Pregnancy

Cetirizine is the preferred antihistamine over levocetirizine during pregnancy, particularly in the first trimester, due to its extensive safety data and established track record, while levocetirizine should be avoided in the first trimester due to limited safety data. 1, 2

First-Line Antihistamine Recommendations

Cetirizine and loratadine are the recommended first-choice second-generation antihistamines when therapy is necessary during pregnancy, including the first trimester. 1

• Both cetirizine and loratadine are FDA Pregnancy Category B, meaning no evidence of fetal harm exists in available studies 1
• Large birth registries, case-control studies, and cohort studies have confirmed the safety of cetirizine during pregnancy 3
• A manufacturer safety database analysis of 228 pregnancies with cetirizine exposure showed 83.7% resulted in live births, with only 2 congenital malformations reported (consistent with background rates) 4
• Most cetirizine exposures in the safety database occurred during the first trimester, when organogenesis is most vulnerable, yet outcomes remained reassuring 4

Why Levocetirizine Should Be Avoided

Levocetirizine should be avoided during the first trimester due to insufficient safety data. 1, 2

• The American Academy of Allergy, Asthma, and Immunology specifically recommends avoiding levocetirizine in the first trimester if possible 2
• The FDA drug label for levocetirizine states that pregnant women should "ask a health professional before use," reflecting the lack of established safety data 5
• Unlike cetirizine (its parent compound), levocetirizine lacks the extensive accumulated safety evidence from large registries and cohort studies 2

Critical Timing Considerations

• The first trimester is when organogenesis occurs, making it the most critical period for concern about medication-induced congenital malformations 1, 2
• While it is best to avoid all antihistamines during the first trimester if possible, none has been proven teratogenic in humans 1
• If antihistamine therapy is medically necessary during the first trimester, cetirizine is preferred over levocetirizine 1, 2

Practical Treatment Algorithm

When antihistamine therapy is required in pregnancy:

• First choice: Cetirizine or loratadine throughout all trimesters 1
• Alternative first-generation option: Chlorpheniramine (longest safety record, though more sedating) 3, 2
• Avoid: Levocetirizine in the first trimester 1, 2
• Never use: Hydroxyzine at any stage of pregnancy (specifically contraindicated) 3, 1

Dosing and Safety Adjustments

• Use the lowest effective dose for the shortest possible time to minimize fetal exposure 3
• Cetirizine dose should be halved in moderate renal impairment and avoided in severe renal impairment (creatinine clearance < 10 mL/min) 3
• Cetirizine may cause mild drowsiness in 13.7% of patients, while loratadine is generally less sedating 1

Common Pitfalls to Avoid

• Do not assume all antihistamines have equivalent safety profiles - they do not, and levocetirizine specifically lacks the safety data that cetirizine possesses 1, 2
• Avoid combining antihistamines with oral decongestants (phenylephrine, pseudoephedrine) during the first trimester due to associations with gastroschisis and small intestinal atresia 3, 2
• Do not combine decongestants with acetaminophen or salicylates, as this increases malformation risk 3, 2

Combination Therapy Options

• For moderate-severe symptoms, combine cetirizine or loratadine with intranasal corticosteroids such as budesonide 1
• Intranasal corticosteroids have a better safety profile than oral medications for nasal symptoms 2