Q:

4/5/2012
Hello, recently I've had patients tell me their pharmacist said they should not take anti-Histamines if they have experienced tachycardia (a-fib or other types), even if rate controlled on meds. These are patients on fexofenadine, loratidine and cetirizine. I just received a letter from the Clinical Pharmacist for Medication Policy of one of our local insurances stating "anti-histamines have anti-cholinergic activity that blocks cholinergic (slowing) activity on heart rate." and the pt should avoid all anti-his since he has a h/o of a-fib with a pacemaker on Diltiazem, Cozaar and Digoxin. I discussed this with his cardiologist who said anti-his are not a concern, just when combined with decongestants. I completely agree. My question is-are there new studies showing anti-His are contraindicated in such patients? The pharmacist makes a blanket statement of all anti-his should be avoided. I've always thought the second generation antiHis were safer in general b/c less crossing of the blood brain barrier. Do you think any are safer in patients with atril fib or other arrythmias? Thank you.

A:

Thank you for your inquiry.

No, I am not aware of any new data indicating that "second-generation" antihistamines have any toxic effect on the heart. These agents, to the best of my knowledge, are devoid of anticholinergic effects (see abstract copied below), and in a very recent thorough review of antihistamines by Estelle and Keith Simons, the lack of cardiac side effects of second-generation antihistamines was emphasized. I have copied for you a quote from their review in this regard.

As you know, cardiac side effects of early second-generation antihistamines (e.g., astemizole) were related to their ability to predispose to torsade de pointes. I assume that the pharmacy bulletin was referring to this phenomenon. The only other thing that I could think of would be the anticholinergic effect. Neither fexofenadine, cetirizine, or loratadine have been shown, to my knowledge, to exhibit anticholinergic activity or predispose to torsade de pointes.

Thus I personally see no reason why they cannot be used in patients with atrial fibrillation. Therefore I have no insight as to where the admonition sent from your clinical pharmacist arose. Perhaps you might contact the clinical pharmacist in question and ask for references to substantiate the claim. If you do find any evidence that contradicts the opinion expressed in this response, we would be very grateful if you would share it with us.

Thank you again for your inquiry and we hope this response is helpful to you.

Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models
European Journal of Pharmacology, Volume 506, Issue 3, 4 January 2005, Pages 257–264
Abstract
We determined the relative rank orders of anticholinergic potencies of 10 antihistamines in two functional bioassays: (1) an in vitro assay measuring inhibition of carbachol-induced contractions of isolated guinea pig trachealis muscle, (2) an in vivo bioassay comparing systemic hypotensive responses to bolus i.v. injections of acetylcholine before and after infusions of an antihistamine in anaesthetized rats. In vitro, the rank order of anticholinergic potencies of the antihistamines was cyproheptadine>promethazine>desloratadine>diphenhydramine>loratadine>chlorpheniramine>hydroxyzine>pyrilamine. The pA2 values ranged from 8.2±0.4 for cyproheptadine to 4.8±0.4 for pyrilamine. Fexofenadine and cetirizine (up to 3×10−4 M) were inactive. In vivo, five antihistamines showed anticholinergic activity: cyproheptadine>promethazine>desloratadine>loratadine>diphenhydramine. The remaining antihistamines had no significant effect at i.v. infusion doses up to 50 ìmol/kg. Cetirizine and fexofenadine did not antagonize cholinergic responses.

Histamine and H1-antihistamines: Celebrating a century of progress
F. Estelle R. Simons, MD, FRCPC, and Keith J. Simons, PhD
Journal of Allergy and Clinical Immunology Vol. 128, Issue 6, Pages 1139-1150.e4
"Concerns are minimal in countries in which regulatory agencies scrutinize second generation
H1-antihistamines for potential cardiac toxicity and do not approve them for use if this is identified."

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology