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Antihistamines: if/when are first generation medications advantageous over newer antihistamines?


I've been reading and hearing more about whether first generation antihistamines should be utilized on a routine basis when we have second and third generation oral antihistamines available. I've tried to locate information directly comparing the two and what I've found is that they are of similar efficacy but the newer generations of course have fewer adverse effects. Are there specific situations you are aware of where a first generation would have an advantage over newer generations? One scenario I am thinking of is with pruritis due to atopic dermatitis, particularly at night. Not sure there is any data on this.


Newer antihistamines are long-acting, which is a significant advantage for management of urticaria, pruritus and allergic rhinitis, and they are more efficacious than first-generation antihistamines. Newer antihistamines are less likely to have clinically significant drug interactions than older antihistamines and the newer agents do not carry the risk of toxicity and death that has been associated with first-generation antihistamines. As you noted, the newer generation antihistamines have favorable side effect profiles to first-generation antihistamines. First-generation antihistamines block both histaminic and muscarinic receptors as well as passing the blood-brain barrier. Second-generation antihistamines mainly block histaminic receptors but do not or only minimally cross the blood-brain barrier. The older first-generation antihistamines cause sedation, drowsiness, fatigue and impaired alertness, concentration, multi-tasking and memory. Consequently, they impair important functions, such as learning and test performance in children and operating machinery and cars in adults. The exception to this that has been raised is severe pruritus, such as in atopic dermatitis or urticaria. In such cases, hydroxyzine may be helpful because the sedation is a potential benefit rather than a risk. Regarding the use of antihistamines in pregnancy, cetirizine and loratadine are the drugs of choice; first-generation agents should be avoided. For all of these reasons, the use of first-generation antihistamines has been generally discouraged.

I have provided some references which I hope will be useful to you.

Church MK and Church DS. Pharmacology of antihistamines. Indian J Dermatol 2013 May-Jun 58(3):2190224.
Simons FE. H1-antihistamines in children. Clin Allergy Immunol. 2002;17:437-64.
Gonzalez-Estrada A and Geraci SA. Allergy medications during pregnancy. Am J Med Sci 2016;352(3):326-331.

I hope this helps you with your patient.
Jacqueline A. Pongracic, MD, FAAAAI