Antihistamines in pregnancy

Some summary information regarding antihistamines in pregnancy (1,2,3):

During pregnancy:

• no evidence of teratogenicity
  
  
• embryotoxicity in animal studies with high doses of hydroxyzine and loratadine
  
  
• best practice to avoid taking drugs in pregnancy, as present knowledge is incomplete
  
  
• none of the currently licensed antihistamines have been shown to be teratogenic in humans, but high doses of hydroxyzine and loratadine have caused embryotoxicity in animal studies
  
  
• data sheets for cetirizine, desloratadine, hydroxyzine and loratadine all advise avoidance in pregnancy
  
  
• pregnant patient should be informed that no antihistamine drug can be considered absolutely safe but that the small risk has to be balanced against the benefits of keeping the mother healthy in the interest of the foetus. Prescribed drugs must be selected cautiously after the patient has been informed of the potential adverse effects
  
  
• chronic urticaria often improves in pregnancy, reducing the need for antihistamine treatment, in some rare cases symptoms of urticaria worsen
  
  
• chlorphenamine and loratadine appear to be associated with no evidence of an increased incidence of congenital abnormality if used during pregnancy
  • with respect to chlorphenamine - there is one case report of neonatal respiratory depression following use in the third trimester and although a causal relationship was not established there is a data sheet warning that use of chlorphenamine in the third trimester may result in reactions in neonates
  • using the lowest dose possible chlorphenamine or loratadine are the antihistamines of choice in pregnancy. There is less clinical experience with cetirizine in pregnancy and therefore it should only be considered as a second-line agent (2)
    

Antihistamines and Breast feeding:

• significant amount of some antihistamines present in milk
  • although not known to be harmful, manufacturers of alimemazine, cetirizine, cinnarizine, cyproheptadine, desloratadine, dimenhydrinate, fexofenadine, hydroxyzine, loratadine, and mizolastine advise avoid
    
    
  • manufacturer of ketotifen advises avoid
    
    
  • adverse effects in infant reported with clemastine
    
    
  • therefore, antihistamines should only be used during lactation when the clinical imperative outweighs the potential harm to the child and the lowest possible dose used for the shortest possible duration. Chlorphenamine has been reported to cause drowsiness and poor feeding
    • both loratadine and cetirizine appear much safer with only low levels found in breast milk and therefore either of these drugs can be considered if required (2)
      
      
  • a review suggests (3)
    • non-sedating antihistamines and breast feeding
      • preferred choice non-sedating antihistamines are cetirizine or loratadine. This is also supported by the British Society for Allergy and Clinical Immunology
      • desloratadine, fexofenadine, and levocetirizine
        • can be used during breastfeeding when preferred choices are not suitable. They have not been studied directly in breastfeeding, but information can be extrapolated from other antihistamines. Therefore clinically significant amounts in milk are not expected
          
          
    • sedating antihistamines and breast feeding
      • preferred choice of sedating antihistamine is chlorphenamine due to extensive experience of safe use
      • hydroxyzine or promethazine can be used when breastfeeding with caution and close monitoring, if chlorphenamine is not suitable
      • considerations
        • if a sedating antihistamine is used, the infant is more likely to experience drowsiness and irritability, and close monitoring is required
        • use the lowest effective dose, for the shortest time possible; occasional doses are preferred
        • avoid use of other sedating medicines if possible
        • the National Institute for Healthcare Excellence (NICE) advises avoiding sharing a bed with the infant when sedating medication has been used, due to the increased risk of sudden unexpected death in infancy
          
          
    • effect on breast milk production
      • is conflicting data on the effect of antihistamines and breast milk production, and the evidence is very limited
        
        
    • monitoring the infant
      • when using either a non-sedating or sedating antihistamine, the infant should be monitored for the following side-effects as a precautionary measure:
        • drowsiness (for example, not waking to feed or sleeping for longer, and more often, than expected)
        • irritability
        • dry mouth
        • changes in feeding (the infant should be feeding well and continue to gain weight as expected)
      • this will quickly pick up any potential issues. Usually, further investigation is required before attributing any side-effects to the medicine
      • younger, exclusively breastfed infants are at greater risk of getting side-effects. Using larger doses of antihistamine and for long courses also increases the risk
      • using sedating antihistamines increases the risk of drowsiness and irritability.

In conclusion (4):

• first-generation antihistamines are considered safe to use during pregnancy. There are relatively fewer data on the nonsedating second-generation antihistamines; however, published studies are reassuring. All antihistamines are considered safe to use during breastfeeding, as minimal amounts are excreted in the breast milk and would not cause any adverse effects on a breastfeeding infant

Reference:

• 1) BNF (September 2009). Appendicies 4 and 5.
• 2) Powell RJ et al; British Society for Allergy and Clinical Immunology (BSACI). BSACI guidelines for the management of chronic urticaria and angio-oedema.Clin Exp Allergy. 2007 May;37(5):631-50.
• 3) NHS Specialist Pharmacy Service (January 2022). Selecting and using antihistamines during breastfeeding
• 4) So M et al. Safety of antihistamines during pregnancy and lactation.Can Fam Physician. 2010 May;56(5):427-9