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Over-the-Counter Allergy Medication in Patients with Epilepsy

Considerations and Recommendations for Healthcare Providers

Certain medications commonly used to treat allergies have the potential to increase the risk of seizures in individuals with epilepsy. When prescribing or recommending allergy medication for patients with a history of seizures or epilepsy, consider the following:


Mechanism of Action and Clinical Implications

Mechanism of Action:

Antihistamines exert their therapeutic effects by blocking or reducing the action of histamine, a biogenic amine released by mast cells and basophils in response to exposure to allergens, such as pollen, pet dander, and dust mites. Histamine is a key mediator of the allergic response, contributing to the vasodilation, increased vascular permeability, and sensory nerve stimulation that underlie the characteristic symptoms of allergic reactions.1,2

First Generation Antihistamines

Clinical Implication:

Central histaminergic neurons play a role in modulating seizure threshold. Higher levels of histamine increase the seizure threshold and may decrease the severity and duration of seizures.3 First-generation antihistamines such as diphenhydramine (Benadryl), chlorpheniramine (Chlor-Trimeton), and doxylamine succinate (Unisom) block the binding of histamine to H1-receptor, a key receptor in eliciting epileptiform activity, and are known to cross the blood-brain barrier more readily.3 Individuals with epilepsy should use these agents with caution, since seizures have occurred at therapeutic doses and especially in overdose settings with first generation antihistamines.4 First-generation antihistamines also bind to other receptors including muscarinic, alpha adrenergic amongst others which increases the risk for autonomic and vascular adverse effects.

Common OTC Products:

Diphenhydramine is a component of many over the counter (OTC) products, including sleep aids, nighttime medicines, cough/cold remedies, anti-emetics, and combination products. Patients should be advised to read labels carefully to avoid inadvertent consumption of these drugs.5

 

Second Generation Antihistamines

Clinical Implication:

Second-generation antihistamines such as loratadine (Claritin) and fexofenadine (Allegra) cross the blood-brain barrier to a much lesser extent. As a result, they are less likely to cause central nervous system (CNS) effects or interact with other CNS-active medications at therapeutic doses, making them generally safer for patients with epilepsy.5 However, there may be exceptions. A post-marketing safety study based on registry data from Nordic countries (Denmark, Finland, Norway, Sweden) and recent case reports suggest that desloratadine exposures in children without a diagnosis of seizures or epilepsy may increase the risk of seizures.6-8 Additionally, Kim and colleagues published a retrospective, cross-sectional study in 2020, finding that amongst the drugs studied for drug-induced seizures, antihistamines as a class including dimenhydrinate, pheniramine, olopatadine and even the second generation cetirizine and levocetirizine, were the most likely to cause drug-induced new-onset seizures.9

 

Non-Antihistamine Options

Intranasal steroids
(i.e., fluticasone, triamcinolone, budesonide)
Cromolyn Sodium
(Nasalcrom)

Expert Opinion and Recommendations for Healthcare Providers

Expert Consensus:

Leading experts in epilepsy and allergy management recommend second-generation antihistamines and non-antihistamine options like intranasal corticosteroids and cromolyn sodium for patients with epilepsy due to their favorable safety profiles.10,11 However, given the recent data, antihistamines in general should be used with caution in persons with epilepsy.

Prescriber information:

Healthcare providers should be vigilant in reviewing the active ingredients of OTC allergy medications and consider the potential impact on seizure control when advising patients with epilepsy.

 

 

Resources & References

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1 Simons FE, Simons KJ. Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011;128(6):1139-1150.e4. doi:10.1016/j.jaci.2011.09.005

2 Simons FE, Simons KJ. H1 antihistamines: current status and future directions. World Allergy Organ J. 2008;1(9):145-155. doi:10.1186/1939-4551-1-9-145.

3 Yokoyama H, Iinuma K. Histamine and Seizures : Implications for the Treatment of Epilepsy. CNS Drugs. 1996;5(5):321-330. doi:10.2165/00023210-199605050-00002

4 Miyata I, Saegusa H, Sakurai M. Seizure-modifying potential of histamine H1 antagonists: a clinical observation. Pediatr Int. 2011;53(5):706-708. doi:10.1111/j.1442-200X.2011.03328.x

5 Epilepsy Foundation. (2023). Seizure Medication and Other Treatments. Retrieved on September 26, 2024 from https://www.epilepsy.com

6 Han X, Zan X, Xiong F, Nie X, Peng L. Epileptic convulsions probably induced by desloratadine: a case report. Eur J Hosp Pharm. 2023;30(4):e17. doi:10.1136/ejhpharm-2021-002774

7 Ersbøll AK, Sengupta K, Pukkala E, et al. Desloratadine Exposure and Incidence of Seizure: A Nordic Post-authorization Safety Study Using a New-User Cohort Study Design, 2001-2015. Drug Saf. 2021;44(11):1231-1242. doi:10.1007/s40264-021-01106-7

8 Cerminara C, El-Malhany N, Roberto D, Lo Castro A, Curatolo P. Seizures induced by desloratadine, a second-generation antihistamine: clinical observations. Neuropediatrics. 2013;44(4):222-224. doi:10.1055/s-0033-1333871

9 Kim H, Kim SH, Kim JB. Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurol Sci. 2021;42(6):2505-2508. doi:10.1007/s10072-021-05043-2

10 Dykewicz MS, Wallace DV, Baroody F, et al. Treatment of seasonal allergic rhinitis: An evidence-based focused 2017 guideline update. Ann Allergy Asthma Immunol. 2017;119(6):489-511.e41. doi:10.1016/j.anai.2017.08.012

11 Epilepsy Foundation. (2024). Over Counter Medications and Epilepsy. Retrieved on September 26, 2024 from https://www.epilepsy.com

12 FDA warns about serious problems with high doses of allergy medicine diphenhydramine (Benadryl). https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-problems-high-doses-allergy-medicine-diphenhydramine-benadryl. Accessed July 29, 2024.

13 Thundiyil JG, Kearney TE, Olson KR. Evolving epidemiology of drug-induced seizures reported to a Poison Control Center System. J Med Toxicol 2007;3:15–19.

 

This information was curated by the AES Treatments Committee to offer providers guidance on approved over-the-counter (OTC) drugs with an emphasis on their use by people with epilepsy. The information presented on this page is designed to be informational for a broad audience and is not medical advice. For personalized recommendations, speak to a pharmacist or healthcare provider.